00733nas a2200205 4500008004100000245010300041210006900144260003900213300001200252520010200264653001100366653002200377100001600399700001700415700001200432700001300444700001400457700002000471856003600491 1992 eng d00aRespondent Burden in Studies of the Elderly: Experience from the Cardiovascular Health Study (CHS)0 aRespondent Burden in Studies of the Elderly Experience from the bMarion Merrell Dow Incc1993-01-01 a135-1523 aACC Workshop entitled "Inclusion of Elderly Individuals in Clinical Trials" September 15-16, 199210aHealth10arespondent burden1 aManolio, TA1 aHermanson, B1 aHill, J1 aMeyer, M1 aCruise, G1 aAnton-Culver, H uhttps://chs-nhlbi.org/node/152602616nas a2200301 4500008004100000022001400041245009700055210006900152260001300221300001100234490000600245520179400251653000902045653002202054653002802076653001902104653002602123653001102149653001102160653000902171100001502180700001502195700001702210700001702227700001702244700001702261856003602278 1993 eng d a1047-279700aRecruitment of adults 65 years and older as participants in the Cardiovascular Health Study.0 aRecruitment of adults 65 years and older as participants in the c1993 Jul a358-660 v33 a
Few large-scale epidemiologic studies have enrolled older adults; hence, little is known about the feasibility of recruiting this group for long-term population-based studies. In this article we present the recruitment experience of the Cardiovascular Health Study (CHS), a population-based, longitudinal study of cardiovascular diseases in adults 65 years and older. Participants were sampled from the Health Care Financing Administration's (HCFA) Medicare eligibility lists in four US communities. Letters were mailed to 11,955 sampled individuals. Persons recruited were required to complete an extensive home interview and then a 4-hour in-clinic examination. Excluded were persons who were expected to be able to complete the baseline examination and who were not expected to return for the 3-year follow-up. Some 3654 participants were recruited from those randomly selected from the Medicare sampling frame. In addition, 1547 other age-eligible persons living in the household with the sampled individuals also participated, yielding a total of 5201 participants. Of those who were contacted, 9.6% were ineligible and 34.9% refused participation. Among those eligible, 38.6% refused and 57.3% were enrolled (the remaining did not refuse but were not enrolled before the recruitment ended). Data from a subsample indicate that compared to those who were ineligible or who refused, enrolled participants were younger, more highly educated, more likely to be married, and less likely to report limitations in activity. Compared to those who were eligible but refused, enrolled participants were less likely to have high blood pressure and stroke and more likely to have quit smoking and to perceive their health status as very good or excellent.(ABSTRACT TRUNCATED AT 250 WORDS)
10aAged10aAged, 80 and over10aCardiovascular Diseases10aCohort Studies10aEpidemiologic Methods10aFemale10aHumans10aMale1 aTell, G, S1 aFried, L P1 aHermanson, B1 aManolio, T A1 aNewman, A, B1 aBorhani, N O uhttps://chs-nhlbi.org/node/143602834nas a2200325 4500008004100000022001400041245019000055210006900245260001300314300001100327490000700338520187600345653000902221653002202230653002102252653002102273653001902294653001102313653001102324653000902335653001202344653002002356100001502376700001602391700001502407700001802422700001702440700001502457856003602472 1994 eng d a0009-732200aRelation of smoking with carotid artery wall thickness and stenosis in older adults. The Cardiovascular Health Study. The Cardiovascular Health Study (CHS) Collaborative Research Group.0 aRelation of smoking with carotid artery wall thickness and steno c1994 Dec a2905-80 v903 aBACKGROUND: Cigarette smoking has been associated with increased risk of atherosclerotic diseases in hospital-based studies and in studies of middle-aged populations but not in population-based studies of older adults with and without clinical cardiovascular disease.
METHODS AND RESULTS: We investigated the relation of smoking to carotid artery atherosclerotic disease, expressed as intimal-medial wall thickness and arterial lumen narrowing (stenosis) measured by ultrasound. Subjects were 5116 older adults participating in the baseline examination of the Cardiovascular Health Study, a community-based study of cardiovascular diseases in older age. With increased smoking there was significantly greater internal and common carotid wall thickening and internal carotid stenosis: current smokers > former smokers > never-smokers; for instance, the unadjusted percent stenosis was 24%, 20%, and 16%, respectively (P < .0001). A significant dose-response relation was seen with pack-years of smoking. These findings persisted after adjusting for other cardiovascular risk factors and were also confirmed when analyses were restricted to those without prevalent cardiovascular disease. The difference in internal carotid wall thickness between current smokers and nonsmokers was greater than the difference associated with 10 years of age among never-smoking participants (0.39 mm versus 0.31 mm). Among all participants, the prevalence of clinically significant (> or = 50%) internal carotid stenosis increased from 4.4% in never-smokers to 7.3% in former smokers to 9.5% in current smokers (P < .0001).
CONCLUSIONS: These findings extend previous reports of a positive relation between smoking and carotid artery disease to a population-based sample of older adults using several different indicators of atherosclerotic disease.
10aAged10aAged, 80 and over10aCarotid Arteries10aCarotid Stenosis10aCohort Studies10aFemale10aHumans10aMale10aSmoking10aUltrasonography1 aTell, G, S1 aPolak, J, F1 aWard, B, J1 aKittner, S, J1 aSavage, P, J1 aRobbins, J uhttps://chs-nhlbi.org/node/142602295nas a2200373 4500008004100000022001400041245012500055210006900180260001300249300001000262490000800272520124200280653000901522653002201531653001001553653002201563653002801585653001101613653001101624653000901635653002401644653002101668653003101689653002401720653001701744653002401761653001201785100001801797700001801815700001701833700001901850700001601869856003601885 1994 eng d a1073-449X00aRespiratory muscle strength in the elderly. Correlates and reference values. Cardiovascular Health Study Research Group.0 aRespiratory muscle strength in the elderly Correlates and refere c1994 Feb a430-80 v1493 aMaximal inspiratory pressure (MIP) was assessed in 4,443 ambulatory participants of the Cardiovascular Health Study, 65 yr of age and older, sampled from four communities. Maximal expiratory pressure (MEP) was also measured in 790 participants from a single clinic. Positive predictors of MIP included male sex, FVC, handgrip strength, and higher levels of lean body mass (or low bioelectric resistance). Negative predictors were age, current smoking, self-reported fair to poor general health, and waist size. Both participant and technician learning effects were noted, but there was no independent effect of race, hypertension, cardiovascular disease, or diabetes. A healthy subgroup was identified by excluding current smokers, those with fair to poor general health, or an FEV1 less than 65% of predicted. Mean values determined from the healthy group were 57/116 cm H2O (MIP/MEP) for women, and 83/174 for men. Lower limits of the normal range (fifth percentiles) were 45 to 60% of the mean predicted values. The reference equations derived from this group of healthy 65 to 85-yr-olds may be used by pulmonary function laboratories and respiratory therapists who evaluate the respiratory muscle strength of elderly patients.
10aAged10aAged, 80 and over10aAging10aBody Constitution10aCardiovascular Diseases10aFemale10aHumans10aMale10aProspective Studies10aReference Values10aRespiratory Function Tests10aRespiratory Muscles10aRisk Factors10aSex Characteristics10aSmoking1 aEnright, P, L1 aKronmal, R, A1 aManolio, T A1 aSchenker, M, B1 aHyatt, R, E uhttps://chs-nhlbi.org/node/143902656nas a2200361 4500008004100000022001400041245015500055210006900210260001300279300001000292490000800302520159900310653001601909653000901925653002201934653002101956653001101977653002901988653001102017653001702028653003402045653000902079653001602088653003102104653001902135100001802154700001802172700001602190700001602206700001902222700001702241856003602258 1995 eng d a0012-369200aReduced vital capacity in elderly persons with hypertension, coronary heart disease, or left ventricular hypertrophy. The Cardiovascular Health Study.0 aReduced vital capacity in elderly persons with hypertension coro c1995 Jan a28-350 v1073 aThe Cardiovascular Health Study provided the opportunity to determine the association of subclinical and clinical cardiovascular disease with pulmonary function in a population sample of elderly adults. Included were 2,955 women and 2,246 men over age 64 years who were recruited for this observational study from four communities and completed extensive examinations that included spirometry, echocardiograms, and blood pressure. Current smokers, past smokers with >20 pack-years of smoking, and persons with a history of asthma, chronic bronchitis, or emphysema were excluded from this analysis, leaving 2,784 (55%) of the cohort. Systolic hypertension or coronary artery disease was associated with 40- to 100-mL decrements in FEV1, and 50- to 150-mL decrements in FVC, while a history of congestive heart failure was associated with 200 to 300 mL lower FEV1 and FVC values (p < 0.0001), after correcting for age, height, and waist size. Higher left ventricular (LV) mass was also significantly associated with a decrease in FEV1 and FVC in multivariate models. This relationship was strongest with the end-diastolic LV posterior wall thickness component of LV mass. In summary, FEV1 and FVC are reduced in elderly persons with hypertension, ischemic heart disease, higher disease, higher LV mass, and congestive heart failure, though the magnitude of these associations is relatively small unless heart failure supervenes. Substantial decrements in percent predicted FEV1 and FVC should not be attributed to the presence of uncomplicated ischemic heart disease or hypertension alone.
10aAge Factors10aAged10aAged, 80 and over10aCoronary Disease10aFemale10aForced Expiratory Volume10aHumans10aHypertension10aHypertrophy, Left Ventricular10aMale10aMiddle Aged10aVentricular Function, Left10aVital Capacity1 aEnright, P, L1 aKronmal, R, A1 aSmith, V, E1 aGardin, J M1 aSchenker, M, B1 aManolio, T A uhttps://chs-nhlbi.org/node/141902779nas a2200409 4500008004100000022001400041245010900055210006900164260001300233300001100246490000700257520166200264653000901926653001801935653003101953653001901984653002802003653001902031653001602050653001102066653001102077653000902088653001602097653001902113653001502132653003102147653001702178653001202195653002002207653001802227100001702245700001802262700002202280700001602302700001502318856003602333 1996 eng d a1079-564200aRisk factors for abdominal aortic aneurysms in older adults enrolled in The Cardiovascular Health Study.0 aRisk factors for abdominal aortic aneurysms in older adults enro c1996 Aug a963-700 v163 aB-mode ultrasound examinations of the abdominal aorta were performed from 1990 to 1992 to evaluate the prevalence of abdominal aortic aneurysm (AAA) in a subgroup of the Pittsburgh cohort (656 participants, aged 65 to 90 years) of the Cardiovascular Health Study (CHS). In this pilot study, we evaluated various definitions of aneurysm and the reproducibility of the measurements. In year 5 (1992 to 1993) of the CHS, the entire cohort (4741 participants) was examined. AAA was defined as an infrarenal aortic diameter of > or= 3.0 cm, or a ratio of infrarenal to suprarenal diameter of > or= 1.2, or a history of AAA repair. For the entire CHS cohort, prevalence of aneurysms was 9.5% (451/4741) overall, with a prevalence among men of 14.2% (278/1956) and prevalence among women of 6.2% (173/2785). Variables significantly related to AAA were older age; male sex; history of angina, coronary heart disease, and myocardial infarction; lower ankle-arm blood pressure ratio; higher maximum carotid stenosis; greater intima-media thickness of the internal carotid artery; higher creatinine; lower HDL levels and higher LDL levels; and cigarette smoking. The study has documented the strong association of cardiovascular risk factors and measures of clinical and subclinical atherosclerosis and cardiovascular disease and prevalence of aneurysms. We used a definition that is more sensitive than previously reported (diameter or ratio), which allowed the detection of smaller aneurysms and possibly those at an earlier stage of development. Follow-up of this cohort may lead to new criteria for determining the risk factors for progression of aneurysms.
10aAged10aAnthropometry10aAortic Aneurysm, Abdominal10aBlood Pressure10aCardiovascular Diseases10aCohort Studies10aComorbidity10aFemale10aHumans10aMale10aMiddle Aged10aPilot Projects10aPrevalence10aReproducibility of Results10aRisk Factors10aSmoking10aUltrasonography10aUnited States1 aAlcorn, H, G1 aWolfson, S, K1 aSutton-Tyrrell, K1 aKuller, L H1 aO'Leary, D uhttps://chs-nhlbi.org/node/145902957nas a2200349 4500008004100000022001400041245017400055210006900229260001300298300001100311490000700322520194700329653000902276653001002285653002302295653002802318653002502346653001102371653001102382653000902393653002402402653001602426100001502442700001902457700001502476700001502491700001602506700001502522700001802537700001602555856003602571 1997 eng d a1079-564200aRelationship of C-reactive protein to risk of cardiovascular disease in the elderly. Results from the Cardiovascular Health Study and the Rural Health Promotion Project.0 aRelationship of Creactive protein to risk of cardiovascular dise c1997 Jun a1121-70 v173 aMarkers of inflammation, such as C-reactive protein (CRP), are related to risk of cardiovascular disease (CVD) events in those with angina, but little is known about individuals without prevalent clinical CVD. We performed a prospective, nested case-control study in the Cardiovascular Health Study (CHS; 5201 healthy elderly men and women). Case subjects (n = 146 men and women with incident CVD events including angina, myocardial infarction, and death) and control subjects (n = 146) were matched on the basis of sex and the presence or absence of significant subclinical CVD at baseline (average follow-up, 2.4 years). In women but not men, the mean CRP level was higher for case subjects than for control subjects (P < or = .05). In general, CRP was higher in those with subclinical disease. Most of the association of CRP with female case subjects versus control subjects was in the subgroup with subclinical disease; 3.33 versus 1.90 mg/L, P < .05, adjusted for age and time of follow-up. Case-control differences were greatest when the time between baseline and the CVD event was shortest. The strongest associations were with myocardial infarction, and there was an overall odds ratio for incident myocardial infarction for men and women with subclinical disease (upper quartile versus lower three quartiles) of 2.67 (confidence interval [CI] = 1.04 to 6.81), with the relationship being stronger in women (4.50 [CI = 0.97 to 20.8]) than in men (1.75 [CI = 0.51 to 5.98]). We performed a similar study in the Rural Health Promotion Project, in which mean values of CRP were higher for female case subjects than for female control subjects, but no differences were apparent for men. Comparing the upper quintile with the lower four, the odds ratio for CVD case subjects was 2.7 (CI = 1.10 to 6.60). In conclusion, CRP was associated with incident events in the elderly, especially in those with subclinical disease at baseline.
10aAged10aAging10aC-Reactive Protein10aCardiovascular Diseases10aCase-Control Studies10aFemale10aHumans10aMale10aProspective Studies10aSex Factors1 aTracy, R P1 aLemaitre, R, N1 aPsaty, B M1 aIves, D, G1 aEvans, R, W1 aCushman, M1 aMeilahn, E, N1 aKuller, L H uhttps://chs-nhlbi.org/node/148403278nas a2200481 4500008004100000022001400041245010400055210006900159260001300228300001100241490000700252520195900259653003902218653000902257653002202266653001002288653002802298653002402326653001402350653002402364653004002388653001102428653001302439653001802452653001102470653003102481653000902512653002702521653003002548653001702578653001602595653001802611100001602629700001702645700001502662700001202677700001302689700001302702700001602715700001302731700001602744856003602760 1998 eng d a0039-249900aRelationship between ApoE, MRI findings, and cognitive function in the Cardiovascular Health Study.0 aRelationship between ApoE MRI findings and cognitive function in c1998 Feb a388-980 v293 aBACKGROUND AND PURPOSE: We determined the relationship between apolipoprotein (Apo)E, MRI, and low cognitive scores.
METHODS: The relationship between age, education, ApoE genotype, MRI examination of the brain, subclinical and clinical cardiovascular disease, and low (<80) score on the Modified Mini-Mental State Examination (3MSE, as modified by Teng and Chui) was evaluated for 3469 black and white participants in the Cardiovascular Health Study (CHS) in years 5 and 6 of the study. The participants were followed for up to 3 years.
RESULTS: The prevalence of scores <80 in years 5 and 6 of the CHS was 8.2% for participants without and 20.4% for those with prior history of stroke. Age, race, and education were important determinants of low 3MSE scores. The prevalence of ApoE-4 (odds ratio [OR], 1.6 [1.1 to 2.1]) was directly related to scores <80, as was high ventricular volume (OR, 1.6 [1.2 to 2.3]), high white matter grade (OR, 1.4 [1.1 to 1.9]), and infarctlike lesions (OR, 1.6 [1.2 to 2.1]) on the MRI in the multivariate analysis. A five-point or greater decline in scores over up to 3 years was more often observed for participants with low 3MSE scores at year 5, at older ages, with lower education, and experiencing incident stroke (OR, 3.6 [1.2 to 10.6]), ApoE-4 genotype (OR, 1.8 [1.4 to 2.3]), and with MRI findings of high ventricular volume (OR, 2.0 [1.5 to 2.7]), and infarctlike lesions (OR, 1.2 [0.9 to 1.5]).
CONCLUSIONS: These results demonstrate that vascular changes on MRI, measures of brain atrophy, ApoE-4, and age, education, and race are associated with low cognitive scores among older individuals. The MRI of the brain provides valuable information related to cognitive tests and decline over time. The potential exists for using MRI measurements to identify high-risk individuals for dementia and to test potential interventions to reduce the risk of dementia.
10aAfrican Continental Ancestry Group10aAged10aApolipoproteins E10aBrain10aCardiovascular Diseases10aCerebral Infarction10aCognition10aCognition Disorders10aEuropean Continental Ancestry Group10aFemale10aGenotype10aHealth Status10aHumans10aMagnetic Resonance Imaging10aMale10aMental Status Schedule10aPolymerase Chain Reaction10aRisk Factors10aSex Factors10aUnited States1 aKuller, L H1 aShemanski, L1 aManolio, T1 aHaan, M1 aFried, L1 aBryan, N1 aBurke, G, L1 aTracy, R1 aBhadelia, R uhttps://chs-nhlbi.org/node/149402386nas a2200301 4500008004100000022001400041245010700055210006900162260001300231300000900244490000700253520156300260653002101823653000901844653001001853653002001863653001101883653001101894653003101905653000901936653002101945653001701966100001501983700002001998700001302018700001702031856003602048 1998 eng d a0003-994200aRelationship between balance and abnormalities in cerebral magnetic resonance imaging in older adults.0 aRelationship between balance and abnormalities in cerebral magne c1998 Jan a73-90 v553 aBACKGROUND: Falling is a major cause of disability and morbidity among older adults. Because poor balance is a major reason for frequent falls, assessment of balance and its risk factors are important. In this study, we postulated that cerebral changes identified on magnetic resonance (MR) imaging are related to balance, and that older adults with balance problems would have significantly greater prevalence of such brain abnormalities than older adults without balance problems.
DESIGN AND MEASUREMENTS: Several measures of balance were examined in more than 700 community-dwelling older men and women, blacks and whites. Balance measures included dynamic posturography, functional reach, Romberg and 1-foot stand tests, tandem stand, and 1-foot stand. Cerebral MR imaging assessments included ventricular size, sulcal widening, white matter disease, and ischemic infarctions. Cardiovascular disease and hypertension were determined and controlled for in the analyses.
RESULTS: A summary of the balance measures was significantly related to each of the 4 MR imaging measures, with those with poorer balance having more disease. The strongest associations with balance were seen for white matter disease and ventricular size. All but the ischemic infarction variable remained significantly associated with balance after adjustments for sex, race, age, cardiovascular disease, and hypertension.
CONCLUSION: Cerebral changes identified by MR imaging are associated with poorer balance among older adults.
10aAccidental Falls10aAged10aAging10aCerebral Cortex10aFemale10aHumans10aMagnetic Resonance Imaging10aMale10aPostural Balance10aRisk Factors1 aTell, G, S1 aLefkowitz, D, S1 aDiehr, P1 aElster, A, D uhttps://chs-nhlbi.org/node/149202753nas a2200301 4500008004100000022001400041245007800055210006900133260001600202300001100218490000700229520192500236653001102161653002002172653003102192653002002223653002602243653001702269100001802286700001902304700001502323700001702338700001602355700001402371700001502385700001602400856003502416 1998 eng d a0161-810500aReliability of scoring respiratory disturbance indices and sleep staging.0 aReliability of scoring respiratory disturbance indices and sleep c1998 Nov 01 a749-570 v213 aSTUDY OBJECTIVES: Unattended, home-based polysomnography (PSG) is increasingly used in both research and clinical settings as an alternative to traditional laboratory-based studies, although the reliability of the scoring of these studies has not been described. The purpose of this study is to describe the reliability of the PSG scoring in the Sleep Heart Health Study (SHHS), a multicenter study of the relation between sleep-disordered breathing measured by unattended, in-home PSG using a portable sleep monitor, and cardiovascular outcomes.
DESIGN: The reliability of SHHS scorers was evaluated based on 20 randomly selected studies per scorer, assessing both interscorer and intrascorer reliability.
RESULTS: Both inter- and intrascorer comparisons on epoch-by-epoch sleep staging showed excellent reliability (kappa statistics >0.80), with stage 1 having the greatest discrepancies in scoring and stage 3/4 being the most reliably discriminated. The arousal index (number of arousals per hour of sleep) was moderately reliable, with an intraclass correlation (ICC) of 0.54. The scorers were highly reliable on various respiratory disturbance indices (RDIs), which incorporate an associated oxygen desaturation in the definition of respiratory events (2% to 5%) with or without the additional use of associated EEG arousal in the definition of respiratory events (ICC>0.90). When RDI was defined without considering oxygen desaturation or arousals to define respiratory events, the RDI was moderately reliable (ICC=0.74). The additional use of associated EEG arousals, but not oxygen desaturation, in defining respiratory events did little to increase the reliability of the RDI measure (ICC=0.77).
CONCLUSIONS: The SHHS achieved a high degree of intrascorer and interscorer reliability for the scoring of sleep stage and RDI in unattended in-home PSG studies.
10aHumans10aPolysomnography10aReproducibility of Results10aResearch Design10aSleep Apnea Syndromes10aSleep Stages1 aWhitney, C, W1 aGottlieb, D, J1 aRedline, S1 aNorman, R, G1 aDodge, R, R1 aShahar, E1 aSurovec, S1 aNieto, F, J uhttps://chs-nhlbi.org/node/64303834nas a2200409 4500008004100000022001400041245008800055210006900143260001600212300001100228490000800239520272800247653002202975653000902997653002203006653002803028653001903056653001103075653002203086653001903108653001103127653000903138653001403147653003203161653002403193653001703217653001803234100001503252700001803267700001703285700001503302700002103317700001603338700001803354700001603372856003603388 1998 eng d a0098-748400aRisk factors for 5-year mortality in older adults: the Cardiovascular Health Study.0 aRisk factors for 5year mortality in older adults the Cardiovascu c1998 Feb 25 a585-920 v2793 aCONTEXT: Multiple factors contribute to mortality in older adults, but the extent to which subclinical disease and other factors contribute independently to mortality risk is not known.
OBJECTIVE: To determine the disease, functional, and personal characteristics that jointly predict mortality in community-dwelling men and women aged 65 years or older.
DESIGN: Prospective population-based cohort study with 5 years of follow-up and a validation cohort of African Americans with 4.25-year follow-up.
SETTING: Four US communities.
PARTICIPANTS: A total of 5201 and 685 men and women aged 65 years or older in the original and African American cohorts, respectively.
MAIN OUTCOME MEASURES: Five-year mortality.
RESULTS: In the main cohort, 646 deaths (12%) occurred within 5 years. Using Cox proportional hazards models, 20 characteristics (of 78 assessed) were each significantly (P<.05) and independently associated with mortality: increasing age, male sex, income less than $50000 per year, low weight, lack of moderate or vigorous exercise, smoking for more than 50 pack-years, high brachial (>169 mm Hg) and low tibial (< or = 127 mm Hg) systolic blood pressure, diuretic use by those without hypertension or congestive heart failure, elevated fasting glucose level (>7.2 mmol/L [130 mg/dL]), low albumin level (< or = 37 g/L), elevated creatinine level (> or = 106 micromol/L [1.2 mg/dL]), low forced vital capacity (< or = 2.06 mL), aortic stenosis (moderate or severe) and abnormal left ventricular ejection fraction (by echocardiography), major electrocardiographic abnormality, stenosis of internal carotid artery (by ultrasound), congestive heart failure, difficulty in any instrumental activity of daily living, and low cognitive function by Digit Symbol Substitution test score. Neither high-density lipoprotein cholesterol nor low-density lipoprotein cholesterol was associated with mortality. After adjustment for other factors, the association between age and mortality diminished, but the reduction in mortality with female sex persisted. Finally, the risk of mortality was validated in the second cohort; quintiles of risk ranged from 2% to 39% and 0% to 26% for the 2 cohorts.
CONCLUSIONS: Objective measures of subclinical disease and disease severity were independent and joint predictors of 5-year mortality in older adults, along with male sex, relative poverty, physical activity, smoking, indicators of frailty, and disability. Except for history of congestive heart failure, objective, quantitative measures of disease were better predictors of mortality than was clinical history of disease.
10aAfrican Americans10aAged10aAged, 80 and over10aCardiovascular Diseases10aCohort Studies10aFemale10aFollow-Up Studies10aHealth Surveys10aHumans10aMale10aMortality10aProportional Hazards Models10aProspective Studies10aRisk Factors10aUnited States1 aFried, L P1 aKronmal, R, A1 aNewman, A, B1 aBild, D, E1 aMittelmark, M, B1 aPolak, J, F1 aRobbins, J, A1 aGardin, J M uhttps://chs-nhlbi.org/node/149801938nas a2200277 4500008004100000022001400041245011500055210006900170260001300239300001200252490000700264520116100271653000901432653001501441653001501456653001101471653001101482653000901493653002301502653001601525653002701541653002601568100001601594700001401610856003601624 1998 eng d a1079-501400aThe role of neuroticism and mastery in spouse caregivers' assessment of and response to a contextual stressor.0 arole of neuroticism and mastery in spouse caregivers assessment c1998 May aP155-640 v533 aData from more than 300 spousal caregivers and their care recipients were analyzed to demonstrate the effects of caregivers' personality attributes--neuroticism and mastery--on their assessment of a contextual stressor (the care recipient's behavioral and functional impairment) and on their experience of distress associated with that stressor. Caregivers who were high in neuroticism and/or low in mastery reported higher levels of behavioral and functional impairment in their disabled spouse and experienced more strain and depressive symptoms associated with caregiving relative to caregivers with lower neuroticism or higher mastery scores. We further showed that the widely reported association between caregiver-assessed impairment of the care recipient and caregiver outcomes can in part be explained by caregivers' personality attributes, such as neuroticism and mastery. Our findings that caregivers' personality variables are related to their assessment of a given objective stressor and their response to a given level of stress have implications for interventions targeting caregivers and for the use of caregivers as proxy informants.
10aAged10aCaregivers10aDepression10aFemale10aHumans10aMale10aNeurotic Disorders10aPersonality10aPersonality Assessment10aStress, Psychological1 aBookwala, J1 aSchulz, R uhttps://chs-nhlbi.org/node/150503060nas a2200385 4500008004100000022001400041245009800055210006900153260001600222300001100238490000700249520200000256653000902256653002202265653001202287653001002299653002002309653002402329653002302353653001102376653002602387653001802413653001102431653003102442653000902473653002702482653002402509653002402533100001702557700001702574700001602591700001602607700001602623856003502639 1999 eng d a0028-387800aRelation of education to brain size in normal aging: implications for the reserve hypothesis.0 aRelation of education to brain size in normal aging implications c1999 Jul 13 a189-960 v533 aOBJECTIVE: To examine the relations between education and age-related changes in brain structure in a nonclinical sample of elderly adults.
BACKGROUND: Education may protect against cognitive decline in late life--an observation that has led to the "reserve" hypothesis of brain aging. Little is known, however, about the effect of education on age-related changes in brain structure.
METHODS: Quantitative MRI of the brain was performed in 320 elderly volunteers (age range, 66 to 90 years) living independently in the community (Mini-Mental State Examination scores > or =24), all of whom were participants in the Cardiovascular Health Study. Blinded measurements of global and regional brain size were made from T1-weighted axial images using computer-assisted edge detection and trace methodology. High measurement reliabilities were obtained.
RESULTS: Regression analyses (adjusting for the effects of intracranial size, sex, age, age-by-sex interactions, and potential confounders) revealed significant main effects of education on peripheral (sulcal) CSF volume-a marker of cortical atrophy. Each year of education was associated with an increase in peripheral CSF volume of 1.77 mL (p<0.03). As reported previously, main effects of age (but not education) were observed for all of the remaining brain regions examined, including cerebral hemisphere volume, frontal region area, temporoparietal region area, parieto-occipital region area, lateral (Sylvian) fissure volume, lateral ventricular volume, and third ventricle volume.
CONCLUSIONS: The authors' findings demonstrate a relation between education and age-related cortical atrophy in a nonclinical sample of elderly persons, and are consistent with the reserve hypothesis as well as with a small number of brain imaging studies in patients with dementia. The neurobiological basis and functional correlates of this education effect require additional investigation.
10aAged10aAged, 80 and over10aAtrophy10aBrain10aCerebral Cortex10aCerebrospinal Fluid10aEducational Status10aFemale10aFunctional Laterality10aHealth Status10aHumans10aMagnetic Resonance Imaging10aMale10aMental Status Schedule10aRegression Analysis10aSex Characteristics1 aCoffey, C, E1 aSaxton, J, A1 aRatcliff, G1 aBryan, R, N1 aLucke, J, F uhttps://chs-nhlbi.org/node/59802701nas a2200397 4500008004100000022001400041245009100055210006900146260001300215300001000228490000800238520158700246653000901833653002801842653002801870653003801898653001101936653001101947653000901958653001601967653002001983653001602003653002602019653003002045653002602075653003102101100001902132700001802151700001802169700001202187700001602199700001602215700001602231700002002247856003602267 1999 eng d a1073-449X00aRelation of sleepiness to respiratory disturbance index: the Sleep Heart Health Study.0 aRelation of sleepiness to respiratory disturbance index the Slee c1999 Feb a502-70 v1593 aObstructive sleep apnea syndrome is a well recognized cause of excessive sleepiness; however, the relation of sleepiness to mild sleep-disordered breathing (SDB), which affects as much as half the adult population, is uncertain. In order to explore this relation, we conducted a cross-sectional cohort study of community-dwelling adults participating in the Sleep Heart Health Study, a longitudinal study of the cardiovascular consequences of SDB. The study sample comprises 886 men and 938 women, with a mean age of 65 (SD 11) yr. Sleepiness was quantified using the Epworth Sleepiness Scale (ESS). Sleep-disordered breathing was quantified by the respiratory disturbance index (RDI), defined as the number of apneas plus hypopneas per hour of sleep, measured during in-home polysomnography. When RDI was categorized into four groups (< 5, 5 to < 15, 15 to < 30, >/= 30), a significantly progressive increase in mean ESS score was seen across all four levels of SDB, from 7.2 (4.3) in subjects with RDI < 5 to 9.3 (4.9) in subjects with RDI >/= 30 (p < 0.001). There was no significant modification of this effect by age, sex, body mass index, or evidence of chronic restriction of sleep time or periodic limb movement disorder. The percentage of subjects with excessive sleepiness, defined as an ESS score >/= 11, increased from 21% in subjects with RDI < 5 to 35% in those with RDI >/= 30 (p < 0. 001). We conclude that SDB is associated with excess sleepiness in community-dwelling, middle-aged and older adults, not limited to those with clinically apparent sleep apnea.
10aAged10aCardiovascular Diseases10aCross-Sectional Studies10aDisorders of Excessive Somnolence10aFemale10aHumans10aMale10aMiddle Aged10aPolysomnography10aRespiration10aRetrospective Studies10aSeverity of Illness Index10aSleep Apnea Syndromes10aSurveys and Questionnaires1 aGottlieb, D, J1 aWhitney, C, W1 aBonekat, W, H1 aIber, C1 aJames, G, D1 aLebowitz, M1 aNieto, F, J1 aRosenberg, C, E uhttps://chs-nhlbi.org/node/152302513nas a2200325 4500008004100000022001400041245016700055210006900222260001300291300001200304490000700316520158200323653000901905653002801914653001501942653001601957653001101973653001501984653001101999653000902010653002602019653001702045100001502062700001702077700001602094700001302110700001502123700001402138856003502152 1999 eng d a1079-564200aThe relationship of fibrinogen and factors VII and VIII to incident cardiovascular disease and death in the elderly: results from the cardiovascular health study.0 arelationship of fibrinogen and factors VII and VIII to incident c1999 Jul a1776-830 v193 aLittle is known about the prospective associations of fibrinogen, factor VII, or factor VIII with cardiovascular disease (CVD) and mortality in the elderly. At baseline in the Cardiovascular Health Study (5888 white and African American men and women; aged >/=65 years), we measured fibrinogen, factor VIII, and factor VII. We used sex-stratified stepwise Cox survival analysis to determine relative risks (RRs) for CVD events and all-cause mortality (up to 5 years of follow-up), both unadjusted and adjusted for CVD risk factors and subclinical CVD. After adjustment, comparing the fifth quintile to the first, fibrinogen was significantly associated in men with coronary heart disease events (RR=2.1) and stroke or transient ischemic attack (RR=1.3), and also with mortality within 2.5 years of follow-up (RR=5.8) and later (RR=1.7). Factor VIII was significantly associated in men with coronary heart disease events (RR=1.5) and mortality (RR=1.8), and in women with stroke/transient ischemic attack (RR=1.4). For both factors, values were higher in those who died, whether causes were CVD-related or non-CVD-related, but highest in CVD death. Factor VII exhibited associations with incident angina (RR=1.44) in men and with death in women (RR, middle quintile compared with first=0.66). However, in general, factor VII was not consistently associated with CVD events in this population. We conclude that, if confirmed in other studies, the measurement of fibrinogen and/or factor VIII may help identify older individuals at higher risk for CVD events and mortality.
10aAged10aCardiovascular Diseases10aFactor VII10aFactor VIII10aFemale10aFibrinogen10aHumans10aMale10aMultivariate Analysis10aRisk Factors1 aTracy, R P1 aArnold, A, M1 aEttinger, W1 aFried, L1 aMeilahn, E1 aSavage, P uhttps://chs-nhlbi.org/node/59503503nas a2200445 4500008004100000022001400041245010400055210006900159260001300228300001200241490000700253520222500260653000902485653002202494653002402516653002802540653003702568653001902605653002102624653003002645653004002675653001102715653001702726653001702743653001102760653002302771653000902794653002602803653002602829653003802855653001702893100001902910700001502929700001502944700001702959700001502976700001602991700001503007856003503022 1999 eng d a1079-564200aRelationship of plasmin generation to cardiovascular disease risk factors in elderly men and women.0 aRelationship of plasmin generation to cardiovascular disease ris c1999 Mar a499-5040 v193 aPlasmin-alpha2-antiplasmin complex (PAP) marks plasmin generation and fibrinolytic balance. We recently observed that elevated levels of PAP predict acute myocardial infarction in the elderly, yet little is known about the correlates of PAP. We measured PAP in 800 elderly subjects who were free of clinical cardiovascular disease in 2 cohort studies: the Cardiovascular Health Study and the Honolulu Heart Program. Median PAP levels did not differ between the Cardiovascular Health Study (6.05+/-1.46 nmol/L) and the Honolulu Heart Program (6.11+/-1.44 nmol/L), and correlates of PAP were similar in both cohorts. In CHS, PAP levels increased with age (r=0. 30), procoagulant factors (eg, factor VIIc, r=0.15), thrombin activity (prothrombin fragment F1+2, r=0.29), and inflammation-sensitive proteins (eg, fibrinogen, r=0.44; factor VIIIc, r=0.37). PAP was associated with increased atherosclerosis as measured by the ankle-arm index (AAI) (P for trend, =0.001). PAP was negatively related to factors associated with the insulin resistance syndrome (IRS) (eg, fasting insulin, r=-0.26; body mass index, r=-0.26), possibly reflecting an association with plasminogen activator inhibitor-1 (r=-0.29). Although our study did not have sufficient power to detect a significant interaction, PAP and AAI appeared to be more weakly associated in subjects with more manifestations of the IRS: PAP appeared more strongly associated with AAI in the subgroup with 0 or 1 metabolic disorders (P=0.001; slope estimate, -0.14) compared with the subgroup with 2 or more metabolic disorders (P=0.10; slope estimate, -0.08) and in those with non-insulin-dependent diabetes mellitus (P=0.46; slope estimate, -0.04). Although PAP reflects reactive fibrinolysis and is associated with subclinical atherosclerosis, this relationship may be weaker in populations with characteristics of the IRS, possibly reflecting the inhibitory effects of plasminogen activator inhibitor-1 on PAP. Decreased fibrinolysis in the presence of subclinical disease in subjects with hyperinsulinemia or glucose intolerance is consistent with the premise that depressed plasmin generation may enhance the progression of atherosclerosis in these people.
10aAged10aAged, 80 and over10aalpha-2-Antiplasmin10aAntifibrinolytic Agents10aAsian Continental Ancestry Group10aCohort Studies10aCoronary Disease10aDiabetes Mellitus, Type 210aEuropean Continental Ancestry Group10aFemale10aFibrinolysin10aFibrinolysis10aHumans10aInsulin Resistance10aMale10aMultivariate Analysis10aMyocardial Infarction10aPlasminogen Activator Inhibitor 110aRisk Factors1 aSakkinen, P, A1 aCushman, M1 aPsaty, B M1 aRodriguez, B1 aBoineau, R1 aKuller, L H1 aTracy, R P uhttps://chs-nhlbi.org/node/58502916nas a2200397 4500008004100000022001400041245017200055210006900227260001300296300001100309490000700320520176400327653000902091653002102100653001002121653002602131653002802157653002402185653001902209653002802228653002402256653001102280653001802291653001102309653003102320653000902351653001502360100001702375700001602392700001702408700001302425700001702438700001502455700001202470856003602482 1999 eng d a1079-564200aRelationships of cerebral MRI findings to ultrasonographic carotid atherosclerosis in older adults : the Cardiovascular Health Study. CHS Collaborative Research Group.0 aRelationships of cerebral MRI findings to ultrasonographic carot c1999 Feb a356-650 v193 aCerebral magnetic resonance imaging (MRI) has demonstrated a high prevalence of infarct-like lesions, white matter hyperintensities, and evidence of cerebral atrophy in older adults. While these findings are generally believed to be related to ischemia and atherosclerosis, their relationship to atherosclerosis in the carotid arteries remains to be explored. Study subjects were part of the multicenter Cardiovascular Health Study, a cross-sectional study of 3502 women and men >/=65 years of age undergoing cranial MRI and carotid ultrasonography. MRI infarcts were detected in 1068 participants (29.3%) and measurable carotid plaque in 2745 (75.3%). MRI infarcts, ventricular and sulcal widening, and white matter score were strongly associated with carotid intimal-medial thickness (IMT) and stenosis degree after adjustment for age and sex (all P<0. 01). Associations with plaque characteristics were less strong and less consistent; MRI infarcts were weakly associated only with surface irregularity, and ventricular size was weakly associated only with lesion density (both P<0.04). In contrast, sulcal widening was strongly related to plaque characteristics, with scores being higher in those with heterogeneous and irregular plaque (both P<0. 009). Adjustment for other risk factors, and for carotid IMT/stenosis, removed associations of MRI findings with plaque characteristics except for weak relationships remaining between MRI infarcts and surface irregularity and between sulcal score and heterogeneous plaque (both P<0.03). MRI abnormalities show strong and consistent relationships with increasing carotid IMT and stenosis degree but less strong associations with plaque characteristics, especially after adjusting for IMT and stenosis.
10aAged10aArteriosclerosis10aBrain10aCardiovascular System10aCarotid Artery Diseases10aCerebral Infarction10aCohort Studies10aCross-Sectional Studies10aEchoencephalography10aFemale10aHealth Status10aHumans10aMagnetic Resonance Imaging10aMale10aPrevalence1 aManolio, T A1 aBurke, G, L1 aO'Leary, D H1 aEvans, G1 aBeauchamp, N1 aKnepper, L1 aWard, B uhttps://chs-nhlbi.org/node/152502570nas a2200301 4500008004100000022001400041245011700055210006900172260001300241300001000254490000700264520171700271653000901988653001201997653002602009653001202035653001102047653002402058653002302082653001602105653003102121100001502152700001502167700001802182700001502200700001802215856003502233 1999 eng d a0895-435600aThe reliability of medication inventory methods compared to serum levels of cardiovascular drugs in the elderly.0 areliability of medication inventory methods compared to serum le c1999 Feb a143-60 v523 aMedication inventory is more reliable than self-report in assessing prescription drug use in elderly populations. It is not known how strongly medication inventory reflects actual medication use as measured by serum drug levels. In the Cardiovascular Health Study, medication data were collected annually by study interviewers from medication containers brought to the clinic visit. At the fourth clinic visit, venipuncture was performed under 12-hour fasting conditions. Participants were told to take medications as usual. Based on medication inventory results, we randomly selected 55 users and 55 non-users of four cardiovascular drugs: aspirin, propranolol, hydrochlorothiazide, and digoxin. All 110 blood samples for each of the four drugs were analyzed; cut points were based on detectable levels given laboratory limitations. Kappa statistics (K) tested degree of agreement between medication inventory findings and serum detection. Assays were completed on 400 samples (91%). Agreement for aspirin (n=102) was poor: K=0.16 (95% CI: 0.0-0.32). Agreement for propranolol (n = 98) was fair: K=0.43 (95% CI: 0.27-0.59). Agreement for hydrochlorothiazide (n=100) was good: K=0.62 (95% CI: 0.53-0.91). Agreement for digoxin (n=100) was excellent: K=0.94 (95% CI: 0.74-1.0). For four all drugs, lack of agreement was confined primarily to participants who reported use but did not have detectable levels. Excluding aspirin users, only one non-user (0.7%) had drug detected in serum. The medication inventory is a reasonably sensitive and a fairly reliable method for ascertaining non-aspirin cardiovascular drug use in the elderly even though this method may overestimate use as assessed by serum level.
10aAged10aAspirin10aCardiovascular Agents10aDigoxin10aHumans10aHydrochlorothiazide10aPatient Compliance10aPropranolol10aReproducibility of Results1 aSmith, N L1 aPsaty, B M1 aHeckbert, S R1 aTracy, R P1 aCornell, E, S uhttps://chs-nhlbi.org/node/58903451nas a2200349 4500008004100000022001400041245011600055210006900171260001600240300000900256490000800265520247500273653000902748653001002757653001202767653002202779653002802801653002402829653001902853653002202872653001302894653001102907653002702918653002402945653001702969100001502986700001703001700001703018700001703035700001403052856003503066 1999 eng d a0098-748400aThe role of APOE epsilon4 in modulating effects of other risk factors for cognitive decline in elderly persons.0 arole of APOE epsilon4 in modulating effects of other risk factor c1999 Jul 07 a40-60 v2823 aCONTEXT: Cognitive decline in elderly persons is often an early predictor of dementia. Subclinical cardiovascular disease (CVD) and diabetes mellitus may contribute to substantial decline in cognitive function in the elderly. These risks may be modified by gene-environment interactions between apolipoprotein E (APOE) genotype and CVD risk factors or subclinical CVD.
OBJECTIVES: To examine the association between subclinical CVD and decline in cognitive functioning in the elderly and to examine effect modification by the APOE genotype of the association between subclinical disease and cognitive decline.
DESIGN: The Cardiovascular Health Study, a population-based, prospective cohort study.
SETTING AND POPULATION: A total of 5888 randomly selected Medicare-eligible participants from Sacramento County, California; Forsyth County, North Carolina; Washington County, Maryland; and Pittsburgh, Pa, aged 65 years or older, who were recruited in 1989-1990 (n = 5201) and in 1992-1993 (n = 687) and who were followed up for 7 and 5 years, respectively.
MAIN OUTCOME MEASURES: Change over time in scores on the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test as a function of APOE genotype, subclinical CVD, and diabetes mellitus.
RESULTS: Seventy percent of participants had no significant decline on the Modified Mini-Mental State Examination. Systolic blood pressure, the ankle-arm brachial index, atherosclerosis of the internal carotid artery, diabetes mellitus, and several diagnoses of prevalent CVD were significantly associated with declines in scores on the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test. The rate of cognitive decline associated with peripheral vascular disease, atherosclerosis of the common and internal carotid arteries, or diabetes mellitus was increased by the presence of any APOE epsilon4 allele.
CONCLUSIONS: Most healthy elderly people did not experience cognitive decline. Measures of subclinical CVD were modest predictors of cognitive decline. Those with any APOE epsilon4 allele in combination with atherosclerosis, peripheral vascular disease, or diabetes mellitus were at substantially higher risk of cognitive decline than those without the APOE epsilon4 allele or subclinical CVD. High levels of atherosclerosis increased cognitive decline independently of APOE genotype.
10aAged10aAging10aAlleles10aApolipoproteins E10aCardiovascular Diseases10aCognition Disorders10aCohort Studies10aDiabetes Mellitus10aGenotype10aHumans10aMental Status Schedule10aProspective Studies10aRisk Factors1 aHaan, M, N1 aShemanski, L1 aJagust, W, J1 aManolio, T A1 aKuller, L uhttps://chs-nhlbi.org/node/59702927nas a2200385 4500008004100000022001400041245020200055210006900257260001300326300001100339490000700350520174100357653003902098653001602137653000902153653001802162653002402180653004002204653001102244653001102255653003402266653000902300653003002309653001502339653001602354653002002370100002102390700001502411700002002426700001702446700001502463700001302478700001502491856003502506 2000 eng d a0022-073600aRace- and sex-specific ECG models for left ventricular mass in older populations. Factors influencing overestimation of left ventricular hypertrophy prevalence by ECG criteria in African-Americans.0 aRace and sexspecific ECG models for left ventricular mass in old c2000 Jul a205-180 v333 aThe validity of the reported high prevalence of left ventricular hypertrophy (LVH) among African-American men and women has been questioned owing to conflicting echocardiographic evidence. We used echocardiographic left ventricular mass (LVM) from M-mode measurements to evaluate associations between LVM, body size, and electrocardiographic (ECG) variables in 3,627 white and African-American men and women 65 years of age and older who were participants of the Cardiovascular Health Study (CHS), a multicenter cohort study of risk factors for coronary heart disease and stroke. ECG amplitudes used in LVH criteria were substantially higher in African-Americans, with apparent LVH prevalence 2 to 3 times higher in African American men and women than in white men and women, although there was no significant racial difference in echocardiographic LVM. The higher apparent LVH prevalence by Sokolow-Lyon criteria in African-American men is in part owing to smaller lateral chest diameter. In women, reasons for racial differences in ECG LVH prevalence remain largely unexplained although a small part of the excess LVH in African-American women by the Sokolow-Lyon criteria appears to be owing to a larger lateral chest semidiameter in white women. ECG variables alone were too inaccurate for LVM prediction, and it was necessary to incorporate in all ECG models body weight that was properly adjusted for race and sex. This resulted in modest LVM prediction accuracy, with R-square values ranging from .22 to .36. Race- and sex-specific ECG models introduced for LVM estimation with an appropriate adjustment for body size differences are expected to facilitate evaluation of LVH status in contrasting racial population groups.
10aAfrican Continental Ancestry Group10aAge Factors10aAged10aAnthropometry10aElectrocardiography10aEuropean Continental Ancestry Group10aFemale10aHumans10aHypertrophy, Left Ventricular10aMale10aPredictive Value of Tests10aPrevalence10aSex Factors10aUltrasonography1 aRautaharju, P, M1 aPark, L, P1 aGottdiener, J S1 aSiscovick, D1 aBoineau, R1 aSmith, V1 aPowe, N, R uhttps://chs-nhlbi.org/node/62102727nas a2200409 4500008004100000022001400041245013200055210006900187260001600256300001000272490000700282520157300289653001601862653002801878653002701906653002101933653002301954653002201977653001101999653001102010653000902021653001602030653001202046653002002058653002402078653003002102653001602132653002602148100001602174700001902190700001802209700001502227700001202242700001202254700001602266856003502282 2000 eng d a0161-810500aRates of sensor loss in unattended home polysomnography: the influence of age, gender, obesity, and sleep-disordered breathing.0 aRates of sensor loss in unattended home polysomnography the infl c2000 Aug 01 a682-80 v233 aOBJECTIVES: To evaluate study failure and sensor loss in unattended home polysomnography and their relationship to age, gender, obesity, and severity of sleep-disordered breathing (SDB).
DESIGN: A cross-sectional analysis of data gathered prospectively for the Sleep Heart Health Study (SHHS).
SETTING: Unattended polysomnography was performed in participants' homes by the staff of the sites that are involved in SHHS.
PARTICIPANTS: 6,802 individuals who met the inclusion criteria (age >40 years, no history of treatment of sleep apnea, no tracheostomy, no current home oxygen therapy) for SHHS.
RESULTS: A total of 6802 participants had 7151 studies performed. 6161 of 6802 initial studies (90.6%) were acceptable. Obesity was associated with a decreased likelihood of a successful initial study. After one or more attempts, 6440 participants (94.7%) had studies that were judged as acceptable. The mean duration of scorable signals for specific channels ranged from 5.7 to 6.8 hours. The magnitudes of the effects of age, gender, BMI, and RDI on specific signal durations were not clinically significant.
CONCLUSION: Unattended home PSG as performed for SHHS was usually successful. Participant characteristics had very weak associations with duration of scorable signal. This study suggests that unattended home PSG, when performed with proper protocols and quality controls, has reasonable success rates and signal quality for the evaluation of SDB in clinical and research settings.
10aAge Factors10aCross-Sectional Studies10aElectroencephalography10aElectromyography10aElectrooculography10aEquipment Failure10aFemale10aHumans10aMale10aMiddle Aged10aObesity10aPolysomnography10aProspective Studies10aSeverity of Illness Index10aSex Factors10aSleep Apnea Syndromes1 aKapur, V, K1 aRapoport, D, M1 aSanders, M, H1 aEnright, P1 aHill, J1 aIber, C1 aRomaniuk, J uhttps://chs-nhlbi.org/node/62003483nas a2200433 4500008004100000022001400041245013200055210006900187260001300256300001300269490000700282520226300289653000902552653002202561653001902583653002102602653001502623653002802638653002102666653001102687653001702698653001102715653001702726653003402743653000902777653002102786653001702807653001802824653001802842653001702860653003102877100001702908700001802925700002002943700001702963700001802980700001602998856003503014 2001 eng d a0263-635200aRelation of hemodynamics and risk factors to ventricular-vascular interactions in the elderly: the Cardiovascular Health Study.0 aRelation of hemodynamics and risk factors to ventricularvascular c2001 Oct a1893-9030 v193 aOBJECTIVE: To investigate the interaction between left ventricular (LV) geometry, carotid structure and arterial compliance in relation to hemodynamic stimuli and risk factors (plasma cholesterol, body mass index, insulin resistance, smoking habit, age, sex and race).
DESIGN: Cross-sectional.
METHODS: Echocardiography and carotid ultrasound were performed in 2375 elderly subjects without signs or history of prevalent cardiovascular disease, diabetes or renal disease (795 men; 298 non-whites; 1215 hypertensive), from the cohort of the Cardiovascular Health Study. Arterial compliance was estimated by the prognostically validated ratio of stroke volume to pulse pressure (SV/PP) as the percent deviation (Delta%) from the value predicted by individual age, heart rate and body weight.
RESULTS: Intima-medial thickness (IMT) was higher in the presence of LV hypertrophy (LVH) in normotensive and hypertensive subjects and was greatest in the presence of concentric LVH. Maximum carotid lumen diameter (CLD) was also higher in the presence of LVH (and was greatest with eccentric LVH, in association with relatively high values for stroke volume). After adjusting for blood pressure, maximum carotid lumen diameter was directly correlated with stroke volume, and IMT to LV mass (all P < 0.001). Similarly, IMT was also related to maximum carotid lumen diameter, independently of prevalent risk factors (P < 0.001). SV/PP-Delta% was reduced in both groups with concentric LV remodeling (both P < 0.0001) or concentric LVH (both P < 0.05). Adjusting for risk factors did not affect these associations in normotensives, but made them insignificant in hypertensives. In normotensives, IMT was inversely related to SV/PP-Delta% (P < 0.001), independently of risk factors, whereas no significant relation was found in hypertensives.
CONCLUSIONS: The magnitudes of carotid intima-medial thickness and lumen diameter parallel levels of LV mass and geometry, and are directly related to stroke volume and arterial stiffness; this interaction is most evident in the presence of normal blood pressure, whereas it is affected by other cardiovascular risk factors when arterial hypertension is present.
10aAged10aAged, 80 and over10aBlood Pressure10aCarotid Arteries10aCompliance10aCross-Sectional Studies10aEchocardiography10aFemale10aHemodynamics10aHumans10aHypertension10aHypertrophy, Left Ventricular10aMale10aReference Values10aRisk Factors10aStroke Volume10aTunica Intima10aTunica Media10aVentricular Function, Left1 ade Simone, G1 aMcClelland, R1 aGottdiener, J S1 aCelentano, A1 aKronmal, R, A1 aGardin, J M uhttps://chs-nhlbi.org/node/66402810nas a2200397 4500008004100000022001400041245013300055210006900188260001300257300001100270490000700281520171100288653000901999653001502008653001802023653002302041653002802064653001902092653002202111653001102133653001102144653001702155653001702172653002502189653000902214653002102223653001702244100001902261700001502280700001802295700001502313700001602328700001802344700001502362856003502377 2001 eng d a0012-179700aThe relation of markers of inflammation to the development of glucose disorders in the elderly: the Cardiovascular Health Study.0 arelation of markers of inflammation to the development of glucos c2001 Oct a2384-90 v503 aSeveral studies suggest that inflammation plays a role in the pathogenesis of some glucose disorders in adults. We tested this hypothesis in a longitudinal cohort study of older individuals who had normal fasting glucose (FG) values at baseline. We compared the baseline levels of six inflammatory markers in participants who had developed glucose disorders at follow-up with those of participants whose FG remained normal at follow-up. Participants were members of the Cardiovascular Health Study, a prospective study of risk factors for cardiovascular disease in adults > or =65 years. All 5,888 participants had baseline testing, including FG and markers of inflammation: white blood cell and platelet counts and albumin, fibrinogen, C-reactive protein (CRP), and factor VIIIc levels. At 3-4 years of follow-up, 4,481 (84.5%) of those who were alive had FG levels retested. Participants who developed diabetes (n = 45) had higher median levels of CRP at baseline than those who remained normoglycemic. On multivariate analysis, those with elevated CRP levels (75th percentile [2.86 mg/l] vs. 25th percentile [0.82 mg/l]) were 2.03 times (95% confidence intervals, 1.44-2.86) more likely to have diabetes on follow-up. Adjustment for confounders and other inflammatory markers did not appreciably change this finding. There was no relationship between the development of diabetes and other markers of inflammation. Inflammation, as measured by CRP levels, is associated with the development of diabetes in the elderly. Understanding the role of inflammation in the pathogenesis of glucose disorders in this age-group may lead to better classification and treatment of glucose disorders among them.
10aAged10aBiomarkers10aBlood Glucose10aC-Reactive Protein10aCardiovascular Diseases10aCohort Studies10aDiabetes Mellitus10aFemale10aHumans10aHypoglycemia10aInflammation10aLongitudinal Studies10aMale10aReference Values10aRisk Factors1 aBarzilay, J, I1 aAbraham, L1 aHeckbert, S R1 aCushman, M1 aKuller, L H1 aResnick, H, E1 aTracy, R P uhttps://chs-nhlbi.org/node/66102542nas a2200421 4500008004100000022001400041245011300055210006900168260001600237300000900253490000800262520136000270653001001630653000901640653002501649653002801674653002801702653002801730653001101758653001101769653001801780653002501798653000901823653001601832653002001848653001701868653002601885653001801911100001701929700001601946700001401962700001501976700001501991700002002006700001502026710004402041856003502085 2001 eng d a0002-926200aRelation of sleep-disordered breathing to cardiovascular disease risk factors: the Sleep Heart Health Study.0 aRelation of sleepdisordered breathing to cardiovascular disease c2001 Jul 01 a50-90 v1543 aAssociations between sleep-disordered breathing and cardiovascular disease (CVD) may be mediated by higher cardiovascular risk factor levels in those with sleep-disordered breathing. The authors examined these relations in the Sleep Heart Health Study, a multiethnic cohort of 6,440 men and women over age 40 years conducted from October 1995 to February 1998 and characterized by home polysomnography. In 4,991 participants who were free of self-reported CVD at the time of the sleep study, moderate levels of sleep-disordered breathing were common, with a median Respiratory Disturbance Index (RDI) of 4.0 (interquartile range, 1.25-10.7). The level of RDI was associated cross-sectionally with age, body mass index, waist-to-hip ratio, hypertension, diabetes, and lipid levels. These relations were more pronounced in those under age 65 years than in those over age 65. Women under age 65 years with RDI in the higher quartiles were more obese than men with similar RDI. Although the pattern of associations was consistent with greater obesity in those with higher RDI, higher body mass index did not explain all of these associations. If sleep-disordered breathing is shown in future follow-up to increase the risk for incident CVD events, part of the risk is likely to be due to the higher cardiovascular risk factors in those with higher RDI.
10aAdult10aAged10aAnalysis of Variance10aCardiovascular Diseases10aChi-Square Distribution10aCross-Sectional Studies10aFemale10aHumans10aLinear Models10aLongitudinal Studies10aMale10aMiddle Aged10aPolysomnography10aRisk Factors10aSleep Apnea Syndromes10aUnited States1 aNewman, A, B1 aNieto, F, J1 aGuidry, U1 aLind, B, K1 aRedline, S1 aPickering, T, G1 aQuan, S, F1 aSleep Heart Health Study Research Group uhttps://chs-nhlbi.org/node/65403470nas a2200469 4500008004100000022001400041245012400055210006900179260001300248300001100261490000700272520212500279653003102404653002102435653000902456653002202465653004402487653001902531653001202550653002802562653001102590653003202601653002002633653001102653653001402664653000902678653002602687653003002713653003202743653002402775653001702799653001202816653001802828100001702846700001802863700001902881700001702900700001602917700001702933700001502950856003502965 2001 eng d a0002-861400aRisk factors for hospitalized gastrointestinal bleeding among older persons. Cardiovascular Health Study Investigators.0 aRisk factors for hospitalized gastrointestinal bleeding among ol c2001 Feb a126-330 v493 aOBJECTIVES: We sought to estimate the incidence of hospitalization for upper and lower gastrointestinal bleeding among older persons and to identify independent risk factors.
DESIGN: Prospective cohort study.
SETTING: The Cardiovascular Health Study (CHS).
PARTICIPANTS: 5,888 noninstitutionalized men and women age 65 years or older in four U.S. communities enrolled in the CHS.
MEASUREMENTS: Gastrointestinal bleeding events during the period 1989 through 1998 were identified using hospital discharge diagnosis codes and confirmed by medical records review. Risk-factor information was collected in a standardized fashion at study baseline and annually during follow-up.
RESULTS: Among CHS participants (mean baseline age 73.3 years, 42% male), the incidence of hospitalized gastrointestinal bleeding was 6.8/1,000 person-years. In multivariate analyses, advanced age, male sex, unmarried status, cardiovascular disease, difficulty with daily activities, use of multiple medications, and use of oral anticoagulants were independent risk factors. Compared with nonsmokers, subjects who smoked more than half a pack per day had a multivariate-adjusted hazard ratio (HR) of 2.14 (95% confidence interval [CI] = 1.22-3.75) for upper gastrointestinal bleeding and a multivariate-adjusted HR of 0.21 (95% CI = 0.03-1.54) for lower gastrointestinal bleeding. Aspirin users did not have an elevated risk of upper gastrointestinal bleeding (HR = 0.76, 95% CI = 0.52-1.11), and users of other nonsteroidal anti-inflammatory drugs had a HR of 1.54 (95 % CI = 0.99-2.36). Low ankle-arm systolic blood pressure index was associated with higher risk of gastrointestinal bleeding among subjects with clinical cardiovascular disease but not among those without clinical cardiovascular disease.
CONCLUSION: This study identifies risk factors for gastrointestinal bleeding, such as disability, that may be amenable to modification. The findings will help clinicians to identify older persons who are at high risk for gastrointestinal bleeding.
10aActivities of Daily Living10aAge Distribution10aAged10aAged, 80 and over10aAnti-Inflammatory Agents, Non-Steroidal10aAnticoagulants10aAspirin10aCardiovascular Diseases10aFemale10aGastrointestinal Hemorrhage10aHospitalization10aHumans10aIncidence10aMale10aMultivariate Analysis10aPredictive Value of Tests10aProportional Hazards Models10aProspective Studies10aRisk Factors10aSmoking10aUnited States1 aKaplan, R, C1 aHeckbert, S R1 aKoepsell, T, D1 aFurberg, C D1 aPolak, J, F1 aSchoen, R, E1 aPsaty, B M uhttps://chs-nhlbi.org/node/63502111nas a2200385 4500008004100000022001400041245009200055210006900147260001300216300001200229490000700241520101100248653000901259653002001268653003201288653003001320653001901350653001601369653002201385653001101407653001101418653003001429653000801459653000901467653001501476653003201491653003101523100001701554700001801571700002201589700001601611700001601627710004701643856003501690 2001 eng d a0895-435600aThe role of comorbidity in the assessment of intermittent claudication in older adults.0 arole of comorbidity in the assessment of intermittent claudicati c2001 Mar a294-3000 v543 aThe prevalence of intermittent claudication (IC) in older adults by questionnaire is less than 5% while the prevalence of peripheral arterial disease (PAD) by non-invasive testing is 2-4-fold higher. Comorbid conditions may result in under-reporting intermittent claudication (IC) as assessed by the Rose Questionnaire. We examined characteristics of those who report leg pain in relationship to other comorbid conditions and disability in 5888 participants of the Cardiovascular Health Study (CHS). Older adults with exertional leg pain, not meeting criteria for IC, had a higher prevalence of PAD on non-invasive testing with the ankle-arm index than those without pain, as well as a higher prevalence of arthritis. The pattern of responses suggested that pain for both conditions was reported together. The Rose Questionnaire for IC is specific for PAD, but a negative questionnaire does not indicate a lack of symptoms, rather the presence of PAD along with other conditions that can cause pain.
10aAged10aAngina Pectoris10aArterial Occlusive Diseases10aCerebrovascular Disorders10aCohort Studies10aComorbidity10aDiabetes Mellitus10aFemale10aHumans10aIntermittent Claudication10aLeg10aMale10aPrevalence10aSensitivity and Specificity10aSurveys and Questionnaires1 aNewman, A, B1 aNaydeck, B, L1 aSutton-Tyrrell, K1 aPolak, J, F1 aKuller, L H1 aCardiovascular Health Study Research Group uhttps://chs-nhlbi.org/node/63802062nas a2200349 4500008004100000022001400041245007300055210006900128260001600197300001100213490000700224520111300231653001601344653000901360653001501369653001901384653002801403653001101431653001101442653002001453653000901473653001701482653001601499653003101515100002001546700002401566700001801590700002401608700002401632700002101656856003501677 2002 eng d a1524-463600aRacial differences in coronary artery calcification in older adults.0 aRacial differences in coronary artery calcification in older adu c2002 Mar 01 a424-300 v223 aReports on race-related differences in coronary artery calcium (CAC) are just beginning to emerge and have not been well studied in the elderly. This study was undertaken to assess whether such differences exist and the relationship between CAC and cardiovascular risk factors in a cohort of elderly community-dwelling adults. CAC was measured by using electron-beam tomography in 614 adults (aged 67 to 99 years), of whom 59% were women and 23% were black. The median CAC score was lower in blacks than in whites for men (159 versus 787, respectively; P<0.001) and for women (134 versus 233, respectively; P=0.02) after adjustment for age, cardiovascular disease, and risk factors for cardiovascular disease, although this difference was stronger and remained significant among men only. Lower CAC scores were also observed in the subgroup of blacks with a history of myocardial infarction. The lower CAC scores in blacks compared with whites observed in this study is consistent with either a lower prevalence of coronary artery disease or a lower extent of calcification of coronary artery disease.
10aAge Factors10aAged10aCalcinosis10aCohort Studies10aCoronary Artery Disease10aFemale10aHumans10aLogistic Models10aMale10aRisk Factors10aSex Factors10aTomography, X-Ray Computed1 aNewman, Anne, B1 aNaydeck, Barbara, L1 aWhittle, Jeff1 aSutton-Tyrrell, Kim1 aEdmundowicz, Daniel1 aKuller, Lewis, H uhttps://chs-nhlbi.org/node/68201489nas a2200289 4500008004100000022001400041245008500055210006900140260001300209300000900222490000700231520067800238653000900916653000900925653002100934653001100955653001700966653002400983653002401007653001701031100001701048700002401065700002301089700002001112710003201132856003501164 2002 eng d a1047-279700aA regression model for longitudinal change in the presence of measurement error.0 aregression model for longitudinal change in the presence of meas c2002 Jan a34-80 v123 aPURPOSE: The analysis of change in measured variables has become quite popular in studies where data are collected repeatedly over time. The authors describe some of the potential pitfalls in the analysis of change when the variable for change is measured with error. They show that regression analysis is often biased, possibly leading to erroneous results.
METHODS: A simple method to correct for measurement error bias in regression models that model change is presented.
RESULTS AND CONCLUSIONS: The two examples illustrate how measurement error can adversely affect an analysis. The bias-corrected approach yields valid results.
10aAged10aBias10aCoronary Disease10aHumans10aLipoproteins10aModels, Statistical10aRegression Analysis10aRisk Factors1 aYanez, David1 aKronmal, Richard, A1 aShemanski, Lynn, R1 aPsaty, Bruce, M1 aCardiovascular Health Study uhttps://chs-nhlbi.org/node/67202593nas a2200289 4500008004100000022001400041245006100055210005900116260001600175300001100191490000700202520180400209653000902013653001502022653002802037653002102065653001402086653002402100653001102124653001502135653003102150653002402181653002402205100002102229700001802250856003502268 2002 eng d a0277-671500aRegression-based variable clustering for data reduction.0 aRegressionbased variable clustering for data reduction c2002 Mar 30 a921-410 v213 aIn many studies it is of interest to cluster states, counties or other small regions in order to obtain improved estimates of disease rates or other summary measures, and a more parsimonious representation of the country as a whole. This may be the case if there are too many to summarize concisely, and/or many regions with a small number of cases. By merging the regions into larger geographic areas, we obtain more cases within each area (and hence lower standard errors for parameter estimates), as well as fewer areas to summarize in terms of disease rates. The resulting clusters should be such that regions within the same cluster are similar in terms of their disease rates. In this paper we present a clustering algorithm which uses data at the subject-specific level in order to cluster the original regions into a reduced set of larger areas. The proposed clustering algorithm expresses the clustering goals in terms of a regression framework. This formulation of the problem allows the regions to be clustered in terms of their association with the response, and confounding variables measured at the subject-specific level may be easily incorporated during the clustering process. Additionally, this framework allows estimation and testing of the association between the areas and the response. The statistical properties and performance of the algorithm were evaluated via simulation studies, and the results are promising. Additional simulations illustrate the importance of controlling for confounding variables during the clustering process, rather than after the clusters are determined. The algorithm is illustrated with data from the Cardiovascular Health Study. Although developed with a specific application in mind, the method is applicable to a wide range of problems.
10aAged10aAlgorithms10aCardiovascular Diseases10aCluster Analysis10aCognition10aComputer Simulation10aHumans10aInfarction10aMagnetic Resonance Imaging10aModels, Statistical10aRegression Analysis1 aMcClelland, R, L1 aKronmal, R, A uhttps://chs-nhlbi.org/node/68103590nas a2200469 4500008004100000022001400041245013400055210006900189260001300258300001000271490000700281520225800288653001702546653000902563653002202572653002102594653001702615653001902632653001902651653003002670653002502700653001102725653001102736653002502747653000902772653001502781653002402796653002402820653001702844653001702861653001702878100001802895700002102913700002102934700002102955700002202976700002402998700002203022700002203044700001903066856003503085 2002 eng d a0007-116100aThe relation of atherosclerotic cardiovascular disease to retinopathy in people with diabetes in the Cardiovascular Health Study.0 arelation of atherosclerotic cardiovascular disease to retinopath c2002 Jan a84-900 v863 aAIMS: To describe the association of retinopathy with atherosclerosis and atherosclerotic risk factors in people with diabetes.
METHODS: 296 of the 558 people classified as having diabetes by the American Diabetes Association criteria, from a population based cohort of adults (ranging in age from 69 to 102 years) living in four United States communities (Allegheny County, Pennsylvania; Forsyth County, North Carolina; Sacramento County, California; and Washington County, Maryland) were studied from 1997 to 1998. Lesions typical of diabetic retinopathy were determined by grading a 45 degrees colour fundus photograph of one eye of each participant, using a modification of the Airlie House classification system.
RESULTS: Retinopathy was present in 20% of the diabetic cohort, with the lowest prevalence (16%), in those 80 years of age or older. Retinopathy was detected in 20.3% of the 296 people with diabetes; 2.7% of the 296 had signs of proliferative retinopathy and 2.1% had signs of macular oedema. The prevalence of diabetic retinopathy was higher in black people (35.4%) than white (16.0%). Controlling for age, sex, and blood glucose, retinopathy was more frequent in black people than white (odds ratio (OR) 2.26, 95% confidence interval (CI) 1.01, 5.05), in those with longer duration of diabetes (OR (per 5 years of diabetes) 1.42, 95% CI 1.18, 1.70), in those with subclinical cardiovascular disease (OR 1.49, 95% CI 0.51, 4.31), or coronary heart disease or stroke (OR 3.23, 95% CI 1.09, 9.56) than those without those diseases, in those with higher plasma low density lipoprotein (LDL) cholesterol (OR (per 10 mg/dl of LDL cholesterol) 1.12, 95% CI 1.02, 1.23), and in those with gross proteinuria (OR 4.76, 95% CI 1.53, 14.86).
CONCLUSION: Data from this population based study suggest a higher prevalence of retinopathy in black people than white people with diabetes and the association of cardiovascular disease, elevated plasma LDL cholesterol, and gross proteinuria with diabetic retinopathy. However, any conclusions or explanations regarding associations described here must be made with caution because only about one half of those with diabetes mellitus were evaluated.
10aAge of Onset10aAged10aAged, 80 and over10aArteriosclerosis10aBlack People10aBlood Pressure10aCohort Studies10aDiabetes Mellitus, Type 210aDiabetic Retinopathy10aFemale10aHumans10aLongitudinal Studies10aMale10aOdds Ratio10aProspective Studies10aRegression Analysis10aRisk Factors10aTime Factors10aWhite People1 aKlein, Ronald1 aMarino, Emily, K1 aKuller, Lewis, H1 aPolak, Joseph, F1 aTracy, Russell, P1 aGottdiener, John, S1 aBurke, Gregory, L1 aHubbard, Larry, D1 aBoineau, Robin uhttps://chs-nhlbi.org/node/67403104nas a2200421 4500008004100000022001400041245007700055210006900132260001600201300001100217490000700228520188500235653001002120653002002130653001902150653003002169653002802199653003802227653001102265653001802276653001102294653000902305653001602314653003802330653002002368653001502388653003002403653002902433653002202462100002202484700001902506700001802525700002002543700002002563700002602583710003802609856003502647 2002 eng d a0161-810500aThe relationship between chronically disrupted sleep and healthcare use.0 arelationship between chronically disrupted sleep and healthcare c2002 May 01 a289-960 v253 aSTUDY OBJECTIVES: To determine whether chronic sleep deprivation, sleep disruption, sleepiness, insomnia, and OSA are associated with increased healthcare use in a community-based population.
DESIGN: Cross-sectional study.
SETTING/PARTICIPANTS: 6440 Sleep Heart Health Study (SHHS) participants recruited from ongoing cohort studies.
INTERVENTIONS: N/A.
MEASUREMENTS: Polysomnography results (Apnea Hypopnea Index (AHI), percent of sleep time with oxyhemoglobin saturation below 90% (CT90), arousal index) as well as data on sleep related symptoms, medication use, and chronic illness. The indirect measure of predicted healthcare utilization was the modified Chronic Disease Score (CDS) calculated from medication data.
RESULTS: After adjustment for age, gender, BMI and study site, subjects in the highest quartiles of AHI, CT90 and Epworth score had CDS that were 6%-9% higher than the lowest quartiles. The adjusted mean CDS for subjects with sleep apnea was similar to that for subjects with hypertension, chronic bronchitis or asthma and 18% greater than the mean CDS for subjects without sleep apnea. Among subjects who did not have significant sleep-disordered breathing, complaints of insomnia, sleepiness, fatigue, and not getting enough sleep were associated with increased CDS.
CONCLUSIONS: This study demonstrated an association between subjective complaints of daytime sleepiness, inadequate sleep time, insomnia as well as objective measures of severity of SDB, and an indirect measure of healthcare utilization in a community-based sample. Though the percent increases in healthcare utilization observed were modest, the prevalence of these factors in the general population is high, and may therefore be associated with a substantial cost burden to the healthcare system.
10aAdult10aChronic Disease10aCohort Studies10aCommunity Health Services10aCross-Sectional Studies10aDisorders of Excessive Somnolence10aFemale10aHealth Status10aHumans10aMale10aMiddle Aged10aPatient Acceptance of Health Care10aPolysomnography10aPrevalence10aSeverity of Illness Index10aSleep Apnea, Obstructive10aSleep Deprivation1 aKapur, Vishesh, K1 aRedline, Susan1 aNieto, Javier1 aYoung, Terry, B1 aNewman, Anne, B1 aHenderson, Jeffrey, A1 aSleep Heart Health Research Group uhttps://chs-nhlbi.org/node/68802775nas a2200445 4500008004100000022001400041245012900055210006900184260001600253300001100269490000700280520149700287653000901784653002201793653001501815653002801830653002101858653001901879653002801898653001501926653001101941653001101952653000901963653001501972653001701987653003202004653001602036653003102052653001802083653001702101100002002118700002402138700002402162700002402186700002002210700002102230700002202251700002102273856003502294 2002 eng d a1524-463600aRelationship between coronary artery calcification and other measures of subclinical cardiovascular disease in older adults.0 aRelationship between coronary artery calcification and other mea c2002 Oct 01 a1674-90 v223 aBACKGROUND: In the Cardiovascular Health Study, subclinical cardiovascular disease (CVD) predicted CVD events in older adults. The extent to which this measure or its components reflect calcified coronary disease is unknown.
METHODS AND RESULTS: Coronary artery calcium (CAC) was assessed with electron beam tomography in 414 participants without clinical CVD and examined using cut points (CAC> or =400 and CAC> or =800) and the log(CAC); 274 had subclinical CVD by ankle-arm index, ECG, or carotid ultrasound. Cut points for subclinical disease as previously defined in the Cardiovascular Health Study were examined as well as continuous measures to produce receiver operating characteristic curve curves. A low ankle-arm index was highly specific for a high CAC score. The internal carotid artery intima-media thickness was most strongly correlated with CAC (r=0.30) and was significantly related to both CAC cut points and to the log(CAC) score independently of all other measures.
CONCLUSIONS: In these community-dwelling older adults without clinical CVD, internal carotid artery intima-media thickness was most closely related to CAC. However, 17.5% of those with a CAC> or =400 would be missed in the ascertainment of subclinical atherosclerosis using the previously published composite of subclinical atherosclerosis. Prospective follow-up will determine whether the CAC score improves prediction of CVD events over other noninvasive measures.
10aAged10aAged, 80 and over10aCalcinosis10aCardiovascular Diseases10aCarotid Stenosis10aCohort Studies10aCoronary Artery Disease10aDemography10aFemale10aHumans10aMale10aPrevalence10aRisk Factors10aSensitivity and Specificity10aSex Factors10aTomography, X-Ray Computed10aTunica Intima10aTunica Media1 aNewman, Anne, B1 aNaydeck, Barbara, L1 aSutton-Tyrrell, Kim1 aEdmundowicz, Daniel1 aO'Leary, Daniel1 aKronmal, Richard1 aBurke, Gregory, L1 aKuller, Lewis, H uhttps://chs-nhlbi.org/node/70402789nas a2200241 4500008004100000022004300041024003600084245009200120210006900212260001500281300000800296490000700304520208500311653001202396653001202408653001602420653001802436100001302454700001402467700001602481700001402497856003602511 2002 eng d a1606-6359 print: ISSN 1476-7392 online aDOI 10.1080/160663502100001028900aReproducibility of two approaches for assessing alcohol consumption among older adults.0 aReproducibility of two approaches for assessing alcohol consumpt c2002-01-01 a3850 v103 aObjectives: In this study, we hypothesized that there is greater disclosure in self reports of alcohol intake when details of quantity-frequency measures of alcohol consumption are ascertained in the context of a general health and life style questionnaire as compared to a directed interview on usual drinking habits. Methods: Data are from the 1993 to 1994 follow-up of the Washington County cohort of men and women 65 years and older, participating in the Cardiovascular Health Study. A total of 918 subjects completed a questionnaire evaluation of their usual alcohol consumption by two separate approaches: (1) alcohol intake was derived from responses to questions contained within a medical and personal history questionnaire; (2) the same questions were within a medical and personal history questionnaire. Results: The mean alcohol intake for the entire cohort, and for drinkers alone were almost identical when assessed by either questionnaire, with high correlation between the two estimates, irrespective of beverage type. There was 89% agreement classifying drinkers versus nondrinkers by both approaches, with the strength of the agreement good (k=0.76). This agreement became moderate if drinkers were further categorized into three levels of alcohol intake. Predictors of the differences in alcohol intake between the two questionnaires were explored by multiple regression. Differences were largest for those who stated that the reason they drank was because they were no longer working, and for those drinking on average more than 24g (greater than approximately 2 drinks) of alcohol daily. Discussion: Although agreement between the two approaches was generally comparable, some findings may indicate that older adults who are problem drinkers or drink heavily report lower consumption patterns when administered a more directed questionnaire specifically focusing on drinking behavior. These findings have implications in the design of studies measuring alcohol consumption among elderly persons with a relatively low background alcohol intake. 10aalcohol10aelderly10ameasurement10aquestionnaire1 aCrum, RM1 aPuddey, I1 aGilbert, CG1 aFried, LP uhttps://chs-nhlbi.org/node/152903202nas a2200397 4500008004100000022001400041245010900055210006900164260001300233300001200246490000700258520214600265653000902411653002202420653001902442653001902461653002502480653000802505653001102513653001102524653000902535653002102544653002402565653001102589653002102600100001502621700001802636700001302654700001702667700001502684700001902699700002002718700001302738700001802751856003502769 2002 eng d a0007-116100aRetinal microvascular abnormalities and blood pressure in older people: the Cardiovascular Health Study.0 aRetinal microvascular abnormalities and blood pressure in older c2002 Sep a1007-130 v863 aAIM: To examine the relation between blood pressure and retinal microvascular abnormalities in older people.
METHODS: The Cardiovascular Health Study is a prospective cohort study conducted in four US communities initiated in 1989 to 1990. Blood pressure was measured according to standardised protocols at each examination. During the 1997-8 examination, retinal photographs were taken of 2405 people aged 69-97 years (2056 without diabetes and 349 with diabetes). Signs of focal microvascular abnormalities (focal arteriolar narrowing, arteriovenous nicking, and retinopathy) were evaluated from photographs according to standardised methods. To quantify generalised arteriolar narrowing, the photographs were digitised and diameters of individual arterioles were measured and summarised.
RESULTS: In non-diabetic people, elevated concurrent blood pressure taken at the time of retinal photography was strongly associated with presence of all retinal microvascular lesions. The multivariable adjusted odds ratios, comparing the highest to lowest quintile of concurrent systolic blood pressure, were 4.0 (95% confidence intervals (CI): 2.4 to 6.9, p test of trend<0.001) for focal arteriolar narrowing, 2.9 (95% CI: 1.6 to 5.3, p<0.001) for arteriovenous nicking, 2.8 (95% CI: 1.5 to 5.2, p<0.001) for retinopathy, and 2.1 (95% CI: 1.4 to 3.1, p<0.001) for generalised arteriolar narrowing. Generalised arteriolar narrowing and possibly arteriovenous nicking were also significantly associated with past blood pressure measured up to 8 years before retinal photography, even after adjustment for concurrent blood pressure. These associations were somewhat weaker in people with diabetes.
CONCLUSIONS: Retinal microvascular abnormalities are related to elevated concurrent blood pressure in older people. Additionally, generalised retinal arteriolar narrowing and possibly arteriovenous nicking are related to previously elevated blood pressure, independent of concurrent blood pressure. These data suggest that retinal microvascular changes reflect severity and duration of hypertension.
10aAged10aAged, 80 and over10aBlood Pressure10aCohort Studies10aDiabetic Retinopathy10aEye10aFemale10aHumans10aMale10aMicrocirculation10aProspective Studies10aRetina10aRetinal Diseases1 aWong, T, Y1 aHubbard, L, D1 aKlein, R1 aMarino, E, K1 aKronmal, R1 aSharrett, A, R1 aSiscovick, D, S1 aBurke, G1 aTielsch, J, M uhttps://chs-nhlbi.org/node/69903028nas a2200421 4500008004100000022001400041245013400055210006900189260001300258300001000271490000600281520176500287653001002052653002002062653002802082653002702110653002102137653001902158653003802177653001802215653002302233653001102256653001702267653002202284653002002306653002402326653003002350653002602380653003102406653001802437100002002455700002202475700001802497700001702515700001902532700002002551856003502571 2003 eng d a1520-951200aRecruitment of healthy adults into a study of overnight sleep monitoring in the home: experience of the Sleep Heart Health Study.0 aRecruitment of healthy adults into a study of overnight sleep mo c2003 Mar a13-240 v73 aThe Sleep Heart Health Study (SHHS) is a prospective cohort study using participants from several ongoing cardiovascular and respiratory disease research projects to investigate the relationship between sleep-disordered breathing and cardiovascular disease. This study design required unusual and different recruiting techniques to meet the study's enrollment goal of between 6000 and 6600 participants. Individuals were recruited to undergo an overnight home polysomnogram, completion of several questionnaires, and collection of a small amount of physical examination data. This article describes the methods used to recruit these participants and how these procedures influenced the final participation rate and the representativeness of SHHS to its parent cohorts. Of 30,773 people eligible for recruitment into SHHS, attempts were made to enroll 11,145 (36%). Of those contacted, 6441 ultimately agreed to participate (58%). Recruitment rates (38 to 91%) varied among sites. SHHS participants were slightly younger (63.0 vs. 65.0 years, p < 0.001), had more years of education (14.1 vs. 13.7, p < 0.001), more likely to snore (34% vs. 23%, p < 0.001), had higher Epworth sleepiness scores (7.7 vs. 6.5, p < 0.001), slightly higher higher systolic and diastolic blood pressures (127.6/73.9 vs. 127.2/72.1, p < 0.001 for diastolic only), and a slightly higher body mass index (BMI) (28.5 vs. 27.5, p < 0.001). We conclude that it is feasible to recruit existing participants from one large-scale epidemiologic study into another with a high degree of success. However, the characteristics of the new cohort may vary in several respects from their original cohorts and therefore interpretation of study results will have to consider these differences.
10aAdult10aBody Mass Index10aCardiovascular Diseases10aCatchment Area, Health10aCircadian Rhythm10aCohort Studies10aDisorders of Excessive Somnolence10aHealth Status10aHome Care Services10aHumans10aHypertension10aPatient Selection10aPolysomnography10aProspective Studies10aSeverity of Illness Index10aSleep Apnea Syndromes10aSurveys and Questionnaires10aUnited States1 aLind, Bonnie, K1 aGoodwin, James, L1 aHill, Joel, G1 aAli, Tauqeer1 aRedline, Susan1 aQuan, Stuart, F uhttps://chs-nhlbi.org/node/73602843nas a2200325 4500008004100000022001400041245011600055210006900171260001300240300001200253490000700265520188600272653003902158653000902197653002202206653002102228653004002249653001102289653001102300653000902311653001502320653001502335653001802350100001902368700002002387700002802407700002702435700002002462856003502482 2003 eng d a0885-318500aRegional and racial differences in the prevalence of physician-diagnosed essential tremor in the United States.0 aRegional and racial differences in the prevalence of physiciandi c2003 Sep a1035-400 v183 aFor reasons that are unclear, prevalence estimates of essential tremor (ET) differ considerably across the United States. Separate communities have never been sampled within the framework of the same study to substantiate these differences. We estimated the prevalence of physician-diagnosed ET in the elderly in four communities in the United States in whom the same screening questions were used, and examined whether this prevalence differed between Caucasians and African Americans. The Cardiovascular Health Study recruited a sample of Medicare beneficiaries >/=65 years of age from four communities in different regions of the United States. In 1998 to 1999, 3,494 participants (mean age, 80.0 years; range, 70-103 years) answered a 12-question screen for ET, including the question, "has a doctor diagnosed you as having familial tremor or benign essential tremor?" Fifty-four participants reported that a doctor had diagnosed them as having ET (1.5%; 95% confidence interval, [CI], 1.1-2.0%). Prevalence was similar across the four communities (1.1-2.0%). A larger proportion of Caucasians than African Americans reported a diagnosis of ET (1.7% vs. 0.4%; odds ratio = 4.9; 95% CI, 1.2-20.2; P = 0.028). In a logistic regression analysis, physician-diagnosed ET was associated with Caucasian ethnicity (P = 0.038) but not with age, gender, education, mental status or depression scores, income, smoking status, or alcohol consumption. When a standardized screening question was used, the proportion of participants with physician-diagnosed ET was similar across four communities, suggesting that the prevalence of this condition may be less variable than is often reported. Caucasians were five times more likely to have physician-diagnosed ET than were African Americans. This study does not provide an explanation for this difference, which deserves further study.
10aAfrican Continental Ancestry Group10aAged10aAged, 80 and over10aEssential Tremor10aEuropean Continental Ancestry Group10aFemale10aHumans10aMale10aPhysicians10aPrevalence10aUnited States1 aLouis, Elan, D1 aFried, Linda, P1 aFitzpatrick, Annette, L1 aLongstreth, William, T1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/75002224nas a2200325 4500008004100000022001400041245010800055210006900163260001300232300001200245490000700257520130800264653000901572653002801581653002101609653000901630653001801639653001101657653002201668653001801690653001101708653001401719653001801733653000901751653004001760653001801800100001701818700002801835856003501863 2003 eng d a0895-435600aThe relation of dietary patterns to future survival, health, and cardiovascular events in older adults.0 arelation of dietary patterns to future survival health and cardi c2003 Dec a1224-350 v563 aBACKGROUND: There have been few long-term follow-up studies of older adults who follow different dietary patterns.
METHODS: We cluster-analyzed data on dietary fat, fiber, protein, carbohydrate, and calorie consumption from the U.S. Cardiovascular Health Study (mean age=73), and examined the relationship of the dietary clusters to outcomes 10 years later.
RESULTS: The five clusters were named "Healthy diet" (relatively high in fiber and carbohydrate and low in fat), "Unhealthy diet" (relatively high in protein and fat, relatively low in carbohydrates and fiber); "High Calorie," "Low Calorie," and "Low 4," which was distinguished by higher alcohol consumption. The clusters were strongly associated with demographic factors, health behaviors, and baseline health status. The Healthy diet cluster had the most years of life and years of healthy life, and the Unhealthy diet cluster had the fewest. The Low 4 cluster had the best cardiovascular outcomes. Differences were not usually large.
CONCLUSIONS: Older adults who followed the healthy eating pattern had somewhat longer and healthier lives, and the cluster with more alcohol consumption was associated with fewer cardiovascular events. The unhealthy eating pattern had the worst outcomes.
10aAged10aCardiovascular Diseases10aCluster Analysis10aDiet10aEnergy Intake10aFemale10aFollow-Up Studies10aHealth Status10aHumans10aIncidence10aLinear Models10aMale10aNutritional Physiological Phenomena10aSurvival Rate1 aDiehr, Paula1 aBeresford, Shirley, A A uhttps://chs-nhlbi.org/node/76003244nas a2200349 4500008004100000022001400041245012500055210006900180260001300249300001000262490000700272520223000279653000902509653001902518653001102537653001102548653001702559653001102576653002002587653000902607653002402616653003702640653002202677100002402699700002502723700002302748700002202771700002302793700002202816700002102838856003502859 2003 eng d a1523-683800aRelationships between renovascular disease, blood pressure, and renal function in the elderly: a population-based study.0 aRelationships between renovascular disease blood pressure and re c2003 May a990-60 v413 aBACKGROUND: The purpose of this study is to examine the associations between renovascular disease (RVD) and cross-sectional measures of blood pressure and renal function among participants in the Cardiovascular Health Study (CHS).
METHODS: The CHS is a prospective cohort study of cardiovascular disease among elderly Americans. As part of an ancillary study, participants in the Forsyth County, NC, cohort of the CHS were invited to undergo renal duplex sonography (RDS) to define the presence or absence of RVD (defined as any focal peak systolic velocity > or = 1.8 milliseconds or the absence of a Doppler shifted signal from an imaged artery). Demographic, risk factor, blood pressure, and serum creatinine data were obtained at the time of RDS and from the annual CHS examination.
RESULTS: Eight hundred thirty-four CHS participants (including 525 women [63%], 309 men [37%], 194 African Americans [23%], and 635 Caucasians [76%]) with a mean age of 77.2 +/- 4.9 years underwent successful RDS. RVD was present in 57 participants (6.8%). When examined according to the presence or absence of RVD, significant univariate differences were observed in the prevalence of clinical hypertension (72% versus 50%; P = 0.001), systolic blood pressure (145 versus 136 mm Hg; P = 0.001), and renal insufficiency (16% versus 8%; P = 0.041). Multivariate analyses showed significant and independent associations for the presence of RVD with increasing systolic blood pressure (P = 0.034), clinical hypertension (odds ratio, 2.68; 95% confidence interval, 1.44 to 4.99; P = 0.002), increasing serum creatinine level, and renal insufficiency (odds ratio, 2.21; 95% confidence interval, 1.02 to 4.79; P = 0.043). A significant interaction was observed between the presence of RVD and increasing systolic blood pressure in association with increasing serum creatinine levels (P = 0.041).
CONCLUSION: These results suggest important population-based associations between RVD and cross-sectional measures of blood pressure and renal function. Furthermore, the observed relationship between RVD and increasing serum creatinine level was influenced strongly by increasing blood pressure.
10aAged10aBlood Pressure10aFemale10aHumans10aHypertension10aKidney10aKidney Diseases10aMale10aProspective Studies10aUltrasonography, Doppler, Duplex10aVascular Diseases1 aEdwards, Matthew, S1 aHansen, Kimberley, J1 aCraven, Timothy, E1 aCherr, Gregory, S1 aBleyer, Anthony, J1 aBurke, Gregory, L1 aDean, Richard, H uhttps://chs-nhlbi.org/node/73703093nas a2200385 4500008004100000022001400041245010400055210006900159260001600228300001200244490000700256520198500263653000902248653002802257653002502285653001502310653001102325653001802336653001102354653003002365653002802395653000902423653001502432653003002447653002202477100002002499700002402519700001702543700002302560700002402583700002402607700002102631700002002652856003502672 2003 eng d a0735-109700aRenal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals.0 aRenal insufficiency as a predictor of cardiovascular outcomes an c2003 Apr 16 a1364-720 v413 aOBJECTIVES: This study was designed to evaluate the relationship between elevated creatinine levels and cardiovascular events.
BACKGROUND: End-stage renal disease is associated with high cardiovascular morbidity and mortality. The association of mild to moderate renal insufficiency with cardiovascular outcomes remains unclear.
METHODS: We analyzed data from the Cardiovascular Health Study, a prospective population-based study of subjects, aged >65 years, who had a serum creatinine measured at baseline (n = 5,808) and were followed for a median of 7.3 years. Proportional hazards models were used to examine the association of creatinine to all-cause mortality and incident cardiovascular mortality and morbidity. Renal insufficiency was defined as a creatinine level > or =1.5 mg/dl in men or > or =1.3 mg/dl in women.
RESULTS: An elevated creatinine level was present in 648 (11.2%) participants. Subjects with elevated creatinine had higher overall (76.7 vs. 29.5/1,000 years, p < 0.001) and cardiovascular (35.8 vs. 13.0/1,000 years, p < 0.001) mortality than those with normal creatinine levels. They were more likely to develop cardiovascular disease (54.0 vs. 31.8/1,000 years, p < 0.001), stroke (21.1 vs. 11.9/1,000 years, p < 0.001), congestive heart failure (38.7 vs. 17/1,000 years, p < 0.001), and symptomatic peripheral vascular disease (10.6 vs. 3.5/1,000 years, p < 0.001). After adjusting for cardiovascular risk factors and subclinical disease measures, elevated creatinine remained a significant predictor of all-cause and cardiovascular mortality, total cardiovascular disease (CVD), claudication, and congestive heart failure (CHF). A linear increase in risk was observed with increasing creatinine.
CONCLUSIONS: Elevated creatinine levels are common in older adults and are associated with increased risk of mortality, CVD, and CHF. The increased risk is apparent early in renal disease.
10aAged10aCardiovascular Diseases10aConfidence Intervals10aCreatinine10aFemale10aHeart Failure10aHumans10aIntermittent Claudication10aKidney Failure, Chronic10aMale10aOdds Ratio10aPredictive Value of Tests10aSurvival Analysis1 aFried, Linda, F1 aShlipak, Michael, G1 aCrump, Casey1 aBleyer, Anthony, J1 aGottdiener, John, S1 aKronmal, Richard, A1 aKuller, Lewis, H1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/73502708nas a2200421 4500008004100000022001400041245007600055210006900131260001700200300001000217490000700227520155000234653000901784653002201793653002201815653002801837653002401865653001301889653001101902653001301913653001101926653003101937653000901968653001501977653003001992653003202022653001702054100002102071700002002092700001702112700002502129700001602154700002102170700002502191700001702216700001802233856003502251 2003 eng d a0251-535000aRisk factors for dementia in the cardiovascular health cognition study.0 aRisk factors for dementia in the cardiovascular health cognition c2003 Jan-Feb a13-220 v223 aBACKGROUND: The Cardiovascular Health Cognition Study has evaluated the determinants of dementia among 3,608 participants that had a magnetic resonance imaging (MRI) of the brain in 1991 and were followed to 1998-1999.
METHODS: There were 480 incident dementia cases, 330 (69%) were classified as Alzheimer's disease (AD).
RESULTS: In univariate analysis, low scores on the Modified Mini-Mental State Examination (3MSE) and on the Digit Symbol Substitution Test as well as declines in scores over time prior to the development of dementia were significant predictors of dementia. A high ventricular grade on the MRI (atrophy) as well as high white matter grade, a number of brain infarcts on the MRI were all determinants of dementia. Apolipoprotein E epsilon4 (Apo(E-4)) was also a powerful predictor of dementia. In a multivariate Cox proportional hazards model controlling for race, gender and grade, the hazard ratios for age (1.1), 3MSE score (0.9), ventricular size (1.4), white matter grade (1.8), presence of large infarcts >3 mm (1.3) and Apo(E-4) (2.1) were significant predictors of dementia. The combination of an Apo(E-4) genotype, 3MSE score <90, > or =5 ventricular grade, > or =3 white matter grade at the time of the MRI were associated with a 17-fold increased risk (95% CI: 8.6-34.9) of dementia as compared to individuals with none of the above attributes.
CONCLUSIONS: Measures of cognition, Apo(E-4) and MRI of the brain are strong predictors of both dementia and of AD.
10aAged10aAged, 80 and over10aApolipoproteins E10aCardiovascular Diseases10aCognition Disorders10aDementia10aFemale10aGenotype10aHumans10aMagnetic Resonance Imaging10aMale10aOdds Ratio10aPredictive Value of Tests10aProportional Hazards Models10aRisk Factors1 aKuller, Lewis, H1 aLopez, Oscar, L1 aNewman, Anne1 aBeauchamp, Norman, J1 aBurke, Greg1 aDulberg, Corinne1 aFitzpatrick, Annette1 aFried, Linda1 aHaan, Mary, N uhttps://chs-nhlbi.org/node/72403994nas a2200493 4500008004100000022001400041245010700055210006900162260001300231300001100244490000700255520261100262653000902873653002202882653002202904653001002926653002802936653002402964653001902988653002403007653001103031653001103042653002003053653002503073653003103098653000903129653001903138653001703157653001503174653001703189100002003206700002303226700002103249700002103270700002303291700002503314700001903339700002603358700001903384700001903403700002203422700002103444856003503465 2003 eng d a0003-994200aRisk factors for mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 2.0 aRisk factors for mild cognitive impairment in the Cardiovascular c2003 Oct a1394-90 v603 aOBJECTIVE: To examine the risk factors for mild cognitive impairment (MCI) in a longitudinal population study-the Cardiovascular Health Study Cognition Study.
DESIGN: We examined the factors that in the period 1991 through 1994 predicted the development of MCI in all participants of the Cardiovascular Health Study Cognition Study. Further examination was conducted in the Pittsburgh, Pa, cohort (n = 927), where participants with MCI were classified as having either the MCI amnestic-type or the MCI multiple cognitive deficits-type.
SETTING: Multicenter population study.
PATIENTS: This study includes all participants of the Cardiovascular Health Study Cognition Study (n = 3608) who had a magnetic resonance imaging (MRI) scan of the brain between 1991 and 1994, and detailed neuropsychological, neurological, and medical evaluations to identify the presence of MCI or dementia in the period 1998 to 1999. The mean time between the closest clinical examination to the MRI and the diagnostic evaluation for cognitive disorders was 5.8 years for the Cardiovascular Health Study Cognition Study cohort and 6.0 years for the Pittsburgh cohort.
MAIN OUTCOME MEASURES: Risk factors for MCI at the time of the MRI were identified using logistic regression, controlling for age, race, educational level, baseline Modified Mini-Mental State Examination and Digit Symbol Test scores, measurements of depression, MRI findings (atrophy, ventricular volume, white matter lesions, and infarcts), the presence of the apolipoprotein E (APOE) epsilon4 allele, hypertension, diabetes mellitus, and heart disease.
RESULTS: Mild cognitive impairment (n = 577) was associated with race (African American), low educational level, low Modified Mini-Mental State Examination and Digit Symbol Test scores, cortical atrophy, MRI-identified infarcts, and measurements of depression. The MCI amnestic-type was associated with MRI-identified infarcts, the presence of the APOE epsilon4 allele, and low Modified Mini-Mental State Examination scores. The MCI multiple cognitive deficits-type was associated with low Modified Mini-Mental State Examination and Digit Symbol Test scores.
CONCLUSIONS: The development of MCI is associated with measurements of cognition and depression, racial and constitutional factors, and cerebrovascular disease. Early cognitive deficits seem to be a common denominator for the 2 forms of MCI; the presence of cerebrovascular disease and the APOE epsilon4 allele is associated with the amnestic type of MCI.
10aAged10aApolipoprotein E410aApolipoproteins E10aBrain10aCardiovascular Diseases10aCognition Disorders10aCohort Studies10aDepressive Disorder10aFemale10aHumans10aLogistic Models10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aMood Disorders10aPennsylvania10aPopulation10aRisk Factors1 aLopez, Oscar, L1 aJagust, William, J1 aDulberg, Corinne1 aBecker, James, T1 aDeKosky, Steven, T1 aFitzpatrick, Annette1 aBreitner, John1 aLyketsos, Constantine1 aJones, Beverly1 aKawas, Claudia1 aCarlson, Michelle1 aKuller, Lewis, H uhttps://chs-nhlbi.org/node/75602995nas a2200349 4500008004100000022001400041245007200055210006900127260001300196300001100209490000800220520199600228653003902224653000902263653002002272653001902292653002602311653004002337653001102377653001102388653002602399653001802425653001702443653001702460100002002477700002202497700002402519700002202543700002002565700002502585856003502610 2004 eng d a1097-674400aRacial differences in endothelial function in postmenopausal women.0 aRacial differences in endothelial function in postmenopausal wom c2004 Oct a606-110 v1483 aOBJECTIVE: Racial differences in cardiovascular mortality among women remain largely unexplained. Preliminary data suggest that African American and Caucasian differences in endothelial function may parallel differential cardiovascular disease (CVD) risk in women. To further study differences in endothelial function between African American and Caucasian women, we analyzed measures of brachial artery flow-mediated dilation (FMD) in women enrolled in the Cardiovascular Health Study (CHS).
METHODS AND RESULTS: Brachial artery FMD was measured in the fasting state using established ultrasound techniques in 1330 Caucasian and 297 African American female participants in CHS (mean age 78.4 +/- 4.4 years). General linear models were used to compare FMD between African American and Caucasian women after adjusting for baseline brachial diameter, hypertension, diabetes, smoking, cholesterol, systolic blood pressure, body mass index, waist/hip ratio, age, education, income level; use of angiotensin-converting enzyme inhibitors, beta-blockers, nitroglycerin, estrogens and lipid-lowering drugs; and presence of clinical or subclinical disease. Adjusted absolute change and percent change in brachial artery diameter was significantly reduced in African American women compared with Caucasian women (P <.0001 and P =.0002, respectively). Similar results were found when the women were stratified by history of CVD (- CVD, P =.02; + CVD, P =.001) and CVD or subclinical vascular disease (- disease, P =.01, + disease, P =.03).
CONCLUSIONS: In this cohort, brachial artery FMD was lower in African American women compared to Caucasian women, and this difference persisted after adjustment by multivariable analysis. The increased CVD risk in African American women may be related to impaired endothelial function. It remains to be determined whether African American women may uniquely benefit by interventions designed to improve endothelial health.
10aAfrican Continental Ancestry Group10aAged10aBrachial Artery10aCohort Studies10aEndothelium, Vascular10aEuropean Continental Ancestry Group10aFemale10aHumans10aMultivariate Analysis10aPostmenopause10aRisk Factors10aVasodilation1 aLoehr, Laura, R1 aEspeland, Mark, A1 aSutton-Tyrrell, Kim1 aBurke, Gregory, L1 aCrouse, John, R1 aHerrington, David, M uhttps://chs-nhlbi.org/node/80603224nas a2200493 4500008004100000022001400041245017200055210006900227260001300296300001000309490000700319520182100326653002102147653000902168653002202177653001602199653001502215653002002230653001602250653002102266653002802287653002202315653001102337653001102348653001702359653001702376653002002393653000902413653002602422653001502448653001702463653001202480653002002492100002402512700001702536700001802553700002302571700001602594700002002610700002202630700001802652700002502670856003502695 2004 eng d a1523-683800aThe relationship of cardiovascular risk factors to microalbuminuria in older adults with or without diabetes mellitus or hypertension: the cardiovascular health study.0 arelationship of cardiovascular risk factors to microalbuminuria c2004 Jul a25-340 v443 aBACKGROUND: Microalbuminuria is a risk factor for coronary heart disease (CHD). It occurs most commonly in the settings of diabetes and hypertension. The mechanisms by which it increases CHD risk are uncertain.
METHODS: We examined the cross-sectional association of microalbuminuria with a broad range of CHD risk factors in 3 groups of adults aged 65 years or older with and without microalbuminuria: those with (1) no diabetes or hypertension (n = 1,098), (2) hypertension only (n = 1,450), and (3) diabetes with or without hypertension (n = 465).
RESULTS: Three factors were related to microalbuminuria in all 3 groups: age, elevated systolic blood pressure, and markers of systemic inflammation. In patients with neither diabetes nor hypertension, increasing C-reactive protein levels were associated with microalbuminuria (odds ratio per 1-mg/L increase, 1.46; 95% confidence interval [CI], 1.15 to 1.84). Among those with diabetes, an increase in white blood cell (WBC) count was associated with microalbuminuria (odds ratio per 1,000-cell/mL increase, 2.57; 95% CI, 1.12 to 5.89). Among those with hypertension, an increase in WBC count (odds ratio per 1,000-cell/mL increase, 1.83; 95% CI, 1.04 to 3.23) and fibrinogen level (odds ratio per 10-mg/dL increase, 1.02; 95% CI, 1.00 to 1.05) were significantly associated with microalbuminuria. In all 3 groups, prevalent CHD was related to an elevated WBC count. In none of the 3 groups was brachial artery reactivity to ischemia, an in vivo marker of endothelial function, related to microalbuminuria.
CONCLUSION: Microalbuminuria is associated with age, systolic blood pressure, and markers of inflammation. These associations reflect potential mechanisms by which microalbuminuria is related to CHD risk.
10aAge Distribution10aAged10aAged, 80 and over10aAlbuminuria10aBiomarkers10aBrachial Artery10aComorbidity10aCoronary Disease10aCross-Sectional Studies10aDiabetes Mellitus10aFemale10aHumans10aHypertension10aInflammation10aLogistic Models10aMale10aMultivariate Analysis10aOdds Ratio10aRisk Factors10aSmoking10aUltrasonography1 aBarzilay, Joshua, I1 aPeterson, Do1 aCushman, Mary1 aHeckbert, Susan, R1 aCao, Jie, J1 aBlaum, Caroline1 aTracy, Russell, P1 aKlein, Ronald1 aHerrington, David, M uhttps://chs-nhlbi.org/node/79402446nas a2200373 4500008004100000022001400041245013900055210006900194260001300263300001100276490000700287520137500294653000901669653001901678653002101697653003001718653001201748653001101760653002201771653001101793653002401804653001401828653001201842653000901854653002101863653001701884100002401901700002401925700002201949700002101971700002301992700002202015856003502037 2004 eng d a0021-972X00aThe relationship of fasting serum radioimmune insulin levels to incident coronary heart disease in an insulin-treated diabetic cohort.0 arelationship of fasting serum radioimmune insulin levels to inci c2004 Jun a2852-80 v893 aIt is not known whether insulin levels, in the setting of insulin treatment, are an independent risk factor for coronary heart disease (CHD). We studied a cohort of 116 insulin-treated individuals, 65 yr or older, who were followed for 5.6-9 yr. All were free of CHD at baseline. There were 47 incident CHD events. In Cox proportional hazards modeling, with fasting immune-reactive insulin levels as a continuous variable, the hazard ratio for CHD was statistically significant (P < 0.0001). When insulin levels were divided into intervals, those in the third interval [43-150 microU/ml (258-900 pmol/liter)] had an adjusted 30% increased relative risk (95% confidence interval, 0.57, 2.98) compared with those in the first interval [<20 microU/ml (<120 pmol/liter)]. Those in the fourth interval [151-400 microU/ml (906-2400 pmol/liter)] had an adjusted 5.6-fold increased risk (2.3-13.1; P < 0.0001). Approximately 15% of the cohort had such elevated insulin levels. Immune-reactive insulin levels were strongly correlated with specific insulin, proinsulin, and insulin antibody levels. Markedly elevated fasting immune-reactive insulin levels were an independent risk factor for CHD in this study of insulin-treated older adults. These observational findings should be confirmed through larger prospective studies, given their implications for insulin therapy.
10aAged10aCohort Studies10aCoronary Disease10aDiabetes Mellitus, Type 110aFasting10aFemale10aFollow-Up Studies10aHumans10aHypoglycemic Agents10aIncidence10aInsulin10aMale10aRadioimmunoassay10aRisk Factors1 aKronmal, Richard, A1 aBarzilay, Joshua, I1 aTracy, Russell, P1 aSavage, Peter, J1 aOrchard, Trevor, J1 aBurke, Gregory, L uhttps://chs-nhlbi.org/node/78902390nas a2200361 4500008004100000022001400041245008000055210006900135260001300204300001100217490000700228520139900235653002801634653001101662653002201673653002901695653001101724653000901735653003401744653002401778653002401802653001701826653001901843100002101862700001401883700001701897700001401914700001701928700001501945700001801960700001501978856003501993 2004 eng d a0040-637600aRespiratory muscle strength and the risk of incident cardiovascular events.0 aRespiratory muscle strength and the risk of incident cardiovascu c2004 Dec a1063-70 v593 aBACKGROUND: Maximal inspiratory pressure (MIP) is a measure of inspiratory muscle strength. The prognostic importance of MIP for cardiovascular events among elderly community dwelling individuals is unknown. Diminished forced vital capacity (FVC) is a risk factor for cardiovascular events which remains largely unexplained.
METHODS: MIP was measured at the baseline examination of the Cardiovascular Health Study. Participants had to be free of prevalent congestive heart failure (CHF), myocardial infarction (MI), and stroke.
RESULTS: Subjects in the lowest quintile of MIP had a 1.5-fold increased risk of MI (HR 1.48, 95% CI 1.07 to 2.06) and cardiovascular disease (CVD) death (HR 1.54, 95% CI 1.09 to 2.15) after adjustment for non-pulmonary function covariates. There was a potential inverse relationship with stroke (HR 1.36, 95% CI 0.97 to 1.90), but there was little evidence of an association between MIP and CHF (HR 1.22, 95% CI 0.93 to 1.60). The addition of FVC to models attenuated the HR associated with MIP only modestly; similarly, addition of MIP attenuated the HR associated with FVC only modestly.
CONCLUSIONS: A reduced MIP is an independent risk factor for MI and CVD death, and a suggestion of an increased risk for stroke. This association with MIP appeared to be mediated through mechanisms other than inflammation.
10aCardiovascular Diseases10aFemale10aFollow-Up Studies10aForced Expiratory Volume10aHumans10aMale10aMaximal Voluntary Ventilation10aProspective Studies10aRespiratory Muscles10aRisk Factors10aVital Capacity1 avan der Palen, J1 aRea, T, D1 aManolio, T A1 aLumley, T1 aNewman, A, B1 aTracy, R P1 aEnright, P, L1 aPsaty, B M uhttps://chs-nhlbi.org/node/81102896nas a2200421 4500008004100000022001400041245010700055210006900162260001300231300001200244490000700256520170000263653003301963653000901996653002802005653002202033653001902055653001902074653001402093653001102107653001802118653001102136653001702147653000902164653001702173653004102190653001802231100002102249700002302270700002102293700002302314700002102337700001902358700002102377700002102398700002002419856003502439 2004 eng d a0002-861400aRisk of congestive heart failure in an elderly population treated with peripheral alpha-1 antagonists.0 aRisk of congestive heart failure in an elderly population treate c2004 Oct a1648-540 v523 aOBJECTIVES: To compare the risk of congestive heart failure (CHF) in elderly individuals treated with any peripheral alpha-1 antagonist for hypertension with any thiazide, test whether the risk persists in subjects without cardiovascular disease (CVD) at baseline, and examine CHF risk in normotensive men with prostatism treated with alpha antagonists.
DESIGN: Prospective cohort study.
SETTING: Four U.S. sites: Washington County, Maryland; Allegheny County, Pennsylvania; Sacramento County, California; and Forsyth County, North Carolina.
PARTICIPANTS: A total of 5,888 community-dwelling subjects aged 65 and older.
MEASUREMENTS: Adjudicated incident CHF.
RESULTS: The 3,105 participants with treated hypertension were at risk for CHF; 22% of men and 8% of women took alpha antagonists during follow-up. The age-adjusted risk of CHF in those receiving monotherapy treated with alpha antagonists was 1.90 (95% confidence interval=1.03-3.50) compared with thiazides. In subjects without CVD at baseline receiving monotherapy, women taking an alpha antagonist had a 3.6 times greater age-adjusted risk of CHF, whereas men had no difference in risk. Adjustment for systolic blood pressure attenuated statistical differences in risk. There were 930 men without hypertension at risk for CHF; 5% used alpha antagonists during follow-up, with no observed increase in CHF risk.
CONCLUSION: Subjects receiving alpha antagonist monotherapy for hypertension had a two to three times greater risk of incident CHF, also seen in lower-risk subjects, but differences in blood pressure control partly explained this.
10aAdrenergic alpha-Antagonists10aAged10aAntihypertensive Agents10aBenzothiadiazines10aBlood Pressure10aCohort Studies10aDiuretics10aFemale10aHeart Failure10aHumans10aHypertension10aMale10aRisk Factors10aSodium Chloride Symporter Inhibitors10aUnited States1 aBryson, Chris, L1 aSmith, Nicholas, L1 aKuller, Lewis, H1 aChaves, Paulo, H M1 aManolio, Teri, A1 aLewis, William1 aBoyko, Edward, J1 aFurberg, Curt, D1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/80403279nas a2200541 4500008004100000022001400041245008300055210006900138260001300207300001100220490000700231520176200238653002202000653000902022653001002031653002102041653001902062653002802081653001902109653001502128653002802143653001302171653002402184653004002208653001102248653001102259653003102270653001102301653002002312653002602332653000902358653001702367653002902384653002202413653001702435653002102452653001202473653003702485653001802522100002302540700002402563700002302587700002402610700002202634700002102656700002502677856003502702 2005 eng d a1523-683800aRenal duplex parameters, blood pressure, and renal function in elderly people.0 aRenal duplex parameters blood pressure and renal function in eld c2005 May a842-500 v453 aBACKGROUND: Changes in renal artery and renal parenchyma perfusion are believed to correlate with severity of hypertension and worsened renal function, but population-based studies of these associations are not available. This study examines relationships between parameters derived from renal duplex sonography (RDS), blood pressure (BP), and excretory renal function in a population-based cohort of elderly Americans.
METHODS: Through an ancillary study to the Cardiovascular Health Study, 758 participants (37% men; mean age, 77 years) underwent RDS in which flow velocities and frequency shifts were determined from spectral analysis of Doppler-shifted signals obtained from the renal artery and parenchyma. Associations of these duplex parameters with BP and inverse serum creatinine were examined by using multivariate regression techniques.
RESULTS: Main renal artery peak systolic flow velocity (PSV) showed independent associations with BP, with an SD increase in PSV (0.53 m/s) associated with a 3.3-mm Hg increase in systolic BP (SBP) and a 2.4-mm Hg decrease in diastolic BP (DBP). An SD decrease in end-diastolic frequency shift (EDF; 131 kHz) was associated with a 6.0-mm Hg increase in SBP, a 4.2-mm Hg decrease in DBP, and a significant 3.7% decrease in inverse serum creatinine.
CONCLUSION: Increases in renal artery PSV and decreases in parenchymal EDF are associated with increased SBP and decreased DBP. Moreover, decreased parenchymal EDF showed significant associations with impaired excretory renal function. These results suggest that renal duplex parameters are associated with renal parenchymal changes caused by hypertension and progressive renal dysfunction in elderly people.
10aAfrican Americans10aAged10aAging10aArteriosclerosis10aBlood Pressure10aCardiovascular Diseases10aCohort Studies10aCreatinine10aCross-Sectional Studies10aDiastole10aDisease Progression10aEuropean Continental Ancestry Group10aFemale10aHumans10aHypertension, Renovascular10aKidney10aKidney Diseases10aKidney Function Tests10aMale10aRenal Artery10aRenal Artery Obstruction10aRenal Circulation10aRisk Factors10aSampling Studies10aSystole10aUltrasonography, Doppler, Duplex10aUnited States1 aPearce, Jeffrey, D1 aEdwards, Matthew, S1 aCraven, Timothy, E1 aEnglish, William, P1 aMondi, Matthew, M1 aReavis, Scott, W1 aHansen, Kimberley, J uhttps://chs-nhlbi.org/node/83603313nas a2200493 4500008004100000022001400041245012000055210006900175260001600244300001100260490000800271520188900279653002102168653000902189653002202198653002502220653001902245653001602264653002102280653001102301653002502312653002502337653001102362653003102373653001402404653002602418653000902444653002602453653001602479653001402495653002402509653002002533653003002553653002102583653001802604653002902622653001802651100002402669700002302693700002202716700002102738700002502759856003502784 2005 eng d a0003-992600aRenovascular disease and the risk of adverse coronary events in the elderly: a prospective, population-based study.0 aRenovascular disease and the risk of adverse coronary events in c2005 Jan 24 a207-130 v1653 aBACKGROUND: Renovascular disease is a cause of secondary hypertension and renal insufficiency and is suspected to contribute to morbidity and mortality of coronary heart disease. This investigation prospectively examined associations between renovascular disease and adverse coronary events among a population-based sample of elderly Americans.
METHODS: The Cardiovascular Health Study is a prospective, multicenter cohort study of cardiovascular disease risk factors, morbidity, and mortality among Americans older than 65 years. Renal duplex sonography was performed on 870 individuals between January 1995 and February 1997. Renovascular disease was defined as any focal peak systolic velocity of 1.8 m/s or greater (renal artery stenosis) or the absence of a Doppler-shifted signal from an imaged artery (renal artery occlusion). Adverse coronary events were defined as hospitalized angina, fatal or nonfatal myocardial infarction, and coronary revascularization.
RESULTS: During a mean follow-up of 14 months, 68 participants experienced incident or recurrent adverse coronary events. The presence of renovascular disease demonstrated a significant relationship with adverse coronary events (hazard ratio, 1.96; 95% confidence interval, 1.00-3.83; P = .05) that remained after controlling for the effects of coexisting atherosclerotic risk factors and prevalent cardiovascular disease. The relationship between renovascular disease and adverse coronary events was not dependent on the effects of increased blood pressure.
CONCLUSIONS: The presence of renovascular disease was associated with an increase in the risk of adverse coronary events in this sample. The increment in risk was not dependent on the effects of associated atherosclerotic risk factors, other prevalent cardiovascular disease, or increased blood pressure.
10aAge Distribution10aAged10aAged, 80 and over10aAnalysis of Variance10aCohort Studies10aComorbidity10aCoronary Disease10aFemale10aGeriatric Assessment10aHeart Function Tests10aHumans10aHypertension, Renovascular10aIncidence10aKidney Function Tests10aMale10aMultivariate Analysis10aProbability10aPrognosis10aProspective Studies10aRisk Assessment10aSeverity of Illness Index10aSex Distribution10aSurvival Rate10aUltrasonography, Doppler10aUnited States1 aEdwards, Matthew, S1 aCraven, Timothy, E1 aBurke, Gregory, L1 aDean, Richard, H1 aHansen, Kimberley, J uhttps://chs-nhlbi.org/node/81902852nas a2200373 4500008004100000022001400041245012100055210006900176260001600245300001300261490000800274520178900282653000902071653002202080653001002102653002002112653002802132653001102160653001102171653000902182653003302191653002002224653001702244100002202261700001702283700002102300700002302321700002002344700002102364700002202385700001802407700001802425856003502443 2005 eng d a0003-992600aRisk factors for declining ankle-brachial index in men and women 65 years or older: the Cardiovascular Health Study.0 aRisk factors for declining anklebrachial index in men and women c2005 Sep 12 a1896-9020 v1653 aBACKGROUND: An ankle-brachial index (ABI) of less than 0.9 is a noninvasive measure of lower extremity arterial disease and a predictor of cardiovascular events. Little information is available on longitudinal change in ABI or on risk factors for declining ABI in a community-based population.
METHODS: To assess risk factors for ABI decline, we studied 5888 participants in the Cardiovascular Health Study cohort (men and women 65 years or older). We measured ABI in 1992-1993 and again in 1998-1999. At baseline, we excluded individuals with an ABI less than 0.9, ABI greater than 1.4, or confirmed symptomatic lower extremity arterial disease (n = 823). The group with ABI decline included 218 participants with decline greater than 0.15 and to 0.9 or less. The comparison group comprised the remaining 2071 participants with follow-up ABI.
RESULTS: The percentage of participants with ABI decline was 9.5% over 6 years of follow-up. The mean +/- SD decline was 0.33 +/- 0.12 in cases of ABI decline and 0.02 +/- 0.13 in non-cases. Independent predictors of ABI decline, reported as odds ratios, were age, 1.96 (95% confidence interval [CI], 1.42-2.71) for 75 to 84 years and 3.79 (95% CI, 1.36-10.5) for those older than 85 years compared with those younger than 75 years; current cigarette use, 1.74 (95% CI, 1.02-2.96); hypertension, 1.64 (95% CI, 1.18-2.28); diabetes, 1.77 (95% CI, 1.14-2.76); higher low-density lipoprotein cholesterol level, 1.60 (95% CI, 1.03-2.51), and lipid-lowering drug use 1.74 (95% CI, 1.05-2.89).
CONCLUSION: Worsening lower extremity arterial disease, assessed as ABI decline, occurred in 9.5% of this elderly cohort over 6 years and was associated with modifiable vascular disease risk factors.
10aAged10aAged, 80 and over10aAnkle10aBrachial Artery10aCardiovascular Diseases10aFemale10aHumans10aMale10aPeripheral Vascular Diseases10aRisk Assessment10aRisk Factors1 aKennedy, Margaret1 aSolomon, Cam1 aManolio, Teri, A1 aCriqui, Michael, H1 aNewman, Anne, B1 aPolak, Joseph, F1 aBurke, Gregory, L1 aEnright, Paul1 aCushman, Mary uhttps://chs-nhlbi.org/node/85502656nas a2200385 4500008004100000022001400041245015100055210006900206260001300275300001100288490000700299520155000306653001001856653001601866653000901882653002801891653001101919653001501930653001101945653000901956653002701965653002401992653002402016653001702040653001602057653001202073653001702085110003702102700002002139700001502159700002302174700002102197700001702218856003502235 2006 eng d a0300-577100aRegression dilution methods for meta-analysis: assessing long-term variability in plasma fibrinogen among 27,247 adults in 15 prospective studies.0 aRegression dilution methods for metaanalysis assessing longterm c2006 Dec a1570-80 v353 aBACKGROUND: Within-person variability in measured values of a risk factor can bias its association with disease. The extent of this regression dilution bias for plasma fibrinogen was investigated using repeat measurement data collected at varying time intervals on 27 247 adults in 15 prospective studies.
METHODS: Regression dilution ratios (RDRs) were estimated from a linear regression of repeat measurements on baseline values in each study and for each time interval, and pooled allowing for within- and between-study heterogeneity. RDRs were estimated both without and with adjustment for confounders, and factors were investigated that might influence the RDRs.
RESULTS: The unadjusted overall RDR was 0.51 (95% CI: 0.47, 0.55), which decreased to 0.46 (95% CI: 0.42, 0.49) after adjustment for age, sex and measured values of other established vascular risk factors. The RDR did not vary materially by assay method, age, sex or smoking status, but decreased at higher levels of baseline fibrinogen.
CONCLUSION: It is appropriate to use an RDR of 0.5 to correct approximately for regression dilution bias in plasma fibrinogen values; however, this correction factor may produce somewhat conservative hazard ratios in adjusted analyses, at higher fibrinogen concentrations and in follow-up beyond a decade. More generally, the methods described in this report have widespread applicability to quantifying regression dilution bias in repeatability data from multiple prospective studies.
10aAdult10aAge Factors10aBias10aCardiovascular Diseases10aFemale10aFibrinogen10aHumans10aMale10aMeta-Analysis as Topic10aProspective Studies10aRegression Analysis10aRisk Factors10aSex Factors10aSmoking10aTime Factors1 aFibrinogen Studies Collaboration1 aWood, Angela, M1 aWhite, Ian1 aThompson, Simon, G1 aLewington, Sarah1 aDanesh, John uhttps://chs-nhlbi.org/node/93102624nas a2200313 4500008004100000022001400041245010600055210006900161260001300230300001200243490000700255520175400262653000902016653002202025653001002047653001002057653001102067653000902078653001102087653003102098653000902129653002402138653002102162100002102183700002602204700002502230700002002255856003502275 2007 eng d a1079-500600aA regions-of-interest volumetric analysis of mobility limitations in community-dwelling older adults.0 aregionsofinterest volumetric analysis of mobility limitations in c2007 Sep a1048-550 v623 aBACKGROUND: In community-dwelling older adults, greater mobility impairment is associated with greater burden of diffuse brain structural abnormalities, such as higher white matter hyperintensities. This study examined the association between gray matter volumes of regions related to motor control, gait, and balance and whether this association is independent of burden of white matter hyperintensities.
METHODS: A random sample of 327 participants of the Cardiovascular Health Study (78.3 +/- 4.1 years old, 57% women) contributed brain magnetic resonance imaging (MRI) and mobility data. A brain imaging automated method measured gray matter volume in cerebellum, basal ganglia, and prefrontal and parietal cortex in both hemispheres. Gait speed was measured while walking 15 feet at usual pace. Standing balance was assessed by timing tandem stance. Associations between each region's volume and gait speed or balance were measured before and after adjustment for demographics, head size, cardiovascular risk factors, and 0-9 grading scores of white matter hyperintensities.
RESULTS: Smaller left cerebellum and left prefrontal regions were associated with slower gait, independently of covariates and of white matter hyperintensities. Smaller right putamen, right posterior superior parietal cortex, and both left and right cerebellum were associated with balance difficulty, independently of covariates and white matter hyperintensities.
CONCLUSIONS: Smaller gray matter volumes in regions crucial for motor control are associated with slower gait and poorer balance, and the association appears to be independent of other diffuse brain abnormalities such as white matter hyperintensities.
10aAged10aAged, 80 and over10aAging10aBrain10aFemale10aGait10aHumans10aMagnetic Resonance Imaging10aMale10aMobility Limitation10aPostural Balance1 aRosano, Caterina1 aAizenstein, Howard, J1 aStudenski, Stephanie1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/98802785nas a2200409 4500008004100000022001400041245009700055210006900152260001600221300001100237490000600248520162700254653001001881653002301891653001101914653001801925653001101943653000901954653001601963653002001979653001801999653004702017653001702064653003102081653001702112653001602129100002302145700002202168700002302190700002002213700002402233700001702257700002402274700002202298700002002320856003502340 2007 eng d a1550-938900aRelationship between reported and measured sleep times: the sleep heart health study (SHHS).0 aRelationship between reported and measured sleep times the sleep c2007 Oct 15 a622-300 v33 aSTUDY OBJECTIVE: Subjective and objective assessments of sleep may be discrepant due to sleep misperception and measurement effects, the latter of which may change the quality and quantity of a person's usual sleep. This study compared sleep times from polysomnography (PSG) with self-reports of habitual sleep and sleep estimated on the morning after a PSG in adults.
DESIGN: Total sleep time and sleep onset latency obtained from unattended home PSGs were compared to sleep times obtained from a questionnaire completed before the PSG and a Morning Survey completed the morning after the PSG.
PARTICIPANTS: A total of 2,113 subjects who were > or = 40 years of age were included in this analysis.
MEASURES AND RESULTS: Subjects were 53% female, 75% Caucasian, and 38% obese. The mean habitual sleep time (HABTST), morning estimated sleep time (AMTST), and PSG total sleep times (PSGTST) were 422 min, 379 min, and 363 min, respectively. The mean habitual sleep onset latency, morning estimated sleep onset latency, and PSG sleep onset latency were 17.0 min, 21.8 min, and 16.9 min, respectively. Models adjusting for related demographic factors showed that HABTST and AMTST differ significantly from PSGTST by 61 and 18 minutes, respectively. Obese and higher educated people reported less sleep time than their counterparts. Similarly, small but significant differences were seen for sleep latency.
CONCLUSIONS: In a community population, self-reported total sleep times and sleep latencies are overestimated even on the morning following overnight PSG.
10aAdult10aAttitude to Health10aFemale10aHealth Status10aHumans10aMale10aMiddle Aged10aPolysomnography10aPsychometrics10aSleep Initiation and Maintenance Disorders10aSleep Stages10aSurveys and Questionnaires10aTime Factors10aWakefulness1 aSilva, Graciela, E1 aGoodwin, James, L1 aSherrill, Duane, L1 aArnold, Jean, L1 aBootzin, Richard, R1 aSmith, Terry1 aWalsleben, Joyce, A1 aBaldwin, Carol, M1 aQuan, Stuart, F uhttps://chs-nhlbi.org/node/99602730nas a2200361 4500008004100000022001400041245016200055210006900217260001300286300001100299490000700310520169000317653000902007653002202016653002502038653001802063653001202081653001102093653002402104653001502128653001102143653000902154653002302163653001702186100001602203700001902219700002202238700001702260700002002277700001802297700001802315856003502333 2007 eng d a0742-307100aThe relationship of heart rate and heart rate variability to non-diabetic fasting glucose levels and the metabolic syndrome: the Cardiovascular Health Study.0 arelationship of heart rate and heart rate variability to nondiab c2007 Aug a855-630 v243 aBACKGROUND: Increased heart rate (HR) and diminished heart rate variability (HRV) are signs of early cardiovascular autonomic neuropathy. We tested the hypotheses that increased HR and diminished HRV are present in people: (i) with increased fasting glucose (FG) levels not in the range of diabetes mellitus (DM), and (ii) in people with the metabolic syndrome (MetS) independent of elevated FG levels.
METHODS: HR and HRV were determined in 1267 adults (mean age 72 years) who had Holter monitoring and FG measures: 536 had normal FG levels (NORM, FG 4.5-5.5 mmol/l), 363 had mildly impaired FG (IFG-1, FG 5.6-6.0 mmol/l), 182 had significantly impaired FG (IFG-2, FG 6.1-6.9 mmol/l) and 178 had DM (FG > 6.9 mmol/l or use of glucose-lowering agents/insulin). HR and HRV in NORM/IFG-1 was further compared by the number of components of the MetS and compared by the presence or absence of MetS in IFG-2/DM.
RESULTS: HRV indices were more impaired in IFG-2 and DM than in NORM or IFG-1. There were few differences in HRV indices between NORM and IFG-1 or between IFG-2 and DM. In NORM/IFG-1 participants, having > or = 2 components of the MetS was associated with a greater decrease in HRV compared with having no or one components. In IFG-2/DM participants, MetS was associated with decreased HRV compared with no MetS.
CONCLUSIONS: Increased HR and diminished HRV occur in the non-diabetic FG range. Diminished HRV is associated with the MetS, independent of FG levels. Both these results suggest that factors associated with increasing non-diabetic FG levels and the MetS play a role in the onset of cardiac autonomic impairment.
10aAged10aAged, 80 and over10aArrhythmias, Cardiac10aBlood Glucose10aFasting10aFemale10aGlucose Intolerance10aHeart Rate10aHumans10aMale10aMetabolic Syndrome10aRisk Factors1 aStein, P, K1 aBarzilay, J, I1 aDomitrovich, P, P1 aChaves, P, M1 aGottdiener, J S1 aHeckbert, S R1 aKronmal, R, A uhttps://chs-nhlbi.org/node/95202989nas a2200385 4500008004100000022001400041245006600055210006500121260001300186300001100199490000700210520194000217653000902157653002202166653001902188653002802207653002402235653001102259653003102270653001102301653002002312653000902332653002402341653001402365100002102379700002402400700001602424700002002440700002002460700002402480700002202504700002202526700002002548856003502568 2007 eng d a1523-683800aRelationship of uric acid with progression of kidney disease.0 aRelationship of uric acid with progression of kidney disease c2007 Aug a239-470 v503 aBACKGROUND: Uric acid levels are increased in patients with kidney dysfunction. We tested the hypothesis that uric acid may be associated with kidney disease progression.
STUDY DESIGN: Cohort study.
SETTING & PARTICIPANTS: 5,808 participants of the Cardiovascular Health Study.
PREDICTOR: Uric acid levels.
OUTCOMES & MEASUREMENTS: Kidney disease progression was defined as a decrease in estimated glomerular filtration rate (GFR) of 3 mL/min/1.73 m(2) per year or greater (>or=0.05 mL/s) and as incident chronic kidney disease (CKD). Measures of kidney function were estimated GFR using the Modification of Diet in Renal Disease Study equation.
RESULTS: Higher quintiles of uric acid levels were associated with greater prevalences of estimated GFR less than 60 mL/min/1.73 m(2) (<1.00 mL/s) of 7%, 14%, 12%, 25%, and 42% for quintiles 1 (
LIMITATIONS: Measurements of albuminuria were not available.
CONCLUSIONS: Uric acid levels are associated strongly with prevalent CKD. In comparison, greater uric acid levels had a significant, but much weaker, association with progression of kidney disease.
10aAged10aAged, 80 and over10aCohort Studies10aCross-Sectional Studies10aDisease Progression10aFemale10aGlomerular Filtration Rate10aHumans10aKidney Diseases10aMale10aProspective Studies10aUric Acid1 aChonchol, Michel1 aShlipak, Michael, G1 aKatz, Ronit1 aSarnak, Mark, J1 aNewman, Anne, B1 aSiscovick, David, S1 aKestenbaum, Bryan1 aCarney, Jan, Kirk1 aFried, Linda, F uhttps://chs-nhlbi.org/node/97203109nas a2200409 4500008004100000022001400041245011700055210006900172260001300241300001100254490000700265520193500272653000902207653002202216653002802238653001402266653002802280653001302308653001102321653001102332653002502343653000902368653002102377653002902398653002002427653001702447100002302464700002802487700002102515700001802536700002402554700002402578700002102602700002102623700002002644856003502664 2007 eng d a1524-462800aRetinal microvascular signs, cognitive function, and dementia in older persons: the Cardiovascular Health Study.0 aRetinal microvascular signs cognitive function and dementia in o c2007 Jul a2041-70 v383 aBACKGROUND AND PURPOSE: Cerebral microvascular disease may be a risk factor for the development of dementia in elderly persons. We describe the association of retinal microvascular signs with cognitive function and dementia among older individuals.
METHODS: In the population-based Cardiovascular Health Study, 2211 persons aged 69 to 97 years at recruitment had retinal photography. Photographs were evaluated for retinopathy (eg, microaneurysms, retinal hemorrhages), focal arteriolar narrowing, arteriovenous nicking, and retinal arteriolar and venular caliber. Cognitive status was determined from the Digit-Symbol Substitution Test and Modified Mini-Mental State Examination. Participants were also further evaluated for the presence of dementia with detailed neuropsychological testing. Persons with a prior stroke or taking antipsychotic or antidepressant medications were excluded.
RESULTS: After adjusting for age, gender, race, field center, education level, internal carotid intima-media thickness, body mass index, hypertension, diabetes, and cigarette smoking status, persons with retinopathy had lower mean Digit-Symbol Substitution Test scores but not Modified Mini-Mental State Examination than those without retinopathy (39 versus 41, P=0.002). In hypertensive persons, retinopathy (multivariable-adjusted OR, 2.10; 95% CI, 1.04 to 4.24) and focal arteriolar narrowing (OR, 3.02; 95% CI, 1.51 to 6.02) were associated with dementia. These associations were not present in individuals without hypertension.
CONCLUSIONS: In older persons, our study shows a modest cross-sectional association between retinopathy signs with poorer cognitive function and, in persons with hypertension, with dementia. These data support a possible role of cerebral microvascular disease in the pathogenesis of impaired cognitive function and dementia in older hypertensive persons.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aCognition10aCross-Sectional Studies10aDementia10aFemale10aHumans10aLongitudinal Studies10aMale10aMicrocirculation10aNeuropsychological Tests10aRetinal Vessels10aRisk Factors1 aBaker, Michelle, L1 aLarsen, Emily, K Marino1 aKuller, Lewis, H1 aKlein, Ronald1 aKlein, Barbara, E K1 aSiscovick, David, S1 aBernick, Charles1 aManolio, Teri, A1 aWong, Tien, Yin uhttps://chs-nhlbi.org/node/96502680nas a2200421 4500008004100000022001400041245007700055210006900132260001300201300001200214490000700226520153900233653002201772653002101794653002401815653002101839653001101860653002201871653001101893653001701904653001401921653000901935653001601944653002601960653003001986653001502016653002402031653001702055653001102072653001802083100002302101700002102124700002002145700001702165700002302182700001802205856003502223 2007 eng d a1524-462800aRisk factors for intracerebral hemorrhage in a pooled prospective study.0 aRisk factors for intracerebral hemorrhage in a pooled prospectiv c2007 Oct a2718-250 v383 aBACKGROUND AND PURPOSE: Few prospective studies have reported risk factors for intracerebral hemorrhage (ICH), and results are inconsistent. We studied risk factors for ICH in a pooled cohort of the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS).
METHODS: The ARIC cohort was recruited in 1987 to 1989 and involves 15 792 men and women, aged 45 to 64 years at baseline, sampled from 4 US communities. The CHS cohort was recruited in 1989 to 1993 and involves 5888 men and women, aged 65 or over at baseline, sampled from 4 US communities. Baseline measurements included many potential vascular risk factors. The cohorts were followed for incident stroke events.
RESULTS: Over 263 489 person-years of follow-up, 135 incident ICH events occurred. In a multivariable model, age, African-American ethnicity (versus Whites), and hypertension were positively associated with incident ICH, whereas low-density lipoprotein cholesterol and triglycerides were inversely related to incident ICH. Participants with systolic blood pressure >or=160 mm Hg or diastolic blood pressure >/=110 mm Hg had 5.55 (95% CI 3.07 to 10.0) times the rate of ICH as nonhypertensives. Sex, smoking, alcohol intake, body mass index, waist-to-hip ratio, waist circumference, and diabetes were not related to ICH.
CONCLUSIONS: In this pooled cohort the risk factors for ICH were older age, African-American ethnicity, hypertension, lower LDL-C, and lower triglycerides.
10aAfrican Americans10aAge Distribution10aCerebral Hemorrhage10aCholesterol, LDL10aFemale10aFollow-Up Studies10aHumans10aHypertension10aIncidence10aMale10aMiddle Aged10aMultivariate Analysis10aPredictive Value of Tests10aPrevalence10aProspective Studies10aRisk Factors10aStroke10aTriglycerides1 aSturgeon, Jared, D1 aFolsom, Aaron, R1 aLongstreth, W T1 aShahar, Eyal1 aRosamond, Wayne, D1 aCushman, Mary uhttps://chs-nhlbi.org/node/97702916nas a2200349 4500008004100000022001400041245007000055210006900125260001600194300001100210490000800221520198600229653000902215653002802224653001502252653001402267653001102281653003102292653001102323653001102334653000902345653001402354100002002368700002402388700001602412700002002428700002102448700002102469700002002490700002002510856003602530 2008 eng d a1538-367900aRapid kidney function decline and mortality risk in older adults.0 aRapid kidney function decline and mortality risk in older adults c2008 Nov 10 a2212-80 v1683 aBACKGROUND: Impaired kidney function is associated with increased mortality risk in older adults. It remains unknown, however, whether longitudinal declines in kidney function are independently associated with increased cardiovascular and all-cause mortality in older adults.
METHODS: The Cardiovascular Health Study evaluated a cohort of community-dwelling older adults enrolled from 1989 to 1993 in 4 US communities with follow-up through 2005. Among 4380 participants, the slope of annual decline in estimated glomerular filtration rate (eGFR) was estimated using both serum creatinine (eGFR(creat)) and cystatin C (eGFR(cys)) rates, which were measured at baseline, year 3, and year 7 of follow-up. Rapid decline in eGFR was defined as a loss greater than 3 mL/min/1.73 m(2) per year, and cardiovascular and all-cause mortality were assessed over a mean of 9.9 years of follow-up.
RESULTS: Mean (SD) levels of creatinine and cystatin C were 0.93 (0.30) mg/dL and 1.03 (0.25) mg/L, respectively; mean (SD) eGFR(creat) and eGFR(cys) were 79 (23) mL/min/1.73 m(2) and 79 (19) mL/min/1.73 m(2), respectively. Individuals with rapid decline measured by eGFR(creat) (n = 714; 16%) had increased risk of cardiovascular (adjusted hazard ratio [AHR], 1.70; 95% confidence interval [CI], 1.40-2.06) and all-cause (AHR, 1.73; 95% CI, 1.54-1.94) mortality. Individuals with rapid decline measured by eGFR(cys) (n = 1083; 25%) also had increased risk of cardiovascular (AHR, 1.53; 95% CI, 1.29-1.80) and all-cause (AHR, 1.53; 95% CI, 1.38-1.69) mortality. The association of rapid decline in eGFR with elevated mortality risk did not differ across subgroups based on baseline kidney function, age, sex, race, or prevalent coronary heart disease.
CONCLUSION: Rapid decline in eGFR is associated with an increased risk of cardiovascular and all-cause mortality in older adults, independent of baseline eGFR and other demographic variables.
10aAged10aCardiovascular Diseases10aCreatinine10aCystatins10aFemale10aGlomerular Filtration Rate10aHumans10aKidney10aMale10aMortality1 aRifkin, Dena, E1 aShlipak, Michael, G1 aKatz, Ronit1 aFried, Linda, F1 aSiscovick, David1 aChonchol, Michel1 aNewman, Anne, B1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/106202453nas a2200337 4500008004100000022001400041245008900055210006900144260001300213300001100226490000800237520153300245653000901778653002101787653002801808653001101836653001101847653000901858653001601867653001501883653001701898653002601915653001801941653001701959653002001976100002701996700001702023700002302040700001702063856003502080 2008 eng d a1879-148400aRelation of sleep-disordered breathing to carotid plaque and intima-media thickness.0 aRelation of sleepdisordered breathing to carotid plaque and inti c2008 Mar a125-310 v1973 aBACKGROUND: Sleep-disordered breathing (SDB) is associated with clinical cardiovascular disease (CVD), but its relation to subclinical atherosclerosis remains to be determined.
METHODS: We analyzed the cross-sectional associations of SDB, measured by the respiratory disturbance index (RDI), a hypoxemia index, and an arousal index, with carotid plaque and carotid intima-media thickness (IMT), measured by ultrasound. The sample included 985 participants in the Sleep Heart Health Study (mean age-62, median RDI-8.7) with no history of coronary heart disease and stroke, of whom 396 had evidence of a carotid plaque.
RESULTS: As compared with the first quartile of the RDI (0-1.2), the crude odds ratio for carotid plaque was 1.14, 1.27, and 1.48 for the second (1.3-4.1), third (4.2-10.7), and fourth (>10.7) quartile, respectively. After adjustment for CVD risk factors, the corresponding odds ratios were reduced (1.00, 1.04, 1.07, and 1.25). Similarly, the unadjusted mean carotid IMT increased with RDI, but adjusted means (mm) were similar (0.84, 0.85, 0.84, 0.85). Spline regression models did not show monotonicity of the dose-response functions at the right end of the RDI distribution. Neither the hypoxemia index nor the arousal index was associated with carotid plaque or carotid IMT.
CONCLUSION: The results of this study suggest that crude, positive associations between SDB and subclinical atherosclerosis can be attributed to confounding by CVD risk factors.
10aAged10aCarotid Arteries10aCarotid Artery Diseases10aFemale10aHumans10aMale10aMiddle Aged10aOdds Ratio10aRisk Factors10aSleep Apnea Syndromes10aTunica Intima10aTunica Media10aUltrasonography1 aWattanakit, Keattiyoat1 aBoland, Lori1 aPunjabi, Naresh, M1 aShahar, Eyal uhttps://chs-nhlbi.org/node/95702762nas a2200361 4500008004100000022001400041245014700055210006900202260001300271300001000284490000800294520172200302653001602024653000902040653002202049653002002071653002102091653002802112653001902140653001102159653001702170653001102187653000902198653001802207653001702225653002002242653001702262100001902279700002202298700002002320700002502340856003502365 2008 eng d a1879-148400aRelationship between brachial flow-mediated dilation and carotid intima-media thickness in an elderly cohort: the Cardiovascular Health Study.0 aRelationship between brachial flowmediated dilation and carotid c2008 Apr a840-50 v1973 aOBJECTIVE: The aim of this study was to determine the relationship between brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT) in a large multi-ethnic elderly cohort.
BACKGROUND: Brachial flow-mediated dilation (FMD) is a physiologic measure and carotid IMT is an anatomic structural measure of subclinical atherosclerosis. Both brachial FMD and carotid IMT have been associated with cardiovascular risk factors and cardiovascular events. The relationship between brachial FMD and carotid IMT is less clear especially in older adults.
METHODS: Brachial FMD, carotid IMT and traditional cardiovascular risk factors were measured in 2338 adults, age 72-98 years who were participants in the Cardiovascular Health Study. The relationship between FMD and IMT was assessed both unadjusted and also after adjusting for age, gender and race/ethnicity, BMI, HDL, LDL, systolic and diastolic blood pressure, serum creatinine, current smoking, diabetes mellitus, hormone therapy and prior CVD.
RESULTS: Both brachial FMD and carotid IMT correlated significantly with age, HDL levels, waist/hip ratio, serum cholesterol and number of CV risk factors. Brachial FMD was not associated with CCA IMT in this elderly cohort (Pearson partial correlation coefficient=-0.0252, p=0.222). In the adjusted linear regression model with CCA IMT as the dependent variable, brachial FMD was also not associated with CCA IMT (beta coefficient=-0.006, p=0.470).
CONCLUSION: Brachial FMD and CCA IMT are not related in population-based older adults. Brachial FMD and CCA IMT may be distinct and independent stages in the complex atherosclerotic process.
10aAge Factors10aAged10aAged, 80 and over10aBrachial Artery10aCarotid Arteries10aCarotid Artery Diseases10aCohort Studies10aFemale10aHemorheology10aHumans10aMale10aTunica Intima10aTunica Media10aUltrasonography10aVasodilation1 aYeboah, Joseph1 aBurke, Gregory, L1 aCrouse, John, R1 aHerrington, David, M uhttps://chs-nhlbi.org/node/98002767nas a2200397 4500008004100000022001400041245008700055210006900142260001300211300001100224490000700235520168000242653000901922653002201931653002501953653001901978653002201997653001302019653001102032653001102043653000902054653001502063653001702078653001802095653002202113100002802135700002402163700001902187700001802206700002102224700002002245700002102265700002402286700002302310856003602333 2008 eng d a1532-541500aThe relationship between exercise and risk of venous thrombosis in elderly people.0 arelationship between exercise and risk of venous thrombosis in e c2008 Mar a517-220 v563 aOBJECTIVES: To study whether exercise is associated with the risk of venous thrombosis in elderly people.
DESIGN: Observational study with a median follow-up of 11.6 years.
SETTING: The Cardiovascular Health Study in four U.S. communities.
PARTICIPANTS: People aged 65 and older without prior venous thrombosis (deep venous thrombosis or pulmonary embolism).
MEASUREMENTS: Self-reported exercise was measured two or three times during follow-up and was defined as expending more than 500 kcal/wk on exercise, including walking for exercise. Venous thrombosis cases were verified using medical record review.
RESULTS: Of 5,534 participants, 171 developed a first venous thrombosis. Self-reported exercise at baseline was not related to the risk of venous thrombosis after adjustment for sex, age, race, self-reported health, and body mass index (adjusted hazard ratio (HR(adj))=1.16, 95% confidence interval (CI)=0.84-1.61), although with exercise modeled as a time-varying exposure, overall results were in the direction of greater risk of venous thrombosis (HR(adj)=1.38, 95% CI=0.99-1.91). For mild-intensity exercise, such as walking, there was a nonsignificant finding in the direction of benefit (HR(adj)=0.75, 95% CI=0.49-1.16), but strenuous exercise, such as jogging, was associated with greater risk of venous thrombosis (HR(adj)=1.75, 95% CI=1.08-2.83) than no exercise at all.
CONCLUSION: In elderly people, strenuous exercise was associated with a higher risk of venous thrombosis than no exercise at all. Future studies are needed to explain this unexpected higher risk.
10aAged10aAged, 80 and over10aCase-Control Studies10aCohort Studies10aEnergy Metabolism10aExercise10aFemale10aHumans10aMale10aPrevalence10aRisk Factors10aUnited States10aVenous Thrombosis1 avan Stralen, Karlijn, J1 aDoggen, Carine, J M1 aLumley, Thomas1 aCushman, Mary1 aFolsom, Aaron, R1 aPsaty, Bruce, M1 aSiscovick, David1 aRosendaal, Frits, R1 aHeckbert, Susan, R uhttps://chs-nhlbi.org/node/100702434nas a2200337 4500008004100000022001400041245010100055210006900156260001300225300001100238490000700249520148300256653003101739653000901770653002801779653002601807653001301833653001101846653000901857653001801866653001101884653000901895653001701904653001901921653003101940100002301971700002101994700002502015700002002040856003602060 2008 eng d a1532-821X00aThe reliability and validity of measures of gait variability in community-dwelling older adults.0 areliability and validity of measures of gait variability in comm c2008 Dec a2293-60 v893 aOBJECTIVE: To examine the test-retest reliability and concurrent validity of variability of gait characteristics.
DESIGN: Cross-sectional study.
SETTING: Research laboratory.
PARTICIPANTS: Older adults (N=558) from the Cardiovascular Health Study.
INTERVENTIONS: Not applicable.
MAIN OUTCOME MEASURES: Gait characteristics were measured using a 4-m computerized walkway. SD determined from the steps recorded were used as the measures of variability. Intraclass correlation coefficients (ICC) were calculated to examine test-retest reliability of a 4-m walk and two 4-m walks. To establish concurrent validity, the measures of gait variability were compared across levels of health, functional status, and physical activity using independent t tests and analysis of variances.
RESULTS: Gait variability measures from the two 4-m walks demonstrated greater test-retest reliability than those from the single 4-m walk (ICC=.22-.48 and ICC=.40-.63, respectively). Greater step length and stance time variability were associated with poorer health, functional status and physical activity (P<.05).
CONCLUSIONS: Gait variability calculated from a limited number of steps has fair to good test-retest reliability and concurrent validity. Reliability of gait variability calculated from a greater number of steps should be assessed to determine if the consistency can be improved.
10aActivities of Daily Living10aAged10aCross-Sectional Studies10aDisability Evaluation10aExercise10aFemale10aGait10aHealth Status10aHumans10aMale10aPennsylvania10aRehabilitation10aReproducibility of Results1 aBrach, Jennifer, S1 aPerera, Subashan1 aStudenski, Stephanie1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/106502978nas a2200397 4500008004100000022001400041245013200055210006900187260001600256300001100272490000800283520181200291653002202103653001602125653000902141653002202150653001902172653003402191653004002225653001102265653001802276653001102294653001402305653000902319653003202328653001602360653001802376100002202394700001602416700002302432700002102455700002102476700002302497700002402520856003602544 2009 eng d a1879-191300aRace, gender, and mortality in adults > or =65 years of age with incident heart failure (from the Cardiovascular Health Study).0 aRace gender and mortality in adults or 65 years of age with inci c2009 Apr 15 a1120-70 v1033 aIn patients with heart failure (HF), mortality is lower in women versus men. However, it is unknown whether the survival advantage in women compared with men is present in both whites and African Americans with HF. The inception cohort consisted of adults > or =65 years with incident HF after enrollment in the CHS, a prospective population-based study of cardiovascular disease. Of 5,888 CHS subjects, 1,264 developed new HF and were followed up for 3 years. Subjects were categorized into 4 race-gender groups, and Cox proportional hazard regression models were used to examine whether 3-year total and cardiovascular mortality differed among the 4 groups after adjusting for sociodemographic factors, co-morbidities, and treatment. A gender-race interaction was also tested for each outcome. In subjects with incident HF, African Americans had more hypertension and diabetes than whites, and white men had more coronary heart disease than other gender-race groups. Receipt of cardiovascular treatments among the 4 groups was similar. Mortality rates after HF were lower in women compared with men (for white women, African-American women, African-American men, and white men, total mortality was 35.5, 33.6, 44.4, and 40.5/100 person-years, and cardiovascular mortality was 18.4, 19.5, 20.2, and 22.7/100 person-years, respectively). After adjusting for covariates, women had a 15% to 20% lower risk of total and cardiovascular mortality compared with men, but there was no significant difference in outcome by race. The gender-race interaction for either outcome was not significant. In conclusion, in older adults with HF, women had significantly better survival than men irrespective of race, suggesting that gender-based survival differences may be more important than race-based differences.
10aAfrican Americans10aAge Factors10aAged10aAged, 80 and over10aCohort Studies10aContinental Population Groups10aEuropean Continental Ancestry Group10aFemale10aHeart Failure10aHumans10aIncidence10aMale10aProportional Hazards Models10aSex Factors10aUnited States1 aParashar, Susmita1 aKatz, Ronit1 aSmith, Nicholas, L1 aArnold, Alice, M1 aVaccarino, Viola1 aWenger, Nanette, K1 aGottdiener, John, S uhttps://chs-nhlbi.org/node/109002675nas a2200445 4500008004100000022001400041245008300055210006900138260001300207300001200220490000700232520145100239653000901690653002201699653002801721653001501749653001501764653001101779653003101790653001801821653001101839653002501850653000901875653002601884653003301910653003301943653001701976653001101993653001702004653001802021100002402039700001602063700002202079700002102101700001702122700001702139700001702156700002002173856003602193 2009 eng d a1533-345000aRapid decline of kidney function increases cardiovascular risk in the elderly.0 aRapid decline of kidney function increases cardiovascular risk i c2009 Dec a2625-300 v203 aChronic kidney disease (CKD), defined at a specific time point, is an important risk factor for cardiovascular disease. Whether the rate of kidney function decline contributes additional cardiovascular risk is unknown. In the Cardiovascular Health Study, we compared the associations of changes in kidney function during the first 7 yr with the incidence of heart failure (HF), myocardial infarction (MI), stroke, and peripheral arterial disease (PAD) during the subsequent 8 yr. We defined a rapid decline in cystatin C-based estimated GFR as >3 ml/min per 1.73 m(2)/yr, on the basis of determination at baseline, year 3, and year 7. Among eligible participants, 1083 (24%) had rapid kidney decline. The incidence of each type of cardiovascular event was significantly higher among patients with rapid decline (all P < 0.001). After multivariate adjustment for demographics, cardiovascular disease risk factors, and baseline kidney function, rapid kidney function decline was significantly associated with HF (adjusted hazard ratio [HR] 1.32; 95% confidence interval [CI] 1.13 to 1.53), MI (HR 1.48; 95% CI 1.21 to 1.83), and PAD (HR 1.67; 95% CI 1.02 to 2.75) but not with stroke (HR 1.19; 95% CI 0.97 to 1.45). The association of rapid decline with each outcome did not differ by the presence or absence of CKD. In conclusion, declining kidney function associates with higher risk for HF, MI, and PAD among patients with or without CKD.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aCreatinine10aCystatin C10aFemale10aGlomerular Filtration Rate10aHeart Failure10aHumans10aLongitudinal Studies10aMale10aMyocardial Infarction10aPeripheral Vascular Diseases10aRenal Insufficiency, Chronic10aRisk Factors10aStroke10aTime Factors10aUnited States1 aShlipak, Michael, G1 aKatz, Ronit1 aKestenbaum, Bryan1 aSiscovick, David1 aFried, Linda1 aNewman, Anne1 aRifkin, Dena1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/114402550nas a2200373 4500008004100000022001400041245009900055210006900154260000900223300001000232490000700242520153600249653001601785653000901801653001501810653001501825653002401840653001101864653003101875653001101906653001101917653002001928653000901948653001701957100002401974700001601998700002202014700002002036700002002056700002402076700002002100700002002120856003602140 2009 eng d a1421-967000aRate of kidney function decline in older adults: a comparison using creatinine and cystatin C.0 aRate of kidney function decline in older adults a comparison usi c2009 a171-80 v303 aBACKGROUND/AIMS: The aim of this study was to determine the decline in the estimated glomerular filtration rate (eGFR) in elderly persons and to compare estimates based on creatinine and cystatin C.
METHODS: In the Cardiovascular Health Study, GFR changes in an elderly cohort were estimated from serum creatinine and cystatin C measured at baseline, year 3 and year 7 in 4,380 participants (age 72 +/- 5 years at entry). Outcomes were mean eGFR decline, incident chronic kidney disease (CKD) and rapid decline in eGFR (annual loss >3 ml/min/1.73 m(2)).
RESULTS: Mean annual eGFR loss as estimated from creatinine was 0.4 +/- 3.6 ml/min/1.73 m(2), with 16% of the participants experiencing a rapid decline. Mean eGFR loss as estimated from cystatin C was 1.8 +/- 2.6, with 25% of the participants experiencing a rapid decline (p < 0.001 for both). Among participants without baseline CKD, incident CKD was detected at year 7 in 10% (n = 263) using creatinine and 19% (n = 544) using cystatin C (p < 0.001). Increasing age was the strongest predictor of rapid decline; adjusted odds ratios were 1.38 (1.16-1.65), 1.62 (1.31-1.99) and 2.96 (2.28-3.84) for participants aged 70-74, 75-79 and 80+ at baseline, compared with those aged 65-69.
CONCLUSION: In elderly persons, cystatin C estimated substantially larger declines in kidney function than creatinine did. Defining the optimal measurement of kidney function in elderly persons should be a high priority for future research.
10aAge Factors10aAged10aCreatinine10aCystatin C10aDisease Progression10aFemale10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Diseases10aMale10aRisk Factors1 aShlipak, Michael, G1 aKatz, Ronit1 aKestenbaum, Bryan1 aFried, Linda, F1 aNewman, Anne, B1 aSiscovick, David, S1 aStevens, Lesley1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/108901428nas a2200517 4500008004100000022001400041245013100055210006900186260001300255300001100268490000600279653001500285653001000300653000900310653002200319653002500341653001900366653001100385653003200396653003800428653002200466653001500488653001500503653001100518653001400529653000900543653001400552653001600566653003600582653003100618653000900649653001800658653002200676653001600698100001500714700001800729700001700747700001600764700001500780700001800795700001400813700001500827700001700842700001500859856003600874 2009 eng d a1538-783600aReplication of findings on the association of genetic variation in 24 hemostasis genes and risk of incident venous thrombosis.0 aReplication of findings on the association of genetic variation c2009 Oct a1743-60 v710aAdolescent10aAdult10aAged10aAged, 80 and over10aCase-Control Studies10aCohort Studies10aFemale10aGenetic Association Studies10aGenetic Predisposition to Disease10aGenetic Variation10aHaplotypes10aHemostasis10aHumans10aIncidence10aMale10aMenopause10aMiddle Aged10aPolymorphism, Single Nucleotide10aReproducibility of Results10aRisk10aThrombophilia10aVenous Thrombosis10aYoung Adult1 aSmith, N L1 aWiggins, K, L1 aReiner, A, P1 aLange, L, A1 aCushman, M1 aHeckbert, S R1 aLumley, T1 aRice, K, M1 aFolsom, A, R1 aPsaty, B M uhttps://chs-nhlbi.org/node/112102515nas a2200373 4500008004100000022001400041245014800055210006900203260001300272300001100285490000800296520142800304653001601732653000901748653002601757653003301783653001101816653001101827653000901838653001601847653001101863653001401874653002501888653001801913653002701931100001901958700002101977700001801998700002202016700002102038700002302059700002302082856003602105 2010 eng d a1365-214100aReproductive history, hormone replacement, and incidence of venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology.0 aReproductive history hormone replacement and incidence of venous c2010 May a606-120 v1493 aNumerous studies have established that hormone replacement therapy increases the risk of venous thromboembolism (VTE), but an association of endogenous oestrogen exposure with the incidence of VTE is not fully established. Using a prospective design combining the Atherosclerosis Risk in Communities and the Cardiovascular Health Study cohort, we studied the 12-year risk of VTE in relation to hormone replacement therapy use, age at menopause, parity number, and type of menopause in 8236 post-menopausal women. There were no significant associations of age at menopause, parity number, or type of menopause with incidence of VTE. Women currently using hormone replacement had a 1.6-times higher multivariate-adjusted rate ratio (RR) of VTE compared with those without hormone use in the time-dependent model (RR=1.60, 95% confidence interval [CI], 1.06-2.36; Population attributable fraction=6.7%, 95%CI, 1.0-10.3). When we excluded women with 1-year or more duration of hormone therapy at baseline, the association was stronger (RR=2.02, 95%CI, 1.31-3.12). The multivariate-adjusted RRs of VTE for current users tended to be higher in those with idiopathic VTE (RR=2.40, 95%CI, 1.40-4.12) than those with secondary VTE (RR=1.08, 95%CI, 0.63-1.85). Hormone replacement therapy is associated with increased risk of VTE, but reproductive history markers of endogenous oestrogen exposure were not associated with VTE.
10aAge Factors10aAged10aEpidemiologic Methods10aEstrogen Replacement Therapy10aFemale10aHumans10aMale10aMiddle Aged10aParity10aPregnancy10aReproductive History10aUnited States10aVenous Thromboembolism1 aOhira, Tetsuya1 aFolsom, Aaron, R1 aCushman, Mary1 aWhite, Richard, H1 aHannan, Peter, J1 aRosamond, Wayne, D1 aHeckbert, Susan, R uhttps://chs-nhlbi.org/node/117503482nas a2200481 4500008004100000022001400041245014000055210006900195260001300264300001000277490000600287520214200293653000902435653002202444653001002466653001502476653002802491653002502519653001902544653001302563653002002576653001102596653002202607653001802629653001102647653001402658653000902672653002202681653001302703653003002716653001602746653002402762653001802786653001802804100001802822700002402840700002202864700002302886700001402909700001902923700002202942856003602964 2011 eng d a1941-329700aThe relationship between serum markers of collagen turnover and cardiovascular outcome in the elderly: the Cardiovascular Health Study.0 arelationship between serum markers of collagen turnover and card c2011 Nov a733-90 v43 aBACKGROUND: The deposition of collagen fibrils in the myocardial extracellular matrix increases with age and plays a key role in the pathophysiology of heart failure (HF). We sought to determine the predictive value of serum markers of collagen turnover for incident HF and cardiovascular (CV) morbidity, mortality, and all-cause mortality in elderly individuals.
METHODS AND RESULTS: In 880 participants in the Cardiovascular Health Study (mean age, 77±6 years; 48% women), serum levels of carboxyl-terminal peptide of procollagen type I (PIP), carboxyl-terminal telopeptide of collagen type I (CITP), and amino-terminal peptide of procollagen type III (PIIINP) were measured in 4 groups: HF with reduced ejection fraction (HFREF; n=146, EF <55%); HF with preserved EF (HFPEF; n=175, EF ≥55%), control subjects with CV risk factors but not HF (CVD; n=280), and healthy control subjects free of CV disease (n=279). Relationships between these serum markers and outcome at follow-up of 12±4 years (range, 3-17 years) was determined in six models including those adjusted for conventional risk factors, renal function, NT-proBNP and agents which interfere with collagen synthesis. For the entire cohort, in unadjusted and adjusted models, both PIIINP and CITP were associated with myocardial infarction, incident HF, hospitalization for HF, cardiovascular and all-cause mortality. In healthy control subjects, CITP and PIIINP were associated with all-cause death. In control subjects with risk factors, CITP was associated with incident HF, and in participants with HFPEF, CITP was associated with hospitalization for HF. No collagen biomarker was associated with outcome in participants with HFREF, and PIP was not associated with outcome in the cohort or its subgroups.
CONCLUSIONS: In both healthy and elderly individuals with CV disease at risk of developing HF, CITP and PIIINP are significantly associated with multiple adverse cardiac outcomes including myocardial infarction, HF, and death. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005133.
10aAged10aAged, 80 and over10aAging10aBiomarkers10aCardiovascular Diseases10aCase-Control Studies10aCohort Studies10aCollagen10aCollagen Type I10aFemale10aFollow-Up Studies10aHeart Failure10aHumans10aIncidence10aMale10aPeptide Fragments10aPeptides10aPredictive Value of Tests10aProcollagen10aProspective Studies10aStroke Volume10aSurvival Rate1 aBarasch, Eddy1 aGottdiener, John, S1 aAurigemma, Gerard1 aKitzman, Dalane, W1 aHan, Jing1 aKop, Willem, J1 aTracy, Russell, P uhttps://chs-nhlbi.org/node/132102825nas a2200349 4500008004100000022001400041245013900055210006900194260001300263300001000276490000700286520178800293653000902081653002302090653002802113653001602141653003602157653001102193653001102204653001402215653000902229653002002238653001702258653002402275653002202299653001802321653001802339653003602357100002202393700002402415856003602439 2011 eng d a1540-816700aRelationship of abnormal heart rate turbulence and elevated CRP to cardiac mortality in low, intermediate, and high-risk older adults.0 aRelationship of abnormal heart rate turbulence and elevated CRP c2011 Feb a122-70 v223 aINTRODUCTION: We examined whether heart rate turbulence (HRT) and C-reactive protein (CRP) add to traditional risk factors for cardiac mortality in older adults at low, intermediate, and high risk.
METHODS AND RESULTS: One thousand two hundred and seventy-two individuals, age ≥ 65 years, with 24-hour Holter recordings were studied. HRT, which quantifies heart rate response to ventricular premature contractions, was categorized as: both turbulence onset (TO) and turbulence slope (TS) normal; TO abnormal; TS abnormal; or both abnormal. Independent risks for cardiac mortality associated with HRT or, for comparison, elevated CRP (>3.0 mg/L), were calculated using Cox regression analysis adjusted for traditional cardiovascular disease risk factors and stratified by the presence of no, isolated subclinical (i.e., intermediate risk) or clinical cardiovascular disease. Having TS + TO abnormal compared to both normal was associated with cardiac mortality in the low-risk group [HR 7.9, 95% confidence interval (CI) 2.8-22.5, (P < 0.001)]. In the high and intermediate risk groups, abnormal TS and TS + TO ([HR 2.2, 95% CI 1.5-4.0, P = 0.016] and [HR 2.7, 95% CI 1.2-5.9, P = 0.012]), respectively, were also significantly associated with cardiac mortality. In contrast, elevated CRP was associated with increased cardiac mortality risk only in low-risk individuals [HR 2.5, 95% CI 1.3-5.1, P = 0.009]. Among low risk, the c-statistic was 0.706 for the base model, 0.725 for the base model with CRP, and 0.767 for the base model with HRT.
CONCLUSIONS: Abnormal HRT independently adds to risk stratification of low, intermediate and high-risk individuals, but HRT and CRP appear to both add to stratification of those considered low risk.
10aAged10aC-Reactive Protein10aCardiovascular Diseases10aComorbidity10aElectrocardiography, Ambulatory10aFemale10aHumans10aIncidence10aMale10aRisk Assessment10aRisk Factors10aStatistics as Topic10aSurvival Analysis10aSurvival Rate10aUnited States10aVentricular Premature Complexes1 aStein, Phyllis, K1 aBarzilay, Joshua, I uhttps://chs-nhlbi.org/node/125502896nas a2200361 4500008004100000022001400041245010300055210006900158260001300227300001200240490000700252520185800259653000902117653002802126653002402154653001702178653001102195653002102206653002902227653002102256653002002277653001702297100001902314700002002333700001702353700002402370700001802394700002202412700002002434700002202454700002202476856003602498 2011 eng d a1524-462800aRetinal microvascular signs and functional loss in older persons: the cardiovascular health study.0 aRetinal microvascular signs and functional loss in older persons c2011 Jun a1589-950 v423 aBACKGROUND AND PURPOSE: We hypothesized that retinal microvascular signs are associated with executive dysfunction, slow gait, and depressive mood, which are characteristic features of microvascular disease affecting frontal subcortical regions of the brain.
METHODS: In the Cardiovascular Health Study, 1744 participants (mean age, 78) free of stroke had retinal photographs and carotid ultrasound during the 1997 to 1998 visit. We examined the cross-sectional association of retinal signs with the digit-symbol substitution test (DSST) score, gait speed, the Center for Epidemiologic Studies-Depression score, and depressive mood, defined as Center for Epidemiologic Studies-Depression score >9 or antidepressant use.
RESULTS: After adjusting for potential confounders, retinal signs were associated with lower DSST score (generalized arteriolar narrowing and arteriovenous nicking), slower gait (retinopathy), and depressive mood (generalized arteriolar narrowing). A higher number of retinal signs was associated with lower DSST score (-0.76 and -2.79 points for 1 sign and ≥2 signs versus none; P<0.001) and slower gait (-0.009 and -0.083 m/s; P=0.047), but not with the square root of Center for Epidemiologic Studies-Depression score (0.079 and -0.208; P=0.072). In addition, coexistence of retinal signs (generalized arteriolar narrowing and arteriovenous nicking) and carotid atherosclerosis was associated with lower DSST score compared with either process alone (P for interaction <0.01). Notably, further adjustment for ventricular size, white matter disease, and infarcts on MRI did not attenuate the association.
CONCLUSIONS: Retinal signs are associated with executive dysfunction and slow gait, and possibly with depressive mood, suggesting a common process involving small vessels.
10aAged10aCardiovascular Diseases10aDepressive Disorder10aFrontal Lobe10aHumans10aMicrocirculation10aNeuropsychological Tests10aRetinal Diseases10aRetinal Vessels10aRisk Factors1 aKim, Dae, Hyun1 aNewman, Anne, B1 aHajjar, Ihab1 aStrotmeyer, Elsa, S1 aKlein, Ronald1 aNewton, Elizabeth1 aSarnak, Mark, J1 aBurke, Gregory, L1 aLipsitz, Lewis, A uhttps://chs-nhlbi.org/node/128302470nas a2200361 4500008004100000022001400041245013000055210006900185260001300254300001100267490000700278520143200285653003101717653001601748653000901764653002201773653002601795653002101821653001101842653001801853653001801871653001101889653002501900653000901925653001701934100002401951700001701975700001701992700002302009700002002032700002002052856003602072 2011 eng d a1532-841400aRisk factors for onset of disability among older persons newly diagnosed with heart failure: the Cardiovascular Health Study.0 aRisk factors for onset of disability among older persons newly d c2011 Sep a764-700 v173 aBACKGROUND: As the heart failure population continues to age, disability is becoming an increasingly important issue. Our objective was to identify risk factors for the onset of disability in activities of daily living among older persons with heart failure.
METHODS: The study population included participants with newly diagnosed heart failure from the Cardiovascular Health Study, a longitudinal study of community-living, older persons. Data were collected through annual examinations. Cox regression modeling was used to examine associations between time-dependent predictors and onset of disability.
RESULTS: Of 461 participants newly diagnosed with heart failure (mean age 78.7 [SD 5.89]), 23% subsequently developed disability. The first year after heart failure diagnosis was the period of greatest risk for onset of disability (chi-square P value <.001). Factors that were independently associated with disability included: impaired gait speed (HR 2.29, 95% CI 1.34-3.90); impaired cognition (HR 1.87, 95% CI 1.14-3.05); and depressive symptoms (HR 1.72, 95% CI 1.04-2.83).
CONCLUSIONS: Onset of disability is a common occurrence among older persons newly diagnosed with heart failure. Risk factors for onset of disability in this population are potentially modifiable, and should be routinely assessed in an effort to reduce disability in this growing population.
10aActivities of Daily Living10aAge Factors10aAged10aAged, 80 and over10aDisability Evaluation10aDisabled Persons10aFemale10aHealth Status10aHeart Failure10aHumans10aLongitudinal Studies10aMale10aRisk Factors1 aChaudhry, Sarwat, I1 aMcAvay, Gail1 aNing, Yuming1 aAllore, Heather, G1 aNewman, Anne, B1 aGill, Thomas, M uhttps://chs-nhlbi.org/node/131702768nas a2200421 4500008004100000022001400041245010100055210006900156260000900225300001000234490000700244520167200251653000901923653001501932653001901947653001101966653001101977653000901988653001301997653001902010653002202029653001702051653002402068653001702092653002102109653001602130653001402146100001202160700001402172700001902186700001202205700001802217700001702235700002002252700002102272700001702293856003602310 2011 eng d a1423-020800aThe risk of Parkinson disease associated with urate in a community-based cohort of older adults.0 arisk of Parkinson disease associated with urate in a communityba c2011 a223-90 v363 aBACKGROUND/AIMS: Studies suggest an inverse association between urate concentration and the risk of Parkinson disease (PD). We investigated this in the Cardiovascular Health Study in an elderly community-based cohort of adults.
METHODS: The association of baseline urate (µmol/l) and incident PD over 14 years was assessed with locally weighted scatterplot smoothing (LOESS) regression from which categories of low (<300 µmol/l), middle (300-500 µmol/l), and high (>500 µmol/l) urate ranges were derived. Multivariate logistic regression models assessed the risk of PD for each urate range. Linear and quadratic terms were tested when modeling the association between urate and the risk of PD.
RESULTS: Women had significantly lower urate concentrations than did men [316.8 µmol/l (SD 88.0) vs. 367.4 µmol/l (SD 87.7), p < 0.0001] and in women no associations between urate and PD risk were observed. In men, LOESS curves suggested a U-shaped or threshold effect between urate and PD risk. With the middle range as reference, the risk of developing PD was significantly increased for urate <300 µmol/l (OR 1.69, 95% CI 1.03-2.78) but not for urate >500 µmol/l (OR 1.55, 95% CI 0.72-3.32) in men. A negative linear term was significant for urate <500 µmol/l, and across the entire range a convex quadratic term was significant.
CONCLUSIONS: Results suggest a more complex relationship than previously reported between urate levels and the risk of PD in men. Low urate concentrations were associated with a higher PD risk and high urate concentrations were not associated with a further decrease in PD risk.
10aAged10aCalifornia10aCohort Studies10aFemale10aHumans10aMale10aMaryland10aNorth Carolina10aParkinson Disease10aPennsylvania10aProspective Studies10aRisk Factors10aSex Distribution10aSex Factors10aUric Acid1 aJain, S1 aTon, T, G1 aBoudreau, R, M1 aYang, M1 aThacker, E, L1 aStudenski, S1 aLongstreth, W T1 aStrotmeyer, E, S1 aNewman, A, B uhttps://chs-nhlbi.org/node/129703266nas a2200421 4500008004100000022001400041245022000055210006900275260001600344300000900360490000800369520191700377653003902294653001602333653000902349653002202358653002002380653002802400653001902428653003402447653001802481653004002499653001102539653002202550653001102572653002502583653000902608653001602617653003002633653001702663100002302680700001802703700001702721700001902738700002402757700002702781856003602808 2012 eng d a1524-453900aRacial differences in risks for first cardiovascular events and noncardiovascular death: the Atherosclerosis Risk in Communities study, the Cardiovascular Health Study, and the Multi-Ethnic Study of Atherosclerosis.0 aRacial differences in risks for first cardiovascular events and c2012 Jul 03 a50-90 v1263 aBACKGROUND: No studies have compared first cardiovascular disease (CVD) events and non-CVD death between races in a competing risks framework, which examines risks for numerous events simultaneously.
METHODS AND RESULTS: We used competing Cox models to estimate hazards for first CVD events and non-CVD death within and between races in 3 multicenter, National Heart, Lung, and Blood Institute-sponsored cohorts. Of 14 569 Atherosclerosis Risk in Communities (ARIC) study participants aged 45 to 64 years with mean follow-up of 10.5 years, 11.6% had CVD and 5.0% had non-CVD death as first events; among 4237 Cardiovascular Health Study (CHS) study participants aged 65 to 84 years and followed for 8.5 years, these figures were 43.2% and 15.7%, respectively. Middle-aged blacks were significantly more likely than whites to experience any CVD as a first event; this disparity disappeared by older adulthood and after adjustment for CVD risk factors. The pattern of results was similar for Multi-Ethnic Study of Atherosclerosis (MESA) participants. Traditional Cox and competing risks models yielded different results for coronary heart disease risk. Black men appeared somewhat more likely than white men to experience coronary heart disease with use of a standard Cox model (hazard ratio 1.06; 95% CI 0.90, 1.26), whereas they appeared less likely than white men to have a first coronary heart disease event with use of a competing risks model (hazard ratio, 0.77; 95% CI, 0.60, 1.00).
CONCLUSIONS: CVD affects blacks at an earlier age than whites; this may be attributable in part to elevated CVD risk factor levels among blacks. Racial disparities in first CVD incidence disappear by older adulthood. Competing risks analyses may yield somewhat different results than traditional Cox models and provide a complementary approach to examining risks for first CVD events.
10aAfrican Continental Ancestry Group10aAge Factors10aAged10aAged, 80 and over10aAtherosclerosis10aCardiovascular Diseases10aCohort Studies10aContinental Population Groups10aEthnic Groups10aEuropean Continental Ancestry Group10aFemale10aFollow-Up Studies10aHumans10aLongitudinal Studies10aMale10aMiddle Aged10aResidence Characteristics10aRisk Factors1 aFeinstein, Matthew1 aNing, Hongyan1 aKang, Joseph1 aBertoni, Alain1 aCarnethon, Mercedes1 aLloyd-Jones, Donald, M uhttps://chs-nhlbi.org/node/139003128nas a2200469 4500008004100000022001400041245008300055210006900138260001300207300001000220490000800230520178800238653003102026653000902057653002802066653002402094653004402118653002602162653002202188653001102210653001702221653001402238653002602252653002102278653003002299653001502329653001402344653002402358653002102382653001702403653001202420100001902432700002302451700002002474700001802494700002002512700002202532700002402554700002202578700002202600856003602622 2012 eng d a1538-360100aRetinal microvascular signs and disability in the Cardiovascular Health Study.0 aRetinal microvascular signs and disability in the Cardiovascular c2012 Mar a350-60 v1303 aOBJECTIVE: To study the associations of retinal microvascular changes, which are associated with systemic conditions and cognitive decline, with disability in performing activities of daily living (ADL).
DESIGN: Prospective cohort study of 1487 community-dwelling participants in the Cardiovascular Health Study (mean age, 78 years) who were free of ADL disability and had available data on retinal signs and carotid intima-media thickness at the 1998-1999 visit. Main outcome measures were incident ADL disability, defined as self-reported difficulty in performing any ADL, by the presence of retinal signs and advanced carotid atherosclerosis, defined by carotid intima-media thickness in the 80th percentile or more or 25% or more stenosis, and potential mediation by cerebral microvascular disease on brain imaging or by executive dysfunction, slow gait, and depressive mood, which are symptoms of frontal subcortical dysfunction.
RESULTS: During the median follow-up of 3.1 years (maximum, 7.8 years), participants with 2 or more retinal signs had a higher rate of disability than those with fewer than 2 retinal signs (10.1% vs 7.1%; adjusted hazard ratio, 1.45; 95% confidence interval, 1.24-1.69; P < .001). There was no evidence of interaction by advanced carotid atherosclerosis (P > .10). The association seemed to be partially mediated by executive dysfunction, slow gait, and depressive symptoms but not by cerebral microvascular disease on brain imaging.
CONCLUSIONS: These results provide further support for the pathophysiologic and prognostic significance of microvascular disease in age-related disability. However, it remains to be determined how to best use retinal photography in clinical risk prediction.
10aActivities of Daily Living10aAged10aCarotid Artery Diseases10aCognition Disorders10aDiagnostic Techniques, Ophthalmological10aDisability Evaluation10aFollow-Up Studies10aHumans10aHypertension10aIncidence10aKaplan-Meier Estimate10aMicrocirculation10aPredictive Value of Tests10aPrevalence10aPrognosis10aProspective Studies10aRetinal Diseases10aRisk Factors10aSmoking1 aKim, Dae, Hyun1 aChaves, Paulo, H M1 aNewman, Anne, B1 aKlein, Ronald1 aSarnak, Mark, J1 aNewton, Elizabeth1 aStrotmeyer, Elsa, S1 aBurke, Gregory, L1 aLipsitz, Lewis, A uhttps://chs-nhlbi.org/node/135102611nas a2200337 4500008004100000022001400041245008200055210006900137260001300206300001100219490000700230520170400237653000901941653001901950653001101969653003101980653002002011653001102031653001402042653001102056653000902067653001702076100002502093700001602118700002202134700002002156700001702176700002002193700002402213856003602237 2012 eng d a1523-683800aThe risk of infection-related hospitalization with decreased kidney function.0 arisk of infectionrelated hospitalization with decreased kidney f c2012 Mar a356-630 v593 aBACKGROUND: Moderate kidney disease may predispose to infection. We sought to determine whether decreased kidney function, estimated by serum cystatin C level, was associated with the risk of infection-related hospitalization in older individuals.
STUDY DESIGN: Cohort study.
SETTING & PARTICIPANTS: 5,142 Cardiovascular Health Study (CHS) participants with measured serum creatinine and cystatin C and without estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m(2) at enrollment.
PREDICTOR: The primary exposure of interest was eGFR using serum cystatin C level (eGFR(SCysC)).
OUTCOME: Infection-related hospitalizations during a median follow-up of 11.5 years.
RESULTS: In adjusted analyses, eGFR(SCysC) categories of 60-89, 45-59, and 15-44 mL/min/1.73 m(2) were associated with 16%, 37%, and 64% greater risk of all-cause infection-related hospitalization, respectively, compared with eGFR(SCysC) ≥90 mL/min/1.73 m(2). When cause-specific infection was examined, eGFR(SCysC) of 15-44 mL/min/1.73 m(2) was associated with an 80% greater risk of pulmonary and 160% greater risk of genitourinary infection compared with eGFR(SCysC) ≥90 mL/min/1.73 m(2).
LIMITATIONS: No measures of urinary protein, study limited to principal discharge diagnosis.
CONCLUSIONS: Lower kidney function, estimated using cystatin C level, was associated with a linear and graded risk of infection-related hospitalization. These findings highlight that even moderate degrees of decreased kidney function are associated with clinically significant higher risks of serious infection in older individuals.
10aAged10aCohort Studies10aFemale10aGlomerular Filtration Rate10aHospitalization10aHumans10aInfection10aKidney10aMale10aRisk Factors1 aDalrymple, Lorien, S1 aKatz, Ronit1 aKestenbaum, Bryan1 ade Boer, Ian, H1 aFried, Linda1 aSarnak, Mark, J1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/132202456nas a2200325 4500008004100000022001400041245011400055210006900169260001300238300001000251490000700261520152300268653002401791653001901815653001101834653001101845653001401856653002901870653001801899653003101917653000901948653001601957653001701973100002101990700002102011700002202032700002002054700002002074856003602094 2012 eng d a1531-824900aRisk of intraparenchymal hemorrhage with magnetic resonance imaging-defined leukoaraiosis and brain infarcts.0 aRisk of intraparenchymal hemorrhage with magnetic resonance imag c2012 Apr a552-90 v713 aOBJECTIVE: To determine whether the burden of leukoaraiosis and the number of brain infarcts, defined by magnetic resonance imaging (MRI), are prospectively and independently associated with intraparenchymal hemorrhage (IPH) incidence in a pooled population-based study.
METHODS: Among 4,872 participants initially free of clinical stroke in the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study, we assessed white matter grade (range, 0-9), reflecting increasing leukoaraiosis, and brain infarcts using MRI. Over a median of 13 years of follow-up, 71 incident, spontaneous IPH events occurred.
RESULTS: After adjustment for other IPH risk factors, the hazard ratios (95% confidence intervals) across white matter grades 0 to 1, 2, 3, and 4 to 9 were 1.00, 1.68 (0.86-3.30), 3.52 (1.80-6.89), and 3.96 (1.90-8.27), respectively (p for trend <0.0001). These hazard ratios were weakened only modestly (p for trend = 0.0003) with adjustment for MRI-defined brain infarcts. The IPH hazard ratios for 0, 1, 2, or ≥3 MRI-defined brain infarcts were 1.00, 1.97 (1.10-3.54), 2.00 (0.83-4.78), and 3.12 (1.31-7.43) (p for trend = 0.002), but these were substantially attenuated when adjusted for white matter grade (p for trend = 0.049).
INTERPRETATION: Greater MRI-defined burden of leukoaraiosis is a risk factor for spontaneous IPH. Spontaneous IPH should be added to the growing list of potential poor outcomes in people with leukoaraiosis.
10aCerebral Infarction10aCohort Studies10aFemale10aHumans10aIncidence10aIntracranial Hemorrhages10aLeukoaraiosis10aMagnetic Resonance Imaging10aMale10aMiddle Aged10aRisk Factors1 aFolsom, Aaron, R1 aYatsuya, Hiroshi1 aMosley, Thomas, H1 aPsaty, Bruce, M1 aLongstreth, W T uhttps://chs-nhlbi.org/node/138102377nas a2200349 4500008004100000022001400041245013400055210006900189260001300258300001100271490000700282520138400289653000901673653002401682653003401706653001101740653002201751653001101773653001401784653000901798653001501807653002001822653001701842653001101859653001801870100002001888700002101908700001901929700002001948700002301968856003601991 2013 eng d a1532-541500aRacial differences in the incidence of and risk factors for atrial fibrillation in older adults: the cardiovascular health study.0 aRacial differences in the incidence of and risk factors for atri c2013 Feb a276-800 v613 aThis study examined whether different associations between risk factors and atrial fibrillation (AF) according to race could explain the lower incidence of AF in blacks. Baseline risk factor information was obtained from interviews, clinical examinations, and echocardiography in 4,774 white and 911 black Cardiovascular Health Study participants aged 65 and older without a history of AF at baseline in 1989/90 or 1992/93. Incident AF was determined according to hospital discharge diagnosis or annual study electrocardiogram. Cox regression was used to assess associations between risk factors and race and incident AF. During a mean 11.2 years of follow-up, 1,403 whites and 182 blacks had incident AF. Associations between all examined risk factors were similar in both races, except left ventricular posterior wall thickness, which was more strongly associated with AF in blacks (per 0.2 cm, blacks: hazard ratio (HR) = 1.72, 95% confidence interval (CI) = 1.44-2.06; whites: HR = 1.30, 95% CI = 1.18-1.43). Overall, the relative risk of AF was 25% lower in blacks than whites after adjustment for age and sex (HR = 0.75, 95% CI = 0.64-0.87) and 45% lower after adjustment for all considered risk factors (HR = 0.55, 95% CI = 0.35-0.88). Different associations of the considered risk factors and incident AF by race do not explain the lower incidence of AF in blacks.
10aAged10aAtrial Fibrillation10aContinental Population Groups10aFemale10aFollow-Up Studies10aHumans10aIncidence10aMale10aPrevalence10aRisk Assessment10aRisk Factors10aStroke10aUnited States1 aJensen, Paul, N1 aThacker, Evan, L1 aDublin, Sascha1 aPsaty, Bruce, M1 aHeckbert, Susan, R uhttps://chs-nhlbi.org/node/585203235nas a2200445 4500008004100000022001400041245014100055210006900196260001600265300001100281490000800292520194000300653001002240653000902250653001502259653002802274653002102302653002402323653001102347653002202358653002102380653001102401653001402412653000902426653002202435653001602457653002402473653002402497653001802521653001402539100003302553700002202586700002202608700002402630700002002654700002402674700003002698700002502728856003602753 2013 eng d a1879-191300aRelation of vitamin D and parathyroid hormone to cardiac biomarkers and to left ventricular mass (from the Cardiovascular Health Study).0 aRelation of vitamin D and parathyroid hormone to cardiac biomark c2013 Feb 01 a418-240 v1113 aVitamin D and parathyroid hormone (PTH) may affect cardiovascular health in patients with kidney disease and in the general population. The aim of this study was to investigate associations of serum 25-hydroxyvitamin D (25(OH)D) and PTH concentrations with a comprehensive set of biochemical, electrocardiographic, and echocardiographic measurements of cardiac structure and function in the Cardiovascular Health Study. A total of 2,312 subjects who were free of cardiovascular disease at baseline were studied. Serum 25(OH)D and intact PTH concentrations were measured using mass spectrometry and a 2-site immunoassay. Outcomes were N-terminal pro-B-type natriuretic peptide, cardiac troponin T, electrocardiographic measures of conduction, and echocardiographic measures of left ventricular mass and diastolic dysfunction. At baseline, subjects had a mean age of 73.9 ± 4.9 years, 69.7% were women, and 21% had chronic kidney disease (glomerular filtration rate <60 ml/min). Mean 25(OH)D was 25.2 ± 10.2 ng/ml, and median PTH was 51 pg/ml (range 39 to 65). After adjustment, 25(OH)D was not associated with any of the biochemical, conduction, or echocardiographic outcomes. Serum PTH levels ≥65 pg/ml were associated with greater N-terminal pro-B-type natriuretic peptide, cardiac troponin T, and left ventricular mass in patients with chronic kidney disease. The regression coefficients were: 120 pg/ml (95% confidence interval 36.1 to 204), 5.2 pg/ml (95% confidence interval 3.0 to 7.4), and 17 g (95% confidence interval 6.2 to 27.8) (p <0.001). In subjects with normal kidney function, PTH was not associated with the outcomes. In conclusion, in older adults with chronic kidney disease, PTH excess is associated with higher N-terminal pro-B-type natriuretic peptide, cardiac troponin T, and left ventricular mass. These findings suggest a role for PTH in cardiovascular health and the prevention of cardiac diseases.
10aAdult10aAged10aBiomarkers10aCardiovascular Diseases10aEchocardiography10aElectrocardiography10aFemale10aFollow-Up Studies10aHeart Ventricles10aHumans10aIncidence10aMale10aMass Spectrometry10aMiddle Aged10aParathyroid Hormone10aProspective Studies10aUnited States10aVitamin D1 avan Ballegooijen, Adriana, J1 aVisser, Marjolein1 aKestenbaum, Bryan1 aSiscovick, David, S1 ade Boer, Ian, H1 aGottdiener, John, S1 adeFilippi, Christopher, R1 aBrouwer, Ingeborg, A uhttps://chs-nhlbi.org/node/155905044nas a2200541 4500008004100000022001400041245015700055210006900212260001300281300001300294490000700307520354200314653001603856653002803872653001103900653003403911653001303945653001103958653001303969653001403982653003603996100001604032700001804048700001904066700002404085700001804109700001404127700001304141700002004154700001304174700001804187700002004205700001504225700001204240700001704252700001704269700001904286700002304305700001504328700001704343700001904360700001704379700001704396700002004413700001404433700001904447856003604466 2013 eng d a1460-235000aReplication of genetic loci for ages at menarche and menopause in the multi-ethnic Population Architecture using Genomics and Epidemiology (PAGE) study.0 aReplication of genetic loci for ages at menarche and menopause i c2013 Jun a1695-7060 v283 aSTUDY QUESTION: Do genetic associations identified in genome-wide association studies (GWAS) of age at menarche (AM) and age at natural menopause (ANM) replicate in women of diverse race/ancestry from the Population Architecture using Genomics and Epidemiology (PAGE) Study?
SUMMARY ANSWER: We replicated GWAS reproductive trait single nucleotide polymorphisms (SNPs) in our European descent population and found that many SNPs were also associated with AM and ANM in populations of diverse ancestry.
WHAT IS KNOWN ALREADY: Menarche and menopause mark the reproductive lifespan in women and are important risk factors for chronic diseases including obesity, cardiovascular disease and cancer. Both events are believed to be influenced by environmental and genetic factors, and vary in populations differing by genetic ancestry and geography. Most genetic variants associated with these traits have been identified in GWAS of European-descent populations.
STUDY DESIGN, SIZE, DURATION: A total of 42 251 women of diverse ancestry from PAGE were included in cross-sectional analyses of AM and ANM.
MATERIALS, SETTING, METHODS: SNPs previously associated with ANM (n = 5 SNPs) and AM (n = 3 SNPs) in GWAS were genotyped in American Indians, African Americans, Asians, European Americans, Hispanics and Native Hawaiians. To test SNP associations with ANM or AM, we used linear regression models stratified by race/ethnicity and PAGE sub-study. Results were then combined in race-specific fixed effect meta-analyses for each outcome. For replication and generalization analyses, significance was defined at P < 0.01 for ANM analyses and P < 0.017 for AM analyses.
MAIN RESULTS AND THE ROLE OF CHANCE: We replicated findings for AM SNPs in the LIN28B locus and an intergenic region on 9q31 in European Americans. The LIN28B SNPs (rs314277 and rs314280) were also significantly associated with AM in Asians, but not in other race/ethnicity groups. Linkage disequilibrium (LD) patterns at this locus varied widely among the ancestral groups. With the exception of an intergenic SNP at 13q34, all ANM SNPs replicated in European Americans. Three were significantly associated with ANM in other race/ethnicity populations: rs2153157 (6p24.2/SYCP2L), rs365132 (5q35/UIMC1) and rs16991615 (20p12.3/MCM8). While rs1172822 (19q13/BRSK1) was not significant in the populations of non-European descent, effect sizes showed similar trends.
LIMITATIONS, REASONS FOR CAUTION: Lack of association for the GWAS SNPs in the non-European American groups may be due to differences in locus LD patterns between these groups and the European-descent populations included in the GWAS discovery studies; and in some cases, lower power may also contribute to non-significant findings.
WIDER IMPLICATIONS OF THE FINDINGS: The discovery of genetic variants associated with the reproductive traits provides an important opportunity to elucidate the biological mechanisms involved with normal variation and disorders of menarche and menopause. In this study we replicated most, but not all reported SNPs in European descent populations and examined the epidemiologic architecture of these early reported variants, describing their generalizability and effect size across differing ancestral populations. Such data will be increasingly important for prioritizing GWAS SNPs for follow-up in fine-mapping and resequencing studies, as well as in translational research.
10aAge Factors10aCross-Sectional Studies10aFemale10aGenome-Wide Association Study10aGenotype10aHumans10aMenarche10aMenopause10aPolymorphism, Single Nucleotide1 aCarty, C, L1 aSpencer, K, L1 aSetiawan, V, W1 aFernandez-Rhodes, L1 aMalinowski, J1 aBuyske, S1 aYoung, A1 aJorgensen, N, W1 aCheng, I1 aCarlson, C, S1 aBrown-Gentry, K1 aGoodloe, R1 aPark, A1 aParikh, N, I1 aHenderson, B1 aLe Marchand, L1 aWactawski-Wende, J1 aFornage, M1 aMatise, T, C1 aHindorff, L, A1 aArnold, A, M1 aHaiman, C, A1 aFranceschini, N1 aPeters, U1 aCrawford, D, C uhttps://chs-nhlbi.org/node/610603716nas a2200577 4500008004100000022001400041245012600055210006900181260001600250300001200266490000800278520196800286653001502254653003102269653002802300653004202328653004202370653003102412653001102443653002202454653003802476653001302514653001102527653002502538653000902563653001802572653001602590653002602606653001402632653003602646653001702682653002402699653002702723100002302750700002002773700001902793700002102812700002002833700001902853700002502872700002902897700001902926700001802945700002202963700002102985700002003006700002103026700002503047700003003072856003603102 2013 eng d a1524-453900aResequencing and clinical associations of the 9p21.3 region: a comprehensive investigation in the Framingham heart study.0 aResequencing and clinical associations of the 9p213 region a com c2013 Feb 19 a799-8100 v1273 aBACKGROUND: 9p21.3 is among the most strongly replicated regions for cardiovascular disease. There are few reports of sequencing the associated 9p21.3 interval. We set out to sequence the 9p21.3 region followed by a comprehensive study of genetic associations with clinical and subclinical cardiovascular disease and its risk factors, as well as with copy number variation and gene expression, in the Framingham Heart Study (FHS).
METHODS AND RESULTS: We sequenced 281 individuals (94 with myocardial infarction, 94 with high coronary artery calcium levels, and 93 control subjects free of elevated coronary artery calcium or myocardial infarction), followed by genotyping and association in >7000 additional FHS individuals. We assessed genetic associations with clinical and subclinical cardiovascular disease, risk factor phenotypes, and gene expression levels of the protein-coding genes CDKN2A and CDKN2B and the noncoding gene ANRIL in freshly harvested leukocytes and platelets. Within this large sample, we found strong associations of 9p21.3 variants with increased risk for myocardial infarction, higher coronary artery calcium levels, and larger abdominal aorta diameters and no evidence for association with traditional cardiovascular disease risk factors. No common protein-coding variation, variants in splice donor or acceptor sites, or copy number variation events were observed. By contrast, strong associations were observed between genetic variants and gene expression, particularly for a short isoform of ANRIL and for CDKN2B.
CONCLUSIONS: Our thorough genomic characterization of 9p21.3 suggests common variants likely account for observed disease associations and provides further support for the hypothesis that complex regulatory variation affecting ANRIL and CDKN2B gene expression may contribute to increased risk for clinically apparent and subclinical coronary artery disease and aortic disease.
10aCalcinosis10aChromosomes, Human, Pair 910aCoronary Artery Disease10aCyclin-Dependent Kinase Inhibitor p1510aCyclin-Dependent Kinase Inhibitor p1610aDNA Copy Number Variations10aFemale10aFollow-Up Studies10aGenetic Predisposition to Disease10aGenotype10aHumans10aLongitudinal Studies10aMale10aMassachusetts10aMiddle Aged10aMyocardial Infarction10aPhenotype10aPolymorphism, Single Nucleotide10aRisk Factors10aRNA, Long Noncoding10aSequence Analysis, DNA1 aJohnson, Andrew, D1 aHwang, Shih-Jen1 aVoorman, Arend1 aMorrison, Alanna1 aPeloso, Gina, M1 aHsu, Yi-Hsiang1 aThanassoulis, George1 aNewton-Cheh, Christopher1 aRogers, Ian, S1 aHoffmann, Udo1 aFreedman, Jane, E1 aFox, Caroline, S1 aPsaty, Bruce, M1 aBoerwinkle, Eric1 aCupples, Adrienne, L1 aO'Donnell, Christopher, J uhttps://chs-nhlbi.org/node/607401869nas a2200349 4500008004100000022001400041245012800055210006900183260000900252300001000261490000700271520082100278653003101099653000901130653001401139653002701153653002801180653003701208653001101245653001101256653002501267653000901292653003701301653002401338653001901362100001701381700001701398700002401415700002101439700002301460856003601483 2013 eng d a1096-465700aResults differ by applying distinctive multiple imputation approaches on the longitudinal cardiovascular health study data.0 aResults differ by applying distinctive multiple imputation appro c2013 a27-430 v393 aUNLABELLED: BACKGROUND/STUDY CONTEXT: The objective of this study was to examine sequential and simultaneous approaches to multiple imputation of missing data in a longitudinal data set where losses due to death were common.
METHODS: Comparison of results from analyses and simulations of time to incident difficulty of activities of daily living (ADL) in the Cardiovascular Health Study when missing data were imputed simultaneously or sequentially.
RESULTS: Results differed with imputation methods. The largest proportional differences in 12 risk factor parameter estimates were heart failure by 106%, social support by 33%, and arthritis by 27%.
CONCLUSION: Decedents' final characteristics were influential on future imputations of those with missing values.
10aActivities of Daily Living10aAged10aArthritis10aCardiac Rehabilitation10aCardiovascular Diseases10aData Interpretation, Statistical10aFemale10aHumans10aLongitudinal Studies10aMale10aOutcome Assessment (Health Care)10aRegression Analysis10aSocial Support1 aNing, Yuming1 aMcAvay, Gail1 aChaudhry, Sarwat, I1 aArnold, Alice, M1 aAllore, Heather, G uhttps://chs-nhlbi.org/node/585303418nas a2200457 4500008004100000022001400041245014300055210006900198260001600267300001100283490000700294520210000301653001602401653000902417653002202426653001602448653003502464653001102499653002502510653001902535653001802554653002002572653001102592653002502603653000902628653002202637653002002659653001702679653003002696653001802726653002202744653001802766100002402784700001702808700001402825700002102839700002002860700002402880700002002904856003602924 2013 eng d a1558-359700aRisk factors for hospital admission among older persons with newly diagnosed heart failure: findings from the Cardiovascular Health Study.0 aRisk factors for hospital admission among older persons with new c2013 Feb 12 a635-420 v613 aOBJECTIVES: This study sought to identify risk factors for the occurrence of all-cause hospital admissions among older persons after heart failure diagnosis, and to determine whether geriatric conditions would emerge as independent risk factors for admission when evaluated in the context of other relevant clinical data.
BACKGROUND: Efforts to reduce costs in heart failure have focused on hospital utilization, yet few studies have examined how geriatric conditions affect the long-term risk for hospital admission after heart failure diagnosis. With the aging of the population with heart failure, geriatric conditions such as slow gait and muscle weakness are becoming increasingly common.
METHODS: The study population included participants with a new diagnosis of heart failure in the Cardiovascular Health Study, a longitudinal study of community-living older persons. Data were collected through annual examinations and medical-record reviews. Geriatric conditions assessed were slow gait, muscle weakness (defined as weak grip), cognitive impairment, and depressive symptoms. Anderson-Gill regression modeling was used to determine the predictors of hospital admission after heart failure diagnosis.
RESULTS: Of the 758 participants with a new diagnosis of heart failure, the mean rate of hospital admission was 7.9 per 10 person-years (95% CI: 7.4 to 8.4). Independent risk factors for hospital admission included diabetes mellitus (HR: 1.36; 95% CI: 1.13 to 1.64), New York Heart Association functional class III or IV (HR: 1.32; 95% CI: 1.11 to 1.57), chronic kidney disease (HR: 1.32; 95% CI: 1.14 to 1.53), slow gait (HR: 1.28; 95% CI: 1.06 to 1.55), depressed ejection fraction (HR: 1.25; 95% CI: 1.04 to 1.51), depression (HR: 1.23; 95% CI: 1.05 to 1.45), and muscle weakness (HR: 1.19; 95% CI: 1.00 to 1.42).
CONCLUSIONS: Geriatric conditions are important, and potentially modifiable, risk factors for hospital admission in heart failure that should be routinely assessed at the time of heart failure diagnosis.
10aAge Factors10aAged10aAged, 80 and over10aComorbidity10aEffect Modifier, Epidemiologic10aFemale10aGeriatric Assessment10aHealth Surveys10aHeart Failure10aHospitalization10aHumans10aLongitudinal Studies10aMale10aMental Competency10aRisk Assessment10aRisk Factors10aSeverity of Illness Index10aStroke Volume10aTime-to-Treatment10aUnited States1 aChaudhry, Sarwat, I1 aMcAvay, Gail1 aChen, Shu1 aWhitson, Heather1 aNewman, Anne, B1 aKrumholz, Harlan, M1 aGill, Thomas, M uhttps://chs-nhlbi.org/node/585102978nas a2200457 4500008004100000022001400041245015700055210007000212260001600282300001200298490000800310520164700318653001401965653001601979653000901995653002202004653001002026653002102036653001902057653002802076653003002104653001102134653001102145653001402156653002302170653002802193653001102221653000902232653002402241653001702265653002602282653001802308100002102326700002402347700002002371700002502391700001902416700002402435700002502459856003602484 2013 eng d a1476-625600aRisk factors for type 2 diabetes mellitus preceded by β-cell dysfunction, insulin resistance, or both in older adults: the Cardiovascular Health Study.0 aRisk factors for type 2 diabetes mellitus preceded by βcell dysf c2013 Jun 15 a1418-290 v1773 aInsulin resistance (IR) and pancreatic β-cell dysfunction lead to type 2 diabetes mellitus (DM). We tested whether risk factors would differ for DM that was preceded predominantly by IR, β-cell dysfunction, or both among 4,384 older adults (mean age, 72.7 (standard deviation, 5.6) years) in the Cardiovascular Health Study, which was conducted in North Carolina, California, Maryland, and Pennsylvania (1989-2007). When evaluating established risk factors, we found older age, greater adiposity, higher systolic blood pressure, a lower high-density lipoprotein cholesterol level, a higher triglyceride level, and a lower alcohol intake to be independently associated with greater IR but, conversely, with better β-cell function (P < 0.001). The prospective associations between some risk factors and incident DM varied significantly depending on whether DM was preceded predominantly by IR, β-cell dysfunction, or both. For example, obesity and lower high-density lipoprotein cholesterol levels were positively associated with DM preceded predominantly by IR (hazard ratio (HR) = 5.02, 95% confidence interval (CI): 2.81, 9.00; and HR = 1.97, 95% CI: 1.32, 2.93, respectively), with a significant association with and an insignificant trend toward a lower risk of DM preceded predominantly by β-cell dysfunction (HR = 0.33, 95% CI: 0.14, 0.80; and HR = 0.78, 95% CI: 0.43, 1.39, respectively). In conclusion, among older adults, DM risk factors were differentially associated with DM preceded predominantly by IR or β-cell dysfunction. Biologic and clinical implications of putative subtypes of DM require further investigation.
10aAdiposity10aAge Factors10aAged10aAged, 80 and over10aAging10aAlcohol Drinking10aBlood Pressure10aCross-Sectional Studies10aDiabetes Mellitus, Type 210aFemale10aHumans10aIncidence10aInsulin Resistance10aInsulin-Secreting Cells10aLipids10aMale10aProspective Studies10aRisk Factors10aSocioeconomic Factors10aUnited States1 aImamura, Fumiaki1 aMukamal, Kenneth, J1 aMeigs, James, B1 aLuchsinger, José, A1 aIx, Joachim, H1 aSiscovick, David, S1 aMozaffarian, Dariush uhttps://chs-nhlbi.org/node/599404055nas a2200673 4500008004100000022001400041245023000055210006900285260001300354300001100367490000700378520196600385653002502351653001302376653003802389653001102427653004902438653001602487653001702503653002702520100002202547700002402569700002302593700001702616700002002633700002102653700001702674700002102691700002202712700002402734700002402758700001802782700001902800700001702819700002702836700001902863700002002882700001702902700001602919700002702935700002302962700002102985700003203006700002303038700002003061700002603081700003003107700001803137700002403155700002603179700001903205700002003224700001903244700002203263700001703285700002203302700002103324856003603345 2013 eng d a1573-728400aRisk of venous thromboembolism associated with single and combined effects of Factor V Leiden, Prothrombin 20210A and Methylenetethraydrofolate reductase C677T: a meta-analysis involving over 11,000 cases and 21,000 controls.0 aRisk of venous thromboembolism associated with single and combin c2013 Aug a621-470 v283 aGenetic and environmental factors interact in determining the risk of venous thromboembolism (VTE). The risk associated with the polymorphic variants G1691A of factor V (Factor V Leiden, FVL), G20210A of prothrombin (PT20210A) and C677T of methylentetrahydrofolate reductase (C677T MTHFR) genes has been investigated in many studies. We performed a pooled analysis of case-control and cohort studies investigating in adults the association between each variant and VTE, published on Pubmed, Embase or Google through January 2010. Authors of eligible papers, were invited to provide all available individual data for the pooling. The Odds Ratio (OR) for first VTE associated with each variant, individually and combined with the others, were calculated with a random effect model, in heterozygotes and homozygotes (dominant model for FVL and PT20210A; recessive for C677T MTHFR). We analysed 31 databases, including 11,239 cases and 21,521 controls. No significant association with VTE was found for homozygous C677T MTHFR (OR: 1.38; 95 % confidence intervals [CI]: 0.98-1.93), whereas the risk was increased in carriers of either heterozygous FVL or PT20210 (OR = 4.22; 95 % CI: 3.35-5.32; and OR = 2.79;95 % CI: 2.25-3.46, respectively), in double heterozygotes (OR = 3.42; 95 %CI 1.64-7.13), and in homozygous FVL or PT20210A (OR = 11.45; 95 %CI: 6.79-19.29; and OR: 6.74 (CI 95 % 2.19-20.72), respectively). The stratified analyses showed a stronger effect of FVL on individuals ≤ 45 years (p value for interaction = 0.036) and of PT20210A in women using oral contraceptives (p-value for interaction = 0.045). In this large pooled analysis, inclusive of large studies like MEGA, no effect was found for C677T MTHFR on VTE; FVL and PT20210A were confirmed to be moderate risk factors. Notably, double carriers of the two genetic variants produced an impact on VTE risk significantly increased but weaker than previously thought.
10aCase-Control Studies10aFactor V10aGenetic Predisposition to Disease10aHumans10aMethylenetetrahydrofolate Reductase (NADPH2)10aProthrombin10aRisk Factors10aVenous Thromboembolism1 aSimone, Benedetto1 aDe Stefano, Valerio1 aLeoncini, Emanuele1 aZacho, Jeppe1 aMartinelli, Ida1 aEmmerich, Joseph1 aRossi, Elena1 aFolsom, Aaron, R1 aAlmawi, Wassim, Y1 aScarabin, Pierre, Y1 aHeijer, Martin, den1 aCushman, Mary1 aPenco, Silvana1 aVaya, Amparo1 aAngchaisuksiri, Pantep1 aOkumus, Gulfer1 aGemmati, Donato1 aCima, Simona1 aAkar, Nejat1 aOguzulgen, Kivilcim, I1 aDucros, Véronique1 aLichy, Christoph1 aFernandez-Miranda, Consuelo1 aSzczeklik, Andrzej1 aNieto, José, A1 aTorres, Jose, Domingo1 aLe Cam-Duchez, Véronique1 aIvanov, Petar1 aCantu-Brito, Carlos1 aShmeleva, Veronika, M1 aStegnar, Mojka1 aOgunyemi, Dotun1 aEid, Suhair, S1 aNicolotti, Nicola1 aDe Feo, Emma1 aRicciardi, Walter1 aBoccia, Stefania uhttps://chs-nhlbi.org/node/600702829nas a2200409 4500008004100000022001400041245009700055210006900152260001600221300001100237490000800248520163800256653003901894653000901933653001901942653004001961653001102001653001102012653002502023653000902048653001602057653001502073653003202088653002402120653003002144653001702174653001802191653002702209100001902236700002302255700002102278700002302299700002102322700002202343700001802365856003602383 2014 eng d a1524-453900aRacial and regional differences in venous thromboembolism in the United States in 3 cohorts.0 aRacial and regional differences in venous thromboembolism in the c2014 Apr 08 a1502-90 v1293 aBACKGROUND: Blacks are thought to have a higher risk of venous thromboembolism (VTE) than whites. However, prior studies are limited to administrative databases that lack specific information on VTE risk factors or have limited geographic scope.
METHODS AND RESULTS: We ascertained VTE from 3 prospective studies: the Atherosclerosis Risk in Communities Study (ARIC), the Cardiovascular Health Study (CHS), and the Reasons for Geographic and Racial Differences in Stroke study (REGARDS). We tested the association of race with VTE using Cox proportional hazard models adjusted for VTE risk factors. Over 438 090 person-years, 916 incident VTE events (302 in blacks) occurred in 51 149 individuals (17 318 blacks) who were followed up. In risk factor-adjusted models, blacks had a higher rate of VTE than whites in the CHS (hazard ratio, 1.81; 95% confidence interval, 1.20-2.73) but not ARIC (hazard ratio, 1.21; 95% confidence interval, 0.96-1.54). In REGARDS, there was a significant region-by-race interaction (P=0.01): Blacks in the Southeast had a significantly higher rate of VTE than blacks in the rest of the United States (hazard ratio, 1.63; 95% confidence interval, 1.08-2.48) that was not seen in whites (hazard ratio, 0.83; 95% confidence interval, 0.61-1.14).
CONCLUSIONS: The association of race with VTE differed in each cohort, which may reflect the different time periods of the studies or different regional rates of VTE. Further studies of environmental and genetic risk factors for VTE are needed to determine which underlie racial and perhaps regional differences in VTE.
10aAfrican Continental Ancestry Group10aAged10aCohort Studies10aEuropean Continental Ancestry Group10aFemale10aHumans10aLongitudinal Studies10aMale10aMiddle Aged10aPrevalence10aProportional Hazards Models10aProspective Studies10aResidence Characteristics10aRisk Factors10aUnited States10aVenous Thromboembolism1 aZakai, Neil, A1 aMcClure, Leslie, A1 aJudd, Suzanne, E1 aSafford, Monika, M1 aFolsom, Aaron, R1 aLutsey, Pamela, L1 aCushman, Mary uhttps://chs-nhlbi.org/node/624002895nas a2200385 4500008004100000022001400041245010400055210006900159260001300228300001200241490000700253520181800260653000902078653002202087653001602109653001502125653001302140653001102153653001802164653001102182653001402193653003102207653000902238653003002247653002902277653002402306653000902330100002102339700002402360700002002384700002102404700002002425700002802445856003602473 2014 eng d a1945-719700aRatio of urine albumin to creatinine attenuates the association of dementia with hip fracture risk.0 aRatio of urine albumin to creatinine attenuates the association c2014 Nov a4116-230 v993 aCONTEXT: Microvascular disease is a leading cause of cognitive impairment. Approximately 50% of people with a hip fracture have cognitive impairment.
OBJECTIVE: We tested the hypothesis that microvascular diseases of the brain (lacunar infarcts and white matter disease [WMD]), kidney (albuminuria [≥ 30 mg/g creatinine] and albumin creatinine ratio [ACR]), and eye (retinal vascular disorders) attenuate the association of cognitive impairment with hip fracture risk.
SETTING: The Cardiovascular Health Cognition Study.
PATIENTS: Three thousand, one-hundred six participants (mean age, ∼ 79 y; 8.84 y median follow-up) with cognitive testing. Subsets received ACR testing (n=2389), brain magnetic resonance imaging scans (n = 2094), and retinal photography (n = 1098).
MAIN OUTCOME MEASURE: Incident hip fracture.
RESULTS: There were 488 participants (16%) with mild cognitive impairment (MCI) and 564 (18%) with dementia. There were 337 incident hip fractures, of which 19% occurred in participants with MCI and 26% in participants with dementia. Adjusted hazard ratios (HR) and 95% confidence interval for hip fracture in participants with MCI were 2.45 (1.67-3.61) and for dementia 2.35 (1.57-3.52). With doubling of ACR, the HR for fracture was attenuated in participants with dementia compared with participants with normal cognition [interaction HR 0.70 (0.55-0.91)]. No such effect was found in participants with MCI. Albuminuria, lacunar infarcts, WMD, and retinal vascular disease (RVD) did not modify the association of dementia or MCI with hip fracture risk.
CONCLUSIONS: ACR attenuates part of the risk of hip fracture in people with dementia, suggesting that these disorders share a common pathogenesis.
10aAged10aAged, 80 and over10aAlbuminuria10aCreatinine10aDementia10aFemale10aHip Fractures10aHumans10aIncidence10aMagnetic Resonance Imaging10aMale10aMild Cognitive Impairment10aNeuropsychological Tests10aProspective Studies10aRisk1 aBůzková, Petra1 aBarzilay, Joshua, I1 aFink, Howard, A1 aRobbins, John, A1 aCauley, Jane, A1 aFitzpatrick, Annette, L uhttps://chs-nhlbi.org/node/662502971nas a2200421 4500008004100000022001400041245006900055210006700124260001300191300001100204490000700215520185500222653000902077653002202086653001202108653001002120653002802130653000902158653002502167653001102192653001102203653001602214653001102230653001502241653003102256653000902287653002402296653003102320100001902351700002202370700002002392700002102412700001802433700002202451700001902473700002102492856003602513 2014 eng d a1873-260700aRegular fish consumption and age-related brain gray matter loss.0 aRegular fish consumption and agerelated brain gray matter loss c2014 Oct a444-510 v473 aBACKGROUND: Brain health may be affected by modifiable lifestyle factors; consuming fish and antioxidative omega-3 fatty acids may reduce brain structural abnormality risk.
PURPOSE: To determine whether dietary fish consumption is related to brain structural integrity among cognitively normal elders.
METHODS: Data were analyzed from 260 cognitively normal individuals from the Cardiovascular Health Study with information on fish consumption from the National Cancer Institute Food Frequency Questionnaire and brain magnetic resonance imaging (MRI). The relationship between fish consumption data collected in 1989-1990 and brain structural MRI obtained in 1998-1999 was assessed using voxel-based morphometry in multiple regression analyses in 2012. Covariates were age, gender, race, education, white matter lesions, MRI-identified infarcts, waist-hip ratio, and physical activity as assessed by the number of city blocks walked in 1 week. Volumetric changes were further modeled with omega-3 fatty acid estimates to better understand the mechanistic link between fish consumption, brain health, and Alzheimer disease.
RESULTS: Weekly consumption of baked or broiled fish was positively associated with gray matter volumes in the hippocampus, precuneus, posterior cingulate, and orbital frontal cortex even after adjusting for covariates. These results did not change when including omega-3 fatty acid estimates in the analysis.
CONCLUSIONS: Dietary consumption of baked or broiled fish is related to larger gray matter volumes independent of omega-3 fatty acid content. These findings suggest that a confluence of lifestyle factors influence brain health, adding to the growing body of evidence that prevention strategies for late-life brain health need to begin decades earlier.
10aAged10aAged, 80 and over10aAnimals10aBrain10aCross-Sectional Studies10aDiet10aFatty Acids, Omega-310aFemale10aFishes10aGray Matter10aHumans10aLife Style10aMagnetic Resonance Imaging10aMale10aRegression Analysis10aSurveys and Questionnaires1 aRaji, Cyrus, A1 aErickson, Kirk, I1 aLopez, Oscar, L1 aKuller, Lewis, H1 aGach, Michael1 aThompson, Paul, M1 aRiverol, Mario1 aBecker, James, T uhttps://chs-nhlbi.org/node/659203288nas a2200529 4500008004100000022001400041245016400055210006900219260001600288300001100304490000800315520171900323653001602042653001702058653000902075653001502084653002802099653003002127653003802157653001102195653002202206653001802228653001102246653001402257653000902271653001402280653002402294653001502318653003002333653001802363653003102381100002002412700002002432700002102452700002002473700001802493700002402511700001902535700002102554700002402575700002202599700002702621700002402648700003002672700002002702856003602722 2014 eng d a1879-191300aRelations of plasma total and high-molecular-weight adiponectin to new-onset heart failure in adults ≥65 years of age (from the Cardiovascular Health study).0 aRelations of plasma total and highmolecularweight adiponectin to c2014 Jan 15 a328-340 v1133 aAdiponectin exhibits cardioprotective properties in experimental studies, but elevated levels have been linked to increased mortality in older adults and patients with chronic heart failure (HF). The adipokine's association with new-onset HF remains less well defined. The aim of this study was to investigate the associations of total and high-molecular weight (HMW) adiponectin with incident HF (n = 780) and, in a subset, echocardiographic parameters in a community-based cohort of adults aged ≥65 years. Total and HMW adiponectin were measured in 3,228 subjects without prevalent HF, atrial fibrillation or CVD. The relations of total and HMW adiponectin with HF were nonlinear, with significant associations observed only for concentrations greater than the median (12.4 and 6.2 mg/L, respectively). After adjustment for potential confounders, the hazard ratios per SD increment in total adiponectin were 0.93 (95% confidence interval 0.72 to 1.21) for concentrations less than the median and 1.25 (95% confidence interval 1.14 to 1.38) higher than the median. There was a suggestion of effect modification by body mass index, whereby the association appeared strongest in participants with lower body mass indexes. Consistent with the HF findings, higher adiponectin tended to be associated with left ventricular systolic dysfunction and left atrial enlargement. Results were similar for HMW adiponectin. In conclusion, total and HMW adiponectin showed comparable relations with incident HF in this older cohort, with a threshold effect of increasing risk occurring at their median concentrations. High levels of adiponectin may mark or mediate age-related processes that lead to HF in older adults.
10aAdiponectin10aAge of Onset10aAged10aBiomarkers10aCross-Sectional Studies10aEchocardiography, Doppler10aEnzyme-Linked Immunosorbent Assay10aFemale10aFollow-Up Studies10aHeart Failure10aHumans10aIncidence10aMale10aPrognosis10aProspective Studies10aRecurrence10aSeverity of Illness Index10aUnited States10aVentricular Function, Left1 aKaras, Maria, G1 aBenkeser, David1 aArnold, Alice, M1 aBartz, Traci, M1 aDjoussé, Luc1 aMukamal, Kenneth, J1 aIx, Joachim, H1 aZieman, Susan, J1 aSiscovick, David, S1 aTracy, Russell, P1 aMantzoros, Christos, S1 aGottdiener, John, S1 adeFilippi, Christopher, R1 aKizer, Jorge, R uhttps://chs-nhlbi.org/node/613703213nas a2200541 4500008004100000022001400041245011300055210006900168260001300237300001100250490000700261520163100268653001001899653003901909653000901948653002201957653001601979653003701995653002802032653001902060653001502079653004002094653001102134653003102145653001102176653002802187653000902215653001602224653001502240653003302255653001702288100001902305700002502324700001802349700002102367700002002388700001602408700002302424700002302447700001702470700001902487700001902506700002302525700002102548700001802569710004802587856003602635 2014 eng d a1523-175500aRelative risks of chronic kidney disease for mortality and end-stage renal disease across races are similar.0 aRelative risks of chronic kidney disease for mortality and endst c2014 Oct a819-270 v863 aSome suggest race-specific cutpoints for kidney measures to define and stage chronic kidney disease (CKD), but evidence for race-specific clinical impact is limited. To address this issue, we compared hazard ratios of estimated glomerular filtration rates (eGFR) and albuminuria across races using meta-regression in 1.1 million adults (75% Asians, 21% Whites, and 4% Blacks) from 45 cohorts. Results came mainly from 25 general population cohorts comprising 0.9 million individuals. The associations of lower eGFR and higher albuminuria with mortality and end-stage renal disease (ESRD) were largely similar across races. For example, in Asians, Whites, and Blacks, the adjusted hazard ratios (95% confidence interval) for eGFR 45-59 versus 90-104 ml/min per 1.73 m(2) were 1.3 (1.2-1.3), 1.1 (1.0-1.2), and 1.3 (1.1-1.7) for all-cause mortality, 1.6 (1.5-1.7), 1.4 (1.2-1.7), and 1.4 (0.7-2.9) for cardiovascular mortality, and 27.6 (11.1-68.7), 11.2 (6.0-20.9), and 4.1 (2.2-7.5) for ESRD, respectively. The corresponding hazard ratios for urine albumin-to-creatinine ratio 30-299 mg/g or dipstick 1+ versus an albumin-to-creatinine ratio under 10 or dipstick negative were 1.6 (1.4-1.8), 1.7 (1.5-1.9), and 1.8 (1.7-2.1) for all-cause mortality, 1.7 (1.4-2.0), 1.8 (1.5-2.1), and 2.8 (2.2-3.6) for cardiovascular mortality, and 7.4 (2.0-27.6), 4.0 (2.8-5.9), and 5.6 (3.4-9.2) for ESRD, respectively. Thus, the relative mortality or ESRD risks of lower eGFR and higher albuminuria were largely similar among three major races, supporting similar clinical approach to CKD definition and staging, across races.
10aAdult10aAfrican Continental Ancestry Group10aAged10aAged, 80 and over10aAlbuminuria10aAsian Continental Ancestry Group10aCardiovascular Diseases10aCohort Studies10aCreatinine10aEuropean Continental Ancestry Group10aFemale10aGlomerular Filtration Rate10aHumans10aKidney Failure, Chronic10aMale10aMiddle Aged10aOdds Ratio10aRenal Insufficiency, Chronic10aRisk Factors1 aWen, Chi, Pang1 aMatsushita, Kunihiro1 aCoresh, Josef1 aIseki, Kunitoshi1 aIslam, Muhammad1 aKatz, Ronit1 aMcClellan, William1 aPeralta, Carmen, A1 aWang, Haiyan1 ade Zeeuw, Dick1 aAstor, Brad, C1 aGansevoort, Ron, T1 aLevey, Andrew, S1 aLevin, Adeera1 aChronic Kidney Disease Prognosis Consortium uhttps://chs-nhlbi.org/node/629502615nas a2200385 4500008004100000022001400041245012400055210006900179260000900248300001100257490000900268520150100277653000901778653002801787653002301815653001101838653001101849653001401860653002301874653002001897653002501917653000901942653002401951653003001975653001802005100002002023700002402043700002502067700001902092700001502111700002102126700002202147700002402169856003602193 2014 eng d a1687-981300aResidential relocation by older adults in response to incident cardiovascular health events: a case-crossover analysis.0 aResidential relocation by older adults in response to incident c c2014 a9519710 v20143 aOBJECTIVE: We use a case-crossover analysis to explore the association between incident cardiovascular events and residential relocation to a new home address.
METHODS: We conducted an ambidirectional case-crossover analysis to explore the association between incident cardiovascular events and residential relocation to a new address using data from the Cardiovascular Health Study (CHS), a community-based prospective cohort study of 5,888 older adults from four U.S. sites beginning in 1989. Relocation was assessed twice a year during follow-up. Event occurrences were classified as present or absent for the period preceding the first reported move, as compared with an equal length of time immediately prior to and following this period.
RESULTS: Older adults (65+) that experience incident cardiovascular disease had an increased probability of reporting a change of residence during the following year (OR 1.6, 95% confidence interval (CI) = 1.2-2.1). Clinical conditions associated with relocation included stroke (OR: 2.0, 95% CI: 1.2-3.3), angina (OR: 1.6, 95% CI: 1.0-2.6), and congestive heart failure (OR: 1.5, 95% CI: 1.0-2.1).
CONCLUSIONS: Major incident cardiovascular disease may increase the probability of residential relocation in older adults. Case-crossover analyses represent an opportunity to investigate triggering events, but finer temporal resolution would be crucial for future research on residential relocations.
10aAged10aCardiovascular Diseases10aCross-Over Studies10aFemale10aHumans10aIncidence10aLife Change Events10aLogistic Models10aLongitudinal Studies10aMale10aProspective Studies10aResidence Characteristics10aUnited States1 aLovasi, Gina, S1 aRichardson, John, M1 aRodriguez, Carlos, J1 aKop, Willem, J1 aAhmed, Ali1 aBrown, Arleen, F1 aGreenlee, Heather1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/633503245nas a2200517 4500008004100000022001400041245011100055210006900166260001300235300001100248490000800259520180600267653000902073653002202082653001902104653002302123653002802146653002102174653002102195653002702216653002202243653001102265653001102276653001702287653001102304653002002315653001102335653000902346653003102355653001202386653002202398653001702420100002302437700002402460700002402484700001602508700002502524700002102549700001902570700002002589700002402609700001802633700002002651700002002671856003602691 2014 eng d a1879-148400aRisk factors for cardiovascular disease across the spectrum of older age: the Cardiovascular Health Study.0 aRisk factors for cardiovascular disease across the spectrum of o c2014 Nov a336-420 v2373 aOBJECTIVE: The associations of some risk factors with cardiovascular disease (CVD) are attenuated in older age; whereas others appear robust. The present study aimed to compare CVD risk factors across older age.
METHODS: Participants (n = 4883) in the Cardiovascular Health Study free of prevalent CVD, were stratified into three age groups: 65-74, 75-84, 85+ years. Traditional risk factors included systolic blood pressure (BP), LDL-cholesterol, HDL-cholesterol, obesity, and diabetes. Novel risk factors included kidney function, C-reactive protein (CRP), and N-terminal pro-B-type natriuretic peptide (NT pro-BNP).
RESULTS: There were 1498 composite CVD events (stroke, myocardial infarction, and cardiovascular death) over 5 years. The associations of high systolic BP and diabetes appeared strongest, though both were attenuated with age (p-values for interaction = 0.01 and 0.002, respectively). The demographic-adjusted hazard ratios (HR) for elevated systolic BP were 1.79 (95% confidence interval: 1.49, 2.15), 1.59 (1.37, 1.85) and 1.10 (0.86, 1.41) in participants aged 65-74, 75-84, 85+, and for diabetes, 2.36 (1.89, 2.95), 1.55 (1.27, 1.89), 1.51 (1.10, 2.09). The novel risk factors had consistent associations with the outcome across the age spectrum; low kidney function: 1.69 (1.31, 2.19), 1.61 (1.36, 1.90), and 1.57 (1.16, 2.14) for 65-74, 75-84, and 85+ years, respectively; elevated CRP: 1.54 (1.28, 1.87), 1.33 (1.13, 1.55), and 1.51 (1.15, 1.97); elevated NT pro-BNP: 2.67 (1.96, 3.64), 2.71 (2.25, 3.27), and 2.18 (1.43, 3.45).
CONCLUSIONS: The associations of most traditional risk factors with CVD were minimal in the oldest old, whereas diabetes, eGFR, CRP, and NT pro-BNP were associated with CVD across older age.
10aAged10aAged, 80 and over10aBlood Pressure10aC-Reactive Protein10aCardiovascular Diseases10aCholesterol, HDL10aCholesterol, LDL10aDiabetes Complications10aDiabetes Mellitus10aFemale10aHumans10aInflammation10aKidney10aKidney Diseases10aLipids10aMale10aNatriuretic Peptide, Brain10aObesity10aPeptide Fragments10aRisk Factors1 aOdden, Michelle, C1 aShlipak, Michael, G1 aWhitson, Heather, E1 aKatz, Ronit1 aKearney, Patricia, M1 adeFilippi, Chris1 aShastri, Shani1 aSarnak, Mark, J1 aSiscovick, David, S1 aCushman, Mary1 aPsaty, Bruce, M1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/658802590nas a2200349 4500008004100000022001400041245014300055210006900198260001300267300001100280490000700291520150600298653002401804653002001828653001101848653003401859653001101893653003301904653002701937653002001964653003601984653001602020100001402036700001602050700001702066700002502083700002502108700002202133700002702155700002202182856003602204 2014 eng d a1098-227200aA robust method for genome-wide association meta-analysis with the application to circulating insulin-like growth factor I concentrations.0 arobust method for genomewide association metaanalysis with the a c2014 Feb a162-710 v383 aGenome-wide association studies (GWAS) offer an excellent opportunity to identify the genetic variants underlying complex human diseases. Successful utilization of this approach requires a large sample size to identify single nucleotide polymorphisms (SNPs) with subtle effects. Meta-analysis is a cost-efficient means to achieve large sample size by combining data from multiple independent GWAS; however, results from studies performed on different populations can be variable due to various reasons, including varied linkage equilibrium structures as well as gene-gene and gene-environment interactions. Nevertheless, one should expect effects of the SNP are more similar between similar populations than those between populations with quite different genetic and environmental backgrounds. Prior information on populations of GWAS is often not considered in current meta-analysis methods, rendering such analyses less optimal for the detecting association. This article describes a test that improves meta-analysis to incorporate variable heterogeneity among populations. The proposed method is remarkably simple in computation and hence can be performed in a rapid fashion in the setting of GWAS. Simulation results demonstrate the validity and higher power of the proposed method over conventional methods in the presence of heterogeneity. As a demonstration, we applied the test to real GWAS data to identify SNPs associated with circulating insulin-like growth factor I concentrations.
10aComputer Simulation10aGenetic Linkage10aGenome10aGenome-Wide Association Study10aHumans10aInsulin-Like Growth Factor I10aMeta-Analysis as Topic10aModels, Genetic10aPolymorphism, Single Nucleotide10aSample Size1 aWang, Tao1 aZhou, Baiyu1 aGuo, Tingwei1 aBidlingmaier, Martin1 aWallaschofski, Henri1 aTeumer, Alexander1 aVasan, Ramachandran, S1 aKaplan, Robert, C uhttps://chs-nhlbi.org/node/629604529nas a2200901 4500008004100000022001400041245012300055210006900178260000900247300001300256490000700269520197100276653001002247653002102257653000902278653002802287653003502315653002102350653002102371653001602392653003402408653002202442653001802464653001802482653001102500653002202511653001802533653001102551653001702562653001402579653001802593653000902611653001602620653002602636653001502662653003202677653001702709653001202726653001102738100002602749700002802775700001902803700002802822700002702850700002202877700002202899700002602921700002202947700001902969700002502988700002603013700001603039700002203055700001403077700002003091700002203111700003003133700001703163700002403180700002603204700001803230700002003248700002303268700002303291700002303314700002103337700002503358700002503383700002803408700001903436700002003455700002203475700002103497700002503518700002103543700002703564856003603591 2015 eng d a1932-620300aRace/Ethnic Differences in the Associations of the Framingham Risk Factors with Carotid IMT and Cardiovascular Events.0 aRaceEthnic Differences in the Associations of the Framingham Ris c2015 ae01323210 v103 aBACKGROUND: Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events.
METHODS: We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity.
RESULTS: Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites.
CONCLUSION: The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention.
10aAdult10aAge Distribution10aAged10aCarotid Artery Diseases10aCarotid Intima-Media Thickness10aCholesterol, HDL10aCholesterol, LDL10aComorbidity10aContinental Population Groups10aDiabetes Mellitus10aDyslipidemias10aEthnic Groups10aFemale10aFollow-Up Studies10aGlobal Health10aHumans10aHypertension10aIncidence10aLinear Models10aMale10aMiddle Aged10aMyocardial Infarction10aPrevalence10aProportional Hazards Models10aRisk Factors10aSmoking10aStroke1 aGijsberts, Crystel, M1 aGroenewegen, Karlijn, A1 aHoefer, Imo, E1 aEijkemans, Marinus, J C1 aAsselbergs, Folkert, W1 aAnderson, Todd, J1 aBritton, Annie, R1 aDekker, Jacqueline, M1 aEngström, Gunnar1 aEvans, Greg, W1 ade Graaf, Jacqueline1 aGrobbee, Diederick, E1 aHedblad, Bo1 aHolewijn, Suzanne1 aIkeda, Ai1 aKitagawa, Kazuo1 aKitamura, Akihiko1 ade Kleijn, Dominique, P V1 aLonn, Eva, M1 aLorenz, Matthias, W1 aMathiesen, Ellisiv, B1 aNijpels, Giel1 aOkazaki, Shuhei1 aO'Leary, Daniel, H1 aPasterkamp, Gerard1 aPeters, Sanne, A E1 aPolak, Joseph, F1 aPrice, Jacqueline, F1 aRobertson, Christine1 aRembold, Christopher, M1 aRosvall, Maria1 aRundek, Tatjana1 aSalonen, Jukka, T1 aSitzer, Matthias1 aStehouwer, Coen, D A1 aBots, Michiel, L1 aRuijter, Hester, M den uhttps://chs-nhlbi.org/node/687604841nas a2200685 4500008004100000022001400041245011900055210006900174260001300243300001000256490000700266520281800273653000903091653001903100653001003119653001103129653003803140653002203178653003403200653001103234653000903245653001603254653002003270653005303290653002103343653002403364653002803388653001103416653001803427100001803445700001603463700002203479700002503501700002003526700002003546700002403566700002403590700002803614700001903642700001803661700002503679700002403704700002003728700001603748700001203764700002403776700002003800700001903820700002903839700002103868700002103889700002203910700002503932700002503957700002603982700001904008700002104027710007104048856003604119 2015 eng d a2168-615700aRare and Coding Region Genetic Variants Associated With Risk of Ischemic Stroke: The NHLBI Exome Sequence Project.0 aRare and Coding Region Genetic Variants Associated With Risk of c2015 Jul a781-80 v723 aIMPORTANCE: Stroke is the second leading cause of death and the third leading cause of years of life lost. Genetic factors contribute to stroke prevalence, and candidate gene and genome-wide association studies (GWAS) have identified variants associated with ischemic stroke risk. These variants often have small effects without obvious biological significance. Exome sequencing may discover predicted protein-altering variants with a potentially large effect on ischemic stroke risk.
OBJECTIVE: To investigate the contribution of rare and common genetic variants to ischemic stroke risk by targeting the protein-coding regions of the human genome.
DESIGN, SETTING, AND PARTICIPANTS: The National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP) analyzed approximately 6000 participants from numerous cohorts of European and African ancestry. For discovery, 365 cases of ischemic stroke (small-vessel and large-vessel subtypes) and 809 European ancestry controls were sequenced; for replication, 47 affected sibpairs concordant for stroke subtype and an African American case-control series were sequenced, with 1672 cases and 4509 European ancestry controls genotyped. The ESP's exome sequencing and genotyping started on January 1, 2010, and continued through June 30, 2012. Analyses were conducted on the full data set between July 12, 2012, and July 13, 2013.
MAIN OUTCOMES AND MEASURES: Discovery of new variants or genes contributing to ischemic stroke risk and subtype (primary analysis) and determination of support for protein-coding variants contributing to risk in previously published candidate genes (secondary analysis).
RESULTS: We identified 2 novel genes associated with an increased risk of ischemic stroke: a protein-coding variant in PDE4DIP (rs1778155; odds ratio, 2.15; P = 2.63 × 10(-8)) with an intracellular signal transduction mechanism and in ACOT4 (rs35724886; odds ratio, 2.04; P = 1.24 × 10(-7)) with a fatty acid metabolism; confirmation of PDE4DIP was observed in affected sibpair families with large-vessel stroke subtype and in African Americans. Replication of protein-coding variants in candidate genes was observed for 2 previously reported GWAS associations: ZFHX3 (cardioembolic stroke) and ABCA1 (large-vessel stroke).
CONCLUSIONS AND RELEVANCE: Exome sequencing discovered 2 novel genes and mechanisms, PDE4DIP and ACOT4, associated with increased risk for ischemic stroke. In addition, ZFHX3 and ABCA1 were discovered to have protein-coding variants associated with ischemic stroke. These results suggest that genetic variation in novel pathways contributes to ischemic stroke risk and serves as a target for prediction, prevention, and therapy.
10aAged10aBrain Ischemia10aExome10aFemale10aGenetic Predisposition to Disease10aGenetic Variation10aGenome-Wide Association Study10aHumans10aMale10aMiddle Aged10aMuscle Proteins10aNational Heart, Lung, and Blood Institute (U.S.)10aNuclear Proteins10aOpen Reading Frames10aPalmitoyl-CoA Hydrolase10aStroke10aUnited States1 aAuer, Paul, L1 aNalls, Mike1 aMeschia, James, F1 aWorrall, Bradford, B1 aLongstreth, W T1 aSeshadri, Sudha1 aKooperberg, Charles1 aBurger, Kathleen, M1 aCarlson, Christopher, S1 aCarty, Cara, L1 aChen, Wei-Min1 aCupples, Adrienne, L1 aDeStefano, Anita, L1 aFornage, Myriam1 aHardy, John1 aHsu, Li1 aJackson, Rebecca, D1 aJarvik, Gail, P1 aKim, Daniel, S1 aLakshminarayan, Kamakshi1 aLange, Leslie, A1 aManichaikul, Ani1 aQuinlan, Aaron, R1 aSingleton, Andrew, B1 aThornton, Timothy, A1 aNickerson, Deborah, A1 aPeters, Ulrike1 aRich, Stephen, S1 aNational Heart, Lung, and Blood Institute Exome Sequencing Project uhttps://chs-nhlbi.org/node/684904476nas a2201081 4500008004100000022001400041245011400055210006900169260001600238300001100254490000800265520141200273653001901685653001501704653001601719653001501735653001901750653003201769653002201801653001101823653002601834653003601860653002301896653002601919100002501945700002201970700002401992700002502016700002002041700001802061700002302079700002302102700002002125700001702145700001502162700002502177700003002202700001902232700002102251700002002272700002502292700001802317700002202335700001502357700002002372700002102392700001902413700001802432700002602450700001902476700001502495700002002510700002202530700002802552700002202580700001302602700001802615700001702633700002602650700002102676700002102697700002302718700002402741700001902765700002402784700002402808700002102832700001902853700002402872700002502896700002002921700002202941700002102963700001602984700002303000700002003023700002003043700002403063700001703087700001803104700002003122700002003142700001803162700002103180700002103201700002203222700002203244700001903266700002003285700003003305700002303335856003603358 2015 eng d a1528-002000aRare and low-frequency variants and their association with plasma levels of fibrinogen, FVII, FVIII, and vWF.0 aRare and lowfrequency variants and their association with plasma c2015 Sep 10 ae19-290 v1263 aFibrinogen, coagulation factor VII (FVII), and factor VIII (FVIII) and its carrier von Willebrand factor (vWF) play key roles in hemostasis. Previously identified common variants explain only a small fraction of the trait heritabilities, and additional variations may be explained by associations with rarer variants with larger effects. The aim of this study was to identify low-frequency (minor allele frequency [MAF] ≥0.01 and <0.05) and rare (MAF <0.01) variants that influence plasma concentrations of these 4 hemostatic factors by meta-analyzing exome chip data from up to 76,000 participants of 4 ancestries. We identified 12 novel associations of low-frequency (n = 2) and rare (n = 10) variants across the fibrinogen, FVII, FVIII, and vWF traits that were independent of previously identified associations. Novel loci were found within previously reported genes and had effect sizes much larger than and independent of previously identified common variants. In addition, associations at KCNT1, HID1, and KATNB1 identified new candidate genes related to hemostasis for follow-up replication and functional genomic analysis. Newly identified low-frequency and rare-variant associations accounted for modest amounts of trait variance and therefore are unlikely to increase predicted trait heritability but provide new information for understanding individual variation in hemostasis pathways.
10aCohort Studies10aFactor VII10aFactor VIII10aFibrinogen10aGene Frequency10aGenetic Association Studies10aGenetic Variation10aHumans10aNerve Tissue Proteins10aPolymorphism, Single Nucleotide10aPotassium Channels10avon Willebrand Factor1 aHuffman, Jennifer, E1 ade Vries, Paul, S1 aMorrison, Alanna, C1 aSabater-Lleal, Maria1 aKacprowski, Tim1 aAuer, Paul, L1 aBrody, Jennifer, A1 aChasman, Daniel, I1 aChen, Ming-Huei1 aGuo, Xiuqing1 aLin, Li-An1 aMarioni, Riccardo, E1 aMüller-Nurasyid, Martina1 aYanek, Lisa, R1 aPankratz, Nathan1 aGrove, Megan, L1 ade Maat, Moniek, P M1 aCushman, Mary1 aWiggins, Kerri, L1 aQi, Lihong1 aSennblad, Bengt1 aHarris, Sarah, E1 aPolasek, Ozren1 aRiess, Helene1 aRivadeneira, Fernando1 aRose, Lynda, M1 aGoel, Anuj1 aTaylor, Kent, D1 aTeumer, Alexander1 aUitterlinden, André, G1 aVaidya, Dhananjay1 aYao, Jie1 aTang, Weihong1 aLevy, Daniel1 aWaldenberger, Melanie1 aBecker, Diane, M1 aFolsom, Aaron, R1 aGiulianini, Franco1 aGreinacher, Andreas1 aHofman, Albert1 aHuang, Chiang-Ching1 aKooperberg, Charles1 aSilveira, Angela1 aStarr, John, M1 aStrauch, Konstantin1 aStrawbridge, Rona, J1 aWright, Alan, F1 aMcKnight, Barbara1 aFranco, Oscar, H1 aZakai, Neil1 aMathias, Rasika, A1 aPsaty, Bruce, M1 aRidker, Paul, M1 aTofler, Geoffrey, H1 aVölker, Uwe1 aWatkins, Hugh1 aFornage, Myriam1 aHamsten, Anders1 aDeary, Ian, J1 aBoerwinkle, Eric1 aKoenig, Wolfgang1 aRotter, Jerome, I1 aHayward, Caroline1 aDehghan, Abbas1 aReiner, Alex, P1 aO'Donnell, Christopher, J1 aSmith, Nicholas, L uhttps://chs-nhlbi.org/node/678802967nas a2200457 4500008004100000022001400041245012500055210006900180260000900249300001100258490000700269520161400276653000901890653002201899653002501921653001001946653003001956653001101986653001101997653004002008653002002048653003102068653000902099653002902108653003302137653003002170653002602200653001702226100001902243700002102262700002002283700001902303700002202322700002402344700001802368700002702386700001702413700002202430700002102452856003602473 2015 eng d a1875-890800aRelationship between Systemic and Cerebral Vascular Disease and Brain Structure Integrity in Normal Elderly Individuals.0 aRelationship between Systemic and Cerebral Vascular Disease and c2015 a319-280 v443 aCerebral white matter lesions (WMLs) are considered a reflection of cerebral and systemic small vessel disease (SVD), and are associated with reductions in brain volume. Like the brain, the kidney is also sensitive to factors that affect vasculature. Glomerular dysfunction due to renal vascular damage can be measured with different biochemical parameters, such as creatinine or cystatin C, although cystatin C is considered to be more accurate than creatinine in the elderly. The purpose of the study was to determine whether manifestations of SVD in the kidney can predict SVD-based damage to the brain. We examined the relationship between glomerular dysfunction as a measure of SVD on WMLs, gray matter (GM) volume, and cognition in 735 cognitively normal participants from the Cardiovascular Health Study Cognition Study. The multivariate analyses controlled for demographic characteristics, hypertension, heart disease, diabetes, Apolipoprotein 4 allele, C reactive protein, lipids, physical activity, smoking, and body mass index (BMI). Elevated cystatin C levels were associated with lower neuropsychological test scores, the presence of MRI-identified brain infarcts, the severity of WMLs, and GM atrophy five years later. In adjusted models, GM volume was significantly associated with cystatin-C only until BMI and severity of WMLs were added to the model, meaning that the effect of SVD on GM volume is mediated by these two variables. These findings suggest that age-related SVD is a process that leads to altered brain structure, and creates a vulnerability state for cognitive decline.
10aAged10aAged, 80 and over10aAnalysis of Variance10aBrain10aCerebrovascular Disorders10aFemale10aHumans10aImage Processing, Computer-Assisted10aLogistic Models10aMagnetic Resonance Imaging10aMale10aNeuropsychological Tests10aPeripheral Vascular Diseases10aPredictive Value of Tests10aRetrospective Studies10aWhite Matter1 aRiverol, Mario1 aBecker, James, T1 aLopez, Oscar, L1 aRaji, Cyrus, A1 aThompson, Paul, M1 aCarmichael, Owen, T1 aGach, Michael1 aLongstreth, William, T1 aFried, Linda1 aTracy, Russell, P1 aKuller, Lewis, H uhttps://chs-nhlbi.org/node/659303239nas a2200517 4500008004100000022001400041245012400055210006900179260001300248300001200261490000600273520178100279653002102060653000902081653002202090653001002112653001902122653001102141653001802152653001502170653001102185653001402196653001002210653000902220653003002229653002402259653000902283653002002292653003002312653002102342653001802363100001702381700002002398700003102418700003102449700002002480700002202500700002902522700002002551700002302571700002202594700002802616700002302644700001802667856003602685 2015 eng d a2047-998000aResting heart rate and risk of incident heart failure: three prospective cohort studies and a systematic meta-analysis.0 aResting heart rate and risk of incident heart failure three pros c2015 Jan ae0013640 v43 aBACKGROUND: The relationship between resting heart rate (RHR) and incident heart failure (HF) has been questioned.
METHODS AND RESULTS: RHR was assessed at baseline in 7073 participants in 3 prospective cohorts (Cardiovascular Health Study, Health ABC study and Kuopio Ischemic Heart Disease Study) that recorded 1189 incident HF outcomes during 92 702 person-years of follow-up. Mean age of participants was 67 (9.9) years and mean RHR was 64.6 (11.1) bpm. Baseline RHR correlated (P<0.001) positively with body mass index (r=0.10), fasting glucose (r=0.18), and C-reactive protein (r=0.20); and inversely with serum creatinine (r=-0.05) and albumin (r=-0.05). Baseline RHR was non-linearly associated with HF risk. The age and sex-adjusted hazard ratio for HF comparing the top (>72 bpm) versus the bottom (<57 bpm) quartile of baseline RHR was 1.48 (95% confidence interval [CI] 1.26 to 1.74) and was modestly attenuated (1.30, 95% CI 1.10 to 1.53) with further adjustment for body mass index, history of diabetes, hypertension, smoking status, serum creatinine, and left ventricular hypertrophy. These findings remained consistent in analyses accounting for incident coronary heart disease, excluding individuals with prior cardiovascular events, or those taking beta-blockers; and in subgroups defined by several individual participant characteristics. In a pooled random effects meta-analysis of 7 population-based studies (43 051 participants and 3476 HF events), the overall hazard ratio comparing top versus bottom fourth of RHR was 1.40 (95% CI: 1.19 to 1.64).
CONCLUSIONS: There is a non-linear association between RHR and incident HF. Further research is needed to understand the physiologic foundations of this association.
10aAge Distribution10aAged10aAged, 80 and over10aAging10aCohort Studies10aFemale10aHeart Failure10aHeart Rate10aHumans10aIncidence10aJapan10aMale10aPredictive Value of Tests10aProspective Studies10aRest10aRisk Assessment10aSeverity of Illness Index10aSex Distribution10aSurvival Rate1 aKhan, Hassan1 aKunutsor, Setor1 aKalogeropoulos, Andreas, P1 aGeorgiopoulou, Vasiliki, V1 aNewman, Anne, B1 aHarris, Tamara, B1 aBibbins-Domingo, Kirsten1 aKauhanen, Jussi1 aGheorghiade, Mihai1 aFonarow, Gregg, C1 aKritchevsky, Stephen, B1 aLaukkanen, Jari, A1 aButler, Javed uhttps://chs-nhlbi.org/node/677103283nas a2200565 4500008004100000022001400041245009400055210006900149260001300218300001000231490000600241520164500247100001301892700001901905700002001924700002301944700001601967700001801983700001902001700002102020700002202041700002602063700001902089700002502108700002102133700002002154700002302174700001902197700001602216700002302232700002302255700001702278700001902295700001902314700001702333700001402350700002202364700002902386700001502415700001702430700001902447700002202466700002302488700002002511700001702531700002902548700002402577710008002601856003602681 2016 eng d a1942-326800aRare Exome Sequence Variants in CLCN6 Reduce Blood Pressure Levels and Hypertension Risk.0 aRare Exome Sequence Variants in CLCN6 Reduce Blood Pressure Leve c2016 Feb a64-700 v93 aBACKGROUND: Rare genetic variants influence blood pressure (BP).
METHODS AND RESULTS: Whole-exome sequencing was performed on DNA samples from 17 956 individuals of European ancestry and African ancestry (14 497, first-stage discovery and 3459, second-stage discovery) to examine the effect of rare variants on hypertension and 4 BP traits: systolic BP, diastolic BP, pulse pressure, and mean arterial pressure. Tests of ≈170 000 common variants (minor allele frequency, ≥1%; statistical significance, P≤2.9×10(-7)) and gene-based tests of rare variants (minor allele frequency, <1%; ≈17 000 genes; statistical significance, P≤1.5×10(-6)) were evaluated for each trait and ancestry, followed by multiethnic meta-analyses. In the first-stage discovery, rare coding variants (splicing, stop-gain, stop-loss, nonsynonymous variants, or indels) in CLCN6 were associated with lower diastolic BP (cumulative minor allele frequency, 1.3%; β=-3.20; P=4.1×10(-6)) and were independent of a nearby common variant (rs17367504) previously associated with BP. CLCN6 rare variants were also associated with lower systolic BP (β=-4.11; P=2.8×10(-4)), mean arterial pressure (β=-3.50; P=8.9×10(-6)), and reduced hypertension risk (odds ratio, 0.72; P=0.017). Meta-analysis of the 2-stage discovery samples showed that CLCN6 was associated with lower diastolic BP at exome-wide significance (cumulative minor allele frequency, 1.1%; β=-3.30; P=5.0×10(-7)).
CONCLUSIONS: These findings implicate the effect of rare coding variants in CLCN6 in BP variation and offer new insights into BP regulation.
1 aYu, Bing1 aPulit, Sara, L1 aHwang, Shih-Jen1 aBrody, Jennifer, A1 aAmin, Najaf1 aAuer, Paul, L1 aBis, Joshua, C1 aBoerwinkle, Eric1 aBurke, Gregory, L1 aChakravarti, Aravinda1 aCorrea, Adolfo1 aDreisbach, Albert, W1 aFranco, Oscar, H1 aEhret, Georg, B1 aFranceschini, Nora1 aHofman, Albert1 aLin, Dan-Yu1 aMetcalf, Ginger, A1 aMusani, Solomon, K1 aMuzny, Donna1 aPalmas, Walter1 aRaffel, Leslie1 aReiner, Alex1 aRice, Ken1 aRotter, Jerome, I1 aVeeraraghavan, Narayanan1 aFox, Ervin1 aGuo, Xiuqing1 aNorth, Kari, E1 aGibbs, Richard, A1 aDuijn, Cornelia, M1 aPsaty, Bruce, M1 aLevy, Daniel1 aNewton-Cheh, Christopher1 aMorrison, Alanna, C1 aCHARGE Consortium and the National Heart, Lung, and Blood Institute GO ESP* uhttps://chs-nhlbi.org/node/693703298nas a2200793 4500008004100000022001400041245008800055210006900143260001300212300001300225490000700238520090200245100002601147700002501173700001901198700002201217700002201239700002101261700002001282700001401302700002101316700002101337700002401358700002301382700002101405700001601426700001801442700003001460700002101490700002601511700002001537700001801557700002001575700002301595700002201618700002001640700002001660700002001680700002101700700002101721700002401742700002301766700002001789700002401809700002101833700002001854700001701874700002801891700002001919700002201939700001901961700003001980700002802010700002202038700001902060700001802079700002002097700002802117700002102145700002002166700002002186700002302206700002402229700002302253710007602276710004502352710007102397856003602468 2016 eng d a1553-740400aRare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease.0 aRare Functional Variant in TM2D3 is Associated with LateOnset Al c2016 Oct ae10063270 v123 aWe performed an exome-wide association analysis in 1393 late-onset Alzheimer's disease (LOAD) cases and 8141 controls from the CHARGE consortium. We found that a rare variant (P155L) in TM2D3 was enriched in Icelanders (~0.5% versus <0.05% in other European populations). In 433 LOAD cases and 3903 controls from the Icelandic AGES sub-study, P155L was associated with increased risk and earlier onset of LOAD [odds ratio (95% CI) = 7.5 (3.5-15.9), p = 6.6x10-9]. Mutation in the Drosophila TM2D3 homolog, almondex, causes a phenotype similar to loss of Notch/Presenilin signaling. Human TM2D3 is capable of rescuing these phenotypes, but this activity is abolished by P155L, establishing it as a functionally damaging allele. Our results establish a rare TM2D3 variant in association with LOAD susceptibility, and together with prior work suggests possible links to the β-amyloid cascade.
1 aJakobsdottir, Johanna1 avan der Lee, Sven, J1 aBis, Joshua, C1 aChouraki, Vincent1 aLi-Kroeger, David1 aYamamoto, Shinya1 aGrove, Megan, L1 aNaj, Adam1 aVronskaya, Maria1 aSalazar, Jose, L1 aDeStefano, Anita, L1 aBrody, Jennifer, A1 aSmith, Albert, V1 aAmin, Najaf1 aSims, Rebecca1 aIbrahim-Verbaas, Carla, A1 aChoi, Seung-Hoan1 aSatizabal, Claudia, L1 aLopez, Oscar, L1 aBeiser, Alexa1 aIkram, Arfan, M1 aGarcia, Melissa, E1 aHayward, Caroline1 aVarga, Tibor, V1 aRipatti, Samuli1 aFranks, Paul, W1 aHallmans, Göran1 aRolandsson, Olov1 aJansson, Jan-Håkon1 aPorteous, David, J1 aSalomaa, Veikko1 aEiriksdottir, Gudny1 aRice, Kenneth, M1 aBellen, Hugo, J1 aLevy, Daniel1 aUitterlinden, André, G1 aEmilsson, Valur1 aRotter, Jerome, I1 aAspelund, Thor1 aO'Donnell, Christopher, J1 aFitzpatrick, Annette, L1 aLauner, Lenore, J1 aHofman, Albert1 aSan Wang, Li-1 aWilliams, Julie1 aSchellenberg, Gerard, D1 aBoerwinkle, Eric1 aPsaty, Bruce, M1 aSeshadri, Sudha1 aShulman, Joshua, M1 aGudnason, Vilmundur1 aDuijn, Cornelia, M1 aCohorts for Heart and Aging Research in Genomic Epidemiology Consortium1 aAlzheimer’s Disease Genetic Consortium1 aGenetic and Environmental Risk in Alzheimer’s Disease consortium uhttps://chs-nhlbi.org/node/726003859nas a2200769 4500008004100000022001400041245014200055210006900197260001300266300001000279490000700289520193000296100001402226700001802240700001802258700001402276700001902290700001402309700001602323700001102339700001902350700001302369700001502382700001702397700001402414700001202428700001402440700001502454700001602469700001702485700001802502700001602520700001702536700001502553700001802568700001402586700002002600700001702620700001602637700001102653700001402664700001902678700001902697700001702716700001502733700001402748700001702762700001202779700001602791700001502807700001702822700001702839700002202856700001702878700001402895700001502909700001402924700001102938700001202949700001502961700001702976700001802993700001203011700001303023700001703036856003603053 2016 eng d a1476-557800aRare, low frequency and common coding variants in CHRNA5 and their contribution to nicotine dependence in European and African Americans.0 aRare low frequency and common coding variants in CHRNA5 and thei c2016 May a601-70 v213 aThe common nonsynonymous variant rs16969968 in the α5 nicotinic receptor subunit gene (CHRNA5) is the strongest genetic risk factor for nicotine dependence in European Americans and contributes to risk in African Americans. To comprehensively examine whether other CHRNA5 coding variation influences nicotine dependence risk, we performed targeted sequencing on 1582 nicotine-dependent cases (Fagerström Test for Nicotine Dependence score⩾4) and 1238 non-dependent controls, with independent replication of common and low frequency variants using 12 studies with exome chip data. Nicotine dependence was examined using logistic regression with individual common variants (minor allele frequency (MAF)⩾0.05), aggregate low frequency variants (0.05>MAF⩾0.005) and aggregate rare variants (MAF<0.005). Meta-analysis of primary results was performed with replication studies containing 12 174 heavy and 11 290 light smokers. Next-generation sequencing with 180 × coverage identified 24 nonsynonymous variants and 2 frameshift deletions in CHRNA5, including 9 novel variants in the 2820 subjects. Meta-analysis confirmed the risk effect of the only common variant (rs16969968, European ancestry: odds ratio (OR)=1.3, P=3.5 × 10(-11); African ancestry: OR=1.3, P=0.01) and demonstrated that three low frequency variants contributed an independent risk (aggregate term, European ancestry: OR=1.3, P=0.005; African ancestry: OR=1.4, P=0.0006). The remaining 22 rare coding variants were associated with increased risk of nicotine dependence in the European American primary sample (OR=12.9, P=0.01) and in the same risk direction in African Americans (OR=1.5, P=0.37). Our results indicate that common, low frequency and rare CHRNA5 coding variants are independently associated with nicotine dependence risk. These newly identified variants likely influence the risk for smoking-related diseases such as lung cancer.
1 aOlfson, E1 aSaccone, N, L1 aJohnson, E, O1 aChen, L-S1 aCulverhouse, R1 aDoheny, K1 aFoltz, S, M1 aFox, L1 aGogarten, S, M1 aHartz, S1 aHetrick, K1 aLaurie, C, C1 aMarosy, B1 aAmin, N1 aArnett, D1 aBarr, R, G1 aBartz, T, M1 aBertelsen, S1 aBorecki, I, B1 aBrown, M, R1 aChasman, D I1 aDuijn, C M1 aFeitosa, M, F1 aFox, E, R1 aFranceschini, N1 aFranco, O, H1 aGrove, M, L1 aGuo, X1 aHofman, A1 aKardia, S, L R1 aMorrison, A, C1 aMusani, S, K1 aPsaty, B M1 aRao, D, C1 aReiner, A, P1 aRice, K1 aRidker, P M1 aRose, L, M1 aSchick, U, M1 aSchwander, K1 aUitterlinden, A G1 aVojinovic, D1 aWang, J-C1 aWare, E, B1 aWilson, G1 aYao, J1 aZhao, W1 aBreslau, N1 aHatsukami, D1 aStitzel, J, A1 aRice, J1 aGoate, A1 aBierut, L, J uhttps://chs-nhlbi.org/node/679301877nas a2200181 4500008004100000022001400041245012000055210006900175260001600244520127500260100001701535700002601552700002201578700001801600700002001618700002101638856003601659 2016 eng d a1473-573300aRelation of coagulation factor XI with incident coronary heart disease and stroke: the Cardiovascular Health Study.0 aRelation of coagulation factor XI with incident coronary heart d c2016 Dec 223 aThe role of coagulation factor XI (FXI) in the cause of arterial thrombotic events remains uncertain. We examined the association of FXI with incident coronary heart disease (CHD), ischemic stroke, and hemorrhagic stroke. Data were from 3394 adults (mean age: 74.5 years) enrolled in the Cardiovascular Health Study who had FXI antigen from plasma samples drawn in 1992-1993 and were followed for cardiovascular events until 30 June 2013. Approximately 63% of participants were women and 17% were black. FXI levels were higher in blacks and women, showed positive associations with high-density lipoprotein and total cholesterol, BMI and diabetes, and negative associations with age and alcohol intake. During median follow-up of 13 years, we identified 1232 incident CHD, 473 ischemic stroke, and 84 hemorrhagic stroke events. In multivariable Cox models adjusted for traditional cardiovascular disease risk factors, the hazard ratio per one SD (32.2 mg/dl) increment of FXI was 1.02 (95% confidence interval: 0.96-1.08) for CHD; 0.94 (0.85-1.04) for ischemic stroke, and 0.85 (0.65-1.10) for hemorrhagic stroke. In this prospective cohort of elderly adults, there was no statistically significant association of higher FXI levels with incident CHD and stroke.
1 aAppiah, Duke1 aFashanu, Oluwaseun, E1 aHeckbert, Susa, R1 aCushman, Mary1 aPsaty, Bruce, M1 aFolsom, Aaron, R uhttps://chs-nhlbi.org/node/736803152nas a2200529 4500008004100000022001400041245014400055210006900199260001300268300001000281490000700291520165800298653000901956653001001965653001801975653002801993653001202021653001102033653002202044653001202066653002702078653001902105653001102124653001402135653000902149653003202158653002402190653002002214653001702234653001802251653001802269100002402287700002002311700002102331700002402352700001902376700002102395700002402416700001802440700001902458700002302477700002202500700002402522700002002546700002002566856003602586 2016 eng d a1758-535X00aRelations of Postload and Fasting Glucose With Incident Cardiovascular Disease and Mortality Late in Life: The Cardiovascular Health Study.0 aRelations of Postload and Fasting Glucose With Incident Cardiova c2016 Mar a370-70 v713 aBACKGROUND: Older adults have a high prevalence of postload hyperglycemia. Postload glucose has shown more robust associations with cardiovascular disease (CVD) and death than fasting glucose, but data in the oldest old are sparse.
METHODS: Fasting and 2-hour postload glucose were measured in community-dwelling older adults, mean age 78, at the 1996-1997 follow-up visit of the Cardiovascular Health Study. We evaluated their associations with atherosclerotic CVD (ASCVD) and mortality using standard Cox regression and competing-risks analyses and assessed improvement in prediction-model discrimination with the c-statistic.
RESULTS: Among 2,394 participants without treated diabetes and available data on glycemic measures, there were 579 ASCVD events and 1,698 deaths during median follow-up of 11.2 years. In fully adjusted models, both fasting and 2-hour glucose were associated with ASCVD (HR per SD, 1.13 [1.03-1.25] and 1.17 [1.07-1.28], respectively) and all-cause mortality (HR 1.12 [1.07-1.18] and 1.14 [1.08-1.20]). After mutual adjustment, however, the associations for fasting glucose with both outcomes were abolished, but those for postload glucose were largely unchanged. Consistent findings were observed for ASCVD in competing-risks models.
CONCLUSION: In adults surviving to advanced old age, postload glucose was associated with ASCVD and mortality independently of fasting glucose, but fasting glucose was not associated with these outcomes independently of postload glucose. These findings affirm the robust association of postload glucose with ASCVD and death late in life.
10aAged10aAging10aBlood Glucose10aCardiovascular Diseases10aFasting10aFemale10aFollow-Up Studies10aGlucose10aGlucose Tolerance Test10aHealth Surveys10aHumans10aIncidence10aMale10aProportional Hazards Models10aProspective Studies10aRisk Assessment10aRisk Factors10aSurvival Rate10aUnited States1 aBrutsaert, Erika, F1 aShitole, Sanyog1 aBiggs, Mary, Lou1 aMukamal, Kenneth, J1 adeBoer, Ian, H1 aThacker, Evan, L1 aBarzilay, Joshua, I1 aDjoussé, Luc1 aIx, Joachim, H1 aSmith, Nicholas, L1 aKaplan, Robert, C1 aSiscovick, David, S1 aPsaty, Bruce, M1 aKizer, Jorge, R uhttps://chs-nhlbi.org/node/685002682nas a2200253 4500008004100000022001400041245011600055210006900171260001600240300001200256490000600268520189400274100002102168700002102189700002302210700001902233700002202252700002702274700002402301700002702325700002102352700001902373856003602392 2016 eng d a1664-545600aRisk Factors for Incident Carotid Artery Revascularization among Older Adults: The Cardiovascular Health Study.0 aRisk Factors for Incident Carotid Artery Revascularization among c2016 Nov 16 a129-1390 v63 aBACKGROUND: Population-based risk factors for carotid artery revascularization are not known. We investigated the association between demographic and clinical characteristics and incident carotid artery revascularization in a cohort of older adults.
METHODS: Among Cardiovascular Health Study participants, a population-based cohort of 5,888 adults aged 65 years or older enrolled in two waves (1989-1990 and 1992-1993), 5,107 participants without a prior history of carotid endarterectomy (CEA) or cerebrovascular disease had a carotid ultrasound at baseline and were included in these analyses. Cox proportional hazards multivariable analysis was used to determine independent risk factors for incident carotid artery revascularization.
RESULTS: Over a mean follow-up of 13.5 years, 141 participants underwent carotid artery revascularization, 97% were CEA. Baseline degree of stenosis and incident ischemic cerebral events occurring during follow-up were the strongest predictors of incident revascularization. After adjustment for these, factors independently associated with an increased risk of incident revascularization were: hypertension (HR 1.53; 95% CI: 1.05-2.23), peripheral arterial disease (HR 2.57; 95% CI: 1.34-4.93), and low-density lipoprotein cholesterol (HR 1.23 per standard deviation [SD] increment [35.4 mg/dL]; 95% CI: 1.04-1.46). Factors independently associated with a lower risk of incident revascularization were: female gender (HR 0.51; 95% CI: 0.34-0.77) and older age (HR 0.69 per SD increment [5.5 years]; 95% CI: 0.56-0.86).
CONCLUSIONS: Even after accounting for carotid stenosis and incident cerebral ischemic events, carotid revascularization is related to age, gender, and cardiovascular risk factors. Further study of these demographic disparities and the role of risk factor control is warranted.
1 aGarg, Parveen, K1 aKoh, Willam, J H1 aDelaney, Joseph, A1 aHalm, Ethan, A1 aHirsch, Calvin, H1 aLongstreth, William, T1 aMukamal, Kenneth, J1 aKucharska-Newton, Anna1 aPolak, Joseph, F1 aCurtis, Lesley uhttps://chs-nhlbi.org/node/724402265nas a2200409 4500008004100000022001400041245012100055210006900176260001300245300001100258490000700269520108600276653003901362653000901401653002201410653002201432653001001454653002801464653001401492653001301506653004001519653001101559653002201570653001101592653003101603653000901634653002901643653001701672653001701689653001201706100002101718700002001739700002101759700001901780700002001799856003601819 2016 eng d a1552-527900aRisk of dementia and death in the long-term follow-up of the Pittsburgh Cardiovascular Health Study-Cognition Study.0 aRisk of dementia and death in the longterm followup of the Pitts c2016 Feb a170-830 v123 aINTRODUCTION: Increasing life expectancy has resulted in a larger population of older individuals at risk of dementia.
METHODS: The Cardiovascular Health Study-Cognition Study followed 532 participants from 1998-99 (mean age 79) to 2013 (mean age 93) for death and dementia.
RESULTS: Risk of death was determined by extent of coronary artery calcium, high-sensitivity cardiac troponin, brain natriuretic peptide, and white matter grade. Significant predictors of dementia were age, apolipoprotein-E4, vocabulary raw score, hippocampal volume, ventricular size, cognitive performance, and number of blocks walked. By 2013, 160 of 532 were alive, including 19 cognitively normal. Those with normal cognition had higher grade education, better cognition test scores, greater hippocampal volume, faster gait speed, and number of blocks walked as compared with survivors who were demented.
DISCUSSION: Few survived free of dementia and disability. Prevention and delay of cognitive decline for this older population is an imperative.
10aAfrican Continental Ancestry Group10aAged10aAged, 80 and over10aApolipoprotein E410aBrain10aCardiovascular Diseases10aCognition10aDementia10aEuropean Continental Ancestry Group10aFemale10aFollow-Up Studies10aHumans10aMagnetic Resonance Imaging10aMale10aNeuropsychological Tests10aPennsylvania10aRisk Factors10aWalking1 aKuller, Lewis, H1 aLopez, Oscar, L1 aBecker, James, T1 aChang, Yuefang1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/687702216nas a2200397 4500008004100000022001400041245018200055210006900237260001200306300001400318490000700332520093100339653002101270653003801291653001101329653005101340653002101391653003601412653001801448100002101466700001801487700002001505700002301525700001801548700002501566700002301591700002501614700002201639700002201661700001601683700002001699700002201719700002201741700001901763856003601782 2016 eng d a1744-804200aRooted in risk: genetic predisposition for low-density lipoprotein cholesterol level associates with diminished low-density lipoprotein cholesterol response to statin treatment.0 aRooted in risk genetic predisposition for lowdensity lipoprotein c2016 10 a1621-16280 v173 aAIMS: To utilize previously reported lead SNPs for low-density lipoprotein cholesterol (LDL-c) levels to find additional loci of importance to statin response, and examine whether genetic predisposition to LDL-c levels associates with differential statin response.
METHODS: We investigated effects on statin response of 59 LDL-c SNPs, by combining summary level statistics from the Global Lipids Genetics and Genomic Investigation of Statin Therapy consortia.
RESULTS: Lead SNPs for APOE, SORT1 and NPC1L1 were associated with a decreased LDL-c response to statin treatment, as was overall genetic predisposition for increased LDL-c levels as quantified with 59 SNPs, with a 5.4% smaller statin response per standard deviation increase in genetically raised LDL-c levels.
CONCLUSION: Genetic predisposition for increased LDL-c level may decrease efficacy of statin therapy.
10aCholesterol, LDL10aGenetic Predisposition to Disease10aHumans10aHydroxymethylglutaryl-CoA Reductase Inhibitors10aPharmacogenetics10aPolymorphism, Single Nucleotide10aTriglycerides1 aSmit, Roelof, Aj1 aPostmus, Iris1 aTrompet, Stella1 aBarnes, Michael, R1 aWarren, Helen1 aArsenault, Benoit, J1 aChasman, Daniel, I1 aCupples, Adrienne, L1 aHitman, Graham, A1 aKrauss, Ronald, M1 aLi, Xiaohui1 aPsaty, Bruce, M1 aStein, Charles, M1 aRotter, Jerome, I1 aJukema, Wouter uhttps://chs-nhlbi.org/node/857117687nas a2205785 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2017 eng d a1546-171800aRare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.0 aRare coding variants in PLCG2 ABI3 and TREM2 implicate microglia c2017 Sep a1373-13840 v493 aWe identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10-10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10-14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.
10aAdaptor Proteins, Signal Transducing10aAlzheimer Disease10aAmino Acid Sequence10aCase-Control Studies10aExome10aGene Expression Profiling10aGene Frequency10aGenetic Predisposition to Disease10aGenotype10aHumans10aImmunity, Innate10aLinkage Disequilibrium10aMembrane Glycoproteins10aMicroglia10aOdds Ratio10aPhospholipase C gamma10aPolymorphism, Single Nucleotide10aProtein Interaction Maps10aReceptors, Immunologic10aSequence Homology, Amino Acid1 aSims, Rebecca1 avan der Lee, Sven, J1 aNaj, Adam, C1 aBellenguez, Céline1 aBadarinarayan, Nandini1 aJakobsdottir, Johanna1 aKunkle, Brian, W1 aBoland, Anne1 aRaybould, Rachel1 aBis, Joshua, C1 aMartin, Eden, R1 aGrenier-Boley, Benjamin1 aHeilmann-Heimbach, Stefanie1 aChouraki, Vincent1 aKuzma, Amanda, B1 aSleegers, Kristel1 aVronskaya, Maria1 aRuiz, Agustin1 aGraham, Robert, R1 aOlaso, Robert1 aHoffmann, Per1 aGrove, Megan, L1 aVardarajan, Badri, N1 aHiltunen, Mikko1 aNöthen, Markus, M1 aWhite, Charles, C1 aHamilton-Nelson, Kara, L1 aEpelbaum, Jacques1 aMaier, Wolfgang1 aChoi, Seung-Hoan1 aBeecham, Gary, W1 aDulary, Cécile1 aHerms, Stefan1 aSmith, Albert, V1 aFunk, Cory, C1 aDerbois, Céline1 aForstner, Andreas, J1 aAhmad, Shahzad1 aLi, Hongdong1 aBacq, Delphine1 aHarold, Denise1 aSatizabal, Claudia, L1 aValladares, Otto1 aSquassina, Alessio1 aThomas, Rhodri1 aBrody, Jennifer, A1 aQu, Liming1 aSánchez-Juan, Pascual1 aMorgan, Taniesha1 aWolters, Frank, J1 aZhao, Yi1 aGarcia, Florentino, Sanchez1 aDenning, Nicola1 aFornage, Myriam1 aMalamon, John1 aNaranjo, Maria, Candida De1 aMajounie, Elisa1 aMosley, Thomas, H1 aDombroski, Beth1 aWallon, David1 aLupton, Michelle, K1 aDupuis, Josée1 aWhitehead, Patrice1 aFratiglioni, Laura1 aMedway, Christopher1 aJian, Xueqiu1 aMukherjee, Shubhabrata1 aKeller, Lina1 aBrown, Kristelle1 aLin, Honghuang1 aCantwell, Laura, B1 aPanza, Francesco1 aMcGuinness, Bernadette1 aMoreno-Grau, Sonia1 aBurgess, Jeremy, D1 aSolfrizzi, Vincenzo1 aProitsi, Petra1 aAdams, Hieab, H1 aAllen, Mariet1 aSeripa, Davide1 aPastor, Pau1 aCupples, Adrienne, L1 aPrice, Nathan, D1 aHannequin, Didier1 aFrank-García, Ana1 aLevy, Daniel1 aChakrabarty, Paramita1 aCaffarra, Paolo1 aGiegling, Ina1 aBeiser, Alexa, S1 aGiedraitis, Vilmantas1 aHampel, Harald1 aGarcia, Melissa, E1 aWang, Xue1 aLannfelt, Lars1 aMecocci, Patrizia1 aEiriksdottir, Gudny1 aCrane, Paul, K1 aPasquier, Florence1 aBoccardi, Virginia1 aHenández, Isabel1 aBarber, Robert, C1 aScherer, Martin1 aTarraga, Lluis1 aAdams, Perrie, M1 aLeber, Markus1 aChen, Yuning1 aAlbert, Marilyn, S1 aRiedel-Heller, Steffi1 aEmilsson, Valur1 aBeekly, Duane1 aBraae, Anne1 aSchmidt, Reinhold1 aBlacker, Deborah1 aMasullo, Carlo1 aSchmidt, Helena1 aDoody, Rachelle, S1 aSpalletta, Gianfranco1 aJr, W, T Longstre1 aFairchild, Thomas, J1 aBossù, Paola1 aLopez, Oscar, L1 aFrosch, Matthew, P1 aSacchinelli, Eleonora1 aGhetti, Bernardino1 aYang, Qiong1 aHuebinger, Ryan, M1 aJessen, Frank1 aLi, Shuo1 aKamboh, Ilyas1 aMorris, John1 aSotolongo-Grau, Oscar1 aKatz, Mindy, J1 aCorcoran, Chris1 aDunstan, Melanie1 aBraddel, Amy1 aThomas, Charlene1 aMeggy, Alun1 aMarshall, Rachel1 aGerrish, Amy1 aChapman, Jade1 aAguilar, Miquel1 aTaylor, Sarah1 aHill, Matt1 aFairén, Mònica, Díez1 aHodges, Angela1 aVellas, Bruno1 aSoininen, Hilkka1 aKloszewska, Iwona1 aDaniilidou, Makrina1 aUphill, James1 aPatel, Yogen1 aHughes, Joseph, T1 aLord, Jenny1 aTurton, James1 aHartmann, Annette, M1 aCecchetti, Roberta1 aFenoglio, Chiara1 aSerpente, Maria1 aArcaro, Marina1 aCaltagirone, Carlo1 aOrfei, Maria, Donata1 aCiaramella, Antonio1 aPichler, Sabrina1 aMayhaus, Manuel1 aGu, Wei1 aLleo, Alberto1 aFortea, Juan1 aBlesa, Rafael1 aBarber, Imelda, S1 aBrookes, Keeley1 aCupidi, Chiara1 aMaletta, Raffaele, Giovanni1 aCarrell, David1 aSorbi, Sandro1 aMoebus, Susanne1 aUrbano, Maria1 aPilotto, Alberto1 aKornhuber, Johannes1 aBosco, Paolo1 aTodd, Stephen1 aCraig, David1 aJohnston, Janet1 aGill, Michael1 aLawlor, Brian1 aLynch, Aoibhinn1 aFox, Nick, C1 aHardy, John1 aAlbin, Roger, L1 aApostolova, Liana, G1 aArnold, Steven, E1 aAsthana, Sanjay1 aAtwood, Craig, S1 aBaldwin, Clinton, T1 aBarnes, Lisa, L1 aBarral, Sandra1 aBeach, Thomas, G1 aBecker, James, T1 aBigio, Eileen, H1 aBird, Thomas, D1 aBoeve, Bradley, F1 aBowen, James, D1 aBoxer, Adam1 aBurke, James, R1 aBurns, Jeffrey, M1 aBuxbaum, Joseph, D1 aCairns, Nigel, J1 aCao, Chuanhai1 aCarlson, Chris, S1 aCarlsson, Cynthia, M1 aCarney, Regina, M1 aCarrasquillo, Minerva, M1 aCarroll, Steven, L1 aDiaz, Carolina, Ceballos1 aChui, Helena, C1 aClark, David, G1 aCribbs, David, H1 aCrocco, Elizabeth, A1 aDeCarli, Charles1 aDick, Malcolm1 aDuara, Ranjan1 aEvans, Denis, A1 aFaber, Kelley, M1 aFallon, Kenneth, B1 aFardo, David, W1 aFarlow, Martin, R1 aFerris, Steven1 aForoud, Tatiana, M1 aGalasko, Douglas, R1 aGearing, Marla1 aGeschwind, Daniel, H1 aGilbert, John, R1 aGraff-Radford, Neill, R1 aGreen, Robert, C1 aGrowdon, John, H1 aHamilton, Ronald, L1 aHarrell, Lindy, E1 aHonig, Lawrence, S1 aHuentelman, Matthew, J1 aHulette, Christine, M1 aHyman, Bradley, T1 aJarvik, Gail, P1 aAbner, Erin1 aJin, Lee-Way1 aJun, Gyungah1 aKarydas, Anna1 aKaye, Jeffrey, A1 aKim, Ronald1 aKowall, Neil, W1 aKramer, Joel, H1 aLaFerla, Frank, M1 aLah, James, J1 aLeverenz, James, B1 aLevey, Allan, I1 aLi, Ge1 aLieberman, Andrew, P1 aLunetta, Kathryn, L1 aLyketsos, Constantine, G1 aMarson, Daniel, C1 aMartiniuk, Frank1 aMash, Deborah, C1 aMasliah, Eliezer1 aMcCormick, Wayne, C1 aMcCurry, Susan, M1 aMcDavid, Andrew, N1 aMcKee, Ann, C1 aMesulam, Marsel1 aMiller, Bruce, L1 aMiller, Carol, A1 aMiller, Joshua, W1 aMorris, John, C1 aMurrell, Jill, R1 aMyers, Amanda, J1 aO'Bryant, Sid1 aOlichney, John, M1 aPankratz, Vernon, S1 aParisi, Joseph, E1 aPaulson, Henry, L1 aPerry, William1 aPeskind, Elaine1 aPierce, Aimee1 aPoon, Wayne, W1 aPotter, Huntington1 aQuinn, Joseph, F1 aRaj, Ashok1 aRaskind, Murray1 aReisberg, Barry1 aReitz, Christiane1 aRingman, John, M1 aRoberson, Erik, D1 aRogaeva, Ekaterina1 aRosen, Howard, J1 aRosenberg, Roger, N1 aSager, Mark, A1 aSaykin, Andrew, J1 aSchneider, Julie, A1 aSchneider, Lon, S1 aSeeley, William, W1 aSmith, Amanda, G1 aSonnen, Joshua, A1 aSpina, Salvatore1 aStern, Robert, A1 aSwerdlow, Russell, H1 aTanzi, Rudolph, E1 aThornton-Wells, Tricia, A1 aTrojanowski, John, Q1 aTroncoso, Juan, C1 aVan Deerlin, Vivianna, M1 aVan Eldik, Linda, J1 aVinters, Harry, V1 aVonsattel, Jean, Paul1 aWeintraub, Sandra1 aWelsh-Bohmer, Kathleen, A1 aWilhelmsen, Kirk, C1 aWilliamson, Jennifer1 aWingo, Thomas, S1 aWoltjer, Randall, L1 aWright, Clinton, B1 aYu, Chang-En1 aYu, Lei1 aGarzia, Fabienne1 aGolamaully, Feroze1 aSeptier, Gislain1 aEngelborghs, Sebastien1 aVandenberghe, Rik1 aDe Deyn, Peter, P1 aFernadez, Carmen, Muñoz1 aBenito, Yoland, Aladro1 aThonberg, Håkan1 aForsell, Charlotte1 aLilius, Lena1 aKinhult-Ståhlbom, Anne1 aKilander, Lena1 aBrundin, RoseMarie1 aConcari, Letizia1 aHelisalmi, Seppo1 aKoivisto, Anne, Maria1 aHaapasalo, Annakaisa1 aDermecourt, Vincent1 aFiévet, Nathalie1 aHanon, Olivier1 aDufouil, Carole1 aBrice, Alexis1 aRitchie, Karen1 aDubois, Bruno1 aHimali, Jayanadra, J1 aKeene, Dirk1 aTschanz, JoAnn1 aFitzpatrick, Annette, L1 aKukull, Walter, A1 aNorton, Maria1 aAspelund, Thor1 aLarson, Eric, B1 aMunger, Ron1 aRotter, Jerome, I1 aLipton, Richard, B1 aBullido, María, J1 aHofman, Albert1 aMontine, Thomas, J1 aCoto, Eliecer1 aBoerwinkle, Eric1 aPetersen, Ronald, C1 aAlvarez, Victoria1 aRivadeneira, Fernando1 aReiman, Eric, M1 aGallo, Maura1 aO'Donnell, Christopher, J1 aReisch, Joan, S1 aBruni, Amalia, Cecilia1 aRoyall, Donald, R1 aDichgans, Martin1 aSano, Mary1 aGalimberti, Daniela1 aSt George-Hyslop, Peter1 aScarpini, Elio1 aTsuang, Debby, W1 aMancuso, Michelangelo1 aBonuccelli, Ubaldo1 aWinslow, Ashley, R1 aDaniele, Antonio1 aWu, Chuang-Kuo1 aPeters, Oliver1 aNacmias, Benedetta1 aRiemenschneider, Matthias1 aHeun, Reinhard1 aBrayne, Carol1 aRubinsztein, David, C1 aBras, Jose1 aGuerreiro, Rita1 aAl-Chalabi, Ammar1 aShaw, Christopher, E1 aCollinge, John1 aMann, David1 aTsolaki, Magda1 aClarimon, Jordi1 aSussams, Rebecca1 aLovestone, Simon1 aO'Donovan, Michael, C1 aOwen, Michael, J1 aBehrens, Timothy, W1 aMead, Simon1 aGoate, Alison, M1 aUitterlinden, André, G1 aHolmes, Clive1 aCruchaga, Carlos1 aIngelsson, Martin1 aBennett, David, A1 aPowell, John1 aGolde, Todd, E1 aGraff, Caroline1 aDe Jager, Philip, L1 aMorgan, Kevin1 aErtekin-Taner, Nilufer1 aCombarros, Onofre1 aPsaty, Bruce, M1 aPassmore, Peter1 aYounkin, Steven, G1 aBerr, Claudine1 aGudnason, Vilmundur1 aRujescu, Dan1 aDickson, Dennis, W1 aDartigues, Jean-François1 aDeStefano, Anita, L1 aOrtega-Cubero, Sara1 aHakonarson, Hakon1 aCampion, Dominique1 aBoada, Merce1 aKauwe, John, Keoni1 aFarrer, Lindsay, A1 aVan Broeckhoven, Christine1 aIkram, Arfan, M1 aJones, Lesley1 aHaines, Jonathan, L1 aTzourio, Christophe1 aLauner, Lenore, J1 aEscott-Price, Valentina1 aMayeux, Richard1 aDeleuze, Jean-Francois1 aAmin, Najaf1 aHolmans, Peter, A1 aPericak-Vance, Margaret, A1 aAmouyel, Philippe1 aDuijn, Cornelia, M1 aRamirez, Alfredo1 aSan Wang, Li-1 aLambert, Jean-Charles1 aSeshadri, Sudha1 aWilliams, Julie1 aSchellenberg, Gerard, D1 aARUK Consortium1 aGERAD/PERADES, CHARGE, ADGC, EADI uhttps://chs-nhlbi.org/node/758703066nas a2200577 4500008004100000022001400041245008100055210006900136260001300205300001300218490000700231520143400238653001101672653002301683653001801706653001101724653004301735653001901778653001701797653001801814653003401832653001101866653001901877653001801896653002001914653000901934653002301943653001401966653001601980653001901996653003602015653003302051653002102084653002302105653002702128100001802155700002302173700002002196700001302216700002502229700002102254700001802275700002002293700001802313700002302331700002502354700002202379700002502401710002602426856003602452 2017 eng d a1553-740400aRare coding variants pinpoint genes that control human hematological traits.0 aRare coding variants pinpoint genes that control human hematolog c2017 Aug ae10069250 v133 aThe identification of rare coding or splice site variants remains the most straightforward strategy to link genes with human phenotypes. Here, we analyzed the association between 137,086 rare (minor allele frequency (MAF) <1%) coding or splice site variants and 15 hematological traits in up to 308,572 participants. We found 56 such rare coding or splice site variants at P<5x10-8, including 31 that are associated with a blood-cell phenotype for the first time. All but one of these 31 new independent variants map to loci previously implicated in hematopoiesis by genome-wide association studies (GWAS). This includes a rare splice acceptor variant (rs146597587, MAF = 0.5%) in interleukin 33 (IL33) associated with reduced eosinophil count (P = 2.4x10-23), and lower risk of asthma (P = 2.6x10-7, odds ratio [95% confidence interval] = 0.56 [0.45-0.70]) and allergic rhinitis (P = 4.2x10-4, odds ratio = 0.55 [0.39-0.76]). The single new locus identified in our study is defined by a rare p.Arg172Gly missense variant (rs145535174, MAF = 0.05%) in plasminogen (PLG) associated with increased platelet count (P = 6.8x10-9), and decreased D-dimer concentration (P = 0.018) and platelet reactivity (P<0.03). Finally, our results indicate that searching for rare coding or splice site variants in very large sample sizes can help prioritize causal genes at many GWAS loci associated with complex human diseases and traits.
10aAsthma10aDatabases, Genetic10aEndometriosis10aFemale10aFibrin Fibrinogen Degradation Products10aGene Frequency10aGenetic Loci10aGenome, Human10aGenome-Wide Association Study10aHumans10aInterleukin-3310aLinear Models10aLogistic Models10aMale10aMutation, Missense10aPhenotype10aPlasminogen10aPlatelet Count10aPolymorphism, Single Nucleotide10aPrincipal Component Analysis10aProtein Splicing10aRhinitis, Allergic10aSequence Analysis, DNA1 aMousas, Abdou1 aNtritsos, Georgios1 aChen, Ming-Huei1 aSong, Ci1 aHuffman, Jennifer, E1 aTzoulaki, Ioanna1 aElliott, Paul1 aPsaty, Bruce, M1 aAuer, Paul, L1 aJohnson, Andrew, D1 aEvangelou, Evangelos1 aLettre, Guillaume1 aReiner, Alexander, P1 aBlood-Cell Consortium uhttps://chs-nhlbi.org/node/757703136nas a2200313 4500008004100000022001400041245012400055210006900179260001600248300001200264490000700276520219200283100002602475700002002501700001802521700001602539700002002555700001502575700002502590700002002615700002402635700002202659700002002681700002002701700002202721700002402743700001902767856003602786 2017 eng d a1555-905X00aThe Relation of Serum Potassium Concentration with Cardiovascular Events and Mortality in Community-Living Individuals.0 aRelation of Serum Potassium Concentration with Cardiovascular Ev c2017 Feb 07 a245-2520 v123 aBACKGROUND AND OBJECTIVES: Hyperkalemia is associated with adverse outcomes in patients with CKD and in hospitalized patients with acute medical conditions. Little is known regarding hyperkalemia, cardiovascular disease (CVD), and mortality in community-living populations. In a pooled analysis of two large observational cohorts, we investigated associations between serum potassium concentrations and CVD events and mortality, and whether potassium-altering medications and eGFR<60 ml/min per 1.73 m(2) modified these associations.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among 9651 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS), who were free of CVD at baseline (2000-2002 in the MESA and 1989-1993 in the CHS), we investigated associations between serum potassium categories (<3.5, 3.5-3.9, 4.0-4.4, 4.5-4.9, and ≥5.0 mEq/L) and CVD events, mortality, and mortality subtypes (CVD versus non-CVD) using Cox proportional hazards models, adjusting for demographics, time-varying eGFR, traditional CVD risk factors, and use of potassium-altering medications.
RESULTS: Compared with serum potassium concentrations between 4.0 and 4.4 mEq/L, those with concentrations ≥5.0 mEq/L were at higher risk for all-cause mortality (hazard ratio, 1.41; 95% confidence interval, 1.12 to 1.76), CVD death (hazard ratio, 1.50; 95% confidence interval, 1.00 to 2.26), and non-CVD death (hazard ratio, 1.40; 95% confidence interval, 1.07 to 1.83) in fully adjusted models. Associations of serum potassium with these end points differed among diuretic users (Pinteraction<0.02 for all), such that participants who had serum potassium ≥5.0 mEq/L and were concurrently using diuretics were at higher risk of each end point compared with those not using diuretics.
CONCLUSIONS: Serum potassium concentration ≥5.0 mEq/L was associated with all-cause mortality, CVD death, and non-CVD death in community-living individuals; associations were stronger in diuretic users. Whether maintenance of potassium within the normal range may improve clinical outcomes requires future study.
1 aHughes-Austin, Jan, M1 aRifkin, Dena, E1 aBeben, Tomasz1 aKatz, Ronit1 aSarnak, Mark, J1 aDeo, Rajat1 aHoofnagle, Andrew, N1 aHomma, Shunichi1 aSiscovick, David, S1 aSotoodehnia, Nona1 aPsaty, Bruce, M1 ade Boer, Ian, H1 aKestenbaum, Bryan1 aShlipak, Michael, G1 aIx, Joachim, H uhttps://chs-nhlbi.org/node/734702701nas a2200241 4500008004100000022001400041245022700055210006900282260001600351300001200367490000800379520184500387100002202232700002202254700002002276700002302296700001802319700002202337700002402359700002002383700002002403856003602423 2017 eng d a1879-191300aRelation of the Myocardial Contraction Fraction, as Calculated from M-Mode Echocardiography, With Incident Heart Failure, Atherosclerotic Cardiovascular Disease and Mortality (Results from the Cardiovascular Health Study).0 aRelation of the Myocardial Contraction Fraction as Calculated fr c2017 Mar 15 a923-9280 v1193 aWe evaluated the association between 2-dimensional (2D) echocardiography (echo)-determined myocardial contraction fraction (MCF) and adverse cardiovascular outcomes including incident heart failure (HF), atherosclerotic cardiovascular disease (ASCVD), and mortality. The MCF, the ratio of left ventricular (LV) stroke volume (SV) to myocardial volume (MV), is a volumetric measure of myocardial shortening that can distinguish pathologic from physiological hypertrophy. Using 2D echo-guided M-mode data from the Cardiovascular Health Study, we calculated MCF in subjects with LV ejection fraction (EF) ≥55% and used Cox models to evaluate its association with incident HF, ASCVD, and all-cause mortality after adjusting for clinical and echo parameters. We assessed whether log2(SV) and log2(MV) were consistent with the expected 1:-1 ratio used in the definition of MCF. Among 2,147 participants (age 72 ± 5 years), average MCF was 59 ± 13%. After controlling for clinical and echo variables, each 10% absolute increment in MCF was associated with lower risk of HF (hazard ratio [HR] 0.88; 95% confidence interval [CI] 0.82, 0.94), ASCVD (HR 0.90; 95% CI 0.85, 0.95), and death (HR 0.93; 95% CI 0.89, 0.97). Moreover, the MCF was still significantly associated with ASCVD and mortality, but not HF, after adjustment for percent-predicted LV mass. Significant departure from the 1:-1 ratio was not observed for ASCVD or death, but did occur for HF, driven by a stronger association for MV than SV. In conclusion, among older adults without CVD or low LV ejection fraction, 2D echo-guided M-mode-derived MCF was independently associated with lower risk of adverse cardiovascular outcomes, but this ratiometric index may not capture the full relation that is apparent when its components are modeled separately in the case of HF.
1 aMaurer, Mathew, S1 aKoh, William, J H1 aBartz, Traci, M1 aVullaganti, Sirish1 aBarasch, Eddy1 aGardin, Julius, M1 aGottdiener, John, S1 aPsaty, Bruce, M1 aKizer, Jorge, R uhttps://chs-nhlbi.org/node/735003009nas a2200265 4500008004100000022001400041245008800055210006900143260001600212300001400228490000700242520222800249100002102477700002102498700001702519700001702536700002002553700002202573700002202595700002302617700002402640700002202664700002102686856003602707 2017 eng d a1558-359700aRelationship Between Physical Activity, Body Mass Index, and Risk of Heart Failure.0 aRelationship Between Physical Activity Body Mass Index and Risk c2017 Mar 07 a1129-11420 v693 aBACKGROUND: Lower leisure-time physical activity (LTPA) and higher body mass index (BMI) are independently associated with risk of heart failure (HF). However, it is unclear if this relationship is consistent for both heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF).
OBJECTIVES: This study sought to quantify dose-response associations between LTPA, BMI, and the risk of different HF subtypes.
METHODS: Individual-level data from 3 cohort studies (WHI [Women's Health Initiative], MESA [Multi-Ethnic Study of Atherosclerosis], and CHS [Cardiovascular Health Study]) were pooled and participants were stratified into guideline-recommended categories of LTPA and BMI. Associations between LTPA, BMI, and risk of overall HF, HFpEF (ejection fraction ≥45%), and HFrEF (ejection fraction <45%) were assessed by using multivariable adjusted Cox models and restricted cubic splines.
RESULTS: The study included 51,451 participants with 3,180 HF events (1,252 HFpEF, 914 HFrEF, and 1,014 unclassified HF). In the adjusted analysis, there was a dose-dependent association between higher LTPA levels, lower BMI, and overall HF risk. Among HF subtypes, LTPA in any dose range was not associated with HFrEF risk. In contrast, lower levels of LTPA (<500 MET-min/week) were not associated with HFpEF risk, and dose-dependent associations with lower HFpEF risk were observed at higher levels. Compared with no LTPA, higher than twice the guideline-recommended minimum LTPA levels (>1,000 MET-min/week) were associated with an 19% lower risk of HFpEF (hazard ratio: 0.81; 95% confidence interval: 0.68 to 0.97). The dose-response relationship for BMI with HFpEF risk was also more consistent than with HFrEF risk, such that increasing BMI above the normal range (≥25 kg/m(2)) was associated with a greater increase in risk of HFpEF than HFrEF.
CONCLUSIONS: Our study findings show strong, dose-dependent associations between LTPA levels, BMI, and risk of overall HF. Among HF subtypes, higher LTPA levels and lower BMI were more consistently associated with lower risk of HFpEF compared with HFrEF.
1 aPandey, Ambarish1 aLaMonte, Michael1 aKlein, Liviu1 aAyers, Colby1 aPsaty, Bruce, M1 aEaton, Charles, B1 aAllen, Norrina, B1 ade Lemos, James, A1 aCarnethon, Mercedes1 aGreenland, Philip1 aBerry, Jarett, D uhttps://chs-nhlbi.org/node/735603140nas a2200289 4500008004100000022001400041245015000055210006900205260001300274300000700287490000700294520224800301100002102549700001302570700002002583700002202603700001902625700002102644700002002665700001802685700002202703700002402725700002102749700002402770700002002794856003602814 2017 eng d a1862-351400aRelationship of bone mineral density with valvular and annular calcification in community-dwelling older people: The Cardiovascular Health Study.0 aRelationship of bone mineral density with valvular and annular c c2017 Dec a520 v123 aAssociations between bone mineral density and aortic valvular, aortic annular, and mitral annular calcification were investigated in a cross-sectional analysis of a population-based cohort of 1497 older adults. Although there was no association between continuous bone mineral density and outcomes, a significant association between osteoporosis and aortic valvular calcification in men was found.
INTRODUCTION: The process of cardiac calcification bears a resemblance to skeletal bone metabolism and its regulation. Experimental studies suggest that bone mineral density (BMD) and valvular calcification may be reciprocally related, but epidemiologic data are sparse.
METHODS: We tested the hypothesis that BMD of the total hip and femoral neck measured by dual-energy X-ray absorptiometry (DXA) is inversely associated with prevalence of three echocardiographic measures of cardiac calcification in a cross-sectional analysis of 1497 older adults from the Cardiovascular Health Study. The adjusted association of BMD with aortic valve calcification (AVC), aortic annular calcification (AAC), and mitral annular calcification (MAC) was assessed with relative risk (RR) regression.
RESULTS: Mean (SD) age was 76.2 (4.8) years; 58% were women. Cardiac calcification was highly prevalent in women and men: AVC, 59.5 and 71.0%; AAC 45.1 and 46.7%; MAC 42.8 and 39.5%, respectively. After limited and full adjustment for potential confounders, no statistically significant associations were detected between continuous BMD at either site and the three measures of calcification. Assessment of WHO BMD categories revealed a significant association between osteoporosis at the total hip and AVC in men (adjusted RR compared with normal BMD = 1.24 (1.01-1.53)). In graded sensitivity analyses, there were apparent inverse associations between femoral neck BMD and AVC with stenosis in men, and femoral neck BMD and moderate/severe MAC in women, but these were not significant.
CONCLUSION: These findings support further investigation of the sex-specific relationships between low BMD and cardiac calcification, and whether processes linking the two could be targeted for therapeutic ends.
1 aMassera, Daniele1 aXu, Shuo1 aBartz, Traci, M1 aBortnick, Anna, E1 aIx, Joachim, H1 aChonchol, Michel1 aOwens, David, S1 aBarasch, Eddy1 aGardin, Julius, M1 aGottdiener, John, S1 aRobbins, John, R1 aSiscovick, David, S1 aKizer, Jorge, R uhttps://chs-nhlbi.org/node/748803467nas a2200673 4500008004100000022001400041245015500055210006900210260001600279520146600295100001701761700002101778700001901799700002201818700001901840700003001859700002401889700002801913700002001941700001901961700001801980700001801998700002202016700002102038700002802059700002102087700002402108700002002132700002402152700002402176700001902200700002402219700002002243700001602263700003502279700001902314700001902333700002002352700002302372700001802395700002502413700002102438700002002459700002002479700001902499700001802518700002102536700002202557700002002579700002002599700002202619700002002641700002102661700001802682700001702700700002302717700001702740856003602757 2017 eng d a1476-625600aREPEATED MEASUREMENTS OF BLOOD PRESSURE AND CHOLESTEROL IMPROVES CARDIOVASCULAR DISEASE RISK PREDICTION: AN INDIVIDUAL-PARTICIPANT-DATA META-ANALYSIS.0 aREPEATED MEASUREMENTS OF BLOOD PRESSURE AND CHOLESTEROL IMPROVES c2017 May 263 aThe added value of incorporating information from repeated measurements of blood pressure and cholesterol for cardiovascular disease (CVD) risk prediction has not been rigorously assessed. We used data from the Emerging Risk Factors Collaboration on 191,445 adults (38 cohorts from across 17 countries with data from 1962-2014) with > 1 million measurements of systolic blood pressure, total cholesterol and high-density lipoprotein cholesterol; over a median 12 years of follow-up, 21,170 CVD events occurred. Risk prediction models using cumulative means of repeated measurements and summary measures from longitudinal modelling of the repeated measurements were compared to models using measurements from a single time point. Risk discrimination (C-index) and net reclassification were calculated, and changes in C-indices were meta-analysed across studies. Compared to the single time point model, the cumulative means and the longitudinal models increased the C-index by 0.0040 (95% CI: 0.0023, 0.0057) and 0.0023 (0.0005, 0.0042), respectively. Reclassification was also improved in both models; compared to the single time point model, overall net reclassification improvements were 0.0369 (0.0303, 0.0436) for the cumulative means model and 0.0177 (0.0110, 0.0243) for the longitudinal model. In conclusion, incorporating repeated measurements of blood pressure and cholesterol into CVD risk prediction models slightly improves risk prediction.
1 aPaige, Ellie1 aBarrett, Jessica1 aPennells, Lisa1 aSweeting, Michael1 aWilleit, Peter1 aDi Angelantonio, Emanuele1 aGudnason, Vilmundur1 aNordestgaard, Børge, G1 aPsaty, Bruce, M1 aGoldbourt, Uri1 aBest, Lyle, G1 aAssmann, Gerd1 aSalonen, Jukka, T1 aNietert, Paul, J1 aVerschuren, Wm, Monique1 aBrunner, Eric, J1 aKronmal, Richard, A1 aSalomaa, Veikko1 aBakker, Stephan, Jl1 aDagenais, Gilles, R1 aSato, Shinichi1 aJansson, Jan-Håkan1 aWilleit, Johann1 aOnat, Altan1 ade la Cámara, Agustin, Gómez1 aRoussel, Ronan1 aVölzke, Henry1 aDankner, Rachel1 aTipping, Robert, W1 aMeade, Tom, W1 aDonfrancesco, Chiara1 aKuller, Lewis, H1 aPeters, Annette1 aGallacher, John1 aKromhout, Daan1 aIso, Hiroyasu1 aKnuiman, Matthew1 aCasiglia, Edoardo1 aKavousi, Maryam1 aPalmieri, Luigi1 aSundström, Johan1 aDavis, Barry, R1 aNjølstad, Inger1 aCouper, David1 aDanesh, John1 aThompson, Simon, G1 aWood, Angela uhttps://chs-nhlbi.org/node/745101869nas a2200205 4500008004100000022001400041245014500055210006900200260001600269300002000285520116300305100002501468700002501493700001701518700002201535700002701557700002301584700002001607856003601627 2017 eng d a1552-688700aRole of Late-Life Depression in the Association of Subclinical Cardiovascular Disease With All-Cause Mortality: Cardiovascular Health Study.0 aRole of LateLife Depression in the Association of Subclinical Ca c2017 Nov 01 a8982643177449213 aOBJECTIVES: To evaluate whether late-life depression mediates the association of subclinical cardiovascular disease (CVD) with all-cause mortality.
METHOD: Using data from 3,473 Cardiovascular Health Study participants, the Cox proportional hazards model was used to examine the direct and indirect (via late-life depression) effects of the association between baseline subclinical CVD and all-cause mortality with weights derived from multivariable logistic regression of late-life depression on subclinical CVD.
RESULTS: Subclinical CVD led to a higher risk of all-cause mortality (hazard ratio [HR] = 1.51, 95% confidence interval, [CI] = [1.42, 1.94]). Total effect of subclinical CVD on all-cause mortality was decomposed into direct (HR = 1.41, 95% CI = [1.37, 1.58]) and indirect (HR = 1.07, 95% CI = [1.01, 1.23]) effects; 16.3% of the total effect of subclinical CVD on all-cause mortality was mediated by late-life depression.
DISCUSSION: Late-life depression accounts for little, if any, of the association between subclinical CVD, a risk factor of all-cause mortality, and all-cause mortality.
1 aArmstrong, Nicole, M1 aCarlson, Michelle, C1 aXue, Qian-Li1 aSchrack, Jennifer1 aCarnethon, Mercedes, R1 aChaves, Paulo, H M1 aGross, Alden, L uhttps://chs-nhlbi.org/node/754502530nas a2200313 4500008004100000022001400041245008500055210006900140260001600209520156200225100002801787700002101815700002301836700002401859700002401883700002001907700002201927700002601949700002601975700002102001700001702022700002202039700002002061700002202081700001902103700002002122710003802142856003602180 2018 eng d a1432-120300aRare loss of function variants in candidate genes and risk of colorectal cancer.0 aRare loss of function variants in candidate genes and risk of co c2018 Sep 283 aAlthough ~ 25% of colorectal cancer or polyp (CRC/P) cases show familial aggregation, current germline genetic testing identifies a causal genotype in the 16 major genes associated with high penetrance CRC/P in only 20% of these cases. As there are likely other genes underlying heritable CRC/P, we evaluated the association of variation at novel loci with CRC/P. We evaluated 158 a priori selected candidate genes by comparing the number of rare potentially disruptive variants (PDVs) found in 84 CRC/P cases without an identified CRC/P risk-associated variant and 2440 controls. We repeated this analysis using an additional 73 CRC/P cases. We also compared the frequency of PDVs in select genes among CRC/P cases with two publicly available data sets. We found a significant enrichment of PDVs in cases vs. controls: 20% of cases vs. 11.5% of controls with ≥ 1 PDV (OR = 1.9, p = 0.01) in the original set of cases. Among the second cohort of CRC/P cases, 18% had a PDV, significantly different from 11.5% (p = 0.02). Logistic regression, adjusting for ancestry and multiple testing, indicated association between CRC/P and PDVs in NTHL1 (p = 0.0001), BRCA2 (p = 0.01) and BRIP1 (p = 0.04). However, there was no significant difference in the frequency of PDVs at each of these genes between all 157 CRC/P cases and two publicly available data sets. These results suggest an increased presence of PDVs in CRC/P cases and support further investigation of the association of NTHL1, BRCA2 and BRIP1 variation with CRC/P.
1 aRosenthal, Elisabeth, A1 aShirts, Brian, H1 aAmendola, Laura, M1 aHorike-Pyne, Martha1 aRobertson, Peggy, D1 aHisama, Fuki, M1 aBennett, Robin, L1 aDorschner, Michael, O1 aNickerson, Deborah, A1 aStanaway, Ian, B1 aNassir, Rami1 aVickers, Kathy, T1 aLi, Christopher1 aGrady, William, M1 aPeters, Ulrike1 aJarvik, Gail, P1 aNHLBI GO Exome Sequencing Project uhttps://chs-nhlbi.org/node/784709584nas a2203049 4500008004100000022001400041245011700055210006900172260001300241300001200254490000700266520112500273100002001398700002101418700002101439700001401460700002301474700001901497700001301516700002401529700001901553700002001572700001701592700001801609700001201627700002301639700001201662700001801674700002001692700001801712700001901730700002301749700002001772700001801792700003601810700002001846700002001866700002001886700002301906700003001929700002101959700002001980700002002000700002102020700001202041700002602053700001302079700002002092700002302112700002202135700001902157700002702176700003202203700002102235700002102256700002002277700002402297700002102321700002502342700002102367700002002388700002002408700002402428700002102452700001602473700001802489700001902507700001902526700001602545700001702561700002202578700002302600700002302623700002102646700002302667700001902690700002202709700002202731700001902753700002402772700002402796700002102820700002002841700002202861700002602883700002002909700002502929700002202954700001402976700001502990700002603005700002503031700001503056700002003071700002503091700002303116700002903139700001703168700001903185700002503204700001803229700002203247700002403269700001803293700002103311700001803332700002003350700001703370700001903387700002103406700001803427700001303445700001503458700001803473700002203491700002703513700002103540700001803561700002103579700001903600700002403619700002303643700001803666700002103684700001503705700002103720700002603741700002203767700002103789700002503810700002303835700002003858700002403878700002103902700002503923700001803948700001803966700001803984700002104002700002004023700001904043700001304062700001604075700001704091700002204108700001904130700002104149700002404170700001904194700002404213700002204237700001904259700002004278700002304298700002004321700002004341700002304361700002404384700002204408700002304430700002404453700002204477700002204499700001504521700002204536700002404558700002204582700002504604700002104629700002204650700001904672700002104691700001804712700002204730700002204752700002304774700002504797700002304822700001904845700002004864700002504884700001804909700002004927700002604947700002404973700002504997700002005022700002105042700001605063700002005079700002405099700002805123700001705151700002305168700002205191700002505213700002905238700002305267700001705290700002005307700001905327700002105346700002005367700002205387700002105409700001605430700001805446700001905464700002605483700002205509700002005531700002405551700001905575700002605594700001905620700002005639700001905659700001205678700001505690700001705705700002005722700002305742700002105765700002605786700002805812700002305840700002105863700001905884700002005903700002105923700001905944700002505963700002005988700002406008700002106032700002206053700002806075700002206103700002306125700002506148700002106173700002406194700002106218700001906239700002506258700002206283700002006305700002106325700002106346700002206367700002206389700002206411710002306433710002106456710002106477856003606498 2018 eng d a1546-171800aRefining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.0 aRefining the accuracy of validated target identification through c2018 Apr a559-5710 v503 aWe aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
1 aMahajan, Anubha1 aWessel, Jennifer1 aWillems, Sara, M1 aZhao, Wei1 aRobertson, Neil, R1 aChu, Audrey, Y1 aGan, Wei1 aKitajima, Hidetoshi1 aTaliun, Daniel1 aRayner, William1 aGuo, Xiuqing1 aLu, Yingchang1 aLi, Man1 aJensen, Richard, A1 aHu, Yao1 aHuo, Shaofeng1 aLohman, Kurt, K1 aZhang, Weihua1 aCook, James, P1 aPrins, Bram, Peter1 aFlannick, Jason1 aGrarup, Niels1 aTrubetskoy, Vassily, Vladimirov1 aKravic, Jasmina1 aKim, Young, Jin1 aRybin, Denis, V1 aYaghootkar, Hanieh1 aMüller-Nurasyid, Martina1 aMeidtner, Karina1 aLi-Gao, Ruifang1 aVarga, Tibor, V1 aMarten, Jonathan1 aLi, Jin1 aSmith, Albert, Vernon1 aAn, Ping1 aLigthart, Symen1 aGustafsson, Stefan1 aMalerba, Giovanni1 aDemirkan, Ayse1 aTajes, Juan, Fernandez1 aSteinthorsdottir, Valgerdur1 aWuttke, Matthias1 aLecoeur, Cécile1 aPreuss, Michael1 aBielak, Lawrence, F1 aGraff, Marielisa1 aHighland, Heather, M1 aJustice, Anne, E1 aLiu, Dajiang, J1 aMarouli, Eirini1 aPeloso, Gina, Marie1 aWarren, Helen, R1 aAfaq, Saima1 aAfzal, Shoaib1 aAhlqvist, Emma1 aAlmgren, Peter1 aAmin, Najaf1 aBang, Lia, B1 aBertoni, Alain, G1 aBombieri, Cristina1 aBork-Jensen, Jette1 aBrandslund, Ivan1 aBrody, Jennifer, A1 aBurtt, Noel, P1 aCanouil, Mickaël1 aChen, Yii-Der Ida1 aCho, Yoon Shin1 aChristensen, Cramer1 aEastwood, Sophie, V1 aEckardt, Kai-Uwe1 aFischer, Krista1 aGambaro, Giovanni1 aGiedraitis, Vilmantas1 aGrove, Megan, L1 ade Haan, Hugoline, G1 aHackinger, Sophie1 aHai, Yang1 aHan, Sohee1 aTybjærg-Hansen, Anne1 aHivert, Marie-France1 aIsomaa, Bo1 aJäger, Susanne1 aJørgensen, Marit, E1 aJørgensen, Torben1 aKäräjämäki, AnneMari1 aKim, Bong-Jo1 aKim, Sung, Soo1 aKoistinen, Heikki, A1 aKovacs, Peter1 aKriebel, Jennifer1 aKronenberg, Florian1 aLäll, Kristi1 aLange, Leslie, A1 aLee, Jung-Jin1 aLehne, Benjamin1 aLi, Huaixing1 aLin, Keng-Hung1 aLinneberg, Allan1 aLiu, Ching-Ti1 aLiu, Jun1 aLoh, Marie1 aMägi, Reedik1 aMamakou, Vasiliki1 aMcKean-Cowdin, Roberta1 aNadkarni, Girish1 aNeville, Matt1 aNielsen, Sune, F1 aNtalla, Ioanna1 aPeyser, Patricia, A1 aRathmann, Wolfgang1 aRice, Kenneth1 aRich, Stephen, S1 aRode, Line1 aRolandsson, Olov1 aSchönherr, Sebastian1 aSelvin, Elizabeth1 aSmall, Kerrin, S1 aStančáková, Alena1 aSurendran, Praveen1 aTaylor, Kent, D1 aTeslovich, Tanya, M1 aThorand, Barbara1 aThorleifsson, Gudmar1 aTin, Adrienne1 aTönjes, Anke1 aVarbo, Anette1 aWitte, Daniel, R1 aWood, Andrew, R1 aYajnik, Pranav1 aYao, Jie1 aYengo, Loic1 aYoung, Robin1 aAmouyel, Philippe1 aBoeing, Heiner1 aBoerwinkle, Eric1 aBottinger, Erwin, P1 aChowdhury, Raj1 aCollins, Francis, S1 aDedoussis, George1 aDehghan, Abbas1 aDeloukas, Panos1 aFerrario, Marco, M1 aFerrieres, Jean1 aFlorez, Jose, C1 aFrossard, Philippe1 aGudnason, Vilmundur1 aHarris, Tamara, B1 aHeckbert, Susan, R1 aHowson, Joanna, M M1 aIngelsson, Martin1 aKathiresan, Sekar1 aKee, Frank1 aKuusisto, Johanna1 aLangenberg, Claudia1 aLauner, Lenore, J1 aLindgren, Cecilia, M1 aMännistö, Satu1 aMeitinger, Thomas1 aMelander, Olle1 aMohlke, Karen, L1 aMoitry, Marie1 aMorris, Andrew, D1 aMurray, Alison, D1 ade Mutsert, Renée1 aOrho-Melander, Marju1 aOwen, Katharine, R1 aPerola, Markus1 aPeters, Annette1 aProvince, Michael, A1 aRasheed, Asif1 aRidker, Paul, M1 aRivadineira, Fernando1 aRosendaal, Frits, R1 aRosengren, Anders, H1 aSalomaa, Veikko1 aSheu, Wayne, H-H1 aSladek, Rob1 aSmith, Blair, H1 aStrauch, Konstantin1 aUitterlinden, André, G1 aVarma, Rohit1 aWiller, Cristen, J1 aBlüher, Matthias1 aButterworth, Adam, S1 aChambers, John, Campbell1 aChasman, Daniel, I1 aDanesh, John1 aDuijn, Cornelia1 aDupuis, Josée1 aFranco, Oscar, H1 aFranks, Paul, W1 aFroguel, Philippe1 aGrallert, Harald1 aGroop, Leif1 aHan, Bok-Ghee1 aHansen, Torben1 aHattersley, Andrew, T1 aHayward, Caroline1 aIngelsson, Erik1 aKardia, Sharon, L R1 aKarpe, Fredrik1 aKooner, Jaspal, Singh1 aKöttgen, Anna1 aKuulasmaa, Kari1 aLaakso, Markku1 aLin, Xu1 aLind, Lars1 aLiu, Yongmei1 aLoos, Ruth, J F1 aMarchini, Jonathan1 aMetspalu, Andres1 aMook-Kanamori, Dennis1 aNordestgaard, Børge, G1 aPalmer, Colin, N A1 aPankow, James, S1 aPedersen, Oluf1 aPsaty, Bruce, M1 aRauramaa, Rainer1 aSattar, Naveed1 aSchulze, Matthias, B1 aSoranzo, Nicole1 aSpector, Timothy, D1 aStefansson, Kari1 aStumvoll, Michael1 aThorsteinsdottir, Unnur1 aTuomi, Tiinamaija1 aTuomilehto, Jaakko1 aWareham, Nicholas, J1 aWilson, James, G1 aZeggini, Eleftheria1 aScott, Robert, A1 aBarroso, Inês1 aFrayling, Timothy, M1 aGoodarzi, Mark, O1 aMeigs, James, B1 aBoehnke, Michael1 aSaleheen, Danish1 aMorris, Andrew, P1 aRotter, Jerome, I1 aMcCarthy, Mark, I1 aExomeBP Consortium1 aMAGIC Consortium1 aGIANT Consortium uhttps://chs-nhlbi.org/node/766803682nas a2200577 4500008004100000022001400041245010400055210006900159260001600228520196600244100002302210700002202233700002202255700001902277700002302296700002502319700002202344700002102366700002302387700001802410700002502428700001902453700002002472700002102492700002102513700002402534700002102558700001902579700001902598700001802617700002102635700002202656700002002678700002202698700002202720700002002742700001802762700002502780700002702805700002002832700001502852700002602867700001902893700002602912700002102938700002502959700002402984700002603008710003403034856003603068 2018 eng d a1945-719700aThe relation between thyroid function and anemia: a pooled analysis of individual participant data.0 arelation between thyroid function and anemia a pooled analysis o c2018 Aug 023 aContext: Anemia and thyroid dysfunction often co-occur and both increase with age. Human data on the relationship between thyroid disease and anemia are scarce.
Objective: To investigate the cross-sectional and longitudinal associations between clinical thyroid status and anemia.
Design: Individual participant data meta-analysis.
Setting: Sixteen cohorts participating in the Thyroid Studies Collaboration (n=42 162).
Main outcome measures: Primary outcome measure was anemia (hemoglobin <130 g/L in men and <120 g/L in women).
Results: Cross-sectionally, participants with abnormal thyroid status had an increased risk of having anemia compared with euthyroid participants (overt hypothyroidism, pooled odds ratio 1.84 [95% CI: 1.35-2.50], subclinical hypothyroidism 1.21 [1.02-1.43], subclinical hyperthyroidism 1.27 [1.03-1.57], overt hyperthyroidism 1.69 [1.00-2.87]). Hemoglobin levels were lower in all groups compared to participants with euthyroidism. In the longitudinal analyses (n=25,466 from 14 cohorts), the pooled hazard ratio for the risk of development of anemia was 1.38 [95% CI: 0.86-2.20] for overt hypothyroidism, 1.18 [1.00-1.38] for subclinical hypothyroidism, 1.15 [0.94-1.42] for subclinical hyperthyroidism and 1.47 [0.91-2.38] for overt hyperthyroidism. Sensitivity analyses excluding thyroid medication or high levels of C-reactive protein yielded similar results. No differences in mean annual change in hemoglobin levels were observed between the thyroid hormone status groups.
Conclusion: Higher odds of having anemia were observed in both participants with hypothyroid function and hyperthyroid function. In addition, reduced thyroid function at baseline showed a trend of increased risk of developing anemia during follow-up. It remains to be assessed in a randomized controlled trial whether treatment is effective in reducing anemia.
1 aWopereis, Daisy, M1 aPuy, Robert, S Du1 avan Heemst, Diana1 aWalsh, John, P1 aBremner, Alexandra1 aBakker, Stephan, J L1 aBauer, Douglas, C1 aCappola, Anne, R1 aCeresini, Graziano1 aDegryse, Jean1 aDullaart, Robin, P F1 aFeller, Martin1 aFerrucci, Luigi1 aFloriani, Carmen1 aFranco, Oscar, H1 aIacoviello, Massimo1 aIervasi, Georgio1 aImaizumi, Misa1 aJukema, Wouter1 aKhaw, Kay-Tee1 aLuben, Robert, N1 aMolinaro, Sabrina1 aNauck, Matthias1 aPatel, Kushang, V1 aPeeters, Robin, P1 aPsaty, Bruce, M1 aRazvi, Salman1 aSchindhelm, Roger, K1 avan Schoor, Natasja, M1 aStott, David, J1 aVaes, Bert1 aVanderpump, Mark, P J1 aVölzke, Henry1 aWestendorp, Rudi, G J1 aRodondi, Nicolas1 aCobbaert, Christa, M1 aGussekloo, Jacobijn1 aElzen, Wendy, P J den1 aThyroid Studies Collaboration uhttps://chs-nhlbi.org/node/781703720nas a2200445 4500008004100000022001400041245015900055210006900214260001600283520232600299100002102625700002102646700002102667700001802688700002102706700002102727700002302748700002602771700002102797700002102818700002402839700001702863700002402880700002302904700002102927700002402948700002302972700002702995700002103022700002003043700002403063700001703087700002503104700002103129700002203150700001903172700001803191710002903209856003603238 2018 eng d a1523-683800aRelationship of Estimated GFR and Albuminuria to Concurrent Laboratory Abnormalities: An Individual Participant Data Meta-analysis in a Global Consortium.0 aRelationship of Estimated GFR and Albuminuria to Concurrent Labo c2018 Oct 193 aRATIONALE & OBJECTIVE: Chronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework.
STUDY DESIGN: Cross-sectional individual participant-level analyses in a global consortium.
SETTING & STUDY POPULATIONS: 17 CKD and 38 general population and high-risk cohorts.
SELECTION CRITERIA FOR STUDIES: Cohorts in the CKD Prognosis Consortium with data for eGFR and albuminuria, as well as a measurement of hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, or calcium, or hypertension.
DATA EXTRACTION: Data were obtained and analyzed between July 2015 and January 2018.
ANALYTICAL APPROACH: We modeled the association of eGFR and albuminuria with hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, and calcium values using linear regression and with hypertension and categorical definitions of each abnormality using logistic regression. Results were pooled using random-effects meta-analyses.
RESULTS: The CKD cohorts (n=254,666 participants) were 27% women and 10% black, with a mean age of 69 (SD, 12) years. The general population/high-risk cohorts (n=1,758,334) were 50% women and 2% black, with a mean age of 50 (16) years. There was a strong graded association between lower eGFR and all laboratory result abnormalities (ORs ranging from 3.27 [95% CI, 2.68-3.97] to 8.91 [95% CI, 7.22-10.99] comparing eGFRs of 15 to 29 with eGFRs of 45 to 59mL/min/1.73m), whereas albuminuria had equivocal or weak associations with abnormalities (ORs ranging from 0.77 [95% CI, 0.60-0.99] to 1.92 [95% CI, 1.65-2.24] comparing urinary albumin-creatinine ratio > 300 vs < 30mg/g).
LIMITATIONS: Variations in study era, health care delivery system, typical diet, and laboratory assays.
CONCLUSIONS: Lower eGFR was strongly associated with higher odds of multiple laboratory result abnormalities. Knowledge of risk associations might help guide management in the heterogeneous group of patients with CKD.
1 aInker, Lesley, A1 aGrams, Morgan, E1 aLevey, Andrew, S1 aCoresh, Josef1 aCirillo, Massimo1 aCollins, John, F1 aGansevoort, Ron, T1 aGutierrez, Orlando, M1 aHamano, Takayuki1 aHeine, Gunnar, H1 aIshikawa, Shizukiyo1 aJee, Sun, Ha1 aKronenberg, Florian1 aLandray, Martin, J1 aMiura, Katsuyuki1 aNadkarni, Girish, N1 aPeralta, Carmen, A1 aRothenbacher, Dietrich1 aSchaeffner, Elke1 aSedaghat, Sanaz1 aShlipak, Michael, G1 aZhang, Luxia1 avan Zuilen, Arjan, D1 aHallan, Stein, I1 aKovesdy, Csaba, P1 aWoodward, Mark1 aLevin, Adeera1 aCKD Prognosis Consortium uhttps://chs-nhlbi.org/node/791502623nas a2200265 4500008004100000022001400041245011400055210006900169260001600238490000600254520180700260100003002067700001902097700002702116700001702143700001302160700002002173700001702193700002602210700001802236700001902254700002402273710002402297856003602321 2018 eng d a2047-998000aReversal of Aging-Induced Increases in Aortic Stiffness by Targeting Cytoskeletal Protein-Protein Interfaces.0 aReversal of AgingInduced Increases in Aortic Stiffness by Target c2018 Jul 180 v73 aBACKGROUND: The proximal aorta normally functions as a critical shock absorber that protects small downstream vessels from damage by pressure and flow pulsatility generated by the heart during systole. This shock absorber function is impaired with age because of aortic stiffening.
METHODS AND RESULTS: We examined the contribution of common genetic variation to aortic stiffness in humans by interrogating results from the AortaGen Consortium genome-wide association study of carotid-femoral pulse wave velocity. Common genetic variation in the N-WASP () locus is associated with carotid-femoral pulse wave velocity (rs600420, =0.0051). Thus, we tested the hypothesis that decoy proteins designed to disrupt the interaction of cytoskeletal proteins such as N-WASP with its binding partners in the vascular smooth muscle cytoskeleton could decrease ex vivo stiffness of aortas from a mouse model of aging. A synthetic decoy peptide construct of N-WASP significantly reduced activated stiffness in ex vivo aortas of aged mice. Two other cytoskeletal constructs targeted to VASP and talin-vinculin interfaces similarly decreased aging-induced ex vivo active stiffness by on-target specific actions. Furthermore, packaging these decoy peptides into microbubbles enables the peptides to be ultrasound-targeted to the wall of the proximal aorta to attenuate ex vivo active stiffness.
CONCLUSIONS: We conclude that decoy peptides targeted to vascular smooth muscle cytoskeletal protein-protein interfaces and microbubble packaged can decrease aortic stiffness ex vivo. Our results provide proof of concept at the ex vivo level that decoy peptides targeted to cytoskeletal protein-protein interfaces may lead to substantive dynamic modulation of aortic stiffness.
1 aNicholson, Christopher, J1 aSingh, Kuldeep1 aSaphirstein, Robert, J1 aGao, Yuan, Z1 aLi, Qian1 aChiu, Joanna, G1 aLeavis, Paul1 aVerwoert, Germaine, C1 aMitchell, G F1 aPorter, Tyrone1 aMorgan, Kathleen, G1 aAortaGen Consortium uhttps://chs-nhlbi.org/node/780708059nas a2201585 4500008004100000022001400041245015200055210006900207260001500276300001400291490000800305520349800313100002003811700002103831700002503852700001903877700002403896700001903920700001703939700001803956700002203974700002103996700001704017700001904034700001904053700002004072700002104092700002904113700001904142700002104161700001904182700002004201700002804221700001604249700002104265700001904286700002104305700002104326700002004347700002104367700002204388700001804410700001804428700002104446700002104467700002004488700003504508700001904543700002304562700002204585700002504607700002204632700002204654700001804676700002004694700001904714700002404733700002304757700002004780700002304800700002604823700002404849700002104873700002404894700002304918700001804941700002004959700001904979700002104998700001905019700002205038700002005060700001605080700002105096700002605117700002105143700002005164700001905184700003105203700001905234700002405253700001705277700002005294700002105314700001805335700002205353700002205375700002005397700002005417700003305437700002205470700002605492700001805518700002605536700003005562700002405592700001905616700001705635700002005652700001805672700002405690700001805714700002005732700002605752700001805778700002205796700002505818700002005843700002205863700002105885700002005906700002305926700002205949700002105971700002005992700002406012700002106036700001806057700002306075700002306098700001406121700001906135700001806154700002306172700002006195700001906215700002406234700001806258700001706276700001706293700003006310700001706340710008006357856003606437 2018 eng d a1474-547X00aRisk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies.0 aRisk thresholds for alcohol consumption combined analysis of ind c2018 04 14 a1513-15230 v3913 aBACKGROUND: Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease.
METHODS: We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose-response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years [5th-95th percentile 1·04-13·5]) from 71 011 participants from 37 studies.
FINDINGS: In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1·14, 95% CI, 1·10-1·17), coronary disease excluding myocardial infarction (1·06, 1·00-1·11), heart failure (1·09, 1·03-1·15), fatal hypertensive disease (1·24, 1·15-1·33); and fatal aortic aneurysm (1·15, 1·03-1·28). By contrast, increased alcohol consumption was log-linearly associated with a lower risk of myocardial infarction (HR 0·94, 0·91-0·97). In comparison to those who reported drinking >0-≤100 g per week, those who reported drinking >100-≤200 g per week, >200-≤350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1-2 years, or 4-5 years, respectively.
INTERPRETATION: In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines.
FUNDING: UK Medical Research Council, British Heart Foundation, National Institute for Health Research, European Union Framework 7, and European Research Council.
1 aWood, Angela, M1 aKaptoge, Stephen1 aButterworth, Adam, S1 aWilleit, Peter1 aWarnakula, Samantha1 aBolton, Thomas1 aPaige, Ellie1 aPaul, Dirk, S1 aSweeting, Michael1 aBurgess, Stephen1 aBell, Steven1 aAstle, William1 aStevens, David1 aKoulman, Albert1 aSelmer, Randi, M1 aVerschuren, W, M Monique1 aSato, Shinichi1 aNjølstad, Inger1 aWoodward, Mark1 aSalomaa, Veikko1 aNordestgaard, Børge, G1 aYeap, Bu, B1 aFletcher, Astrid1 aMelander, Olle1 aKuller, Lewis, H1 aBalkau, Beverley1 aMarmot, Michael1 aKoenig, Wolfgang1 aCasiglia, Edoardo1 aCooper, Cyrus1 aArndt, Volker1 aFranco, Oscar, H1 aWennberg, Patrik1 aGallacher, John1 ade la Cámara, Agustin, Gómez1 aVölzke, Henry1 aDahm, Christina, C1 aDale, Caroline, E1 aBergmann, Manuela, M1 aCrespo, Carlos, J1 aSchouw, Yvonne, T1 aKaaks, Rudolf1 aSimons, Leon, A1 aLagiou, Pagona1 aSchoufour, Josje, D1 aBoer, Jolanda, M A1 aKey, Timothy, J1 aRodriguez, Beatriz1 aMoreno-Iribas, Conchi1 aDavidson, Karina, W1 aTaylor, James, O1 aSacerdote, Carlotta1 aWallace, Robert, B1 aQuiros, Ramon1 aTumino, Rosario1 aBlazer, Dan, G1 aLinneberg, Allan1 aDaimon, Makoto1 aPanico, Salvatore1 aHoward, Barbara1 aSkeie, Guri1 aStrandberg, Timo1 aWeiderpass, Elisabete1 aNietert, Paul, J1 aPsaty, Bruce, M1 aKromhout, Daan1 aSalamanca-Fernandez, Elena1 aKiechl, Stefan1 aKrumholz, Harlan, M1 aGrioni, Sara1 aPalli, Domenico1 aHuerta, José, M1 aPrice, Jackie1 aSundström, Johan1 aArriola, Larraitz1 aArima, Hisatomi1 aTravis, Ruth, C1 aPanagiotakos, Demosthenes, B1 aKarakatsani, Anna1 aTrichopoulou, Antonia1 aKühn, Tilman1 aGrobbee, Diederick, E1 aBarrett-Connor, Elizabeth1 avan Schoor, Natasja1 aBoeing, Heiner1 aOvervad, Kim1 aKauhanen, Jussi1 aWareham, Nick1 aLangenberg, Claudia1 aForouhi, Nita1 aWennberg, Maria1 aDesprés, Jean-Pierre1 aCushman, Mary1 aCooper, Jackie, A1 aRodriguez, Carlos, J1 aSakurai, Masaru1 aShaw, Jonathan, E1 aKnuiman, Matthew1 aVoortman, Trudy1 aMeisinger, Christa1 aTjønneland, Anne1 aBrenner, Hermann1 aPalmieri, Luigi1 aDallongeville, Jean1 aBrunner, Eric, J1 aAssmann, Gerd1 aTrevisan, Maurizio1 aGillum, Richard, F1 aFord, Ian1 aSattar, Naveed1 aLazo, Mariana1 aThompson, Simon, G1 aFerrari, Pietro1 aLeon, David, A1 aSmith, George Davey1 aPeto, Richard1 aJackson, Rod1 aBanks, Emily1 aDi Angelantonio, Emanuele1 aDanesh, John1 aEmerging Risk Factors Collaboration/EPIC-CVD/UK Biobank Alcohol Study Group uhttps://chs-nhlbi.org/node/766402046nas a2200289 4500008004100000022001400041245009700055210006900152260001600221520113600237100002001373700001801393700001801411700002501429700001301454700002001467700002101487700001901508700002001527700002401547700002801571700003101599700002401630700002301654710004301677856003601720 2019 eng d a1552-527900aA rare missense variant of CASP7 is associated with familial late-onset Alzheimer's disease.0 arare missense variant of CASP7 is associated with familial lateo c2019 Jan 033 aINTRODUCTION: The genetic architecture of Alzheimer's disease (AD) is only partially understood.
METHODS: We conducted an association study for AD using whole sequence data from 507 genetically enriched AD cases (i.e., cases having close relatives affected by AD) and 4917 cognitively healthy controls of European ancestry (EA) and 172 enriched cases and 179 controls of Caribbean Hispanic ancestry. Confirmation of top findings from stage 1 was sought in two family-based genome-wide association study data sets and in a whole genome-sequencing data set comprising members from 42 EA and 115 Caribbean Hispanic families.
RESULTS: We identified associations in EAs with variants in 12 novel loci. The most robust finding is a rare CASP7 missense variant (rs116437863; P = 2.44 × 10) which improved when combined with results from stage 2 data sets (P = 1.92 × 10).
DISCUSSION: Our study demonstrated that an enriched case design can strengthen genetic signals, thus allowing detection of associations that would otherwise be missed in a traditional case-control study.
1 aZhang, Xiaoling1 aZhu, Congcong1 aBeecham, Gary1 aVardarajan, Badri, N1 aMa, Yiyi1 aLancour, Daniel1 aFarrell, John, J1 aChung, Jaeyoon1 aMayeux, Richard1 aHaines, Jonathan, L1 aSchellenberg, Gerard, D1 aPericak-Vance, Margaret, A1 aLunetta, Kathryn, L1 aFarrer, Lindsay, A1 aAlzheimer's Disease Sequencing Project uhttps://chs-nhlbi.org/node/793209233nas a2202929 4500008004100000245015900041210006900200260000700269300001400276490000700290520204400297100001802341700001802359700001802377700001502395700001602410700002002426700002302446700002202469700001502491700001802506700001702524700001602541700001902557700002002576700001402596700002102610700002002631700002102651700001902672700001702691700002002708700001402728700002302742700001902765700002002784700001702804700001402821700001402835700001402849700001502863700001302878700001702891700001702908700001402925700001702939700001602956700001802972700001102990700001703001700001503018700001903033700001403052700001303066700002103079700001603100700001503116700001403131700001703145700001403162700001203176700001303188700001303201700001303214700001903227700001403246700001503260700001403275700001703289700001303306700001403319700001503333700001503348700001503363700001403378700002003392700001503412700001403427700001303441700001303454700001303467700001603480700001503496700001303511700001703524700001203541700001803553700001603571700001503587700001703602700001703619700001503636700001703651700001403668700001603682700001703698700001603715700001603731700001603747700001803763700001703781700002103798700001203819700001803831700001603849700001903865700002203884700002003906700001403926700002103940700001803961700001103979700001203990700001704002700001704019700001504036700001604051700001304067700001804080700001704098700001304115700001504128700001704143700001604160700001304176700001204189700001604201700001504217700002304232700002404255700002304279700002204302700001504324700001404339700001604353700001704369700001304386700001504399700001904414700001804433700001304451700001504464700001704479700001704496700001804513700002104531700001804552700001704570700001304587700001604600700001604616700001404632700001504646700001604661700001604677700001404693700001504707700001404722700001604736700001504752700001504767700001604782700001804798700002004816700001804836700001504854700001604869700001504885700001504900700001704915700001904932700002004951700002304971700001904994700001205013700002505025700001805050700001405068700001705082700001605099700001905115700001805134700001505152700002305167700001605190700002305206700001505229700002205244700001605266700001605282700001805298700002505316700001705341700001605358700001705374700001805391700001805409700001605427700002005443700001805463700001905481700002005500700001705520700002005537700001805557700002405575700001405599700001805613700001705631700001405648700001505662700001205677700001605689700001605705700001705721700001705738700001705755700001405772700001705786700001705803700001705820700001605837700001705853700002005870700002305890700002705913700001805940700001805958700002305976700001805999700001506017700002006032700001806052700001906070700001506089700001706104700001906121700001306140700001506153700001806168700001306186700001906199700001306218700001906231700001706250856003606267 2019 eng d00a{Relationship of Estimated GFR and Albuminuria to Concurrent Laboratory Abnormalities: An Individual Participant Data Meta-analysis in a Global Consortium0 aRelationship of Estimated GFR and Albuminuria to Concurrent Labo c02 a206–2170 v733 aChronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework.\ Cross-sectional individual participant-level analyses in a global consortium.\ 17 CKD and 38 general population and high-risk cohorts.\ Cohorts in the CKD Prognosis Consortium with data for eGFR and albuminuria, as well as a measurement of hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, or calcium, or hypertension.\ Data were obtained and analyzed between July 2015 and January 2018.\ We modeled the association of eGFR and albuminuria with hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, and calcium values using linear regression and with hypertension and categorical definitions of each abnormality using logistic regression. Results were pooled using random-effects meta-analyses.\ The CKD cohorts (n=254,666 participants) were 27% women and 10% black, with a mean age of 69 (SD, 12) years. The general population/high-risk cohorts (n=1,758,334) were 50% women and 2% black, with a mean age of 50 (16) years. There was a strong graded association between lower eGFR and all laboratory result abnormalities (ORs ranging from 3.27 [95% CI, 2.68-3.97] to 8.91 [95% CI, 7.22-10.99] comparing eGFRs of 15 to 29 with eGFRs of 45 to 59mL/min/1.73m2), whereas albuminuria had equivocal or weak associations with abnormalities (ORs ranging from 0.77 [95% CI, 0.60-0.99] to 1.92 [95% CI, 1.65-2.24] comparing urinary albumin-creatinine ratio > 300 vs < 30mg/g).\ Variations in study era, health care delivery system, typical diet, and laboratory assays.\ Lower eGFR was strongly associated with higher odds of multiple laboratory result abnormalities. Knowledge of risk associations might help guide management in the heterogeneous group of patients with CKD.1 aInker, L., A.1 aGrams, M., E.1 aLevey, A., S.1 aCoresh, J.1 aCirillo, M.1 aCollins, J., F.1 aGansevoort, R., T.1 aGutierrez, O., M.1 aHamano, T.1 aHeine, G., H.1 aIshikawa, S.1 aJee, S., H.1 aKronenberg, F.1 aLandray, M., J.1 aMiura, K.1 aNadkarni, G., N.1 aPeralta, C., A.1 aRothenbacher, D.1 aSchaeffner, E.1 aSedaghat, S.1 aShlipak, M., G.1 aZhang, L.1 avan Zuilen, A., D.1 aHallan, S., I.1 aKovesdy, C., P.1 aWoodward, M.1 aLevin, A.1 aAstor, B.1 aAppel, L.1 aGreene, T.1 aChen, T.1 aChalmers, J.1 aWoodward, M.1 aArima, H.1 aPerkovic, V.1 aYatsuya, H.1 aTamakoshi, K.1 aLi, Y.1 aHirakawa, Y.1 aCoresh, J.1 aMatsushita, K.1 aGrams, M.1 aSang, Y.1 aPolkinghorne, K.1 aChadban, S.1 aAtkins, R.1 aLevin, A.1 aDjurdjev, O.1 aZhang, L.1 aLiu, L.1 aZhao, M.1 aWang, F.1 aWang, J.1 aSchaeffner, E.1 aEbert, N.1 aMartus, P.1 aLevin, A.1 aDjurdjev, O.1 aTang, M.1 aHeine, G.1 aEmrich, I.1 aSeiler, S.1 aZawada, A.1 aNally, J.1 aNavaneethan, S.1 aSchold, J.1 aZhang, L.1 aZhao, M.1 aWang, F.1 aWang, J.1 aShlipak, M.1 aSarnak, M.1 aKatz, R.1 aHiramoto, J.1 aIso, H.1 aYamagishi, K.1 aUmesawa, M.1 aMuraki, I.1 aFukagawa, M.1 aMaruyama, S.1 aHamano, T.1 aHasegawa, T.1 aFujii, N.1 aWheeler, D.1 aEmberson, J.1 aTownend, J.1 aLandray, M.1 aBrenner, H.1 aSch?ttker, B.1 aSaum, K., U.1 aRothenbacher, D.1 aFox, C.1 aHwang, S., J.1 aK?ttgen, A.1 aKronenberg, F.1 aSchneider, M., P.1 aEckardt, K., U.1 aGreen, J.1 aKirchner, H., L.1 aChang, A., R.1 aHo, K.1 aIto, S.1 aMiyazaki, M.1 aNakayama, M.1 aYamada, G.1 aCirillo, M.1 aIrie, F.1 aSairenchi, T.1 aIshikawa, S.1 aYano, Y.1 aKotani, K.1 aNakamura, T.1 aJee, S., H.1 aKimm, H.1 aMok, Y.1 aChodick, G.1 aShalev, V.1 aWetzels, J., F. M.1 aBlankestijn, P., J.1 avan Zuilen, A., D.1 avan den Brand, J.1 aSarnak, M.1 aInker, L.1 aPeralta, C.1 aHiramoto, J.1 aKatz, R.1 aSarnak, M.1 aKronenberg, F.1 aKollerits, B.1 aRitz, E.1 aNitsch, D.1 aRoderick, P.1 aFletcher, A.1 aBottinger, E.1 aNadkarni, G., N.1 aEllis, S., B.1 aNadukuru, R.1 aSang, Y.1 aUeshima, H.1 aOkayama, A.1 aMiura, K.1 aTanaka, S.1 aUeshima, H.1 aOkamura, T.1 aMiura, K.1 aTanaka, S.1 aMiura, K.1 aOkayama, A.1 aKadota, A.1 aTanaka, S.1 aKenealy, T.1 aElley, C., R.1 aCollins, J., F.1 aDrury, P., L.1 aOhkubo, T.1 aAsayama, K.1 aMetoki, H.1 aKikuya, M.1 aNakayama, M.1 aNelson, R., G.1 aKnowler, W., C.1 aGansevoort, R., T.1 aBakker, S., J.1 aHak, E.1 aHeerspink, H., J. L.1 aBrunskill, N.1 aMajor, R.1 aShepherd, D.1 aMedcalf, J.1 aJassal, S., K.1 aBergstrom, J.1 aIx, J., H.1 aBarrett-Connor, E.1 aKovesdy, C.1 aKalantar-Zadeh, K.1 aSumida, K.1 aGutierrez, O., M.1 aMuntner, P.1 aWarnock, D.1 aMcClellan, W.1 aHeerspink, H., J. L.1 ade Zeeuw, D.1 aBrenner, B.1 aSedaghat, S.1 aIkram, M., A.1 aHoorn, E., J.1 aDehghan, A.1 aCarrero, J., J.1 aGasparini, A.1 aWettermark, B.1 aElinder, C., G.1 aWong, T., Y.1 aSabanayagam, C.1 aCheng, C., Y.1 aVisseren, F., L. J.1 aEvans, M.1 aSegelmark, M.1 aStendahl, M.1 aSch?n, S.1 aTangri, N.1 aSud, M.1 aNaimark, D.1 aWen, C., P.1 aTsao, C., K.1 aTsai, M., K.1 aChen, C., H.1 aKonta, T.1 aHirayama, A.1 aIchikawa, K.1 aLannfelt, L.1 aLarsson, A.1 arnl?v, J., ?1 aBilo, H., J. G.1 aLandman, G., W. D.1 avan Hateren, K., J. J.1 aKleefstra, N.1 aChair, Coresh1 aGansevoort, R., T.1 aGrams, M., E.1 aHallan, S.1 aKovesdy, C., P.1 aLevey, A., S.1 aMatsushita, K.1 aShalev, V.1 aWoodward, M.1 aBallew, S., H.1 aChen, J.1 aCoresh, J.1 aGrams, M., E.1 aKwak, L.1 aMatsushita, K.1 aSang, Y.1 aSurapaneni, A.1 aWoodward, M. uhttps://chs-nhlbi.org/node/851902440nas a2200193 4500008004100000022001400041245013300055210006900188260001600257520178400273100002302057700002302080700002802103700001602131700002002147700002002167700002302187856003602210 2019 eng d a1473-559800aThe role of functional status on the relationship between blood pressure and cognitive decline: the Cardiovascular Health Study.0 arole of functional status on the relationship between blood pres c2019 May 013 aOBJECTIVE: To examine whether self-reported functional status modified the association between blood pressure (BP) and cognitive decline among older adults.
METHODS: The study included 2097 US adults aged 75 years and older from the Cardiovascular Health Study, followed for up to 6 years. Functional status was ascertained by self-reported limitation in activities of daily living (ADL; none vs. any). Cognitive function was assessed by the Modified Mini Mental State Exam (3MSE). We used linear mixed models to examine whether the presence of at least one ADL limitation modified the association between BP and cognitive decline. Potential confounders included demographics, physiologic measures, antihypertensive medication use and apolipoprotein E ε4 allele. We conducted stratified analyses for significant interactions between BP and ADL.
RESULTS: The association between BP and change in 3MSE differed by baseline ADL limitation. Among participants without ADL limitation, elevated systolic BP (≥140 mmHg) was associated with a 0.15 decrease (95% CI -0.24 to -0.07); P value for interaction less than 0.001, whereas in those with an ADL limitation, elevated systolic BP was independently associated with a 0.30 increase in 3MSE scores per year (95% CI 0.06-0.55). Elevated diastolic BP (≥80 mmHg) was associated with an increase in cognitive function in both groups, although the increase was greater in those with ADL limitation (0.47 points per year vs. 0.18 points per year, P value for interaction = 0.01).
CONCLUSION: Elevated BP appears to be associated with a decrease in cognitive scores among functioning older adults, and modest improvements in cognitive function among poorly functioning elders.
1 aMiller, Lindsay, M1 aPeralta, Carmen, A1 aFitzpatrick, Annette, L1 aWu, Chenkai1 aPsaty, Bruce, M1 aNewman, Anne, B1 aOdden, Michelle, C uhttps://chs-nhlbi.org/node/804800515nas a2200145 4500008004100000022001400041245013300055210006900188260001300257300001400270490000700284100002500291700001700316856003600333 2019 eng d a1473-559800aThe role of functional status on the relationship between blood pressure and cognitive decline: the Cardiovascular Health Study.0 arole of functional status on the relationship between blood pres c2019 Dec a2500-25010 v371 aO'Rourke, Michael, F1 aAdji, Audrey uhttps://chs-nhlbi.org/node/820302591nas a2200205 4500008004100000022001400041245012300055210006900178260001600247520190400263100002402167700002102191700002702212700002402239700002602263700002002289700002002309700002002329856003602349 2020 eng d a1879-191300aRelation of Biomarkers of Cardiac Injury, Stress, and Fibrosis With Cardiac Mechanics in Patients ≥ 65 Years of Age.0 aRelation of Biomarkers of Cardiac Injury Stress and Fibrosis Wit c2020 Sep 163 aHigh sensitivity cardiac troponin T (hscTnT), soluble ST2 (sST2), N-terminal B-type natriuretic peptide (NT-proBNP), and galectin-3 are biomarkers of cardiac injury, stress, myocardial stretch, and fibrosis. Elevated levels are associated with poor outcomes. However, their association with cardiac mechanics in older persons is unknown. Associations between these biomarkers and cardiac mechanics derived from speckle tracking echocardiography, including left ventricular longitudinal strain (LVLS), early diastolic strain, and left atrial reservoir strain (LARS) were evaluated using standardized beta coefficients () in a cross sectional analysis with cardiac biomarkers in older patients without cardiovascular disease, low ejection fraction, or wall motion abnormalities. Biomarker associations with strain were attenuated by demographics and risk factors. In adjusted models, LVLS was associated with continuous measures of hscTnT (β-0.06, p = 0.020), sST2 (β -0.05, p = 0.024) and NT-proBNP (β -0.06, p = 0.007). "High" levels (i.e., greater than prognostic cutpoint) of hscTnT (>13 ng/ml), sST2 (>35 ng/ml), and NT-proBNP (>190 pg/ml) were also associated with worse LVLS. In risk factor adjusted models, LARS was associated with hscTnT (β -0.08, p = 0.003) and NT-proBNP (β-0.18, p <0.0001). High hscTnT (>13 ng/ml) and high NT-proBNP (>190 pg/ml) were also both associated with worse LARS. Gal-3 was not associated with any strain measure. In conclusion, in persons ≥ 65 years of age, without cardiovascular disease, low ejection fraction, or wall motion abnormalities, hscTnT, sST2, and NT-proBNP are associated with worse LVLS. HscTnT and NT-proBNP are associated with worse LARS. In conclusion, these subclinical increases in blood biomarkers, and their associations with subtle diastolic and systolic dysfunction, may represent pre-clinical heart failure.
1 aGottdiener, John, S1 aSeliger, Stephen1 aDeFilippi, Christopher1 aChristenson, Robert1 aBaldridge, Abigail, S1 aKizer, Jorge, R1 aPsaty, Bruce, M1 aShah, Sanjiv, J uhttps://chs-nhlbi.org/node/848203741nas a2200625 4500008004100000022001400041245009700055210006900152260001300221300001200234490000700246520194400253100001402197700001402211700002002225700002402245700002302269700002102292700002302313700001702336700001502353700002102368700002402389700001702413700001602430700002502446700002202471700002202493700001502515700002402530700002002554700002002574700002102594700002502615700002002640700002402660700002302684700002602707700001302733700001402746700002002760700002402780700002402804700001802828700002902846700002502875700002002900700001902920700002002939700002202959700002102981700002403002710005303026856003603079 2020 eng d a2574-830000aRole of Rare and Low-Frequency Variants in Gene-Alcohol Interactions on Plasma Lipid Levels.0 aRole of Rare and LowFrequency Variants in GeneAlcohol Interactio c2020 Aug ae0027720 v133 aBACKGROUND: Alcohol intake influences plasma lipid levels, and such effects may be moderated by genetic variants. We aimed to characterize the role of aggregated rare and low-frequency protein-coding variants in gene by alcohol consumption interactions associated with fasting plasma lipid levels.
METHODS: In the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, fasting plasma triglycerides and high- and low-density lipoprotein cholesterol were measured in 34 153 individuals with European ancestry from 5 discovery studies and 32 277 individuals from 6 replication studies. Rare and low-frequency functional protein-coding variants (minor allele frequency, ≤5%) measured by an exome array were aggregated by genes and evaluated by a gene-environment interaction test and a joint test of genetic main and gene-environment interaction effects. Two dichotomous self-reported alcohol consumption variables, current drinker, defined as any recurrent drinking behavior, and regular drinker, defined as the subset of current drinkers who consume at least 2 drinks per week, were considered.
RESULTS: We discovered and replicated 21 gene-lipid associations at 13 known lipid loci through the joint test. Eight loci (, , , , , , , and ) remained significant after conditioning on the common index single-nucleotide polymorphism identified by previous genome-wide association studies, suggesting an independent role for rare and low-frequency variants at these loci. One significant gene-alcohol interaction on triglycerides in a novel locus was significantly discovered (=6.65×10 for the interaction test) and replicated at nominal significance level (=0.013) in .
CONCLUSIONS: In conclusion, this study applied new gene-based statistical approaches and suggested that rare and low-frequency genetic variants interacted with alcohol consumption on lipid levels.
1 aWang, Zhe1 aChen, Han1 aBartz, Traci, M1 aBielak, Lawrence, F1 aChasman, Daniel, I1 aFeitosa, Mary, F1 aFranceschini, Nora1 aGuo, Xiuqing1 aLim, Elise1 aNoordam, Raymond1 aRichard, Melissa, A1 aWang, Heming1 aCade, Brian1 aCupples, Adrienne, L1 ade Vries, Paul, S1 aGiulanini, Franco1 aLee, Jiwon1 aLemaitre, Rozenn, N1 aMartin, Lisa, W1 aReiner, Alex, P1 aRich, Stephen, S1 aSchreiner, Pamela, J1 aSidney, Stephen1 aSitlani, Colleen, M1 aSmith, Jennifer, A1 avan Dijk, Ko, Willems1 aYao, Jie1 aZhao, Wei1 aFornage, Myriam1 aKardia, Sharon, L R1 aKooperberg, Charles1 aLiu, Ching-Ti1 aMook-Kanamori, Dennis, O1 aProvince, Michael, A1 aPsaty, Bruce, M1 aRedline, Susan1 aRidker, Paul, M1 aRotter, Jerome, I1 aBoerwinkle, Eric1 aMorrison, Alanna, C1 aCHARGE Gene-Lifestyle Interactions Working Group uhttps://chs-nhlbi.org/node/840701911nas a2200685 4500008004100000245009900041210006900140260000700209300001000216490000700226520014700233100001300380700002000393700001800413700001300431700001800444700002000462700001800482700001900500700002100519700001500540700001100555700001500566700001200581700002400593700002000617700001700637700001500654700001700669700001500686700001500701700001900716700001800735700001800753700002000771700002000791700001700811700001900828700001700847700001900864700002600883700001600909700001500925700002100940700001800961700001800979700001700997700001801014700001401032700001401046700001601060700001501076700001501091700001701106700001401123700001901137700001201156700002101168856003601189 2021 eng d00a{Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function0 aRare and lowfrequency exonic variants and genebysmoking interact c09 a193650 v113 a. This study investigates the utility of assessing gene-by-smoking interactions and underscores their effects on potential pulmonary function.1 aYang, T.1 aJackson, V., E.1 aSmith, A., V.1 aChen, H.1 aBartz, T., M.1 aSitlani, C., M.1 aPsaty, B., M.1 aGharib, S., A.1 aO'Connor, G., T.1 aDupuis, J.1 aXu, J.1 aLohman, K.1 aLiu, Y.1 aKritchevsky, S., B.1 aCassano, P., A.1 aFlexeder, C.1 aGieger, C.1 aKarrasch, S.1 aPeters, A.1 aSchulz, H.1 aHarris, S., E.1 aStarr, J., M.1 aDeary, I., J.1 aManichaikul, A.1 aOelsner, E., C.1 aBarr, R., G.1 aTaylor, K., D.1 aRich, S., S.1 aBonten, T., N.1 aMook-Kanamori, D., O.1 aNoordam, R.1 aLi-Gao, R.1 aJarvelin, M., R.1 aWielscher, M.1 aTerzikhan, N.1 aLahousse, L.1 aBrusselle, G.1 aWeiss, S.1 aEwert, R.1 aGläser, S.1 aHomuth, G.1 aShrine, N.1 aHall, I., P.1 aTobin, M.1 aLondon, S., J.1 aWei, P.1 aMorrison, A., C. uhttps://chs-nhlbi.org/node/891703136nas a2200697 4500008004100000245015100041210006900192260000800261300001200269490000700281520125300288100001701541700002001558700002101578700001701599700002001616700002001636700001701656700001701673700001701690700001801707700001201725700001601737700001501753700002001768700001501788700001201803700001601815700002101831700001801852700002001870700001701890700001201907700001901919700001801938700002001956700001601976700001701992700001602009700001602025700002102041700002002062700001802082700002102100700002002121700001802141700002102159700001502180700001902195700001902214700001902233700001702252700002002269700001402289700001902303700002102322700002002343700002002363700001902383856003602402 2021 eng d00a{Rare Coding Variants Associated With Electrocardiographic Intervals Identify Monogenic Arrhythmia Susceptibility Genes: A Multi-Ancestry Analysis0 aRare Coding Variants Associated With Electrocardiographic Interv cAug ae0033000 v143 aAlterations in electrocardiographic (ECG) intervals are well-known markers for arrhythmia and sudden cardiac death (SCD) risk. While the genetics of arrhythmia syndromes have been studied, relations between electrocardiographic intervals and rare genetic variation at a population level are poorly understood.\ Using a discovery sample of 29 000 individuals with whole-genome sequencing from Trans-Omics in Precision Medicine and replication in nearly 100 000 with whole-exome sequencing from the UK Biobank and MyCode, we examined associations between low-frequency and rare coding variants with 5 routinely measured electrocardiographic traits (RR, P-wave, PR, and QRS intervals and corrected QT interval).\ ), a marker of SCD risk. Incomplete penetrance of such deleterious variation was common as over 70% of carriers had normal electrocardiographic intervals.\ Our findings indicate that large-scale high-depth sequence data and electrocardiographic analysis identifies monogenic arrhythmia susceptibility genes and rare variants with large effects. Known pathogenic variation in conventional arrhythmia and SCD genes exhibited incomplete penetrance and accounted for only a small fraction of marked electrocardiographic interval prolongation.1 aChoi, S., H.1 aJurgens, S., J.1 aHaggerty, C., M.1 aHall, A., W.1 aHalford, J., L.1 aMorrill, V., N.1 aWeng, L., C.1 aLagerman, B.1 aMirshahi, T.1 aPettinger, M.1 aGuo, X.1 aLin, H., J.1 aAlonso, A.1 aSoliman, E., Z.1 aKornej, J.1 aLin, H.1 aMoscati, A.1 aNadkarni, G., N.1 aBrody, J., A.1 aWiggins, K., L.1 aCade, B., E.1 aLee, J.1 aAustin-Tse, C.1 aBlackwell, T.1 aChaffin, M., D.1 aLee, C., J.1 aRehm, H., L.1 aRoselli, C.1 aRedline, S.1 aMitchell, B., D.1 aSotoodehnia, N.1 aPsaty, B., M.1 aHeckbert, S., R.1 aLoos, R., J. F.1 aVasan, R., S.1 aBenjamin, E., J.1 aCorrea, A.1 aBoerwinkle, E.1 aArking, D., E.1 aRotter, J., I.1 aRich, S., S.1 aWhitsel, E., A.1 aPerez, M.1 aKooperberg, C.1 aFornwalt, B., K.1 aLunetta, K., L.1 aEllinor, P., T.1 aLubitz, S., A. uhttps://chs-nhlbi.org/node/882902976nas a2200265 4500008004100000022001400041245013700055210006900192260001200261300001300273490000700286520215200293653002202445653001602467653003402483653001102517653001402528653003602542653002802578100001702606700001502623700001702638700001902655856003602674 2021 eng d a1553-740400aRare variants in the endocytic pathway are associated with Alzheimer's disease, its related phenotypes, and functional consequences.0 aRare variants in the endocytic pathway are associated with Alzhe c2021 09 ae10097720 v173 aLate-onset Alzheimer's disease (LOAD) is the most common type of dementia causing irreversible brain damage to the elderly and presents a major public health challenge. Clinical research and genome-wide association studies have suggested a potential contribution of the endocytic pathway to AD, with an emphasis on common loci. However, the contribution of rare variants in this pathway to AD has not been thoroughly investigated. In this study, we focused on the effect of rare variants on AD by first applying a rare-variant gene-set burden analysis using genes in the endocytic pathway on over 3,000 individuals with European ancestry from three large whole-genome sequencing (WGS) studies. We identified significant associations of rare-variant burden within the endocytic pathway with AD, which were successfully replicated in independent datasets. We further demonstrated that this endocytic rare-variant enrichment is associated with neurofibrillary tangles (NFTs) and age-related phenotypes, increasing the risk of obtaining severer brain damage, earlier age-at-onset, and earlier age-of-death. Next, by aggregating rare variants within each gene, we sought to identify single endocytic genes associated with AD and NFTs. Careful examination using NFTs revealed one significantly associated gene, ANKRD13D. To identify functional associations, we integrated bulk RNA-Seq data from over 600 brain tissues and found two endocytic expression genes (eGenes), HLA-A and SLC26A7, that displayed significant influences on their gene expressions. Differential expressions between AD patients and controls of these three identified genes were further examined by incorporating scRNA-Seq data from 48 post-mortem brain samples and demonstrated distinct expression patterns across cell types. Taken together, our results demonstrated strong rare-variant effect in the endocytic pathway on AD risk and progression and functional effect of gene expression alteration in both bulk and single-cell resolution, which may bring more insight and serve as valuable resources for future AD genetic studies, clinical research, and therapeutic targeting.
10aAlzheimer Disease10aEndocytosis10aGenome-Wide Association Study10aHumans10aPhenotype10aPolymorphism, Single Nucleotide10aWhole Genome Sequencing1 aZhan, Lingyu1 aLi, Jiajin1 aJew, Brandon1 aSul, Jae, Hoon uhttps://chs-nhlbi.org/node/891808881nas a2202605 4500008004100000022001400041245012200055210006900177260001500246300001000261490000800271520141300279653001201692653001801704653002501722653002601747653002301773653003001796653001001826653003801836653002201874653002501896653003401921653001101955653002101966653001101987653001001998653003402008653003102042653002402073653001402097653003602111100001802147700001902165700002102184700002002205700001802225700003202243700001702275700001702292700003102309700003002340700002102370700002102391700002302412700001602435700002802451700002902479700001802508700002102526700002402547700001902571700001902590700002102609700002502630700002102655700002202676700002102698700002302719700001902742700001902761700001902780700002702799700001702826700002002843700002102863700002002884700002002904700001902924700002902943700002402972700001902996700002503015700002203040700001703062700002203079700002303101700002403124700002803148700002203176700002403198700002103222700002003243700002003263700002303283700002103306700003103327700002803358700001803386700002203404700002203426700002103448700002303469700003903492700002203531700002103553700001803574700001903592700001703611700001903628700001503647700002003662700001903682700001403701700002603715700001703741700002103758700002503779700002603804700002003830700002003850700002403870700001803894700002103912700001903933700001703952700001703969700002003986700002504006700002404031700002204055700002004077700001904097700002104116700001504137700001704152700001804169700002104187700002404208700002104232700001704253700002004270700002204290700002304312700002004335700002804355700003604383700002304419700002504442700002004467700002004487700002204507700001904529700002604548700002304574700001504597700002104612700002204633700002004655700002904675700002404704700002004728700002104748700002204769700002604791700002504817700001904842700002304861700002604884700002104910700002104931700001904952700002104971700002404992700001905016700002005035700002005055700001405075700001405089700001905103700002505122700003105147700002105178700001905199700002405218700002305242700001705265700001905282700001705301700001605318700002105334700001805355700002305373700001905396700002205415700002005437700001905457700002005476700002105496700002105517700002205538700002305560700002405583700002105607700002005628700002705648700003005675700001905705700001605724700001805740700002105758700002105779700002105800700001905821700001905840700002205859700002105881700002205902700002105924700002205945700002305967700002305990700002306013700001906036700002006055710006106075710006506136710003806201856003606239 2022 eng d a1537-660500aRare coding variants in 35 genes associate with circulating lipid levels-A multi-ancestry analysis of 170,000 exomes.0 aRare coding variants in 35 genes associate with circulating lipi c2022 01 06 a81-960 v1093 aLarge-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency < 1%) predicted damaging coding variation by using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels; some of these genes have not been previously associated with lipid levels when using rare coding variation from population-based samples. We prioritize 32 genes in array-based genome-wide association study (GWAS) loci based on aggregations of rare coding variants; three (EVI5, SH2B3, and PLIN1) had no prior association of rare coding variants with lipid levels. Most of our associated genes showed evidence of association among multiple ancestries. Finally, we observed an enrichment of gene-based associations for low-density lipoprotein cholesterol drug target genes and for genes closest to GWAS index single-nucleotide polymorphisms (SNPs). Our results demonstrate that gene-based associations can be beneficial for drug target development and provide evidence that the gene closest to the array-based GWAS index SNP is often the functional gene for blood lipid levels.
10aAlleles10aBlood Glucose10aCase-Control Studies10aComputational Biology10aDatabases, Genetic10aDiabetes Mellitus, Type 210aExome10aGenetic Predisposition to Disease10aGenetic Variation10aGenetics, Population10aGenome-Wide Association Study10aHumans10aLipid Metabolism10aLipids10aLiver10aMolecular Sequence Annotation10aMultifactorial Inheritance10aOpen Reading Frames10aPhenotype10aPolymorphism, Single Nucleotide1 aHindy, George1 aDornbos, Peter1 aChaffin, Mark, D1 aLiu, Dajiang, J1 aWang, Minxian1 aSelvaraj, Margaret, Sunitha1 aZhang, David1 aPark, Joseph1 aAguilar-Salinas, Carlos, A1 aAntonacci-Fulton, Lucinda1 aArdissino, Diego1 aArnett, Donna, K1 aAslibekyan, Stella1 aAtzmon, Gil1 aBallantyne, Christie, M1 aBarajas-Olmos, Francisco1 aBarzilai, Nir1 aBecker, Lewis, C1 aBielak, Lawrence, F1 aBis, Joshua, C1 aBlangero, John1 aBoerwinkle, Eric1 aBonnycastle, Lori, L1 aBottinger, Erwin1 aBowden, Donald, W1 aBown, Matthew, J1 aBrody, Jennifer, A1 aBroome, Jai, G1 aBurtt, Noel, P1 aCade, Brian, E1 aCenteno-Cruz, Federico1 aChan, Edmund1 aChang, Yi-Cheng1 aChen, Yii-der, I1 aCheng, Ching-Yu1 aChoi, Won, Jung1 aChowdhury, Raj1 aContreras-Cubas, Cecilia1 aCórdova, Emilio, J1 aCorrea, Adolfo1 aCupples, Adrienne, L1 aCurran, Joanne, E1 aDanesh, John1 ade Vries, Paul, S1 aDeFronzo, Ralph, A1 aDoddapaneni, Harsha1 aDuggirala, Ravindranath1 aDutcher, Susan, K1 aEllinor, Patrick, T1 aEmery, Leslie, S1 aFlorez, Jose, C1 aFornage, Myriam1 aFreedman, Barry, I1 aFuster, Valentin1 aGaray-Sevilla, Ma, Eugenia1 aGarcía-Ortiz, Humberto1 aGermer, Soren1 aGibbs, Richard, A1 aGieger, Christian1 aGlaser, Benjamin1 aGonzalez, Clicerio1 aGonzalez-Villalpando, Maria, Elena1 aGraff, Mariaelisa1 aGraham, Sarah, E1 aGrarup, Niels1 aGroop, Leif, C1 aGuo, Xiuqing1 aGupta, Namrata1 aHan, Sohee1 aHanis, Craig, L1 aHansen, Torben1 aHe, Jiang1 aHeard-Costa, Nancy, L1 aHung, Yi-Jen1 aHwang, Mi, Yeong1 aIrvin, Marguerite, R1 aIslas-Andrade, Sergio1 aJarvik, Gail, P1 aKang, Hyun, Min1 aKardia, Sharon, L R1 aKelly, Tanika1 aKenny, Eimear, E1 aKhan, Alyna, T1 aKim, Bong-Jo1 aKim, Ryan, W1 aKim, Young, Jin1 aKoistinen, Heikki, A1 aKooperberg, Charles1 aKuusisto, Johanna1 aKwak, Soo, Heon1 aLaakso, Markku1 aLange, Leslie, A1 aLee, Jiwon1 aLee, Juyoung1 aLee, Seonwook1 aLehman, Donna, M1 aLemaitre, Rozenn, N1 aLinneberg, Allan1 aLiu, Jianjun1 aLoos, Ruth, J F1 aLubitz, Steven, A1 aLyssenko, Valeriya1 aMa, Ronald, C W1 aMartin, Lisa, Warsinger1 aMartínez-Hernández, Angélica1 aMathias, Rasika, A1 aMcGarvey, Stephen, T1 aMcPherson, Ruth1 aMeigs, James, B1 aMeitinger, Thomas1 aMelander, Olle1 aMendoza-Caamal, Elvia1 aMetcalf, Ginger, A1 aMi, Xuenan1 aMohlke, Karen, L1 aMontasser, May, E1 aMoon, Jee-Young1 aMoreno-Macias, Hortensia1 aMorrison, Alanna, C1 aMuzny, Donna, M1 aNelson, Sarah, C1 aNilsson, Peter, M1 aO'Connell, Jeffrey, R1 aOrho-Melander, Marju1 aOrozco, Lorena1 aPalmer, Colin, N A1 aPalmer, Nicholette, D1 aPark, Cheol, Joo1 aPark, Kyong, Soo1 aPedersen, Oluf1 aPeralta, Juan, M1 aPeyser, Patricia, A1 aPost, Wendy, S1 aPreuss, Michael1 aPsaty, Bruce, M1 aQi, Qibin1 aRao, D, C1 aRedline, Susan1 aReiner, Alexander, P1 aRevilla-Monsalve, Cristina1 aRich, Stephen, S1 aSamani, Nilesh1 aSchunkert, Heribert1 aSchurmann, Claudia1 aSeo, Daekwan1 aSeo, Jeong-Sun1 aSim, Xueling1 aSladek, Rob1 aSmall, Kerrin, S1 aSo, Wing, Yee1 aStilp, Adrienne, M1 aTai, Shyong, E1 aTam, Claudia, H T1 aTaylor, Kent, D1 aTeo, Yik, Ying1 aThameem, Farook1 aTomlinson, Brian1 aTsai, Michael, Y1 aTuomi, Tiinamaija1 aTuomilehto, Jaakko1 aTusié-Luna, Teresa1 aUdler, Miriam, S1 avan Dam, Rob, M1 aVasan, Ramachandran, S1 aMartinez, Karine, A Viaud1 aWang, Fei, Fei1 aWang, Xuzhi1 aWatkins, Hugh1 aWeeks, Daniel, E1 aWilson, James, G1 aWitte, Daniel, R1 aWong, Tien-Yin1 aYanek, Lisa, R1 aKathiresan, Sekar1 aRader, Daniel, J1 aRotter, Jerome, I1 aBoehnke, Michael1 aMcCarthy, Mark, I1 aWiller, Cristen, J1 aNatarajan, Pradeep1 aFlannick, Jason, A1 aKhera, Amit, V1 aPeloso, Gina, M1 aAMP-T2D-GENES, Myocardial Infarction Genetics Consortium1 aNHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium1 aNHLBI TOPMed Lipids Working Group uhttps://chs-nhlbi.org/node/897504507nas a2201189 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2022 eng d a2397-337400aRare genetic variants explain missing heritability in smoking.0 aRare genetic variants explain missing heritability in smoking c2022 Aug 043 aCommon genetic variants explain less variation in complex phenotypes than inferred from family-based studies, and there is a debate on the source of this 'missing heritability'. We investigated the contribution of rare genetic variants to tobacco use with whole-genome sequences from up to 26,257 unrelated individuals of European ancestries and 11,743 individuals of African ancestries. Across four smoking traits, single-nucleotide-polymorphism-based heritability ([Formula: see text]) was estimated from 0.13 to 0.28 (s.e., 0.10-0.13) in European ancestries, with 35-74% of it attributable to rare variants with minor allele frequencies between 0.01% and 1%. These heritability estimates are 1.5-4 times higher than past estimates based on common variants alone and accounted for 60% to 100% of our pedigree-based estimates of narrow-sense heritability ([Formula: see text], 0.18-0.34). In the African ancestry samples, [Formula: see text] was estimated from 0.03 to 0.33 (s.e., 0.09-0.14) across the four smoking traits. These results suggest that rare variants are important contributors to the heritability of smoking.
1 aJang, Seon-Kyeong1 aEvans, Luke1 aFialkowski, Allison1 aArnett, Donna, K1 aAshley-Koch, Allison, E1 aBarnes, Kathleen, C1 aBecker, Diane, M1 aBis, Joshua, C1 aBlangero, John1 aBleecker, Eugene, R1 aBoorgula, Meher, Preethi1 aBowden, Donald, W1 aBrody, Jennifer, A1 aCade, Brian, E1 aJenkins, Brenda, W Campbell1 aCarson, April, P1 aChavan, Sameer1 aCupples, Adrienne, L1 aCuster, Brian1 aDamrauer, Scott, M1 aDavid, Sean, P1 ade Andrade, Mariza1 aDinardo, Carla, L1 aFingerlin, Tasha, E1 aFornage, Myriam1 aFreedman, Barry, I1 aGarrett, Melanie, E1 aGharib, Sina, A1 aGlahn, David, C1 aHaessler, Jeffrey1 aHeckbert, Susan, R1 aHokanson, John, E1 aHou, Lifang1 aHwang, Shih-Jen1 aHyman, Matthew, C1 aJudy, Renae1 aJustice, Anne, E1 aKaplan, Robert, C1 aKardia, Sharon, L R1 aKelly, Shannon1 aKim, Wonji1 aKooperberg, Charles1 aLevy, Daniel1 aLloyd-Jones, Donald, M1 aLoos, Ruth, J F1 aManichaikul, Ani, W1 aGladwin, Mark, T1 aMartin, Lisa, Warsinger1 aNouraie, Mehdi1 aMelander, Olle1 aMeyers, Deborah, A1 aMontgomery, Courtney, G1 aNorth, Kari, E1 aOelsner, Elizabeth, C1 aPalmer, Nicholette, D1 aPayton, Marinelle1 aPeljto, Anna, L1 aPeyser, Patricia, A1 aPreuss, Michael1 aPsaty, Bruce, M1 aQiao, Dandi1 aRader, Daniel, J1 aRafaels, Nicholas1 aRedline, Susan1 aReed, Robert, M1 aReiner, Alexander, P1 aRich, Stephen, S1 aRotter, Jerome, I1 aSchwartz, David, A1 aShadyab, Aladdin, H1 aSilverman, Edwin, K1 aSmith, Nicholas, L1 aSmith, Gustav1 aSmith, Albert, V1 aSmith, Jennifer, A1 aTang, Weihong1 aTaylor, Kent, D1 aTelen, Marilyn, J1 aVasan, Ramachandran, S1 aGordeuk, Victor, R1 aWang, Zhe1 aWiggins, Kerri, L1 aYanek, Lisa, R1 aYang, Ivana, V1 aYoung, Kendra, A1 aYoung, Kristin, L1 aZhang, Yingze1 aLiu, Dajiang, J1 aKeller, Matthew, C1 aVrieze, Scott uhttps://chs-nhlbi.org/node/916802689nas a2200217 4500008004100000022001400041245012200055210007100177260001600248520198600264100002402250700002102274700001902295700002702314700001702341700001802358700002002376700001702396700002202413856003602435 2022 eng d a1879-191300aRelation of Cigarette Smoking and Heart Failure in Adults ≥65 Years of Age (From the Cardiovascular Health Study).0 aRelation of Cigarette Smoking and Heart Failure in Adults ≥65 Ye c2022 Jan 163 aCigarette smoking is associated with adverse cardiac outcomes, including incident heart failure (HF). However, key components of potential pathways from smoking to HF have not been evaluated in older adults. In a community-based study, we studied cross-sectional associations of smoking with blood and imaging biomarkers reflecting mechanisms of cardiac disease. Serial nested, multivariable Cox models were used to determine associations of smoking with HF, and to assess the influence of biochemical and functional (cardiac strain) phenotypes on these associations. Compared with never smokers, smokers had higher levels of inflammation (C-reactive protein and interleukin-6), cardiomyocyte injury (cardiac troponin T [hscTnT]), myocardial "stress"/fibrosis (soluble suppression of tumorigenicity 2 [sST2], galectin 3), and worse left ventricle systolic and diastolic function. In models adjusting for age, gender, and race (DEMO) and for clinical factors potentially in the causal pathway (CLIN), smoking exposures were associated with C-reactive protein and interleukin-6, sST2, hscTnT, and with N-terminal pro-brain natriuretic protein (in Whites). In DEMO adjusted models, the cumulative burden of smoking was associated with worse left ventricle systolic strain. Current smoking and former smoking were associated with HF in DEMO models (hazard ratio 1.41, 95% confidence interval 1.22 to 1.64 and hazard ratio 1.14, 95% confidence interval 1.03 to 1.25, respectively), and with current smoking after CLIN adjustment. Adjustment for time-varying myocardial infarction, inflammation, cardiac strain, hscTnT, sST2, and galectin 3 did not materially alter the associations. Smoking was associated with HF with preserved and decreased ejection fraction. In conclusion, in older adults, smoking is associated with multiple blood and imaging biomarker measures of pathophysiology previously linked to HF, and to incident HF even after adjustment for clinical intermediates.
1 aGottdiener, John, S1 aBůzková, Petra1 aKahn, Peter, A1 aDeFilippi, Christopher1 aShah, Sanjiv1 aBarasch, Eddy1 aKizer, Jorge, R1 aPsaty, Bruce1 aGardin, Julius, M uhttps://chs-nhlbi.org/node/897400553nas a2200205 4500008004100000245005400041210005200095260000800147300001400155490000700169100001600176700001400192700001800206700001300224700001500237700001900252700001700271700002300288856003600311 2022 eng d00a{Replication study of AD-associated rare variants0 aReplication study of ADassociated rare variants cApr a858–8620 v181 aNeupane, A.1 aLenny, B.1 aBudde, J., P.1 aWang, F.1 aNorton, J.1 aMorris, J., C.1 aCruchaga, C.1 aFernández, M., V. uhttps://chs-nhlbi.org/node/904104538nas a2200997 4500008004100000245012600041210006900167260001600236520164000252100001701892700003201909700001401941700001401955700002401969700002101993700001902014700001902033700002102052700002202073700001902095700002202114700002102136700002202157700002202179700002202201700002202223700002402245700002002269700002002289700002302309700002002332700001802352700002202370700001702392700001402409700002302423700002102446700001602467700002502483700001902508700002202527700002302549700002102572700001402593700002402607700001902631700001702650700001702667700001602684700002002700700001902720700002402739700002002763700002302783700002102806700002502827700002202852700002402874700002402898700001702922700002602939700002602965700002302991700002003014700002303034700002003057700001903077700002503096700002103121700003403142700002103176700002303197700001803220700002203238700002103260700003003281700001403311700001903325700001403344700002203358700001603380700002303396700002003419710006503439856003603504 2023 eng d00aRare variants in long non-coding RNAs are associated with blood lipid levels in the TOPMed Whole Genome Sequencing Study.0 aRare variants in long noncoding RNAs are associated with blood l c2023 Jun 293 aLong non-coding RNAs (lncRNAs) are known to perform important regulatory functions. Large-scale whole genome sequencing (WGS) studies and new statistical methods for variant set tests now provide an opportunity to assess the associations between rare variants in lncRNA genes and complex traits across the genome. In this study, we used high-coverage WGS from 66,329 participants of diverse ancestries with blood lipid levels (LDL-C, HDL-C, TC, and TG) in the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) program to investigate the role of lncRNAs in lipid variability. We aggregated rare variants for 165,375 lncRNA genes based on their genomic locations and conducted rare variant aggregate association tests using the STAAR (variant-Set Test for Association using Annotation infoRmation) framework. We performed STAAR conditional analysis adjusting for common variants in known lipid GWAS loci and rare coding variants in nearby protein coding genes. Our analyses revealed 83 rare lncRNA variant sets significantly associated with blood lipid levels, all of which were located in known lipid GWAS loci (in a ±500 kb window of a Global Lipids Genetics Consortium index variant). Notably, 61 out of 83 signals (73%) were conditionally independent of common regulatory variations and rare protein coding variations at the same loci. We replicated 34 out of 61 (56%) conditionally independent associations using the independent UK Biobank WGS data. Our results expand the genetic architecture of blood lipids to rare variants in lncRNA, implicating new therapeutic opportunities.
1 aWang, Yuxuan1 aSelvaraj, Margaret, Sunitha1 aLi, Xihao1 aLi, Zilin1 aHoldcraft, Jacob, A1 aArnett, Donna, K1 aBis, Joshua, C1 aBlangero, John1 aBoerwinkle, Eric1 aBowden, Donald, W1 aCade, Brian, E1 aCarlson, Jenna, C1 aCarson, April, P1 aChen, Yii-Der Ida1 aCurran, Joanne, E1 ade Vries, Paul, S1 aDutcher, Susan, K1 aEllinor, Patrick, T1 aFloyd, James, S1 aFornage, Myriam1 aFreedman, Barry, I1 aGabriel, Stacey1 aGermer, Soren1 aGibbs, Richard, A1 aGuo, Xiuqing1 aHe, Jiang1 aHeard-Costa, Nancy1 aHildalgo, Bertha1 aHou, Lifang1 aIrvin, Marguerite, R1 aJoehanes, Roby1 aKaplan, Robert, C1 aKardia, Sharon, Lr1 aKelly, Tanika, N1 aKim, Ryan1 aKooperberg, Charles1 aKral, Brian, G1 aLevy, Daniel1 aLi, Changwei1 aLiu, Chunyu1 aLloyd-Jone, Don1 aLoos, Ruth, Jf1 aMahaney, Michael, C1 aMartin, Lisa, W1 aMathias, Rasika, A1 aMinster, Ryan, L1 aMitchell, Braxton, D1 aMontasser, May, E1 aMorrison, Alanna, C1 aMurabito, Joanne, M1 aNaseri, Take1 aO'Connell, Jeffrey, R1 aPalmer, Nicholette, D1 aPreuss, Michael, H1 aPsaty, Bruce, M1 aRaffield, Laura, M1 aRao, Dabeeru, C1 aRedline, Susan1 aReiner, Alexander, P1 aRich, Stephen, S1 aRuepena, Muagututi'a, Sefuiva1 aSheu, Wayne, H-H1 aSmith, Jennifer, A1 aSmith, Albert1 aTiwari, Hemant, K1 aTsai, Michael, Y1 aViaud-Martinez, Karine, A1 aWang, Zhe1 aYanek, Lisa, R1 aZhao, Wei1 aRotter, Jerome, I1 aLin, Xihong1 aNatarajan, Pradeep1 aPeloso, Gina, M1 aNHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium uhttps://chs-nhlbi.org/node/941804184nas a2200829 4500008004100000022001400041245017700055210006900232260001600301300001200317490000800329520172300337653001202060653001502072653002802087653002602115653002502141653001702166100002202183700002102205700002002226700001602246700001902262700002002281700002202301700001802323700001902341700002302360700002102383700002002404700002002424700002202444700002002466700002002486700001902506700002302525700002402548700002102572700002502593700001802618700002402636700002002660700002102680700002602701700002202727700001902749700001902768700001702787700002702804700002502831700001602856700002102872700002402893700001802917700002402935700002402959700001902983700002003002700002203022700002503044700002103069700002003090700002503110700001803135700002003153700002303173700002103196700002503217700001903242710005703261856003603318 2024 eng d a1524-453900aRole of Polyunsaturated Fat in Modifying Cardiovascular Risk Associated With Family History of Cardiovascular Disease: Pooled De Novo Results From 15 Observational Studies.0 aRole of Polyunsaturated Fat in Modifying Cardiovascular Risk Ass c2024 Jan 23 a305-3160 v1493 aBACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium.
METHODS: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were estimated using Cox regression and meta-analyzed. Interactions were assessed by analyzing product terms and calculating relative excess risk due to interaction.
RESULTS: After multivariable adjustments, a significant interaction between low EPA/DHA and family history was observed (product term pooled RR, 1.09 [95% CI, 1.02-1.16]; =0.01). The pooled relative risk of CVD associated with the combined exposure to low EPA/DHA, and family history was 1.41 (95% CI, 1.30-1.54), whereas it was 1.25 (95% CI, 1.16-1.33) for family history alone and 1.06 (95% CI, 0.98-1.14) for EPA/DHA alone, compared with those with neither exposure. The relative excess risk due to interaction results indicated no interactions.
CONCLUSIONS: A significant interaction between biomarkers of low EPA/DHA intake, but not the other PUFA, and a family history was observed. This novel finding might suggest a need to emphasize the benefit of consuming oily fish for individuals with a family history of CVD.
10aAnimals10aBiomarkers10aCardiovascular Diseases10aDocosahexaenoic Acids10aFatty Acids, Omega-310aRisk Factors1 aLaguzzi, Federica1 aÅkesson, Agneta1 aMarklund, Matti1 aQian, Frank1 aGigante, Bruna1 aBartz, Traci, M1 aBassett, Julie, K1 aBirukov, Anna1 aCampos, Hannia1 aHirakawa, Yoichiro1 aImamura, Fumiaki1 aJäger, Susanne1 aLankinen, Maria1 aMurphy, Rachel, A1 aSenn, Mackenzie1 aTanaka, Toshiko1 aTintle, Nathan1 aVirtanen, Jyrki, K1 aYamagishi, Kazumasa1 aAllison, Matthew1 aBrouwer, Ingeborg, A1 ade Faire, Ulf1 aEiriksdottir, Gudny1 aFerrucci, Luigi1 aForouhi, Nita, G1 aGeleijnse, Johanna, M1 aHodge, Allison, M1 aKimura, Hitomi1 aLaakso, Markku1 aRiserus, Ulf1 avan Westing, Anniek, C1 aBandinelli, Stefania1 aBaylin, Ana1 aGiles, Graham, G1 aGudnason, Vilmundur1 aIso, Hiroyasu1 aLemaitre, Rozenn, N1 aNinomiya, Toshiharu1 aPost, Wendy, S1 aPsaty, Bruce, M1 aSalonen, Jukka, T1 aSchulze, Matthias, B1 aTsai, Michael, Y1 aUusitupa, Matti1 aWareham, Nicholas, J1 aOh, Seung-Won1 aWood, Alexis, C1 aHarris, William, S1 aSiscovick, David1 aMozaffarian, Dariush1 aLeander, Karin1 aFatty Acids and Outcomes Research Consortium (FORCE) uhttps://chs-nhlbi.org/node/9587