02981nas a2200433 4500008004100000022001400041245007100055210006900126260001300195300001200208490000700220520183300227653000902060653002202069653002102091653001602112653002102128653001602149653002102165653002102186653001902207653002102226653002802247653001702275653001102292653001102303653001202314653002202326653002302348653002302371653000902394653001602403653002602419100001902445700001802464700001402482700001502496856003602511 1994 eng d a0022-142200aHigh density lipoprotein cholesterol subfractions in older people.0 aHigh density lipoprotein cholesterol subfractions in older peopl c1994 May aM116-220 v493 a
BACKGROUND: High density lipoprotein (HDL) may be an important risk factor for cardiovascular disease in older people. HDL is heterogeneous with several subfractions. This article describes the distribution and correlates of HDL2 cholesterol (C) and HDL3-C in older people.
METHODS: HDL subfraction cholesterols were measured in 1,127 females and 825 males > or = 65 years old who participated in the Cardiovascular Health Study. Distributions of HDL subfraction cholesterols and bivariate and multivariate relationships were determined in cross-sectional analyses.
RESULTS: Mean (+/- SD) concentrations of HDL subfractions were: HDL3-C (M .98 +/- .25, F 1.2 +/- .29 mmol/l), HDL2-C (M .09 +/- .08, F .13 +/- .09 mmol/l). HDL2-C, but not HDL3-C, was slightly higher with age. Using multivariate analysis, both HDL2-C and HDL3-C (in females) were inversely correlated with triglyceride, body weight, and fasting insulin; HDL3-C was inversely correlated with central fat distribution in women. Both HDL2-C and HDL3-C were lower in participants with prevalent cardiovascular disease. However, only HDL3-C was significantly inversely related to carotid stenosis, as measured by ultrasound.
CONCLUSIONS: The slight increase in HDL-C with age appears to be due to an increase in the HDL2-C subfraction. HDL-C subfractions are independently related to triglyceride levels, body weight, and insulin concentrations in older people, all potentially modifiable risk factors. Both HDL2-C and HDL3-C are lower in older people with prevalent cardiovascular disease, although only HDL3-C was correlated with carotid atherosclerosis. These findings are consistent with the hypothesis that HDL subfractions are important risk factors for atherosclerotic cardiovascular disease in the elderly.
10aAged10aAged, 80 and over10aAlcohol Drinking10aBody Weight10aCarotid Stenosis10aCholesterol10aCholesterol, HDL10aCholesterol, LDL10aCohort Studies10aCoronary Disease10aCross-Sectional Studies10aDrug Therapy10aFemale10aHumans10aInsulin10aLipoproteins, HDL10aLipoproteins, HDL210aLipoproteins, HDL310aMale10aSex Factors10aSocioeconomic Factors1 aEttinger, W, H1 aVerdery, R, B1 aWahl, P W1 aFried, L P uhttps://chs-nhlbi.org/node/143202401nas a2200409 4500008004100000022001400041245010300055210006900158260001300227300001000240490000700250520132900257653001601586653000901602653002501611653001501636653002801651653001901679653001101698653001801709653001101727653000901738653001301747653001601760653001901776653001701795653002101812653001701833653002401850100001501874700001201889700001401901700001501915700001201930700001301942856003601955 1995 eng d a0002-861400aHematological and biochemical laboratory values in older Cardiovascular Health Study participants.0 aHematological and biochemical laboratory values in older Cardiov c1995 Aug a855-90 v433 aOBJECTIVE: To define reference hematologic and biochemical lab values in older individuals.
DESIGN: Randomly selected, age- and gender-stratified participants.
SETTING: Visits by participants to four research clinics.
PATIENTS: A total of 5201 participants in the Cardiovascular Health Study, an observational study of older Medicare-eligible individuals living at home.
MEASUREMENT: Information about health status, previous illness, and medication use was obtained from participants and/or their MDs. This information was used to define a healthy subset of the population. Blood samples were obtained for Cholesterol, HDL and LDL cholesterol, fasting and 2-hour postload glucose and insulin, fibrinogen, factors VII and VIII, potassium, creatinine, albumin, uric acid, white blood count, hematocrit, hemoglobin, and platelet count.
RESULTS: Significant differences were found for age group and/or gender for all mean values. Many tests were significantly different from the generally accepted reference ranges used in clinical laboratories.
CONCLUSIONS: In some situations accepted laboratory norms for the general population can not be extrapolated to older adults. There are implications for both research and clinical practice.
10aAge Factors10aAged10aAnalysis of Variance10aCalifornia10aCardiovascular Diseases10aCohort Studies10aFemale10aHealth Status10aHumans10aMale10aMaryland10aMiddle Aged10aNorth Carolina10aPennsylvania10aReference Values10aRisk Factors10aSex Characteristics1 aRobbins, J1 aWahl, P1 aSavage, P1 aEnright, P1 aPowe, N1 aLyles, M uhttps://chs-nhlbi.org/node/141302895nas a2200361 4500008004100000022001400041245009200055210006900147260001300216300001100229490000700240520190600247653000902153653002202162653002002184653002802204653002102232653002102253653002102274653002802295653002202323653001102345653001102356653001902367653001702386653000902403653001502412653001702427100001602444700001802460700001902478856003602497 1995 eng d a0002-861400aHigh density lipoprotein cholesterol is associated with serum cortisol in older people.0 aHigh density lipoprotein cholesterol is associated with serum co c1995 Dec a1345-90 v433 aOBJECTIVE: To determine the associations between serum cortisol and HDL cholesterol, other lipoprotein lipids and cardiovascular risk factors, carotid atherosclerosis, and clinical heart disease in older people.
DESIGN: A cross-sectional, observational, ancillary study of the Cardiovascular Health Study (CHS).
POPULATION: A total of 245 community-dwelling people, 65 to 89 years old, were recruited consecutively for a 2-month period from the CHS cohort in Forsyth County, North Carolina.
METHODS: Cortisol was measured by radioimmunoassay in serum collected between 7:00 and 10:00 AM after an overnight fast. Cortisol levels were correlated with lipoprotein lipids, insulin, glucose, body mass index, waist-hip ratio, prevalent coronary heart disease, hypertension, diabetes, and carotid atherosclerosis by B-mode ultrasound.
RESULTS: Serum cortisol was correlated negatively (r = -.24) with body mass index and waist-hip ratio (r = -.16) but was not related significantly to fasting insulin or glucose. Cortisol was not associated significantly with triglyceride and low density lipoprotein cholesterol but showed a positive correlation (r = .21) with high density lipoprotein cholesterol. The relationship between cortisol and high density lipoprotein cholesterol persisted after adjustment for gender, body mass index, waist-hip ratio, cigarette and alcohol use, triglyceride level, and diabetes. There was a trend toward a negative correlation between cortisol and measures of carotid atherosclerosis, but no significant relationship was indicated between cortisol and prevalent coronary heart disease, hypertension, or diabetes.
CONCLUSION: Endogenous glucocorticoid levels correlated with HDL cholesterol levels and may play a role in the physiologic regulation of high density lipoprotein levels in older people.
10aAged10aBody Constitution10aBody Mass Index10aCardiovascular Diseases10aCarotid Stenosis10aCholesterol, HDL10aCoronary Disease10aCross-Sectional Studies10aDiabetes Mellitus10aFemale10aHumans10aHydrocortisone10aHypertension10aMale10aPrevalence10aRisk Factors1 aVarma, V, K1 aRushing, J, T1 aEttinger, W, H uhttps://chs-nhlbi.org/node/141202450nas a2200313 4500008004100000022001400041245008700055210006900142260001300211300001100224490000600235520155800241653002901799653002601828653002801854653001101882653001701893653003701910100001501947700002001962700001601982700001901998700002002017700001102037700001802048700001702066700001702083856003602100 1996 eng d a0895-706100aHypertension and outcomes research. From clinical trials to clinical epidemiology.0 aHypertension and outcomes research From clinical trials to clini c1996 Feb a178-830 v93 aOutcomes research seeks to identify effective evidence-based methods of providing the best medical care. While randomized clinical trials (RCT) usually provide the clearest answers, they are often not done or not practicable. More than a decade after the introduction of calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors, clinical trial data about their effect on major disease endpoints in patients with hypertension are still not available. The primary alternatives are the use of randomized trials that include surrogate endpoints, such as level of blood pressure or extent of carotid atherosclerosis, and the use of observational studies that include major disease endpoints. Both approaches, their strengths and limitations, are discussed in detail. The possibility of residual confounding limits the strength of inferences that can be drawn from observational studies. Similarly, the possibility of important drug effects, other than those involving the surrogate endpoint, limits the inferences that can be drawn from randomized trials that rely solely on surrogate outcomes as guides to therapy. In the absence of evidence from large clinical trials that include major disease endpoints, treatment decisions and guidelines need to synthesize the best available information from a variety of sources. Consistency of findings across various study designs, outcomes, and populations is critical to the practice of evidence-based medicine and the effort to maximize the health benefits of antihypertensive therapies.
10aClinical Trials as Topic10aEpidemiologic Methods10aEvidence-Based Medicine10aHumans10aHypertension10aOutcome Assessment (Health Care)1 aPsaty, B M1 aSiscovick, D, S1 aWeiss, N, S1 aKoepsell, T, D1 aRosendaal, F, R1 aLin, D1 aHeckbert, S R1 aWagner, E, H1 aFurberg, C D uhttps://chs-nhlbi.org/node/146802262nas a2200421 4500008004100000022001400041245012500055210006900180260001600249300001000265490000700275520108600282653003101368653000901399653001201408653002801420653001501448653003001463653002101493653002001514653001101534653002501545653002001570653001801590653001101608653000901619653003201628653001701660653001201677653002601689100001401715700001401729700001801743700001401761700001401775700001501789856003601804 1997 eng d a0883-661200aHealth effects of caregiving: the caregiver health effects study: an ancillary study of the Cardiovascular Health Study.0 aHealth effects of caregiving the caregiver health effects study c1997 Spring a110-60 v193 aWe propose that two related sources of variability in studies of caregiving health effects contribute to an inconsistent pattern of findings: the sampling strategy used and the definition of what constitutes caregiving. Samples are often recruited through self-referral and are typically comprised of caregivers experiencing considerable distress. In this study, we examine the health effects of caregiving in large population-based samples of spousal caregivers and controls using a wide array of objective and self-report physical and mental health outcome measures. By applying different definitions of caregiving, we show that the magnitude of health effects attributable to caregiving can vary substantially, with the largest negative health effects observed among caregivers who characterize themselves as being strained. From an epidemiological perspective, our data show that approximately 80% of persons living with a spouse with a disability provide care to their spouse, but only half of care providers report mental or physical strain associated with caregiving.
10aActivities of Daily Living10aAged10aArousal10aCardiovascular Diseases10aCaregivers10aCerebrovascular Disorders10aCoronary Disease10aCost of Illness10aFemale10aGeriatric Assessment10aHealth Behavior10aHealth Status10aHumans10aMale10aPsychophysiologic Disorders10aRisk Factors10aSpouses10aStress, Psychological1 aSchulz, R1 aNewsom, J1 aMittelmark, M1 aBurton, L1 aHirsch, C1 aJackson, S uhttps://chs-nhlbi.org/node/150602732nas a2200361 4500008004100000022001400041245005100055210005000106260001300156300001000169490000700179520180100186653002101987653000902008653003002017653004002047653001102087653001802098653001102116653003102127653000902158653001602167653001902183100001702202700001602219700001802235700002002253700001402273700001702287700001502304700001502319856003602334 1997 eng d a0039-249900aHealth status of individuals with mild stroke.0 aHealth status of individuals with mild stroke c1997 Apr a740-50 v283 aBACKGROUND AND PURPOSE: Diminished quality of life and limitations in higher levels of physical functioning are often underestimated in stroke and are not fully captured by measures such as the Barthel Index and the Rankin Outcome Scale. This study used additional measures to assess the health status of 304 persons with mild stroke and to compare these individuals with 184 persons with transient ischemic attack and 654 persons without history of stroke/transient ischemic attack but at elevated risk for stroke (asymptomatic group).
METHODS: Subjects were recruited from the Academic Medical Center Consortium (inpatients), the Cardiovascular Health Study (population-based sample of community-dwelling persons 65 years and older), and United HealthCare (inpatients and outpatients typically younger than 65 years). Subjects were interviewed by telephone or in person to assess activities of daily living (Barthel Index), depression (Center for Epidemiological Studies Depression Scale), health status (MOS-36), and utility for current health state.
RESULTS: Most respondents were independent on all Barthel items. The stroke group was more impaired on the MOS-36 than the asymptomatic group but similar to the group with transient ischemic attack. Health-related quality of life was lowest for persons with stroke. While symptom status and Barthel Index score were the strongest predictors of health status, the Barthel Index showed a consistent ceiling effect when compared with the physical function subscale of the MOS-36.
CONCLUSIONS: The consequences of even mild stroke affect all dimensions of health except pain. Standardized assessment of persons with stroke must evaluate across the entire continuum of health-related functions.
10aAge Distribution10aAged10aCerebrovascular Disorders10aEuropean Continental Ancestry Group10aFemale10aHealth Status10aHumans10aIschemic Attack, Transient10aMale10aMiddle Aged10aSocial Support1 aDuncan, P, W1 aSamsa, G, P1 aWeinberger, M1 aGoldstein, L, B1 aBonito, A1 aWitter, D, M1 aEnarson, C1 aMatchar, D uhttps://chs-nhlbi.org/node/147902604nas a2200397 4500008004100000022001400041245012700055210006900182260001300251300001100264490000700275520149800282653001901780653000901799653002201808653002101830653002801851653002601879653001101905653002501916653001901941653001101960653000901971653001201980653003001992653001202022100001402034700001602048700001902064700001702083700001802100700001502118700002102133700001602154856003602170 1998 eng d a0002-916500aHigh body fatness, but not low fat-free mass, predicts disability in older men and women: the Cardiovascular Health Study.0 aHigh body fatness but not low fatfree mass predicts disability i c1998 Sep a584-900 v683 aUsing data from the Cardiovascular Health Study, we studied the relation between body composition (fat mass and fat-free mass, assessed by bioelectrical impedance) and self-reported, mobility-related disability (difficulty walking or stair climbing) in 2714 women and 2095 men aged 65-100 y. In a cross-sectional analysis at baseline (1989-1990), disability was reported by 26.5% of the women and 16.9% of the men. A positive association was observed between fat mass and disability. The odds ratio for disability in the highest quintile of fat mass was 3.04 (95% CI: 2.18, 4.25) for women and 2.77 (95% CI: 1.82, 4.23) for men compared with those in the lowest quintile. Low fat-free mass was not associated with a higher prevalence of disability. In a longitudinal analysis among persons not reporting disability at baseline, 20.3% of the women and 14.8% of the men reported disability 3 y later. Fat mass at baseline was predictive of disability 3 y later, with odds ratios of 2.83 (95% CI: 1.80, 4.46) for women and 1.72 (95% CI: 1.03, 2.85) for men in the highest quintile of fat. The increased risk was not explained by age, physical activity, chronic disease, or other potential confounders. Low fat-free mass was not predictive of disability. The results showed that high body fatness is an independent predictor of mobility-related disability in older men and women. These findings suggest that high body fatness in old age should be avoided to decrease the risk of disability.
10aAdipose Tissue10aAged10aAged, 80 and over10aBody Composition10aCross-Sectional Studies10aDisability Evaluation10aFemale10aGeriatric Assessment10aHealth Surveys10aHumans10aMale10aObesity10aPredictive Value of Tests10aWalking1 aVisser, M1 aLanglois, J1 aGuralnik, J, M1 aCauley, J, A1 aKronmal, R, A1 aRobbins, J1 aWilliamson, J, D1 aHarris, T B uhttps://chs-nhlbi.org/node/151202829nas a2200397 4500008004100000022001400041245016100055210006900216260001300285300001100298490000800309520163400317653000901951653002201960653002901982653002102011653003002032653001902062653001102081653001102092653003402103653000902137653003202146653000902178653003702187653004302224100001602267700001702283700001702300700001702317700001602334700001702350700001602367700001202383856003602395 1998 eng d a0033-841900aHypoechoic plaque at US of the carotid artery: an independent risk factor for incident stroke in adults aged 65 years or older. Cardiovascular Health Study.0 aHypoechoic plaque at US of the carotid artery an independent ris c1998 Sep a649-540 v2083 aPURPOSE: To investigate the association between incident (first) stroke and the echogenicity of internal carotid arterial plaque at ultrasonography (US).
MATERIALS AND METHODS: A cohort of 4, 886 individuals who, at baseline, were 65 years of age or older and without symptoms of cerebrovascular disease was followed up for an average of 3.3 years. Baseline clinical findings were from color Doppler and duplex US studies of the carotid arteries and a record of traditional risk factors: age, sex, presence of diabetes mellitus, pack-years of cigarette smoking, presence of hypertension, elevated systolic and diastolic blood pressure, elevated low-density lipoprotein cholesterol level.
RESULTS: Incident strokes, excluding hemorrhagic strokes and strokes of cardiac origin, were seen in 104 individuals (2.1%) at risk. Age- and sex-adjusted odds ratios for incident stroke were significant for hypoechoic plaque (odds ratio, 2.53; 95% CI, 1,42,4.53). After controlling for risk factors in a Cox proportional hazards model, the relative risk (RR) of incident stroke was 1.72 (p = .015) for hypoechoic plaque and 2.32 (P = .004) for internal carotid arterial narrowing of at least 50%. In addition, hypoechoic plaque (RR, 2.78; CI, 1.36,5.69) and 50%-100% stenosis (RR, 3.08; CI, 1.28, 7.41) were associated with ipsilateral, nonfatal stroke.
CONCLUSION: In asymptomatic adults aged 65 years or older, that risk of incident stroke was associated with two US features: hypoechoic internal carotid arterial plaque and an estimated internal carotid arterial stenosis of 50%-100%.
10aAged10aAged, 80 and over10aCarotid Artery, Internal10aCarotid Stenosis10aCerebrovascular Disorders10aCohort Studies10aFemale10aHumans10aIntracranial Arteriosclerosis10aMale10aProportional Hazards Models10aRisk10aUltrasonography, Doppler, Duplex10aUltrasonography, Doppler, Transcranial1 aPolak, J, F1 aShemanski, L1 aO'Leary, D H1 aLefkowitz, D1 aPrice, T, R1 aSavage, P, J1 aBrant, W, E1 aReid, C uhttps://chs-nhlbi.org/node/151102974nas a2200373 4500008004100000022001400041245008000055210006900135260001300204300001000217490000700227520198600234653000902220653001502229653002502244653002802269653001402297653001102311653001502322653003202337653001102369653001702380653001502397653002202412653001902434653001802453100001502471700001802486700001502504700001602519700001502535700001502550856003502565 1999 eng d a1079-564200aHormone replacement therapy, inflammation, and hemostasis in elderly women.0 aHormone replacement therapy inflammation and hemostasis in elder c1999 Apr a893-90 v193 aLipid-lowering by postmenopausal hormone therapy (HRT) explains only partly the assumed coronary risk reduction associated with therapy. To explore other possible mechanisms, we studied associations of HRT use with inflammation and hemostasis risk markers in women >/=65 years of age. Subjects were selected from 3393 participants in the fourth year examination of the Cardiovascular Health Study, an observational study of vascular disease risk factors. After excluding women with vascular disease, we compared levels of inflammation and hemostasis variables in the 230 women using unopposed estrogen and 60 using estrogen/progestin, with those of 196 nonusers selected as controls. Compared with nonusers, unopposed estrogen use was associated with 59% higher mean C-reactive protein (P<0.001), but with modestly lower levels of other inflammation indicators, fibrinogen, and alpha-1 acid glycoprotein (P<0.001). Factor VIIc was 16% higher among estrogen users (P<0.001), but this was not associated with higher thrombin production (prothrombin fragment 1-2), or increased fibrin breakdown (D-dimer). Concentration of plasminogen activator inhibitor-1 was 50% lower in both using groups (P<0.001) compared with nonusers, and this was associated with higher plasmin-antiplasmin complex: 8% higher in estrogen and 18% higher in estrogen/progestin users (P<0. 05). Relationships between the markers and hormone use were less pronounced in estrogen/progestin users, with no association for C-reactive protein except in women in upper 2 tertiles of body mass index (P for interaction, 0.02). The direction and strength of the associations of HRT use with inflammation markers differed depending on the protein, so it is not clear whether HRT confers coronary risk reduction through an inflammation-sensitive mechanism. Associations with hemostasis markers indicated no association with evidence of procoagulation and a possible association with increased fibrinolytic activity.
10aAged10aBiomarkers10aCase-Control Studies10aCross-Sectional Studies10aEstrogens10aFemale10aHemostasis10aHormone Replacement Therapy10aHumans10aInflammation10aProgestins10aRandom Allocation10aUnited Kingdom10aUnited States1 aCushman, M1 aMeilahn, E, N1 aPsaty, B M1 aKuller, L H1 aDobs, A, S1 aTracy, R P uhttps://chs-nhlbi.org/node/58802295nas a2200325 4500008004100000022001400041245008100055210006900136260001300205300001000218490000800228520137300236653000901609653002201618653001901640653003301659653001101692653002901703653001101732653002501743653001501768653001901783100001801802700001501820700001801835700001701853700001701870710004701887856003501934 2001 eng d a1073-449X00aHormone replacement therapy is associated with higher FEV1 in elderly women.0 aHormone replacement therapy is associated with higher FEV1 in el c2001 Feb a423-80 v1633 aEstrogen and progesterone use have been associated with improved pulmonary function in premenopausal women. However, little research has examined the relationship between hormone replacement therapy (HRT) and pulmonary function in postmenopausal women. We examined the relationship of HRT with spirometry in 2,353 women aged 65 yr and older participating in the Cardiovascular Health Study in 1993/1994. Current use of HRT was hypothesized to be associated with higher FEV1, higher FVC, and less pulmonary obstruction (FEV1/FVC < 65%). FEV1 was higher among current HRT users compared to noncurrent users in the following groups: overall (1.82 L versus 1.66 L, p < 0.0001), among women without asthma (1.85 L versus 1.69 L, p < 0.0001), among former smokers (1.76 L versus 1.60 L, p = 0.013), and among never smokers (1.90 L versus 1.72 L, p < 0.0001). Overall, HRT use was associated with a lower prevalence of pulmonary obstruction (OR 0.75 [95% CI 0.55, 0.99]). After controlling for potential confounders, HRT use was significantly associated with higher FEV(1) (p = 0.031) and with a lower prevalence of obstruction (OR 0.67 [95% CI 0.48, 0.95]). We conclude that postmenopausal women who use HRT have higher levels of FEV1 and less obstruction, which could not be explained by their lower rates of smoking and other health factors associated with HRT use.
10aAged10aAged, 80 and over10aCohort Studies10aEstrogen Replacement Therapy10aFemale10aForced Expiratory Volume10aHumans10aLongitudinal Studies10aSpirometry10aVital Capacity1 aCarlson, C, L1 aCushman, M1 aEnright, P, L1 aCauley, J, A1 aNewman, A, B1 aCardiovascular Health Study Research Group uhttps://chs-nhlbi.org/node/63103152nas a2200337 4500008004100000022001400041245008600055210006900141260001300210300001100223490000700234520223900241653000902480653002802489653001902517653001502536653001102551653001702562653001402579653000902593653003202602653002402634653000902658653001802667100002202685700001702707700001702724700001802741700002002759856003502779 2001 eng d a1047-279700aHypertension, heart rate, use of antihypertensives, and incident prostate cancer.0 aHypertension heart rate use of antihypertensives and incident pr c2001 Nov a534-420 v113 aPURPOSE: Recent studies have reported conflicting results on a possible relationship between hypertension, heart rate, and prostate cancer. A model has been developed suggesting that high blood pressure and high heart rate may both be markers for increased central sympathetic nervous activity, which may result in androgen-mediated stimulation of prostate cancer growth.
METHODS: In this study we examined the associations between hypertension, heart rate, use of antihypertensive medications, and incident prostate cancer in a cohort of 2442 men. Data from the Cardiovascular Health Study (CHS), an NHLBI-sponsored observational study of adults age 65 or older in four U.S. communities, were analyzed using Cox proportional hazards regression. Seated systolic and diastolic blood pressures were measured using a standardized protocol at the initial clinical examination and annually at follow-up visits. Medications data were transcribed by trained interviewers from prescription medication containers brought into the clinic by participants.
RESULTS: A total of 209 cases of incident prostate cancer were identified from either an ICD-9 code of 185 in hospital medical records (n = 130) or by self-report from annual surveillance interviews (n = 79). An average of 5.6 years of follow-up was available for analyses. No associations between blood pressure measures at entry into the study and prostate cancer were found, although these results may have been affected by subsequent treatment of hypertension. An association between resting heart rate (HR) equal to or greater than 80 beats per minute and incident prostate cancer was found compared to men with a rate of less than 60 beats per minute (HR: 1.6, 95% confidence interval [CI]: 1.03-2.5). An inverse association was found between risk of incident prostate cancer and use of any antihypertensive medication (HR: 0.7, 95% CI: 0.5-0.9). A test of heterogeneity found no difference between use of the specific classes of antihypertensive medication and the association with prostate cancer risk.
CONCLUSIONS: These data tend to support the hypothesized causal pathway between vascular disease markers and prostate cancer.
10aAged10aAntihypertensive Agents10aCohort Studies10aHeart Rate10aHumans10aHypertension10aIncidence10aMale10aProportional Hazards Models10aProstatic Neoplasms10aRisk10aUnited States1 aFitzpatrick, A, L1 aDaling, J, R1 aFurberg, C D1 aKronmal, R, A1 aWeissfeld, J, L uhttps://chs-nhlbi.org/node/66602735nas a2200493 4500008004100000022001400041245006400055210006200119260001600181300001200197490000800209520139200217653002101609653000901630653002001639653001401659653001901673653002501692653003301717653001101750653001101761653002001772653001601792653002601808653001501834653002001849653001801869653001501887653003201902653003001934653002601964653001701990653001802007100001702025700001902042700001702061700002002078700002202098700001802120700002402138700002302162700002102185856003502206 2003 eng d a1073-449X00aHormone replacement therapy and sleep-disordered breathing.0 aHormone replacement therapy and sleepdisordered breathing c2003 May 01 a1186-920 v1673 aDisordered breathing during sleep is more common among postmenopausal women than among their premenopausal counterparts, possibly because of declining levels of estrogen and progesterone. We examined the relationship between the use of replacement hormones and sleep-disordered breathing in a sample of 2,852 noninstitutionalized women, 50 years of age or older, who participated in the Sleep Heart Health Study. The frequency of apneas and hypopneas per hour of sleep (apnea-hypopnea index) was determined by unattended, single-night polysomnography at the participant's home. The prevalence of sleep-disordered breathing (apnea-hypopnea index of 15 or more) among hormone users (61 of 907) was approximately half the prevalence among nonusers (286 of 1,945). Multivariable adjustment for known determinants of the disorder, including age, body mass index, and neck circumference, has attenuated the association, but only moderately (adjusted odds ratio, 0.55; 95% confidence interval, 0.41 to 0.75). The inverse association between hormone use and sleep-disordered breathing was evident in various subgroups and was particularly strong among women 50 to 59 years old (adjusted odds ratio, 0.36; 95% confidence interval, 0.21 to 0.60). If the observed associations are causal, hormone replacement therapy could have a role in preventing or alleviating sleep-disordered breathing.
10aAge Distribution10aAged10aBody Mass Index10aCausality10aCohort Studies10aConfidence Intervals10aEstrogen Replacement Therapy10aFemale10aHumans10aLogistic Models10aMiddle Aged10aMultivariate Analysis10aOdds Ratio10aPolysomnography10aPostmenopause10aPrevalence10aSensitivity and Specificity10aSeverity of Illness Index10aSleep Apnea Syndromes10aSleep Stages10aUnited States1 aShahar, Eyal1 aRedline, Susan1 aYoung, Terry1 aBoland, Lori, L1 aBaldwin, Carol, M1 aNieto, Javier1 aO'Connor, George, T1 aRapoport, David, M1 aRobbins, John, A uhttps://chs-nhlbi.org/node/72103151nas a2200493 4500008004100000022001400041245011600055210006900171260001300240300001100253490000700264520176200271653000902033653002202042653002002064653001902084653003302103653001102136653001802147653001102165653001402176653001502190653001602205653002602221653001202247653003302259653003202292653002402324653000902348653001702357653001802374653001902392100001902411700002002430700002302450700001802473700002002491700001902511700002402530700002302554700002202577700002302599856003502622 2003 eng d a1540-999600aHormone replacement therapy and the risk of incident congestive heart failure: the Cardiovascular Health Study.0 aHormone replacement therapy and the risk of incident congestive c2003 May a341-500 v123 aBACKGROUND: The development of congestive heart failure (CHF) in older persons is related to a variety of mechanisms. Hormone replacement therapy (HRT) affects several of the pathways that may be important in the development of CHF. We hypothesized that HRT would be associated with a decreased risk of incident CHF.
METHODS: Using Cox proportional-hazards regression, we assessed the risk of incident CHF (n = 304) associated with time-dependent past and current use of HRT compared to never use. The Cardiovascular Health Study is a prospective cohort study of community-dwelling adults aged 65 years and older. This analysis included female participants without a history of CHF at baseline (n = 3223).
RESULTS: At baseline, 62% were never users, 26% were past users, and 12% were current users of HRT. Compared with never users, the multivariable relative risk (RR) of CHF was 1.01 (95% confidence interval [95% CI] 0.76,1.34) for past users and 1.34 (0.93,1.94) for current users. Results were similar among most treatment and clinical subgroups, except that the association of current HRT with CHF appeared to depend on body mass index (BMI) or osteoporosis status. The RR was 0.82 (0.43,1.60) for normal weight women, 1.65 (0.95,2.88) for overweight women, and 2.22 (1.06,4.67) for obese women (p = 0.01 for interaction). Similarly, the RR was 0.15 (0.04,0.65) for women with osteoporosis and 1.82 (1.25,2.65) for women without osteoporosis (p = 0.001 for interaction).
CONCLUSIONS: Overall, HRT was not associated with the risk of incident CHF, although BMI and osteoporosis appeared to modify the association of HRT with CHF. The risk of CHF was lower in patients with lower BMI or osteoporosis.
10aAged10aAged, 80 and over10aBody Mass Index10aCohort Studies10aEstrogen Replacement Therapy10aFemale10aHeart Failure10aHumans10aIncidence10aLife Style10aMiddle Aged10aMultivariate Analysis10aObesity10aOsteoporosis, Postmenopausal10aProportional Hazards Models10aProspective Studies10aRisk10aRisk Factors10aUnited States10aWomen's Health1 aRea, Thomas, D1 aPsaty, Bruce, M1 aHeckbert, Susan, R1 aCushman, Mary1 aMeilahn, Elaine1 aOlson, Jean, L1 aLemaitre, Rozenn, N1 aSmith, Nicholas, L1 aSotoodehnia, Nona1 aChaves, Paulo, H M uhttps://chs-nhlbi.org/node/74003245nas a2200397 4500008004100000022001400041245013100055210006900186260001300255300001100268490000700279520209400286653000902380653003502389653002702424653002802451653001102479653001702490653001102507653000902518653001602527653002602543653002102569653001402590653002002604653001502624653002602639100002002665700001502685700002502700700001902725700002402744700002002768700002402788856003502812 2005 eng d a0161-810500aHaptoglobin phenotype, sleep-disordered breathing, and the prevalence of cardiovascular disease: the Sleep Heart Health Study.0 aHaptoglobin phenotype sleepdisordered breathing and the prevalen c2005 Feb a207-130 v283 aBACKGROUND: Diabetes is an independent risk factor for cardiovascular disease, and there is growing evidence that sleep-disordered breathing also may increase the risk of cardiovascular disease. The mechanism responsible for increased susceptibility of people with diabetes to cardiovascular disease is thought to share several features with sleep-disordered breathing, notably increased oxidative stress. We recently demonstrated that a particular haptoglobin phenotype that is associated with differential antioxidant activity is an independent risk factor for cardiovascular disease in individuals with diabetes. We therefore sought to determine whether sleep-disordered breathing and cardiovascular disease are more strongly associated among people with the unfavorable haptoglobin phenotype.
METHODS: We tested this hypothesis in 2612 middle-aged and older participants from the Sleep Heart Health Study. Haptoglobin phenotyping was performed by gel electrophoresis. Respiratory disturbance index was assessed by standard methods. Logistic regression analysis was performed to estimate the association between haptoglobin phenotype and cardiovascular disease, adjusting for known cardiovascular risk factors (age, sex, diabetes, smoking, lipid levels, and hypertension). Possible modification by haptoglobin phenotype of the association of sleep-disordered breathing with cardiovascular disease prevalence was explored by examining interaction terms.
RESULTS: We found no significant association between haptoglobin phenotype and prevalent cardiovascular disease in this cohort, nor were significant interactions found between haptoglobin phenotype and sleep-disordered breathing on the prevalence of cardiovascular disease.
CONCLUSIONS: Sleep-disordered breathing did not appear to interact with haptoglobin phenotype in modifying the association with prevalent cardiovascular disease in the Sleep Heart Health Study. These findings could be due to the absence of association or to survivor bias in these cross-sectional analyses.
10aAged10aAngioplasty, Balloon, Coronary10aCoronary Artery Bypass10aCross-Sectional Studies10aFemale10aHaptoglobins10aHumans10aMale10aMiddle Aged10aMyocardial Infarction10aOxidative Stress10aPhenotype10aPolysomnography10aPrevalence10aSleep Apnea Syndromes1 aLevy, Andrew, P1 aZhang, Lin1 aMiller-Lotan, Rachel1 aRedline, Susan1 aO'Connor, George, T1 aQuan, Stuart, F1 aResnick, Helaine, E uhttps://chs-nhlbi.org/node/85702906nas a2200373 4500008004100000022001400041245013100055210006900186260001300255300001200268490000700280520184800287653000902135653002202144653001402166653001602180653002702196653001102223653002002234653001102254653000902265653001402274653001402288653002402302653004002326653001702366653001202383100002202395700001602417700002402433700001902457700002102476856003502497 2005 eng d a0002-861400aHospitalization for pneumonia in the Cardiovascular Health Study: incidence, mortality, and influence on longer-term survival.0 aHospitalization for pneumonia in the Cardiovascular Health Study c2005 Jul a1108-160 v533 aOBJECTIVES: To estimate the rate of hospitalization for pneumonia in community-dwelling older adults and to assess its risk factors and contribution to mortality.
DESIGN: Prospective observational study.
SETTING: The Cardiovascular Health Study (CHS) in four U.S. communities.
PARTICIPANTS: Five thousand eight hundred eighty-eight men and women aged 65 and older who were followed for a median 10.7 years.
MEASUREMENTS: Participants were interviewed about medical history and demographics; evaluated for lung, physical, and cognitive function; and followed for hospitalizations, cardiovascular disease, and death.
RESULTS: Nearly 10% of the cohort was hospitalized for pneumonia, for a rate of 11.1 per 1,000 person-years (95% confidence interval (CI)=10.2-12.0). Risk factors included older age, male sex, current and past smoking, poor physical and lung function, and history of cardiovascular disease and chronic obstructive pulmonary disease. Ten percent of participants died during their incident pneumonia hospitalization, and death rates were high in those who survived to discharge. Compared with participants who had not been hospitalized for pneumonia, the relative risk of total mortality was 4.9 (95% CI=4.1-6.0) during the first year after hospitalization and 2.6 (95% CI=2.2-3.1) thereafter, adjusted for age, sex, and race. The respective relative risks were 3.9 (95% CI=3.1-4.8) and 2.0 (95% CI=1.6-2.4) after further adjustment for baseline history of cardiovascular disease; diabetes mellitus; smoking; and measures of lung, physical, and cognitive function.
CONCLUSION: In older people, hospitalization for pneumonia is common and is associated with an elevated risk of death, as shown in this population-based, prospective cohort.
10aAged10aAged, 80 and over10aCognition10aComorbidity10aDiabetes Complications10aFemale10aHospitalization10aHumans10aMale10aMortality10aPneumonia10aProspective Studies10aRespiratory Physiological Phenomena10aRisk Factors10aSmoking1 aO'Meara, Ellen, S1 aWhite, Mark1 aSiscovick, David, S1 aLyles, Mary, F1 aKuller, Lewis, H uhttps://chs-nhlbi.org/node/85301769nas a2200289 4500008004100000022001400041245011100055210006900166260001700235300001100252490000700263520094900270653003101219653000901250653001601259653002101275653001101296653001801307653001801325653001701343653001101360653000901371653002001380100002201400700002201422856003501444 2006 eng d a1076-746000aHeart failure at the end of life: symptoms, function, and medical care in the Cardiovascular Health Study.0 aHeart failure at the end of life symptoms function and medical c c2006 Jul-Aug a217-250 v153 aAmong Cardiovascular Health Study participants who died from coronary heart disease, the authors compared those with incident and definite congestive heart failure (CHF) (n=60; 15%) and those with prevalent or probable CHF (n=70; 17.5%) to those with no history of CHF (n=198; 50%) concerning health status at the end of life. Both CHF groups had worse health status before death than the group without CHF. Patients in the CHF groups were more likely to use benzodiazepines (20% and 19% vs. 6%; p=0.001) and to rate their health as fair or poor (68% and 63% vs. 41%; p<0.001). They were more likely to be hospitalized (33% and 28% vs. 11%; p<0.001), to have activity restrictions (79% and 62% vs. 38%; p<0.001), and to report a wide array of physical symptoms. These data suggest that patients who die from coronary heart disease in the presence of CHF have greater need for hospice or palliative care than those with no history of CHF.
10aActivities of Daily Living10aAged10aComorbidity10aCoronary Disease10aFemale10aHealth Status10aHeart Failure10aHospice Care10aHumans10aMale10aPalliative Care1 aSullivan, Mark, D1 aO'Meara, Ellen, S uhttps://chs-nhlbi.org/node/90602653nas a2200469 4500008004100000022001400041245009400055210006900149260001300218300001200231490000700243520139700250653002101647653000901668653001501677653002301692653002401715653001901739653001601758653001101774653001501785653002201800653001101822653002001833653001901853653000901872653001601881653002601897653001501923653001701938653001101955653001801966653001501984653002601999100002302025700002102048700002002069700001702089700002302106700001802129856003602147 2008 eng d a1524-462800aHemostatic and inflammatory risk factors for intracerebral hemorrhage in a pooled cohort.0 aHemostatic and inflammatory risk factors for intracerebral hemor c2008 Aug a2268-730 v393 aBACKGROUND AND PURPOSE: The purpose of this study was to identify novel risk factors for intracerebral hemorrhagic stroke (ICH).
METHODS: Risk factors were assessed at baseline in a pooled cohort of the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS) involving 21,680 adults aged 45 or over. Over 263,489 person-years of follow-up, we identified 135 incident ICH events.
RESULTS: In multivariable models, for each SD higher baseline level of fibrinogen, the relative rate of incident ICH increased 35% (95% CI, 17% to 55%). Fibrinogen was more strongly related to ICH in ARIC than in CHS. In multivariable models, those with von Willebrand factor levels above the median were 1.72 (95% CI, 0.97 to 3.03) times more likely to have an incident ICH as those below the median. Factor VIII was significantly positively related to ICH in ARIC (relative rate per standard deviation of 1.31; 95% CI, 1.07 to 1.62), but not in CHS. There was no relation in multivariable models between lipoprotein (a), Factor VII, white blood cell count, or C-reactive protein and ICH.
CONCLUSIONS: Greater plasma fibrinogen and, to some degree, von Willebrand factor were associated with increased rates of ICH in these prospective studies, whereas Factor VIII was related to ICH in younger ARIC study participants only.
10aAge Distribution10aAged10aBiomarkers10aC-Reactive Protein10aCerebral Hemorrhage10aCohort Studies10aFactor VIII10aFemale10aFibrinogen10aFollow-Up Studies10aHumans10aLeukocyte Count10aLipoprotein(a)10aMale10aMiddle Aged10aMultivariate Analysis10aPrevalence10aRisk Factors10aStroke10aUnited States10aVasculitis10avon Willebrand Factor1 aSturgeon, Jared, D1 aFolsom, Aaron, R1 aLongstreth, W T1 aShahar, Eyal1 aRosamond, Wayne, D1 aCushman, Mary uhttps://chs-nhlbi.org/node/103603025nas a2200397 4500008004100000022001400041245011800055210006900173260001300242300001200255490000800267520183100275653000902106653002202115653001102137653001802148653001102166653001402177653004902191653004902240653003302289653000902322653003002331653002402361653001702385100002202402700002202424700002302446700001802469700002502487700002102512700002102533700001702554700002002571856003602591 2008 eng d a1097-674400aHigh insulinlike growth factor binding protein 1 level predicts incident congestive heart failure in the elderly.0 aHigh insulinlike growth factor binding protein 1 level predicts c2008 Jun a1006-120 v1553 aBACKGROUND: Low levels of insulinlike growth factor 1 (IGF-I) may influence the development of age-related cardiovascular diseases including congestive heart failure (CHF). Insulinlike growth factor binding protein 1 (IGFBP-1), which increases during catabolic states and inhibits anabolic IGF-I effects, is increased in patients with CHF and has been associated prospectively with increased mortality among older adults and survivors of myocardial infarction. We investigated the association between fasting plasma levels of IGF-I, IGFBP-1, IGFBP-3, and insulin and risk of incident CHF in the prospective Cardiovascular Health Study.
METHODS: From among 5,888 adults 65 years old and older in the Cardiovascular Health Study, we studied 566 incident CHF cases and 1,072 comparison subjects after exclusion of underweight individuals (body mass index <18.5 kg/m(2)) and insulin users. Hazard ratios (HRs) with 95% CIs for CHF were estimated after adjustment for age, race, sex, hypertension, systolic blood pressure, lipid levels, left ventricular hypertrophy, coronary disease, C-reactive protein, health status, diabetes, and body mass index.
RESULTS: High baseline IGFBP-1 level was a significant predictor of CHF, independent of established CHF risk factors and inflammation markers. The HR per SD of IGFBP-1 was 1.22 (95% CI 1.07-1.39, P < .01). Relative to the lowest IGFBP-1 tertile, the HR was 1.29 (95% CI 0.96-1.74, P = .09) for the second IGFBP-1 tertile and 1.47 (95% CI 1.06-2.04; P = .02) for the highest IGFBP-1 tertile (tertile cut points 19.5 and 35.8 ng/mL). Total IGF-I, IGFBP-3, or insulin levels had no association with CHF after adjustment for CHF risk factors.
CONCLUSIONS: High circulating IGFBP-1 level may be a CHF risk factor among older adults.
10aAged10aAged, 80 and over10aFemale10aHeart Failure10aHumans10aIncidence10aInsulin-Like Growth Factor Binding Protein 110aInsulin-Like Growth Factor Binding Protein 310aInsulin-Like Growth Factor I10aMale10aPredictive Value of Tests10aProspective Studies10aRisk Factors1 aKaplan, Robert, C1 aMcGinn, Aileen, P1 aPollak, Michael, N1 aKuller, Lewis1 aStrickler, Howard, D1 aRohan, Thomas, E1 aCappola, Anne, R1 aXue, XiaoNan1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/103502289nas a2200337 4500008004100000022001400041245013800055210006900193260001600262300001200278490000800290520128900298653000901587653002301596653002101619653001101640653001101651653001401662653002501676653000901701653001601710653003201726653001801758653002701776100002701803700002101830700002301851700002301874700001801897856003601915 2008 eng d a1528-002000aHigh-density lipoprotein cholesterol and venous thromboembolism in the Longitudinal Investigation of Thromboembolism Etiology (LITE).0 aHighdensity lipoprotein cholesterol and venous thromboembolism i c2008 Oct 01 a2675-800 v1123 aWe determined prospectively the risk of venous thromboembolism (VTE) in relation to baseline high-density lipoprotein cholesterol (HDL-c) in 19 049 participants of the Longitudinal Investigation of Thromboembolism Etiology (LITE), which was composed of 14 490 participants of the Atherosclerosis Risk in Communities (ARIC) study and 4559 participants of the Cardiovascular Health Study (CHS). In addition, we determined the risk of VTE in relation to baseline subfractions of HDL (HDL(2) and HDL(3)) and apolipoprotein A-I (apoA-I) in 14 488 participants of the ARIC study. Age-adjusted incidence rates of VTE by HDL-c quartile ranged from 1.64 to 1.91 per 1000 person-years in men and 1.40 to 1.94 per 1000 person-years in women; however, there was no apparent trend of VTE incidence across HDL-c quartiles for either sex. The multivariate adjusted hazard ratios of VTE by HDL-c quartiles (with quartile 4 as the reference) were nonsignificant for both sexes and ranged between 0.91 and 0.99 for men and 0.78 and 1.22 for women. Results did not differ in separate evaluations of idiopathic and secondary VTE. In the ARIC study, there was no trend of VTE hazard ratios across quartiles of HDL(2), HDL(3), or apoA-I. Low HDL-c does not appear to be an important VTE risk factor.
10aAged10aApolipoprotein A-I10aCholesterol, HDL10aFemale10aHumans10aIncidence10aLongitudinal Studies10aMale10aMiddle Aged10aProportional Hazards Models10aUnited States10aVenous Thromboembolism1 aChamberlain, Alanna, M1 aFolsom, Aaron, R1 aHeckbert, Susan, R1 aRosamond, Wayne, D1 aCushman, Mary uhttps://chs-nhlbi.org/node/104002896nas a2200385 4500008004100000022001400041245022700055210006900282260001300351300001100364490000700375520165900382653000902041653002302050653002802073653002802101653003602129653001102165653001502176653001502191653001102206653002702217653002302244653001802267653000902285653001702294100002202311700002402333700002302357700002102380700002602401700002302427700002402450856003602474 2008 eng d a1532-541500aHigher levels of inflammation factors and greater insulin resistance are independently associated with higher heart rate and lower heart rate variability in normoglycemic older individuals: the Cardiovascular Health Study.0 aHigher levels of inflammation factors and greater insulin resist c2008 Feb a315-210 v563 aOBJECTIVES: To explore the relationship between (1) insulin resistance and inflammation factors with (2) higher heart rate (HR) and lower heart rate variability (HRV) in normoglycemic older adults.
DESIGN: Cross-sectional population-based study.
PARTICIPANTS: Five hundred forty-five adults aged 65 and older with normoglycemia (fasting glucose <100 mg/dL) who participated in the Cardiovascular Health Study.
MEASUREMENTS: Serum levels of three inflammation proteins (C-reactive protein (CRP), interleukin 6 (IL-6), and fibrinogen); insulin resistance, quantified according to the homeostasis assessment model (HOMA-IR); HR; and four representative measures of HRV (the standard deviation of normal beat to beat intervals (SDNN), the root mean square of successive differences (rMSSD), very low frequency power (VLF), and the low- to high-frequency power ratio (LF/HF)) derived from 24-hour Holter recordings.
RESULTS: High CRP and IL-6 levels were associated with higher HR and lower SDNN and VLF after adjustment for multiple covariates, including HOMA-IR and clinical cardiovascular disease. High IL-6 was also associated with lower LF/HF. Significant univariate inverse relationships between HOMA-IR and HR and HRV were also found, but the strengths of these relationships were attenuated after adjustment for inflammation factors.
CONCLUSION: Increased levels of inflammation markers and HOMA-IR are associated with higher HR and lower HRV. These findings suggest that inflammation may contribute to the pathogenesis of cardiovascular autonomic decline in older adults.
10aAged10aC-Reactive Protein10aCardiovascular Diseases10aCross-Sectional Studies10aElectrocardiography, Ambulatory10aFemale10aFibrinogen10aHeart Rate10aHumans10aInflammation Mediators10aInsulin Resistance10aInterleukin-610aMale10aRisk Factors1 aStein, Phyllis, K1 aBarzilay, Joshua, I1 aChaves, Paulo, H M1 aTraber, Jennifer1 aDomitrovich, Peter, P1 aHeckbert, Susan, R1 aGottdiener, John, S uhttps://chs-nhlbi.org/node/100802540nas a2200409 4500008004100000022001400041245007300055210006900128260001300197300001000210490000700220520137800227653002101605653000901626653001001635653003101645653002901676653002801705653002801733653003601761653001101797653001501808653001101823653001701834653000901851653002301860653001501883653002401898653001701922653003601939100002201975700002401997700002302021700002602044700002402070856003602094 2009 eng d a1468-283400aHeart rate variability and its changes over 5 years in older adults.0 aHeart rate variability and its changes over 5 years in older adu c2009 Mar a212-80 v383 aPURPOSE: to characterise the association between age, ageing and heart rate variability (HRV) in older individuals, 585 adults age >65 years with two 24-h Holter recordings in the Cardiovascular Health Study were studied.
METHODS: heart rate (HR), ventricular premature contractions (VPCs), atrial premature contractions (APCs), frequency-domain, ratio-based and non-linear HRV and heart rate turbulence (HRT) were examined cross-sectionally by 5-year age groups and prospectively over 5 years. Analyses adjusted for gender, lower versus elevated cardiovascular (CV) risk and for the change in CV risk.
RESULTS: HR declined, and VPCs and APCs increased per 5-year increase in age. Frequency-domain HRV decreased more at 65-69, less at 70-74 and minimally at > or =75 years, independent of CVD risk or change in CVD risk. Ratio and non-linear HRV continued to decline to > or =75 years old. Ratio HRV and HRT slope were more strongly related to CVD risk than frequency-domain HRV.
CONCLUSIONS: cardiac autonomic function, assessed by frequency-domain HRV, declines most at 65-70 and levels off at age >75. The decline is independent of CVD risk or change in CVD risk. Ratio-based and non-linear HRV and HRT slope continued to change with increasing age and were more closely related to CVD risk than frequency-domain HRV.
10aAge Distribution10aAged10aAging10aAtrial Premature Complexes10aAutonomic Nervous System10aCardiovascular Diseases10aCross-Sectional Studies10aElectrocardiography, Ambulatory10aFemale10aHeart Rate10aHumans10aHypertension10aMale10aNonlinear Dynamics10aPrevalence10aProspective Studies10aRisk Factors10aVentricular Premature Complexes1 aStein, Phyllis, K1 aBarzilay, Joshua, I1 aChaves, Paulo, H M1 aDomitrovich, Peter, P1 aGottdiener, John, S uhttps://chs-nhlbi.org/node/106902837nas a2200409 4500008004100000022001400041245014000055210006900195260001300264300001100277490000700288520164000295653000901935653002001944653001601964653002201980653003702002653003002039653001102069653003202080653001102112653000902123653002602132653002402158653001702182653002102199653002102220653001602241653001402257653002102271100002102292700002102313700001602334700002002350700002102370856003602391 2009 eng d a1945-719700aHigh frequency of and factors associated with thyroid hormone over-replacement and under-replacement in men and women aged 65 and over.0 aHigh frequency of and factors associated with thyroid hormone ov c2009 Apr a1342-50 v943 aCONTEXT: Thyroid hormone use is common in older populations, but the frequency of over- or under-replacement is debated.
OBJECTIVE: We sought to describe the frequency of and factors associated with thyroid hormone over- or under-replacement in a population of older men and women.
DESIGN: Participants were 3678 U.S. community dwelling individuals aged 65 yr or older enrolled in the Cardiovascular Health Study who had thyroid function tests in 1989-1990. Thyroid hormone users (n = 339) were identified and classified into low TSH (<0.45 mU/liter), euthyroid (0.45-4.5 mU/liter), and high TSH (>4.5 mU/liter).
RESULTS: Of the 339 thyroid hormone users, 41% had a low TSH, 16% had a high TSH, and 43% were in the euthyroid range. In multivariable analyses, lower weight (P < 0.001) was independently associated with low TSH status. For every 10 kg lower weight, the likelihood of having low TSH increased by 65% [odd ratio (OR) 1.65; 95% confidence interval (CI) 1.31-2.07]. Those with renal insufficiency were less likely to have low TSH levels (P = 0.02). The presence of diabetes was independently associated with having low (OR 3.35; 95% CI 1.46-7.65) and high TSH levels (OR 2.66; 95% CI 1.14-6.21).
CONCLUSIONS: There is a very high prevalence of thyroid function testing abnormalities in older people taking thyroid hormone preparations, particularly in those of low weight or with diabetes. Because of potential adverse cardiovascular and skeletal effects from over-replacement, older people represent a key population for increased TSH monitoring on therapy.
10aAged10aBody Mass Index10aBody Weight10aDiabetes Mellitus10aDose-Response Relationship, Drug10aDrug Therapy, Combination10aFemale10aHormone Replacement Therapy10aHumans10aMale10aMultivariate Analysis10aRenal Insufficiency10aRisk Factors10aThyroid Diseases10aThyroid Hormones10aThyrotropin10aThyroxine10aTriiodothyronine1 aSomwaru, Lily, L1 aArnold, Alice, M1 aJoshi, Neha1 aFried, Linda, P1 aCappola, Anne, R uhttps://chs-nhlbi.org/node/106703110nas a2200445 4500008004100000022001400041245014600055210006900201260001300270300001200283490000700295520180900302653000902111653002202120653001802142653002802160653002102188653001102209653001102220653001202231653002302243653002302266653001502289653002102304653002602325653001702351653002202368100002102390700002402411700002402435700002202459700002202481700002202503700002002525700002402545700001802569700002002587700002102607856003602628 2009 eng d a1945-719700aHigher serum testosterone concentration in older women is associated with insulin resistance, metabolic syndrome, and cardiovascular disease.0 aHigher serum testosterone concentration in older women is associ c2009 Dec a4776-840 v943 aCONTEXT: Early postmenopausal women with higher testosterone (T) levels have increased insulin resistance (IR) and cardiovascular risk factors, but whether this translates into increased cardiovascular disease later in life is unknown.
OBJECTIVE: The objective of the study was to determine whether higher T levels are associated with IR, the metabolic syndrome (MetSyn), and coronary heart disease (CHD) in elderly women.
DESIGN: Total T and free T by equilibrium dialysis were measured using ultrasensitive assays in 344 women aged 65-98 yr enrolled in the Cardiovascular Health Study. Cross-sectional analyses were performed to examine the associations between total and free T and IR, MetSyn, and CHD.
RESULTS: There was a stepwise increase in the homeostasis model assessment of insulin resistance with increasing total (P = 0.0.003) and free T (P = 0.02) level and a corresponding decrease in Quantitative Insulin Sensitivity Check Index (P < 0.001 and P = 0.002, respectively). In adjusted models, higher levels of both total and free T were strongly associated with abdominal obesity and high fasting glucose, the two MetSyn components most strongly linked to IR. After adjustment, women in the top quartile of total T levels had a 3-fold greater odds of MetSyn (odds ratio 3.15, 95% confidence interval 1.57-6.35) than those in the bottom quartile and a 3-fold greater odds of CHD (odds ratio 2.95, 95% confidence interval 1.2-7.3) than those in second quartile, whereas free T was not significantly associated with MetSyn or CHD.
CONCLUSIONS: Higher levels of T are associated with IR, MetSyn, and CHD in elderly women. Whether T is a marker or mediator of cardiovascular disease in this population merits further investigation.
10aAged10aAged, 80 and over10aBlood Glucose10aCardiovascular Diseases10aCoronary Disease10aFemale10aHumans10aInsulin10aInsulin Resistance10aMetabolic Syndrome10aOdds Ratio10aRadioimmunoassay10aSocioeconomic Factors10aTestosterone10aTreatment Outcome1 aPatel, Shrita, M1 aRatcliffe, Sarah, J1 aReilly, Muredach, P1 aWeinstein, Rachel1 aBhasin, Shalender1 aBlackman, Marc, R1 aCauley, Jane, A1 aSutton-Tyrrell, Kim1 aRobbins, John1 aFried, Linda, P1 aCappola, Anne, R uhttps://chs-nhlbi.org/node/113902541nas a2200385 4500008004100000022001400041245008600055210006900141260001300210300001100223490000700234520142900241653002201670653000901692653002201701653001501723653003201738653004001770653004001810653001101850653001701861653002501878653003601903653003401939653002001973100001101993700001502004700001602019700001802035700001302053700002002066700001802086700001502104856003602119 2009 eng d a1476-552700aHypertension genes and retinal vascular calibre: the Cardiovascular Health Study.0 aHypertension genes and retinal vascular calibre the Cardiovascul c2009 Sep a578-840 v233 aWe examined the associations of single nucleotide polymorphisms (SNPs) in three candidate hypertension genes, alpha-adducin (ADD1/G460W), beta2-adrenergic receptor (ADRB2/Arg16Gly and Gln27Glu) and G-protein beta3 subunit (GNB3/C825T), with retinal arteriolar calibre (an intermediate marker of chronic hypertension) and venular calibre. Data in 1842 participants (1554 whites and 288 African Americans) aged 69-96 years from the Cardiovascular Health Study with genotype and retinal vascular calibre data were included. A computer-assisted method was used to measure retinal vascular calibre. We analysed four SNPs and multilocus interaction for three genes. All SNPs were in Hardy-Weinberg equilibrium in whites and African Americans. The study had sufficient power to detect 0.5% of the total variance of retinal vascular calibre contributed by each SNP in the total population, except for the GNB3 gene variant. No significant associations between these SNPs in the genes studied and mean retinal arteriolar and venular calibre were found in single-gene or multilocus analysis (for example, age-, gender-, race-adjusted mean retinal arteriolar calibre was similar between participants who were ADD1/460W homozygotes and ADD1/G allele carriers, 166.2 vs 167.7 microm). In conclusion, this study found no evidence of an association of SNPs in candidate hypertension genes studied here with retinal vascular calibre.
10aAfrican Americans10aAged10aAged, 80 and over10aArterioles10aCalmodulin-Binding Proteins10aEuropean Continental Ancestry Group10aHeterotrimeric GTP-Binding Proteins10aHumans10aHypertension10aLongitudinal Studies10aPolymorphism, Single Nucleotide10aReceptors, Adrenergic, beta-210aRetinal Vessels1 aSun, C1 aWang, J, J1 aIslam, F, M1 aHeckbert, S R1 aKlein, R1 aSiscovick, D, S1 aKlein, B, E K1 aWong, T, Y uhttps://chs-nhlbi.org/node/107002641nas a2200313 4500008004100000022001400041245015000055210006900205260001300274300001000287490000700297520169900304653003102003653000902034653002202043653003702065653001102102653001802113653001902131653001102150653002502161653000902186653002402195653002402219653001202243100001702255700001902272856003602291 2010 eng d a1758-535X00aHealth benefits of increased walking for sedentary, generally healthy older adults: using longitudinal data to approximate an intervention trial.0 aHealth benefits of increased walking for sedentary generally hea c2010 Sep a982-90 v653 aBACKGROUND: Older adults are often advised to walk more, but randomized trials have not conclusively established the benefits of walking in this age group. Typical analyses based on observational data may have biased results. Here, we propose a "limited-bias," more interpretable estimate of the health benefits to sedentary healthy older adults of walking more, using longitudinal data from the Cardiovascular Health Study.
METHODS: The number of city blocks walked per week, collected annually, was classified as sedentary (<7 blocks per week), somewhat active, or active (>or=28). Analysis was restricted to persons sedentary and healthy in the first 2 years. In Year 3, some became more active (the treatment groups). Self-rated health at Year 5 (follow-up) was regressed on walking at Year 3, with additional covariates from Year 2, when all were sedentary.
RESULTS: At follow-up, 83.5% of those active at baseline had excellent, very good, or good self-rated health, as compared with 63.9% of the sedentary, an apparent benefit of 19.6 percentage points. After covariate adjustment, the limited-bias estimate of the benefit was 11.2 percentage points (95% confidence interval 3.7-18.6). Ten different outcome measures showed a benefit, ranging from 5 to 11 percentage points. Estimates from other study designs were smaller, less interpretable, and potentially more biased.
CONCLUSIONS: In longitudinal studies where walking and health are ascertained at every wave, limited-bias estimates can provide better estimates of the benefits of walking. A surprisingly small increase in walking was associated with meaningful health benefits.
10aActivities of Daily Living10aAged10aAged, 80 and over10aData Interpretation, Statistical10aFemale10aHealth Status10aHealth Surveys10aHumans10aLongitudinal Studies10aMale10aRegression Analysis10aSedentary Lifestyle10aWalking1 aDiehr, Paula1 aHirsch, Calvin uhttps://chs-nhlbi.org/node/120102286nas a2200337 4500008004100000022001400041245008400055210006900139260001300208300001000221490000700231520139500238653000901633653001101642653001801653653001801671653001101689653001401700653000901714653001701723653001801740100001901758700002101777700002001798700002101818700001501839700001501854700002201869700002101891856003601912 2010 eng d a1522-964500aHip fractures and heart failure: findings from the Cardiovascular Health Study.0 aHip fractures and heart failure findings from the Cardiovascular c2010 Jan a77-840 v313 aAIMS: The aim of the study was to find the epidemiology of hip fractures in heart failure. The increasing survival rate for patients with heart failure places them at risk for other diseases of ageing, including osteoporosis.
METHODS AND RESULTS: We included 5613 persons from the Cardiovascular Health Study (CHS) with an average of 11.5 year follow-up. We determined incidence rates and hazard ratios (HRs) in persons with heart failure compared with persons without heart failure and mortality hazards following these fractures. Annualized incidence rates for hip fractures were 14 per 1000 person-years in heart failure and 6.8 per 1000 person-years without heart failure. Unadjusted and multivariable adjusted HRs for hip fracture associated with heart failure in men were 1.87 (95% CI 1.2-2.93) and 1.59 (95% CI 0.93-2.72), respectively. Respective HRs for women were 1.75 (95% CI 1.27-2.4) and 1.41 (95% CI 0.98-2.03). Mortality hazard was approximately 2-fold greater in patients with heart failure and hip fracture compared with those having heart failure alone.
CONCLUSION: Persons with heart failure are at high risk for hip fractures. However, much of the association between hip fractures and heart failure is explained by shared risk factors. Hip fractures are a substantial contributor to mortality in men and women with heart failure.
10aAged10aFemale10aHeart Failure10aHip Fractures10aHumans10aIncidence10aMale10aRisk Factors10aUnited States1 aCarbone, Laura1 aBůzková, Petra1 aFink, Howard, A1 aLee, Jennifer, S1 aChen, Zhao1 aAhmed, Ali1 aParashar, Susmita1 aRobbins, John, R uhttps://chs-nhlbi.org/node/114312698nas a2203781 4500008004100000022001400041245009600055210006900151260001600220300001000236490000800246520210000254653001602354653003102370653001702401653003802418653001802456653003402474653001102508653003602519653003102555653001402586653003602600100002302636700001902659700002202678700002102700700002302721700002602744700002302770700002102793700002202814700002502836700002102861700002002882700002202902700002302924700002802947700002102975700002002996700001803016700001503034700002503049700002603074700002303100700001103123700002603134700001803160700001903178700001803197700001803215700001803233700002503251700002303276700002403299700001703323700002003340700003103360700002403391700001903415700002503434700002103459700001603480700001803496700002003514700001703534700002103551700002103572700001803593700001803611700001903629700002203648700002203670700002403692700002103716700002303737700002103760700001903781700001903800700002003819700002103839700002303860700003203883700002303915700002403938700002103962700001703983700001904000700002004019700002004039700001904059700002104078700001704099700002404116700002704140700001604167700001904183700002104202700002304223700002304246700002004269700001804289700002304307700001904330700001904349700002004368700001204388700002104400700001904421700002304440700002004463700001504483700002404498700002504522700002304547700002204570700002204592700002104614700002204635700001904657700002004676700001904696700001704715700001804732700001704750700001604767700002204783700002404805700002404829700002604853700002204879700002204901700002104923700001904944700002604963700002004989700002105009700002605030700002105056700001605077700001805093700002005111700002305131700002305154700001905177700002105196700001805217700002805235700002205263700002105285700001605306700001605322700001805338700001605356700001905372700002805391700002105419700001805440700002005458700001805478700002005496700001705516700002305533700001705556700002005573700002205593700002105615700002105636700002005657700001905677700002305696700001905719700002705738700001805765700002605783700002205809700002605831700002105857700002905878700001905907700001705926700002605943700001905969700002105988700001906009700002306028700001806051700001606069700001906085700002006104700002006124700002206144700001606166700002506182700002006207700002606227700001906253700002306272700002506295700002006320700002406340700001906364700002406383700001806407700002406425700002406449700002106473700002206494700002006516700002306536700002206559700002006581700001906601700002206620700002406642700001906666700002206685700002206707700001906729700001906748700002006767700002406787700003006811700001906841700001606860700002006876700002006896700002006916700001906936700001906955700001906974700002406993700002307017700002407040700002207064700001807086700002307104700002407127700001907151700002107170700002407191700002507215700002507240700002007265700002107285700002107306700002107327700002407348700002007372700002207392700002207414700001407436700002607450700002807476700002207504700002107526700002007547700002207567700001707589700002107606700002007627700002907647700001907676700001907695700002107714700002307735700002307758700002507781700002207806700002107828700002407849700002007873700002207893700002207915700002707937700002007964700002407984700002408008700002308032700002608055700002408081700001608105700002208121700002408143700001908167700001808186700002108204700001908225700002308244700001708267700002208284700002108306700001908327700002408346700002508370700002108395700002608416700002308442700002208465700002308487700002308510700002008533700002808553700002008581700002808601700002308629700002508652700002008677700002108697700002208718700002008740700002508760700002508785700002108810700002508831700002408856856003608880 2010 eng d a1476-468700aHundreds of variants clustered in genomic loci and biological pathways affect human height.0 aHundreds of variants clustered in genomic loci and biological pa c2010 Oct 14 a832-80 v4673 aMost common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
10aBody Height10aChromosomes, Human, Pair 310aGenetic Loci10aGenetic Predisposition to Disease10aGenome, Human10aGenome-Wide Association Study10aHumans10aMetabolic Networks and Pathways10aMultifactorial Inheritance10aPhenotype10aPolymorphism, Single Nucleotide1 aAllen, Hana, Lango1 aEstrada, Karol1 aLettre, Guillaume1 aBerndt, Sonja, I1 aWeedon, Michael, N1 aRivadeneira, Fernando1 aWiller, Cristen, J1 aJackson, Anne, U1 aVedantam, Sailaja1 aRaychaudhuri, Soumya1 aFerreira, Teresa1 aWood, Andrew, R1 aWeyant, Robert, J1 aSegrè, Ayellet, V1 aSpeliotes, Elizabeth, K1 aWheeler, Eleanor1 aSoranzo, Nicole1 aPark, Ju-Hyun1 aYang, Jian1 aGudbjartsson, Daniel1 aHeard-Costa, Nancy, L1 aRandall, Joshua, C1 aQi, Lu1 aSmith, Albert, Vernon1 aMägi, Reedik1 aPastinen, Tomi1 aLiang, Liming1 aHeid, Iris, M1 aLuan, Jian'an1 aThorleifsson, Gudmar1 aWinkler, Thomas, W1 aGoddard, Michael, E1 aLo, Ken, Sin1 aPalmer, Cameron1 aWorkalemahu, Tsegaselassie1 aAulchenko, Yurii, S1 aJohansson, Asa1 aZillikens, Carola, M1 aFeitosa, Mary, F1 aEsko, Tõnu1 aJohnson, Toby1 aKetkar, Shamika1 aKraft, Peter1 aMangino, Massimo1 aProkopenko, Inga1 aAbsher, Devin1 aAlbrecht, Eva1 aErnst, Florian1 aGlazer, Nicole, L1 aHayward, Caroline1 aHottenga, Jouke-Jan1 aJacobs, Kevin, B1 aKnowles, Joshua, W1 aKutalik, Zoltán1 aMonda, Keri, L1 aPolasek, Ozren1 aPreuss, Michael1 aRayner, Nigel, W1 aRobertson, Neil, R1 aSteinthorsdottir, Valgerdur1 aTyrer, Jonathan, P1 aVoight, Benjamin, F1 aWiklund, Fredrik1 aXu, Jianfeng1 aZhao, Jing Hua1 aNyholt, Dale, R1 aPellikka, Niina1 aPerola, Markus1 aPerry, John, R B1 aSurakka, Ida1 aTammesoo, Mari-Liis1 aAltmaier, Elizabeth, L1 aAmin, Najaf1 aAspelund, Thor1 aBhangale, Tushar1 aBoucher, Gabrielle1 aChasman, Daniel, I1 aChen, Constance1 aCoin, Lachlan1 aCooper, Matthew, N1 aDixon, Anna, L1 aGibson, Quince1 aGrundberg, Elin1 aHao, Ke1 aJunttila, Juhani1 aKaplan, Lee, M1 aKettunen, Johannes1 aKönig, Inke, R1 aKwan, Tony1 aLawrence, Robert, W1 aLevinson, Douglas, F1 aLorentzon, Mattias1 aMcKnight, Barbara1 aMorris, Andrew, P1 aMüller, Martina1 aNgwa, Julius, Suh1 aPurcell, Shaun1 aRafelt, Suzanne1 aSalem, Rany, M1 aSalvi, Erika1 aSanna, Serena1 aShi, Jianxin1 aSovio, Ulla1 aThompson, John, R1 aTurchin, Michael, C1 aVandenput, Liesbeth1 aVerlaan, Dominique, J1 aVitart, Veronique1 aWhite, Charles, C1 aZiegler, Andreas1 aAlmgren, Peter1 aBalmforth, Anthony, J1 aCampbell, Harry1 aCitterio, Lorena1 aDe Grandi, Alessandro1 aDominiczak, Anna1 aDuan, Jubao1 aElliott, Paul1 aElosua, Roberto1 aEriksson, Johan, G1 aFreimer, Nelson, B1 aGeus, Eco, J C1 aGlorioso, Nicola1 aHaiqing, Shen1 aHartikainen, Anna-Liisa1 aHavulinna, Aki, S1 aHicks, Andrew, A1 aHui, Jennie1 aIgl, Wilmar1 aIllig, Thomas1 aJula, Antti1 aKajantie, Eero1 aKilpeläinen, Tuomas, O1 aKoiranen, Markku1 aKolcic, Ivana1 aKoskinen, Seppo1 aKovacs, Peter1 aLaitinen, Jaana1 aLiu, Jianjun1 aLokki, Marja-Liisa1 aMarusic, Ana1 aMaschio, Andrea1 aMeitinger, Thomas1 aMulas, Antonella1 aParé, Guillaume1 aParker, Alex, N1 aPeden, John, F1 aPetersmann, Astrid1 aPichler, Irene1 aPietiläinen, Kirsi, H1 aPouta, Anneli1 aRidderstråle, Martin1 aRotter, Jerome, I1 aSambrook, Jennifer, G1 aSanders, Alan, R1 aSchmidt, Carsten, Oliver1 aSinisalo, Juha1 aSmit, Jan, H1 aStringham, Heather, M1 aWalters, Bragi1 aWiden, Elisabeth1 aWild, Sarah, H1 aWillemsen, Gonneke1 aZagato, Laura1 aZgaga, Lina1 aZitting, Paavo1 aAlavere, Helene1 aFarrall, Martin1 aMcArdle, Wendy, L1 aNelis, Mari1 aPeters, Marjolein, J1 aRipatti, Samuli1 avan Meurs, Joyce, B J1 aAben, Katja, K1 aArdlie, Kristin, G1 aBeckmann, Jacques, S1 aBeilby, John, P1 aBergman, Richard, N1 aBergmann, Sven1 aCollins, Francis, S1 aCusi, Daniele1 aHeijer, Martin, den1 aEiriksdottir, Gudny1 aGejman, Pablo, V1 aHall, Alistair, S1 aHamsten, Anders1 aHuikuri, Heikki, V1 aIribarren, Carlos1 aKähönen, Mika1 aKaprio, Jaakko1 aKathiresan, Sekar1 aKiemeney, Lambertus1 aKocher, Thomas1 aLauner, Lenore, J1 aLehtimäki, Terho1 aMelander, Olle1 aMosley, Tom, H1 aMusk, Arthur, W1 aNieminen, Markku, S1 aO'Donnell, Christopher, J1 aOhlsson, Claes1 aOostra, Ben1 aPalmer, Lyle, J1 aRaitakari, Olli1 aRidker, Paul, M1 aRioux, John, D1 aRissanen, Aila1 aRivolta, Carlo1 aSchunkert, Heribert1 aShuldiner, Alan, R1 aSiscovick, David, S1 aStumvoll, Michael1 aTönjes, Anke1 aTuomilehto, Jaakko1 avan Ommen, Gert-Jan1 aViikari, Jorma1 aHeath, Andrew, C1 aMartin, Nicholas, G1 aMontgomery, Grant, W1 aProvince, Michael, A1 aKayser, Manfred1 aArnold, Alice, M1 aAtwood, Larry, D1 aBoerwinkle, Eric1 aChanock, Stephen, J1 aDeloukas, Panos1 aGieger, Christian1 aGrönberg, Henrik1 aHall, Per1 aHattersley, Andrew, T1 aHengstenberg, Christian1 aHoffman, Wolfgang1 aLathrop, Mark, G1 aSalomaa, Veikko1 aSchreiber, Stefan1 aUda, Manuela1 aWaterworth, Dawn1 aWright, Alan, F1 aAssimes, Themistocles, L1 aBarroso, Inês1 aHofman, Albert1 aMohlke, Karen, L1 aBoomsma, Dorret, I1 aCaulfield, Mark, J1 aCupples, Adrienne, L1 aErdmann, Jeanette1 aFox, Caroline, S1 aGudnason, Vilmundur1 aGyllensten, Ulf1 aHarris, Tamara, B1 aHayes, Richard, B1 aJarvelin, Marjo-Riitta1 aMooser, Vincent1 aMunroe, Patricia, B1 aOuwehand, Willem, H1 aPenninx, Brenda, W1 aPramstaller, Peter, P1 aQuertermous, Thomas1 aRudan, Igor1 aSamani, Nilesh, J1 aSpector, Timothy, D1 aVölzke, Henry1 aWatkins, Hugh1 aWilson, James, F1 aGroop, Leif, C1 aHaritunians, Talin1 aHu, Frank, B1 aKaplan, Robert, C1 aMetspalu, Andres1 aNorth, Kari, E1 aSchlessinger, David1 aWareham, Nicholas, J1 aHunter, David, J1 aO'Connell, Jeffrey, R1 aStrachan, David, P1 aWichmann, H-Erich1 aBorecki, Ingrid, B1 aDuijn, Cornelia, M1 aSchadt, Eric, E1 aThorsteinsdottir, Unnur1 aPeltonen, Leena1 aUitterlinden, André, G1 aVisscher, Peter, M1 aChatterjee, Nilanjan1 aLoos, Ruth, J F1 aBoehnke, Michael1 aMcCarthy, Mark, I1 aIngelsson, Erik1 aLindgren, Cecilia, M1 aAbecasis, Goncalo, R1 aStefansson, Kari1 aFrayling, Timothy, M1 aHirschhorn, Joel, N uhttps://chs-nhlbi.org/node/123402348nas a2200469 4500008004100000022001400041245010400055210006900159260001300228300001000241490000600251520105900257653000901316653002201325653001001347653001901357653002801376653001901404653001101423653000901434653001101443653001401454653000901468653001601477653002801493653002001521100002001541700002001561700002701581700002201608700002101630700002001651700002301671700002101694700001901715700001901734700002601753700002301779700002301802700001701825856003601842 2011 eng d a1945-458900aHealth and function of participants in the Long Life Family Study: A comparison with other cohorts.0 aHealth and function of participants in the Long Life Family Stud c2011 Jan a63-760 v33 aIndividuals from families recruited for the Long Life Family Study (LLFS) (n= 4559) were examined and compared to individuals from other cohorts to determine whether the recruitment targeting longevity resulted in a cohort of individuals with better health and function. Other cohorts with similar data included the Cardiovascular Health Study, the Framingham Heart Study, and the New England Centenarian Study. Diabetes, chronic pulmonary disease and peripheral artery disease tended to be less common in LLFS probands and offspring compared to similar aged persons in the other cohorts. Pulse pressure and triglycerides were lower, high density lipids were higher, and a perceptual speed task and gait speed were better in LLFS. Age-specific comparisons showed differences that would be consistent with a higher peak, later onset of decline or slower rate of change across age in LLFS participants. These findings suggest several priority phenotypes for inclusion in future genetic analysis to identify loci contributing to exceptional survival.
10aAged10aAged, 80 and over10aAging10aBlood Pressure10aCardiovascular Diseases10aCohort Studies10aFemale10aGait10aHumans10aLongevity10aMale10aMiddle Aged10aPsychomotor Performance10aResearch Design1 aNewman, Anne, B1 aGlynn, Nancy, W1 aTaylor, Christopher, A1 aSebastiani, Paola1 aPerls, Thomas, T1 aMayeux, Richard1 aChristensen, Kaare1 aZmuda, Joseph, M1 aBarral, Sandra1 aLee, Joseph, H1 aSimonsick, Eleanor, M1 aWalston, Jeremy, D1 aYashin, Anatoli, I1 aHadley, Evan uhttps://chs-nhlbi.org/node/126303473nas a2200385 4500008004100000022001400041245011000055210006900165260001300234300001000247490000700257520237800264653000902642653002802651653001602679653001102695653002202706653000902728653002502737653001102762653001702773653002502790653003102815653000902846653001702855653003002872100002102902700002702923700002102950700002702971700001202998700002103010700002003031856003603051 2011 eng d a1532-541500aHigh blood pressure accelerates gait slowing in well-functioning older adults over 18-years of follow-up.0 aHigh blood pressure accelerates gait slowing in wellfunctioning c2011 Mar a390-70 v593 aOBJECTIVES: To examine whether the association between hypertension and decline in gait speed is significant in well-functioning older adults and whether other health-related factors, such as brain, kidney, and heart function, can explain it.
DESIGN: Longitudinal cohort study.
SETTING: Cardiovascular Health Study.
PARTICIPANTS: Of 2,733 potential participants with a brain magnetic resonance imaging (MRI) scan, measures of mobility and systolic blood pressure (BP), no self-reported disability in 1992 to 1994 (baseline), and with at least 1 follow-up gait speed measurement through 1997 to 1999, 643 (aged 73.6, 57% female, 15% black) who had received a second MRI in 1997 to 1999 and an additional gait speed measure in 2005 to 2006 were included.
MEASUREMENTS: Mixed models with random slopes and intercepts were adjusted for age, race, and sex. Main explanatory factors included white matter hyperintensity progression, baseline cystatin-C, and left cardiac ventricular mass. Incidence of stroke and dementia, BP trajectories, and intake of antihypertensive medications during follow-up were tested as other potential explanatory factors.
RESULTS: Higher systolic BP was associated with faster rate of gait speed decline in this selected group of 643 participants, and results were similar in the parent cohort (N = 2,733). Participants with high BP (n = 293) had a significantly faster rate of gait speed decline than those with baseline BP less than 140/90 mmHg and no history of hypertension (n = 350). Rates were similar for those with history of hypertension who were uncontrolled (n = 110) or controlled (n = 87) at baseline and for those who were newly diagnosed (n = 96) at baseline. Adjustment for explanatory factors or for other covariates (education, prevalent cardiovascular disease, physical activity, vision, mood, cognition, muscle strength, body mass index, osteoporosis) did not change the results.
CONCLUSION: High BP accelerates gait slowing in well-functioning older adults over a long period of time, even for those who control their BP or develop hypertension later in life. Health-related measurements did not explain these associations. Future studies to investigate the mechanisms linking hypertension to slowing gait in older adults are warranted.
10aAged10aAntihypertensive Agents10aComorbidity10aFemale10aFollow-Up Studies10aGait10aGeriatric Assessment10aHumans10aHypertension10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aRisk Factors10aStatistics, Nonparametric1 aRosano, Caterina1 aLongstreth, William, T1 aBoudreau, Robert1 aTaylor, Christopher, A1 aDu, Yan1 aKuller, Lewis, H1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/127603048nas a2200445 4500008004100000022001400041245018200055210006900237260001300306300001100319490000700330520171200337653001902049653000902068653002202077653002002099653001702119653004302136653001902179653001102198653001102209653001102220653001502231653002602246653003302272653001702305653001302322653001802335100002102353700002402374700002202398700002202420700002202442700002002464700001802484700002102502700002202523700002102545856003602566 2011 eng d a1945-719700aHigher serum free testosterone concentration in older women is associated with greater bone mineral density, lean body mass, and total fat mass: the cardiovascular health study.0 aHigher serum free testosterone concentration in older women is a c2011 Apr a989-960 v963 aCONTEXT: The physiological importance of endogenous testosterone (T) in older women is poorly understood.
OBJECTIVE: The aim of the study was to determine the association of higher total and free T levels with bone mineral density (BMD), lean body mass, and fat mass in elderly women.
DESIGN: Total and free T were measured using sensitive assays in 232 community-dwelling women aged 67-94 yr who were enrolled in the Cardiovascular Health Study and had dual-energy x-ray absorptiometry scans. Cross-sectional analyses were performed to examine associations between total and free T and BMD and body composition.
RESULTS: In adjusted models, total T was directly associated with BMD at the lumbar spine (P = 0.04) and hip (P = 0.001), but not body composition outcomes, in all women, and after excluding estrogen users and adjusting for estradiol (P = 0.04 and 0.01, respectively). Free T was positively related to hip BMD, lean body mass, and body fat (all P < 0.05), with more than 10% differences in each outcome between women at the highest and lowest ends of the free T range, with attenuation after excluding estrogen users and adjusting for estradiol.
CONCLUSIONS: In the setting of the low estradiol levels found in older women, circulating T levels were associated with bone density. Women with higher free T levels had greater lean body mass, consistent with the anabolic effect of T, and, in contrast to men, greater fat mass. Mechanistic studies are required to determine whether a causal relationship exists between T, bone, and body composition in this population and the degree to which any T effects are estrogen-independent.
10aAdipose Tissue10aAged10aAged, 80 and over10aBody Mass Index10aBone Density10aCardiovascular Physiological Phenomena10aCohort Studies10aFemale10aHealth10aHumans10aOrgan Size10aOsmolar Concentration10aOsteoporosis, Postmenopausal10aTestosterone10aThinness10aUp-Regulation1 aRariy, Chevon, M1 aRatcliffe, Sarah, J1 aWeinstein, Rachel1 aBhasin, Shalender1 aBlackman, Marc, R1 aCauley, Jane, A1 aRobbins, John1 aZmuda, Joseph, M1 aHarris, Tamara, B1 aCappola, Anne, R uhttps://chs-nhlbi.org/node/126602837nas a2200409 4500008004100000022001400041245010200055210006900157260001300226300001100239490000700250520170100257653002501958653001901983653001502002653001902017653002302036653001102059653002202070653002002092653001102112653000902123653001502132653003202147653002402179653000902203653001102212653001702223100002602240700001902266700002202285700001902307700002102326700002402347700002002371856003602391 2011 eng d a1524-462800aHospitalization for infection and risk of acute ischemic stroke: the Cardiovascular Health Study.0 aHospitalization for infection and risk of acute ischemic stroke c2011 Jul a1851-60 v423 aBACKGROUND AND PURPOSE: Little is known about the acute precipitants of ischemic stroke, although evidence suggests infections contribute to risk. We hypothesized that acute hospitalization for infection is associated with the short-term risk of stroke.
METHODS: The case-crossover design was used to compare hospitalization for infection during case periods (90, 30, or 14 days before an incident ischemic stroke) and control periods (equivalent time periods exactly 1 or 2 years before stroke) in the Cardiovascular Health Study, a population-based cohort of 5888 elderly participants from 4 US sites. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by conditional logistic regression. Confirmatory analyses assessed hazard ratios of stroke from Cox regression models, with hospitalization for infection as a time-varying exposure.
RESULTS: During a median follow-up of 12.2 years, 669 incident ischemic strokes were observed in participants without a baseline history of stroke. Hospitalization for infection was more likely during case than control time periods; for 90 days before stroke, OR=3.4 (95% CI, 1.8 to 6.5). The point estimates of risks were higher when we examined shorter intervals: for 30 days, OR=7.3 (95% CI, 1.9 to 40.9), and for 14 days, OR=8.0 (95% CI, 1.7 to 77.3). In survival analyses, risk of stroke was associated with hospitalization for infection in the preceding 90 days, adjusted hazard ratio=2.4 (95% CI, 1.6 to 3.4).
CONCLUSIONS: Hospitalization for infection is associated with a short-term increased risk of stroke, with higher risks observed for shorter intervals preceding stroke.
10aBacterial Infections10aBrain Ischemia10aCardiology10aCohort Studies10aCross-Over Studies10aFemale10aFollow-Up Studies10aHospitalization10aHumans10aMale10aOdds Ratio10aProportional Hazards Models10aRegression Analysis10aRisk10aStroke10aTime Factors1 aElkind, Mitchell, S V1 aCarty, Cara, L1 aO'Meara, Ellen, S1 aLumley, Thomas1 aLefkowitz, David1 aKronmal, Richard, A1 aLongstreth, W T uhttps://chs-nhlbi.org/node/128903229nas a2200445 4500008004100000022001400041245014300055210006900198260001600267300001100283490000800294520193600302653000902238653002202247653001002269653002402279653001102303653001102314653001702325653002602342653002502368653003102393653000902424653002102433653002402454653001902478653002902497653002602526653001702552100001702569700001602586700001802602700002302620700002002643700002102663700002102684700002002705700002202725856003602747 2011 eng d a1524-453900aHypertension, white matter hyperintensities, and concurrent impairments in mobility, cognition, and mood: the Cardiovascular Health Study.0 aHypertension white matter hyperintensities and concurrent impair c2011 Mar 01 a858-650 v1233 aBACKGROUND: Our objective was to investigate the association between hypertension and concurrent impairments in mobility, cognition, and mood; the role of brain white matter hyperintensities in mediating this association; and the impact of these impairments on disability and mortality in elderly hypertensive individuals.
METHODS AND RESULTS: -Blood pressure, gait speed, digit symbol substitution test, and the Center for Epidemiological Studies Depression Scale were measured yearly (1992-1999) on 4700 participants in the Cardiovascular Health Study (age: 74.7, 58% women, 17% blacks, 68% hypertension, 3600 had brain magnetic resonance imaging in 1992-1993, survival data 1992-2005). Using latent profile analysis at baseline, we found that 498 (11%) subjects had concurrent impairments and 3086 (66%) were intact on all 3 measures. Between 1992 and 1999, 651 (21%) became impaired in all 3 domains. Hypertensive individuals were more likely to be impaired at baseline (odds ratio 1.23, 95% confidence interval 1.04 to 1.42, P=0.01) and become impaired during the follow-up (hazard ratio=1.3, 95% confidence interval 1.02 to 1.66, P=0.037). A greater degree of white matter hyperintensities was associated with impairments in the 3 domains (P=0.007) and mediated the association with hypertension (P=0.19 for hypertension after adjusting for white matter hyperintensities in the model, 21% hazard ratio change). Impairments in the 3 domains increased subsequent disability with hypertension (P<0.0001). Hypertension mortality also was increased in those impaired (compared with unimpaired hypertensive individuals: HR=1.10, 95% confidence interval 1.04 to 1.17, P=0.004).
CONCLUSIONS: Hypertension increases the risk of concurrent impairments in mobility, cognition, and mood, which increases disability and mortality. This association is mediated in part by microvascular brain injury.
10aAged10aAged, 80 and over10aBrain10aCognition Disorders10aFemale10aHumans10aHypertension10aKaplan-Meier Estimate10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aMicrocirculation10aMobility Limitation10aMood Disorders10aNerve Fibers, Myelinated10aRetrospective Studies10aRisk Factors1 aHajjar, Ihab1 aQuach, Lien1 aYang, Frances1 aChaves, Paulo, H M1 aNewman, Anne, B1 aMukamal, Kenneth1 aLongstreth, Will1 aInzitari, Marco1 aLipsitz, Lewis, A uhttps://chs-nhlbi.org/node/126902489nas a2200373 4500008004100000022001400041245011800055210006900173260000900242300001000251490000800261520146000269653000901729653001901738653002101757653001801778653001101796653001501807653001101822653000901833653002201842653001401864653002401878653001701902653001701919653001201936100001901948700002301967700001901990700002202009700002402031700002402055856003602079 2012 eng d a1421-975100aHeart rate response to a timed walk and cardiovascular outcomes in older adults: the cardiovascular health study.0 aHeart rate response to a timed walk and cardiovascular outcomes c2012 a69-750 v1223 aOBJECTIVES: To determine the relationship between heart rate response during low-grade physical exertion (6-min walk) with mortality and adverse cardiovascular outcomes in the elderly.
METHODS: Participants in the Cardiovascular Health Study who completed a 6-min walk test were included. We used delta heart rate (difference between postwalk heart rate and resting heart rate) as a measure of chronotropic response and examined its association with (1) all-cause mortality and (2) incident coronary heart disease event, using multivariable Cox regression models.
RESULTS: We included 2,224 participants (mean age 77 ± 4 years; 60% women; 85% white). The average delta heart rate was 26 beats/min. Participants in the lowest tertile of delta heart rate (<20 beats/min) had higher risk-adjusted mortality [hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.00-1.40] and incident coronary heart disease (HR 1.37, 95% CI 1.05-1.78) compared to subjects in the highest tertile (≥30 beats/min), with a significant linear trend across tertiles (p for trend <0.05 for both outcomes). This relationship was not significant after adjustment for distance walked.
CONCLUSION: Impaired chronotropic response during a 6-min walk test was associated with an increased risk of mortality and incident coronary heart disease among the elderly. This association was attenuated after adjusting for distance walked.
10aAged10aCause of Death10aCoronary Disease10aExercise Test10aFemale10aHeart Rate10aHumans10aMale10aPhysical Exertion10aPrognosis10aProspective Studies10aRisk Factors10aTime Factors10aWalking1 aGirotra, Saket1 aKitzman, Dalane, W1 aKop, Willem, J1 aStein, Phyllis, K1 aGottdiener, John, S1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/139301866nas a2200205 4500008004100000022001400041245016000055210006900215260000900284300001000293490000600303520117400309100002701483700002701510700002301537700002201560700002001582700002201602856003601624 2012 eng d a1948-175600aHemodynamic fluid shear stress response genes and carotid intima-media thickness: a candidate gene association analysis in the cardiovascular health study.0 aHemodynamic fluid shear stress response genes and carotid intima c2012 a174-80 v33 aOBJECTIVE: This study examined whether carotid artery intimal-medial thickness (cIMT) is associated with genetic variations (SNPs) in a hemodynamics-responsive gene pathway.
METHODS: Subjects were Cardiovascular Health Study participants free of cardiovascular events at baseline (N=3388). Genotype was measured using Illumina 370CNV HumanHap chip. Carotid IMT was measured using ultrasound. Estimated mean differences in cIMT per additional minor allele for 366 SNPs in MAP2K5, MAPK7, MEF2A/C, and KLF2 were adjusted for sex, age, clinic, and medication use. SNP-SNP interactions were examined using logic regression for 71 tagSNPs.
RESULTS: None of the associations was significant after correction for multiple comparisons; smallest P-value=0.065 for MAP2K5 and common cIMT. The best-performing logic regression tree combined two SNPs in MAP2K5-rs745212 and rs12905175- and common cIMT; this association was not significant, corrected P-value=0.062.
CONCLUSION: There was not strong evidence of association between genetic variants in a hemodynamics-responsive gene pathway and atherosclerosis among older adults.
1 aSuchy-Dicey, Astrid, M1 aEnquobahrie, Daniel, A1 aHeckbert, Susan, R1 aRotter, Jerome, I1 aPsaty, Bruce, M1 aMcKnight, Barbara uhttps://chs-nhlbi.org/node/139403370nas a2200553 4500008004100000022001400041245007500055210006900130260000900199300001100208490000600219520184200225653001002067653003902077653000902116653002502125653001302150653001802163653001902181653002002200653002802220653001202248653001102260653003202271653002602303653003702329653002102366653001102387653000902398653001602407653002002423653002302443100002102466700002002487700001902507700002102526700001802547700002002565700001902585700002002604700002102624700002402645700002202669700002002691700002102711700002402732700002402756856003602780 2012 eng d a1932-620300aHemoglobin A1c and arterial and ventricular stiffness in older adults.0 aHemoglobin A1c and arterial and ventricular stiffness in older a c2012 ae479410 v73 aOBJECTIVE: Arterial and ventricular stiffening are characteristics of diabetes and aging which confer significant morbidity and mortality; advanced glycation endproducts (AGE) are implicated in this stiffening pathophysiology. We examined the association between HbA(1c), an AGE, with arterial and ventricular stiffness measures in older individuals without diabetes.
RESEARCH DESIGN & METHODS: Baseline HbA(1c) was measured in 830 participants free of diabetes defined by fasting glucose or medication use in the Cardiovascular Health Study, a population-based cohort study of adults aged ≥ 65 years. We performed cross-sectional analyses using baseline exam data including echocardiography, ankle and brachial blood pressure measurement, and carotid ultrasonography. We examined the adjusted associations between HbA(1c) and multiple arterial and ventricular stiffness measures by linear regression models and compared these results to the association of fasting glucose (FG) with like measures.
RESULTS: HbA(1c) was correlated with fasting and 2-hour postload glucose levels (r = 0.21; p<0.001 for both) and positively associated with greater body-mass index and black race. In adjusted models, HbA(1c) was not associated with any measure of arterial or ventricular stiffness, including pulse pressure (PP), carotid intima-media thickness, ankle-brachial index, end-arterial elastance, or left ventricular mass (LVM). FG levels were positively associated with systolic, diastolic and PP and LVM.
CONCLUSIONS: In this sample of older adults without diabetes, HbA(1c) was not associated with arterial or ventricular stiffness measures, whereas FG levels were. The role of AGE in arterial and ventricular stiffness in older adults may be better assessed using alternate AGE markers.
10aAdult10aAfrican Continental Ancestry Group10aAged10aAnkle Brachial Index10aArteries10aBlood Glucose10aBlood Pressure10aBody Mass Index10aCross-Sectional Studies10aFasting10aFemale10aGenetic Association Studies10aGlycated Hemoglobin A10aGlycation End Products, Advanced10aHeart Ventricles10aHumans10aMale10aMiddle Aged10aUltrasonography10aVascular Stiffness1 aZieman, Susan, J1 aKamineni, Aruna1 aIx, Joachim, H1 aBarzilay, Joshua1 aDjoussé, Luc1 aKizer, Jorge, R1 aBiggs, Mary, L1 ade Boer, Ian, H1 aChonchol, Michel1 aGottdiener, John, S1 aSelvin, Elizabeth1 aNewman, Anne, B1 aKuller, Lewis, H1 aSiscovick, David, S1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/586002853nas a2200409 4500008004100000022001400041245013800055210006900193260001300262300001000275490000700285520166900292653002201961653000901983653001601992653002402008653004002032653001102072653001102083653001402094653000902108653001602117653002602133653003202159653002402191653002002215653001702235653001602252653001702268653001802285100002202303700002102325700002002346700002002366700002102386856003602407 2013 eng d a1532-851100aHeight and risk of incident intraparenchymal hemorrhage: Atherosclerosis Risk in Communities and Cardiovascular Health study cohorts.0 aHeight and risk of incident intraparenchymal hemorrhage Atherosc c2013 May a323-80 v223 aBACKGROUND: Height is inversely associated with incident coronary disease and total stroke, but few studies have examined the association between height and intraparenchymal hemorrhage (IPH). We hypothesized that height would be inversely associated with incident IPH in the combined cohorts of the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study.
METHODS: Data on Caucasian and African American participants were used to estimate the association of height at baseline with incident IPH verified by clinician review of medical records and imaging reports. Sex-specific Cox proportional hazards regression models were used to calculate hazard ratios.
RESULTS: A total of 20,983 participants initially free of stroke (11,788 women and 9195 men) were followed for an average of 15.9 years (standard deviation [SD] 5.1 years). Incident IPH occurred in 115 women and 73 men. Sex, but not age, race, study, or blood pressure, modified the association (P = .03). After adjustment for risk factors (age, systolic blood pressure, triglycerides, low-density lipoprotein cholesterol, fibrinogen, and race), among women, height was significantly inversely associated with incident IPH (hazard ratio [HR] per SD [6.3 cm] was 0.81; 95% confidence interval [CI] 0.66-0.99; P = .04). The HR for tertile 3 vs 1 in women was 0.63 (95% CI 0.37-1.08). Among men, height was not linearly associated with incident IPH (HR per SD [6.7 cm] was 1.09; 95% CI 0.84-1.40; P = .52).
CONCLUSIONS: This large prospective study provides evidence that shorter height may be a risk factor for incident IPH in women.
10aAfrican Americans10aAged10aBody Height10aCerebral Hemorrhage10aEuropean Continental Ancestry Group10aFemale10aHumans10aIncidence10aMale10aMiddle Aged10aMultivariate Analysis10aProportional Hazards Models10aProspective Studies10aRisk Assessment10aRisk Factors10aSex Factors10aTime Factors10aUnited States1 aSmith, Lindsay, G1 aYatsuya, Hiroshi1 aPsaty, Bruce, M1 aLongstreth, W T1 aFolsom, Aaron, R uhttps://chs-nhlbi.org/node/135802864nas a2200457 4500008004100000022001400041245009700055210006900152260001300221300000800234490000700242520162800249653002201877653001601899653000901915653002201924653001101946653002701957653001101984653002201995653001602017653001102033653002002044653000902064653002402073653002002097653001702117653001602134653001802150653001702168653003002185100001902215700002102234700002102255700002002276700002002296700001802316700001802334700001802352856003602370 2013 eng d a1096-865200aHemoglobin decline, function, and mortality in the elderly: the cardiovascular health study.0 aHemoglobin decline function and mortality in the elderly the car c2013 Jan a5-90 v883 aWhile anemia is associated with poor functional and mortality outcomes in the elderly, the impact of hemoglobin decline is less studied. We evaluated the determinants and consequences of hemoglobin decline in 3,758 non-anemic participants from the Cardiovascular Health Study, a prospective cohort of community-dwelling elderly ≥65 years old at baseline and followed for up to 16 years. Hemoglobin was measured at baseline and 3 years later and anemia defined by World Health Organization (WHO) criteria. We modeled hemoglobin decline in two ways: (1) per each 1 g/dL decrease in hemoglobin and (2) development of anemia by the WHO criteria. Among participants without baseline anemia, hemoglobin decreased by 0.4 g/dL and 9% developed anemia over 3 years. Baseline increasing age, female sex, diabetes, and kidney disease predicted hemoglobin decline over 3 years. Baseline increasing age, being African-American, and kidney disease predicted anemia development over 3 years. Hemoglobin decline was associated with subsequent worse cognitive function in men and anemia development with subsequent worse cognitive function in women. Both anemia development (HR 1.39, 95% CI 1.15, 1.69) and hemoglobin decline (HR 1.11, 95% CI 1.04, 1.18 per 1 g/dL decrease) predicted subsequent mortality in men and women. Hemoglobin decreases identified a large group of elderly individuals at risk for subsequent adverse outcomes who would not be identified using the WHO anemia criteria. These data may allow clinicians to identify at-risk elderly individuals for early intervention to improve the quality and quantity of life.
10aAfrican Americans10aAge Factors10aAged10aAged, 80 and over10aAnemia10aDiabetes Complications10aFemale10aFollow-Up Studies10aHemoglobins10aHumans10aKidney Diseases10aMale10aProspective Studies10aQuality of Life10aRisk Factors10aSex Factors10aSurvival Rate10aTime Factors10aWorld Health Organization1 aZakai, Neil, A1 aFrench, Benjamin1 aArnold, Alice, M1 aNewman, Anne, B1 aFried, Linda, F1 aRobbins, John1 aChaves, Paulo1 aCushman, Mary uhttps://chs-nhlbi.org/node/140904700nas a2200961 4500008004100000022001400041245019200055210006900247260001300316300001100329490000800340520188800348653001802236653001102254653001702265653001102282653001202293653001402305653000902319653003602328653001902364653002502383100001702408700002002425700002002445700002402465700001802489700002102507700002302528700002102551700002202572700002202594700002402616700002102640700001902661700001902680700002102699700002002720700002602740700002502766700001802791700001902809700002402828700002002852700002102872700002302893700001702916700002202933700002502955700002202980700001703002700002503019700002903044700002803073700002803101700001903129700002703148700001903175700001503194700002203209700001903231700002103250700002103271700002303292700002503315700002503340700002003365700001703385700002003402700002003422700002003442700002803462700002503490700002103515700002203536700002403558700003003582700002003612700002003632700002303652700002703675856003603702 2013 eng d a1541-610000aHigher magnesium intake is associated with lower fasting glucose and insulin, with no evidence of interaction with select genetic loci, in a meta-analysis of 15 CHARGE Consortium Studies.0 aHigher magnesium intake is associated with lower fasting glucose c2013 Mar a345-530 v1433 aFavorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesium intake and fasting glucose and insulin. Fifteen studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (ln-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [β = -0.009 mmol/L (95% CI: -0.013, -0.005), P < 0.0001] and insulin [-0.020 ln-pmol/L (95% CI: -0.024, -0.017), P < 0.0001]. No magnesium-related SNP or interaction between any SNP and magnesium reached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P = 0.03) with glucose, and rs11558471 in SLC30A8 and rs3740393 near CNNM2 showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted.
10aBlood Glucose10aFemale10aGenetic Loci10aHumans10aInsulin10aMagnesium10aMale10aPolymorphism, Single Nucleotide10aTrace Elements10aTRPM Cation Channels1 aHruby, Adela1 aNgwa, Julius, S1 aRenstrom, Frida1 aWojczynski, Mary, K1 aGanna, Andrea1 aHallmans, Göran1 aHouston, Denise, K1 aJacques, Paul, F1 aKanoni, Stavroula1 aLehtimäki, Terho1 aLemaitre, Rozenn, N1 aManichaikul, Ani1 aNorth, Kari, E1 aNtalla, Ioanna1 aSonestedt, Emily1 aTanaka, Toshiko1 avan Rooij, Frank, J A1 aBandinelli, Stefania1 aDjoussé, Luc1 aGrigoriou, Efi1 aJohansson, Ingegerd1 aLohman, Kurt, K1 aPankow, James, S1 aRaitakari, Olli, T1 aRiserus, Ulf1 aYannakoulia, Mary1 aZillikens, Carola, M1 aHassanali, Neelam1 aLiu, Yongmei1 aMozaffarian, Dariush1 aPapoutsakis, Constantina1 aSyvänen, Ann-Christine1 aUitterlinden, André, G1 aViikari, Jorma1 aGroves, Christopher, J1 aHofman, Albert1 aLind, Lars1 aMcCarthy, Mark, I1 aMikkilä, Vera1 aMukamal, Kenneth1 aFranco, Oscar, H1 aBorecki, Ingrid, B1 aCupples, Adrienne, L1 aDedoussis, George, V1 aFerrucci, Luigi1 aHu, Frank, B1 aIngelsson, Erik1 aKähönen, Mika1 aKao, Linda, W H1 aKritchevsky, Stephen, B1 aOrho-Melander, Marju1 aProkopenko, Inga1 aRotter, Jerome, I1 aSiscovick, David, S1 aWitteman, Jacqueline, C M1 aFranks, Paul, W1 aMeigs, James, B1 aMcKeown, Nicola, M1 aNettleton, Jennifer, A uhttps://chs-nhlbi.org/node/587903095nas a2200553 4500008004100000022001400041245013400055210006900189260001300258300001100271490000700282520158200289653001001871653001601881653000901897653002201906653001001928653001401938653002101952653001901973653001601992653002802008653001502036653001102051653001102062653001702073653002602090653000902116653001602125653001202141653001502153653003302168653001702201653001202218653001802230100002302248700001802271700002302289700002502312700002002337700002002357700001602377700002502393700002202418700002002440700002102460700002402481856003602505 2013 eng d a1873-258500aHypertension and low HDL cholesterol were associated with reduced kidney function across the age spectrum: a collaborative study.0 aHypertension and low HDL cholesterol were associated with reduce c2013 Mar a106-110 v233 aPURPOSE: To determine if the associations among established risk factors and reduced kidney function vary by age.
METHODS: We pooled cross-sectional data from 14,788 nondiabetics aged 40 to 100 years in 4 studies: Cardiovascular Health Study, Health, Aging, and Body Composition Study, Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular End-Stage Disease cohort.
RESULTS: Hypertension and low high-density lipoprotein (HDL) cholesterol were associated with reduced cystatin C-based estimated glomerular filtration rate (eGFR) across the age spectrum. In adjusted analyses, hypertension was associated with a 2.3 (95% confidence interval [CI], 0.1, 4.4), 5.1 (95% CI, 4.1, 6.1), and 6.9 (95% CI, 3.0, 10.4) mL/min/1.73 m(2) lower eGFR in participants 40 to 59, 60 to 79, and at least 80 years, respectively (P for interaction < .001). The association of low HDL cholesterol with reduced kidney function was also greater in the older age groups: 4.9 (95% CI, 3.5, 6.3), 7.1 (95% CI, 6.0, 8.3), 8.9 (95% CI, 5.4, 11.9) mL/min/1.73 m(2) (P for interaction < .001). Smoking and obesity were associated with reduced kidney function in participants under 80 years. All estimates of the potential population impact of the risk factors were modest.
CONCLUSIONS: Hypertension, obesity, smoking, and low HDL cholesterol are modestly associated with reduced kidney function in nondiabetics. The associations of hypertension and HDL cholesterol with reduced kidney function seem to be stronger in older adults.
10aAdult10aAge Factors10aAged10aAged, 80 and over10aAging10aCausality10aCholesterol, LDL10aCohort Studies10aComorbidity10aCross-Sectional Studies10aCystatin C10aFemale10aHumans10aHypertension10aKidney Function Tests10aMale10aNetherlands10aObesity10aPrevalence10aRenal Insufficiency, Chronic10aRisk Factors10aSmoking10aUnited States1 aOdden, Michelle, C1 aTager, Ira, B1 aGansevoort, Ron, T1 aBakker, Stephan, J L1 aFried, Linda, F1 aNewman, Anne, B1 aKatz, Ronit1 aSatterfield, Suzanne1 aHarris, Tamara, B1 aSarnak, Mark, J1 aSiscovick, David1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/585402712nas a2200457 4500008004100000022001400041245012000055210006900175260001300244300001500257490000700272520143400279653001001713653000901723653002001732653001601752653002101768653002701789653001101816653001101827653001701838653001401855653000901869653001601878653002801894653002401922653001701946100002601963700001901989700002102008700001902029700001702048700002202065700002402087700002402111700001902135700001902154700002102173700002402194856003602218 2014 eng d a1873-258500aHeight and risk of sudden cardiac death: the Atherosclerosis Risk in Communities and Cardiovascular Health studies.0 aHeight and risk of sudden cardiac death the Atherosclerosis Risk c2014 Mar a174-179.e20 v243 aPURPOSE: Sudden cardiac death (SCD) is an important cause of mortality in the adult population. Height has been associated with cardiac hypertrophy and an increased risk of arrhythmias but also with decreased risk of coronary heart disease, suggesting a complex association with SCD.
METHODS: We examined the association of adult height with the risk of physician-adjudicated SCD in two large population-based cohorts: the Cardiovascular Health Study and the Atherosclerosis Risk in Communities study.
RESULTS: Over an average follow-up time of 11.7 years in Cardiovascular Health Study, there were 199 (3.6%) cases of SCD among 5556 participants. In Atherosclerosis Risk in Communities study, over 12.6 years, there were 227 (1.5%) cases of SCD among 15,633 participants. In both cohorts, there was a trend toward decreased SCD with taller height. In fixed effects meta-analysis, the pooled hazard ratio per 10 cm of height was 0.84; 95% confidence interval, 0.73-0.98; P = .03. The association of increased height with lower risk of SCD was slightly attenuated after inclusion of risk factors associated with height, such as hypertension and left ventricular hypertrophy. The association appeared stronger among men than women in both cohorts.
CONCLUSIONS: In two population-based prospective cohorts of different ages, greater height was associated with lower risk of SCD.
10aAdult10aAged10aAtherosclerosis10aBody Height10aCoronary Disease10aDeath, Sudden, Cardiac10aFemale10aHumans10aHypertension10aIncidence10aMale10aMiddle Aged10aPopulation Surveillance10aProspective Studies10aRisk Factors1 aRosenberg, Michael, A1 aLopez, Faye, L1 aBůzková, Petra1 aAdabag, Selcuk1 aChen, Lin, Y1 aSotoodehnia, Nona1 aKronmal, Richard, A1 aSiscovick, David, S1 aAlonso, Alvaro1 aBuxton, Alfred1 aFolsom, Aaron, R1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/618703142nas a2200445 4500008004100000022001400041245009800055210006900153260001300222300001100235490000700246520191900253653000902172653001002181653002802191653001102219653003802230653001302268653002002281653001102301653001402312653000902326653001402335653002602349653001702375653001802392653001802410100002202428700002102450700002102471700002102492700002402513700002302537700002002560700002302580700001902603700001802622700002002640856003602660 2014 eng d a1758-535X00aHeritability of and mortality prediction with a longevity phenotype: the healthy aging index.0 aHeritability of and mortality prediction with a longevity phenot c2014 Apr a479-850 v693 aBACKGROUND: Longevity-associated genes may modulate risk for age-related diseases and survival. The Healthy Aging Index (HAI) may be a subphenotype of longevity, which can be constructed in many studies for genetic analysis. We investigated the HAI's association with survival in the Cardiovascular Health Study and heritability in the Long Life Family Study.
METHODS: The HAI includes systolic blood pressure, pulmonary vital capacity, creatinine, fasting glucose, and Modified Mini-Mental Status Examination score, each scored 0, 1, or 2 using approximate tertiles and summed from 0 (healthy) to 10 (unhealthy). In Cardiovascular Health Study, the association with mortality and accuracy predicting death were determined with Cox proportional hazards analysis and c-statistics, respectively. In Long Life Family Study, heritability was determined with a variance component-based family analysis using a polygenic model.
RESULTS: Cardiovascular Health Study participants with unhealthier index scores (7-10) had 2.62-fold (95% confidence interval: 2.22, 3.10) greater mortality than participants with healthier scores (0-2). The HAI alone predicted death moderately well (c-statistic = 0.643, 95% confidence interval: 0.626, 0.661, p < .0001) and slightly worse than age alone (c-statistic = 0.700, 95% confidence interval: 0.684, 0.717, p < .0001; p < .0001 for comparison of c-statistics). Prediction increased significantly with adjustment for demographics, health behaviors, and clinical comorbidities (c-statistic = 0.780, 95% confidence interval: 0.765, 0.794, p < .0001). In Long Life Family Study, the heritability of the HAI was 0.295 (p < .0001) overall, 0.387 (p < .0001) in probands, and 0.238 (p = .0004) in offspring.
CONCLUSION: The HAI should be investigated further as a candidate phenotype for uncovering longevity-associated genes in humans.
10aAged10aAging10aCardiovascular Diseases10aFemale10aGenetic Predisposition to Disease10aGenotype10aHealth Behavior10aHumans10aLongevity10aMale10aPhenotype10aRetrospective Studies10aRisk Factors10aSurvival Rate10aUnited States1 aSanders, Jason, L1 aMinster, Ryan, L1 aBarmada, Michael1 aMatteini, Amy, M1 aBoudreau, Robert, M1 aChristensen, Kaare1 aMayeux, Richard1 aBorecki, Ingrid, B1 aZhang, Qunyuan1 aPerls, Thomas1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/628005324nas a2201021 4500008004100000022001400041245012300055210006900178260001300247300001100260490000800271520242700279653001002706653002002716653001902736653001902755653002802774653000902802653002102811653001802832653004002850653002902890653001102919653003302930653003802963653001103001653000903012653001603021653001203037653003603049653001003085653001603095100002203111700002003133700002003153700002003173700001903193700002403212700001703236700002103253700002503274700002103299700001803320700002503338700001903363700002003382700002403402700001803426700002803444700003103472700001903503700001903522700002403541700001603565700002303581700001503604700001903619700002203638700002303660700001903683700002003702700002003722700001803742700002503760700002403785700002003809700002203829700002403851700002303875700002303898700002203921700002003943700002403963700002503987700002104012700002104033700001904054700002004073700002004093700002304113700002504136700001904161700002104180700002204201700002204223700002104245856003604266 2015 eng d a1938-320700aHabitual sleep duration is associated with BMI and macronutrient intake and may be modified by CLOCK genetic variants.0 aHabitual sleep duration is associated with BMI and macronutrient c2015 Jan a135-430 v1013 aBACKGROUND: Short sleep duration has been associated with greater risks of obesity, hypertension, diabetes, and cardiovascular disease. Also, common genetic variants in the human Circadian Locomotor Output Cycles Kaput (CLOCK) show associations with ghrelin and total energy intake.
OBJECTIVES: We examined associations between habitual sleep duration, body mass index (BMI), and macronutrient intake and assessed whether CLOCK variants modify these associations.
DESIGN: We conducted inverse-variance weighted, fixed-effect meta-analyses of results of adjusted associations of sleep duration and BMI and macronutrient intake as percentages of total energy as well as interactions with CLOCK variants from 9 cohort studies including up to 14,906 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium.
RESULTS: We observed a significant association between sleep duration and lower BMI (β ± SE = 0.16 ± 0.04, P < 0.0001) in the overall sample; however, associations between sleep duration and relative macronutrient intake were evident in age- and sex-stratified analyses only. We observed a significant association between sleep duration and lower saturated fatty acid intake in younger (aged 20-64 y) adults (men: 0.11 ± 0.06%, P = 0.03; women: 0.10 ± 0.05%, P = 0.04) and with lower carbohydrate (-0.31 ± 0.12%, P < 0.01), higher total fat (0.18 ± 0.09%, P = 0.05), and higher PUFA (0.05 ± 0.02%, P = 0.02) intakes in older (aged 65-80 y) women. In addition, the following 2 nominally significant interactions were observed: between sleep duration and rs12649507 on PUFA intake and between sleep duration and rs6858749 on protein intake.
CONCLUSIONS: Our results indicate that longer habitual sleep duration is associated with lower BMI and age- and sex-specific favorable dietary behaviors. Differences in the relative intake of specific macronutrients associated with short sleep duration could, at least in part, explain previously reported associations between short sleep duration and chronic metabolic abnormalities. In addition, the influence of obesity-associated CLOCK variants on the association between sleep duration and macronutrient intake suggests that longer habitual sleep duration could ameliorate the genetic predisposition to obesity via a favorable dietary profile.
10aAdult10aBody Mass Index10aCLOCK Proteins10aCohort Studies10aCross-Sectional Studies10aDiet10aDietary Proteins10aEnergy Intake10aEuropean Continental Ancestry Group10aFatty Acids, Unsaturated10aFemale10aGene-Environment Interaction10aGenetic Predisposition to Disease10aHumans10aMale10aMiddle Aged10aObesity10aPolymorphism, Single Nucleotide10aSleep10aYoung Adult1 aDashti, Hassan, S1 aFollis, Jack, L1 aSmith, Caren, E1 aTanaka, Toshiko1 aCade, Brian, E1 aGottlieb, Daniel, J1 aHruby, Adela1 aJacques, Paul, F1 aLamon-Fava, Stefania1 aRichardson, Kris1 aSaxena, Richa1 aScheer, Frank, A J L1 aKovanen, Leena1 aBartz, Traci, M1 aPerälä, Mia-Maria1 aJonsson, Anna1 aFrazier-Wood, Alexis, C1 aKalafati, Ioanna-Panagiota1 aMikkilä, Vera1 aPartonen, Timo1 aLemaitre, Rozenn, N1 aLahti, Jari1 aHernandez, Dena, G1 aToft, Ulla1 aJohnson, Craig1 aKanoni, Stavroula1 aRaitakari, Olli, T1 aPerola, Markus1 aPsaty, Bruce, M1 aFerrucci, Luigi1 aGrarup, Niels1 aHighland, Heather, M1 aRallidis, Loukianos1 aKähönen, Mika1 aHavulinna, Aki, S1 aSiscovick, David, S1 aRäikkönen, Katri1 aJørgensen, Torben1 aRotter, Jerome, I1 aDeloukas, Panos1 aViikari, Jorma, S A1 aMozaffarian, Dariush1 aLinneberg, Allan1 aSeppälä, Ilkka1 aHansen, Torben1 aSalomaa, Veikko1 aGharib, Sina, A1 aEriksson, Johan, G1 aBandinelli, Stefania1 aPedersen, Oluf1 aRich, Stephen, S1 aDedoussis, George1 aLehtimäki, Terho1 aOrdovas, Jose, M uhttps://chs-nhlbi.org/node/661403293nas a2200541 4500008004100000022001400041245011700055210006900172260001300241300001200254490000800266520179700274653001602071653001602087653000902103653002202112653001002134653002402144653001502168653001102183653001102194653001402205653001802219653000902237653002602246653003102272653002202303653001402325653003202339653002402371653002002395653001702415653001702432653001802449653001802467100001902485700002002504700001802524700001902542700002402561700002102585700002402606700002202630700002302652700002002675700002002695856003602715 2015 eng d a1468-201X00aHigher circulating adiponectin levels are associated with increased risk of atrial fibrillation in older adults.0 aHigher circulating adiponectin levels are associated with increa c2015 Sep a1368-740 v1013 aBACKGROUND: Adiponectin has cardioprotective properties, suggesting that lower levels seen in obesity and diabetes could heighten risk of atrial fibrillation (AF). Among older adults, however, higher adiponectin has been linked to greater incidence of adverse outcomes associated with AF, although recent reports have shown this association to be U-shaped. We postulated that higher adiponectin would be linked to increased risk for AF in older adults in a U-shaped manner.
METHODS: We examined the associations of total and high-molecular-weight (HMW) adiponectin with incident AF among individuals free of prevalent cardiovascular disease (CVD) participating in a population-based cohort study of older adults (n=3190; age=74±5 years).
RESULTS: During median follow-up of 11.4 years, there were 886 incident AF events. Adjusted cubic splines showed a positive and linear association between adiponectin and incident AF. After adjusting for potential confounders, including amino-terminal pro-B-type natriuretic peptide 1-76, the HR (95% CI) for AF per SD increase in total adiponectin was 1.14 (1.05 to 1.24), while that for HMW adiponectin was 1.17 (1.08 to 1.27). Additional adjustment for putative mediators, including subclinical CVD, diabetes, lipids and inflammation, did not significantly affect these estimates.
CONCLUSIONS: The present findings demonstrate that higher, not lower, levels of adiponectin are independently associated with increased risk of AF in older adults despite its documented cardiometabolic benefits. Additional work is necessary to determine if adiponectin is a marker of failed counter-regulatory pathways or whether this hormone is directly harmful in the setting of or as a result of advanced age.
10aAdiponectin10aAge Factors10aAged10aAged, 80 and over10aAging10aAtrial Fibrillation10aBiomarkers10aFemale10aHumans10aIncidence10aLinear Models10aMale10aMultivariate Analysis10aNatriuretic Peptide, Brain10aPeptide Fragments10aPrognosis10aProportional Hazards Models10aProspective Studies10aRisk Assessment10aRisk Factors10aTime Factors10aUnited States10aUp-Regulation1 aMacheret, Fima1 aBartz, Traci, M1 aDjoussé, Luc1 aIx, Joachim, H1 aMukamal, Kenneth, J1 aZieman, Susan, J1 aSiscovick, David, S1 aTracy, Russell, P1 aHeckbert, Susan, R1 aPsaty, Bruce, M1 aKizer, Jorge, R uhttps://chs-nhlbi.org/node/680108133nas a2201957 4500008004100000022001400041245012800055210006900183260001600252300001100268490000800279520256000287653000902847653002002856653001602876653002102892653002102913653003002934653001102964653002002975653001102995653004103006653005103047653000903098653001603107653003603123653004203159653001703201100002403218700001803242700003103260700002303291700002503314700001503339700001803354700002003372700002303392700002103415700002103436700001803457700002203475700001503497700002803512700002103540700001703561700002203578700001403600700001803614700001903632700002203651700001903673700001503692700001703707700002003724700002603744700002103770700002203791700002503813700002103838700003103859700002203890700002403912700002503936700002103961700002303982700002404005700001904029700002304048700002304071700002104094700002504115700002004140700001904160700001804179700002104197700001404218700001904232700002604251700002404277700002004301700001504321700002004336700003404356700002104390700002304411700002604434700002204460700002604482700001804508700001904526700001904545700002204564700002204586700002304608700002004631700002004651700002104671700002104692700002304713700002104736700002004757700002404777700002104801700002304822700002004845700002204865700001904887700001904906700003704925700002104962700002104983700002205004700002305026700002205049700002405071700002105095700002505116700002005141700002405161700001805185700001805203700002105221700002905242700001905271700002105290700002305311700002005334700002305354700001905377700001805396700001705414700001505431700001905446700002205465700002305487700001505510700002105525700002605546700002305572700002205595700001805617700001805635700002505653700002005678700002105698700002205719700002105741700002405762700002405786700001905810700002505829700002405854700002705878700002105905700001805926700001905944700002105963700002005984700002406004700002406028700001906052710002306071710002106094710002406115856003606139 2015 eng d a1474-547X00aHMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials.0 aHMGcoenzyme A reductase inhibition type 2 diabetes and bodyweigh c2015 Jan 24 a351-610 v3853 aBACKGROUND: Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target.
METHODS: We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis.
FINDINGS: Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05-0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18-0·43), waist circumference (0·32 cm, 0·16-0·47), plasma insulin concentration (1·62%, 0·53-2·72), and plasma glucose concentration (0·23%, 0·02-0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00-1·05); the rs12916-T allele association was consistent (1·06, 1·03-1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18-1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10-0·38 in all trials; 0·33 kg, 95% CI 0·24-0·42 in placebo or standard care controlled trials and -0·15 kg, 95% CI -0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9-6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06-1·18 in all trials; 1·11, 95% CI 1·03-1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04-1·22 in intensive-dose vs moderate dose trials).
INTERPRETATION: The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition.
FUNDING: The funding sources are cited at the end of the paper.
10aAged10aBody Mass Index10aBody Weight10aCholesterol, HDL10aCholesterol, LDL10aDiabetes Mellitus, Type 210aFemale10aGenetic Testing10aHumans10aHydroxymethylglutaryl CoA Reductases10aHydroxymethylglutaryl-CoA Reductase Inhibitors10aMale10aMiddle Aged10aPolymorphism, Single Nucleotide10aRandomized Controlled Trials as Topic10aRisk Factors1 aSwerdlow, Daniel, I1 aPreiss, David1 aKuchenbaecker, Karoline, B1 aHolmes, Michael, V1 aEngmann, Jorgen, E L1 aShah, Tina1 aSofat, Reecha1 aStender, Stefan1 aJohnson, Paul, C D1 aScott, Robert, A1 aLeusink, Maarten1 aVerweij, Niek1 aSharp, Stephen, J1 aGuo, Yiran1 aGiambartolomei, Claudia1 aChung, Christina1 aPeasey, Anne1 aAmuzu, Antoinette1 aLi, KaWah1 aPalmen, Jutta1 aHoward, Philip1 aCooper, Jackie, A1 aDrenos, Fotios1 aLi, Yun, R1 aLowe, Gordon1 aGallacher, John1 aStewart, Marlene, C W1 aTzoulaki, Ioanna1 aBuxbaum, Sarah, G1 avan der A, Daphne, L1 aForouhi, Nita, G1 aOnland-Moret, Charlotte, N1 aSchouw, Yvonne, T1 aSchnabel, Renate, B1 aHubacek, Jaroslav, A1 aKubinova, Ruzena1 aBaceviciene, Migle1 aTamosiunas, Abdonas1 aPajak, Andrzej1 aTopor-Madry, Roman1 aStepaniak, Urszula1 aMalyutina, Sofia1 aBaldassarre, Damiano1 aSennblad, Bengt1 aTremoli, Elena1 ade Faire, Ulf1 aVeglia, Fabrizio1 aFord, Ian1 aJukema, Wouter1 aWestendorp, Rudi, G J1 ade Borst, Gert, Jan1 ade Jong, Pim, A1 aAlgra, Ale1 aSpiering, Wilko1 avan der Zee, Anke, H Maitland1 aKlungel, Olaf, H1 ade Boer, Anthonius1 aDoevendans, Pieter, A1 aEaton, Charles, B1 aRobinson, Jennifer, G1 aDuggan, David1 aKjekshus, John1 aDowns, John, R1 aGotto, Antonio, M1 aKeech, Anthony, C1 aMarchioli, Roberto1 aTognoni, Gianni1 aSever, Peter, S1 aPoulter, Neil, R1 aWaters, David, D1 aPedersen, Terje, R1 aAmarenco, Pierre1 aNakamura, Haruo1 aMcMurray, John, J V1 aLewsey, James, D1 aChasman, Daniel, I1 aRidker, Paul, M1 aMaggioni, Aldo, P1 aTavazzi, Luigi1 aRay, Kausik, K1 aSeshasai, Sreenivasa, Rao Kondap1 aManson, JoAnn, E1 aPrice, Jackie, F1 aWhincup, Peter, H1 aMorris, Richard, W1 aLawlor, Debbie, A1 aSmith, George Davey1 aBen-Shlomo, Yoav1 aSchreiner, Pamela, J1 aFornage, Myriam1 aSiscovick, David, S1 aCushman, Mary1 aKumari, Meena1 aWareham, Nick, J1 aVerschuren, W, M Monique1 aRedline, Susan1 aPatel, Sanjay, R1 aWhittaker, John, C1 aHamsten, Anders1 aDelaney, Joseph, A1 aDale, Caroline1 aGaunt, Tom, R1 aWong, Andrew1 aKuh, Diana1 aHardy, Rebecca1 aKathiresan, Sekar1 aCastillo, Berta, A1 aHarst, Pim1 aBrunner, Eric, J1 aTybjaerg-Hansen, Anne1 aMarmot, Michael, G1 aKrauss, Ronald, M1 aTsai, Michael1 aCoresh, Josef1 aHoogeveen, Ronald, C1 aPsaty, Bruce, M1 aLange, Leslie, A1 aHakonarson, Hakon1 aDudbridge, Frank1 aHumphries, Steve, E1 aTalmud, Philippa, J1 aKivimaki, Mika1 aTimpson, Nicholas, J1 aLangenberg, Claudia1 aAsselbergs, Folkert, W1 aVoevoda, Mikhail1 aBobak, Martin1 aPikhart, Hynek1 aWilson, James, G1 aReiner, Alex, P1 aKeating, Brendan, J1 aHingorani, Aroon, D1 aSattar, Naveed1 aDIAGRAM Consortium1 aMAGIC Consortium1 aInterAct Consortium uhttps://chs-nhlbi.org/node/686302284nas a2200361 4500008004100000022001400041245012800055210006900183260001300252300001100265490000700276520127400283653000901557653002601566653001501592653001101607653001901618653001101637653002501648653000901673653001901682653002401701653001201725100001901737700001601756700001801772700001701790700002001807700002001827700002001847700001901867856003601886 2015 eng d a1532-479600aHusbands' and Wives' Physical Activity and Depressive Symptoms: Longitudinal Findings from the Cardiovascular Health Study.0 aHusbands and Wives Physical Activity and Depressive Symptoms Lon c2015 Oct a704-140 v493 aBACKGROUND: When examining older adults' health behaviors and psychological health, it is important to consider the social context.
PURPOSE: The purpose of this study was to examine in older adult marriages whether each spouse's physical activity predicted changes in their own (actor effects) and their partner's (partner effects) depressive symptoms. Gender differences were also examined.
METHOD: Each spouse within 1260 married couples (at baseline) in the Cardiovascular Health Study completed self-report measures at wave 1 (1989-1990), wave 3 (1992-1993), and wave 7 (1996-1997). Dyadic path analyses were performed.
RESULTS: Husbands' physical activity significantly predicted own decreased depressive symptoms (actor effect). For both spouses, own physical activity did not significantly predict the spouse's depressive symptoms (partner effects). However, husbands' physical activity and depressive symptoms predicted wives' physical activity and depressive symptoms (partner effects), respectively. Depressive symptoms did not predict physical activity.
CONCLUSION: Findings suggest that husbands' physical activity is particularly influential for older married couples' psychological health.
10aAged10aCardiovascular System10aDepression10aFemale10aHealth Surveys10aHumans10aLongitudinal Studies10aMale10aMotor Activity10aSex Characteristics10aSpouses1 aMonin, Joan, K1 aLevy, Becca1 aChen, Baibing1 aFried, Terri1 aStahl, Sarah, T1 aSchulz, Richard1 aDoyle, Margaret1 aKershaw, Trace uhttps://chs-nhlbi.org/node/669603088nas a2200289 4500008004100000022001400041245008600055210006900141260001600210300000800226490000700234520224200241653002302483653001802506653001302524653004202537653001102579100001802590700001902608700002902627700002002656700001902676700002102695700003302716700001302749856003602762 2016 eng d a1471-210500aA hybrid computational strategy to address WGS variant analysis in >5000 samples.0 ahybrid computational strategy to address WGS variant analysis in c2016 Sep 10 a3610 v173 aBACKGROUND: The decreasing costs of sequencing are driving the need for cost effective and real time variant calling of whole genome sequencing data. The scale of these projects are far beyond the capacity of typical computing resources available with most research labs. Other infrastructures like the cloud AWS environment and supercomputers also have limitations due to which large scale joint variant calling becomes infeasible, and infrastructure specific variant calling strategies either fail to scale up to large datasets or abandon joint calling strategies.
RESULTS: We present a high throughput framework including multiple variant callers for single nucleotide variant (SNV) calling, which leverages hybrid computing infrastructure consisting of cloud AWS, supercomputers and local high performance computing infrastructures. We present a novel binning approach for large scale joint variant calling and imputation which can scale up to over 10,000 samples while producing SNV callsets with high sensitivity and specificity. As a proof of principle, we present results of analysis on Cohorts for Heart And Aging Research in Genomic Epidemiology (CHARGE) WGS freeze 3 dataset in which joint calling, imputation and phasing of over 5300 whole genome samples was produced in under 6 weeks using four state-of-the-art callers. The callers used were SNPTools, GATK-HaplotypeCaller, GATK-UnifiedGenotyper and GotCloud. We used Amazon AWS, a 4000-core in-house cluster at Baylor College of Medicine, IBM power PC Blue BioU at Rice and Rhea at Oak Ridge National Laboratory (ORNL) for the computation. AWS was used for joint calling of 180 TB of BAM files, and ORNL and Rice supercomputers were used for the imputation and phasing step. All other steps were carried out on the local compute cluster. The entire operation used 5.2 million core hours and only transferred a total of 6 TB of data across the platforms.
CONCLUSIONS: Even with increasing sizes of whole genome datasets, ensemble joint calling of SNVs for low coverage data can be accomplished in a scalable, cost effective and fast manner by using heterogeneous computing platforms without compromising on the quality of variants.
10aDatabases, Genetic10aGenome, Human10aGenomics10aHigh-Throughput Nucleotide Sequencing10aHumans1 aHuang, Zhuoyi1 aRustagi, Navin1 aVeeraraghavan, Narayanan1 aCarroll, Andrew1 aGibbs, Richard1 aBoerwinkle, Eric1 aVenkata, Manjunath, Gorentla1 aYu, Fuli uhttps://chs-nhlbi.org/node/856400567nas a2200181 4500008004100000022001400041245007900055210006900134260001600203300001200219490000800231100002300239700002600262700002100288700002000309700002000329856003600349 2017 eng d a2168-611400aHealth and Functional Status of Adults Aged 90 Years in the United States.0 aHealth and Functional Status of Adults Aged 90 Years in the Unit c2017 May 01 a732-7340 v1771 aOdden, Michelle, C1 aKoh, William, Jen Hoe1 aArnold, Alice, M1 aPsaty, Bruce, M1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/735502910nas a2200265 4500008004100000022001400041245011100055210006900166260001600235520208900251100002402340700001502364700002002379700001502399700001502414700002302429700002102452700002502473700002302498700002102521700002102542700001902563700002602582856003602608 2017 eng d a1873-681500aHidden heterogeneity in Alzheimer's disease: Insights from genetic association studies and other analyses.0 aHidden heterogeneity in Alzheimers disease Insights from genetic c2017 Oct 263 aDespite evident success in clarifying many important features of Alzheimer's disease (AD) the efficient methods of its prevention and treatment are not yet available. The reasons are likely to be the fact that AD is a multifactorial and heterogeneous health disorder with multiple alternative pathways of disease development and progression. The availability of genetic data on individuals participated in longitudinal studies of aging health and longevity, as well as on participants of cross-sectional case-control studies allow for investigating genetic and non-genetic connections with AD and to link the results of these analyses with research findings obtained in clinical, experimental, and molecular biological studies of this health disorder. The objective of this paper is to perform GWAS of AD in several study populations and investigate possible roles of detected genetic factors in developing AD hallmarks and in other health disorders. The data collected in the Framingham Heart Study (FHS), Cardiovascular Health Study (CHS), Health and Retirement Study (HRS) and Late Onset Alzheimer's Disease Family Study (LOADFS) were used in these analyses. The logistic regression and Cox's regression were used as statistical models in GWAS. The results of analyses confirmed strong associations of genetic variants from well-known genes APOE, TOMM40, PVRL2 (NECTIN2), and APOC1 with AD. Possible roles of these genes in pathological mechanisms resulting in development of hallmarks of AD are described. Many genes whose connection with AD was detected in other studies showed nominally significant associations with this health disorder in our study. The evidence on genetic connections between AD and vulnerability to infection, as well as between AD and other health disorders, such as cancer and type 2 diabetes, were investigated. The progress in uncovering hidden heterogeneity in AD would be substantially facilitated if common mechanisms involved in development of AD, its hallmarks, and AD related chronic conditions were investigated in their mutual connection.
1 aYashin, Anatoliy, I1 aFang, Fang1 aKovtun, Mikhail1 aWu, Deqing1 aDuan, Matt1 aArbeev, Konstantin1 aAkushevich, Igor1 aKulminski, Alexander1 aCulminskaya, Irina1 aZhbannikov, Ilya1 aYashkin, Arseniy1 aStallard, Eric1 aUkraintseva, Svetlana uhttps://chs-nhlbi.org/node/759802478nas a2200241 4500008004100000022001400041245012400055210007000179260001600249300000700265490000700272520174300279100001702022700002102039700002002060700001802080700002102098700002402119700002102143700001902164700001702183856003602200 2017 eng d a1471-236900aHigher plasma transforming growth factor (TGF)-β is associated with kidney disease in older community dwelling adults.0 aHigher plasma transforming growth factor TGFβ is associated with c2017 Mar 21 a980 v183 aBACKGROUND: TGF-β is induced in the vasculature with aging suggesting that high plasma TGF-β levels may be a risk factor for chronic kidney disease (CKD) in older adults.
METHODS: We conducted a cross-sectional analysis of the association between plasma TGF-β levels and CKD including data for 1722 older adults who had participated in the 1996/97 visit of the Cardiovascular Health Study (CHS). Prevalent CKD was defined as eGFR < 60 mL/min/1.73 m(2) or urinary albumin/creatinine ratio (ACR) ≥30 mg/g. We also evaluated whether baseline TGF-β levels predicted change in eGFR, cardiovascular (CV) events, or mortality in longitudinal analysis.
RESULTS: Plasma TGF-β levels were significantly and independently associated with lower eGFR in cross-sectional analysis. Doubling of TGF-β was significantly associated with lower eGFR (β estimate after adjusting for CV risk factors = -1.18, 95% CI -2.03, -0.32). We observed no association with albuminuria. There was no association between baseline TGF-β and change in eGFR, but each doubling of TGF-β at baseline was associated with increased risk of a composite outcome of CV events and mortality, adjusted HR 1.10 (95% C.I. 1.02- 1.20, p = 0.006).
CONCLUSION: In this large cohort of community-dwelling older individuals, high plasma TGF-β levels are modestly, but independently associated with lower eGFR but not with albuminuria in cross-sectional analysis. In addition, TGF-β levels are associated with increased risk of CV events and mortality. Further research is needed to determine the direction of association between plasma TGF-β and the risk of CKD and CKD-associated morbidities in older adults.
1 aMehta, Tapan1 aBůzková, Petra1 aKizer, Jorge, R1 aDjoussé, Luc1 aChonchol, Michel1 aMukamal, Kenneth, J1 aShlipak, Michael1 aIx, Joachim, H1 aJalal, Diana uhttps://chs-nhlbi.org/node/735102780nas a2200445 4500008004100000022001400041245010600055210006900161260001600230300001400246490000800260520149600268100002601764700002201790700002501812700001801837700002101855700002101876700002001897700002101917700001701938700001901955700002101974700001801995700002002013700002502033700002202058700002002080700002402100700002402124700002002148700001402168700001602182700002102198700002402219700002002243700001802263700001702281856003602298 2018 eng d a1476-625600aHarmonization of Respiratory Data From 9 US Population-Based Cohorts: The NHLBI Pooled Cohorts Study.0 aHarmonization of Respiratory Data From 9 US PopulationBased Coho c2018 Nov 01 a2265-22780 v1873 aChronic lower respiratory diseases (CLRDs) are the fourth leading cause of death in the United States. To support investigations into CLRD risk determinants and new approaches to primary prevention, we aimed to harmonize and pool respiratory data from US general population-based cohorts. Data were obtained from prospective cohorts that performed prebronchodilator spirometry and were harmonized following 2005 ATS/ERS standards. In cohorts conducting follow-up for noncardiovascular events, CLRD events were defined as hospitalizations/deaths adjudicated as CLRD-related or assigned relevant administrative codes. Coding and variable names were applied uniformly. The pooled sample included 65,251 adults in 9 cohorts followed-up for CLRD-related mortality over 653,380 person-years during 1983-2016. Average baseline age was 52 years; 56% were female; 49% were never-smokers; and racial/ethnic composition was 44% white, 22% black, 28% Hispanic/Latino, and 5% American Indian. Over 96% had complete data on smoking, clinical CLRD diagnoses, and dyspnea. After excluding invalid spirometry examinations (13%), there were 105,696 valid examinations (median, 2 per participant). Of 29,351 participants followed for CLRD hospitalizations, median follow-up was 14 years; only 5% were lost to follow-up at 10 years. The NHLBI Pooled Cohorts Study provides a harmonization standard applied to a large, US population-based sample that may be used to advance epidemiologic research on CLRD.
1 aOelsner, Elizabeth, C1 aBalte, Pallavi, P1 aCassano, Patricia, A1 aCouper, David1 aEnright, Paul, L1 aFolsom, Aaron, R1 aHankinson, John1 aJacobs, David, R1 aKalhan, Ravi1 aKaplan, Robert1 aKronmal, Richard1 aLange, Leslie1 aLoehr, Laura, R1 aLondon, Stephanie, J1 aAcien, Ana, Navas1 aNewman, Anne, B1 aO'Connor, George, T1 aSchwartz, Joseph, E1 aSmith, Lewis, J1 aYeh, Fawn1 aZhang, Yiyi1 aMoran, Andrew, E1 aMwasongwe, Stanford1 aWhite, Wendy, B1 aYende, Sachin1 aBarr, Graham uhttps://chs-nhlbi.org/node/804203043nas a2200253 4500008004100000022001400041245016700055210006900222260000900291300002100300490000600321520221100327100002402538700001702562700002602579700002102605700002102626700001302647700002402660700002402684700002202708700002302730856003602753 2018 eng d a2050-312100aHospital and clinical care costs associated with atrial fibrillation for Medicare beneficiaries in the Cardiovascular Health Study and the Framingham Heart Study.0 aHospital and clinical care costs associated with atrial fibrilla c2018 a20503121187594440 v63 aBackground: Atrial fibrillation is increasingly prevalent as the US population ages and is associated with significant morbidity and mortality. Care for patients with atrial fibrillation can be costly, US health care costs are comparatively high, and there are few cost estimates available that incorporate detailed measurement of comorbidities and their effects on costs.
Methods and Results: In the Cardiovascular Health Study and the Framingham Heart Study, participants aged 65 years or older with newly diagnosed atrial fibrillation were matched on age and follow-up time to referents free of atrial fibrillation. The total clinical and hospital medical costs paid by Medicare Parts A and B (drug costs from Medicare Part D costs were not included) in the year prior to diagnosis (or matching) were compared with costs in the following year. Estimates were adjusted for other medical conditions and adjusted to 2009 dollars. In the Cardiovascular Health Study, 513 participants were diagnosed with new-onset atrial fibrillation and survived 30 days post-atrial fibrillation diagnosis, and 513 referents (as a control cohort) were identified, with a mean age of 77 years. In the Framingham Heart Study, we identified 336 participants diagnosed with atrial fibrillation, who survived 30 days post-atrial fibrillation diagnosis and matched these participants to 336 referents. We compared these new-onset atrial fibrillation participants with referents, using a difference in difference design to account for both time trends and differences between the two groups. The adjusted incremental cost for participants with atrial fibrillation, compared with referents, was US$18,060 (95% confidence interval: US$14,965-US$21,155) in the Cardiovascular Health Study and US$20,012 (95% confidence interval: US$15,057-US$24,966) in the Framingham Heart Study. The pooled estimate was US$18,601 (95% confidence interval: US$15,981-US$21,234).
Conclusion: Atrial fibrillation was associated with increased costs in the year after diagnosis in two community-based cohorts, even after careful accounting for age, time period, and systematically measured comorbidities.
1 aDelaney, Joseph, Ac1 aYin, Xiaoyan1 aFontes, João, Daniel1 aWallace, Erin, R1 aSkinner, Asheley1 aWang, Na1 aHammill, Bradley, G1 aBenjamin, Emelia, J1 aCurtis, Lesley, H1 aHeckbert, Susan, R uhttps://chs-nhlbi.org/node/767702119nas a2200265 4500008004100000022001400041245012000055210006900175260001600244520128100260100002301541700002501564700002101589700001701610700002401627700002901651700002201680700002001702700001401722700001801736700002001754700002001774700002301794856003601817 2019 eng d a1476-625600aHeterogeneous Exposure Associations in Observational Cohort Studies: The Example of Blood Pressure in Older Adults.0 aHeterogeneous Exposure Associations in Observational Cohort Stud c2019 Oct 083 aHeterogeneous exposure associations (HEAs) can be defined as differences in the association of a exposure with an outcome among subgroups that differ by a set of characteristics. This manuscript intends to foster discussion of HEAs in the epidemiological literature, and present a variant of the random forest algorithm that can be used to identify HEAs. We demonstrate the use of this algorithm in the setting of the association of systolic blood pressure and death in older adults. The training set included pooled data from the baseline examination of the Cardiovascular Health Study (1989-1993), the Health, Aging, and Body Composition study (1997-1998), and the Sacramento Area Latino Study on Aging (1998-1999). The test set included data from the National Health and Nutrition Examination Survey (1999-2002). The hazard ratios ranged from 1.25 (95% CI: 1.13, 1.37) per 10 mmHg higher systolic blood pressure in men aged ≤67 years with diastolic blood pressure >80 mmHg, to 1.00 (0.96, 1.03) in women with creatinine <0.7 mg/dL and a history of hypertension. HEAs have the potential to improve our understanding of disease mechanisms in diverse populations, and guide the design of randomized controlled trials to control exposures in heterogeneous populations.
1 aOdden, Michelle, C1 aRawlings, Andreea, M1 aKhodadadi, Abtin1 aFern, Xiaoli1 aShlipak, Michael, G1 aBibbins-Domingo, Kirsten1 aCovinsky, Kenneth1 aKanaya, Alka, M1 aLee, Anne1 aHaan, Mary, N1 aNewman, Anne, B1 aPsaty, Bruce, M1 aPeralta, Carmen, A uhttps://chs-nhlbi.org/node/827801584nas a2200193 4500008004100000022001400041245008300055210006900138260001600207520097900223100002501202700002001227700002101247700002101268700002101289700002001310700002401330856003601354 2019 eng d a1097-025800aHigh-dimensional longitudinal classification with the multinomial fused lasso.0 aHighdimensional longitudinal classification with the multinomial c2019 Jan 303 aWe study regularized estimation in high-dimensional longitudinal classification problems, using the lasso and fused lasso regularizers. The constructed coefficient estimates are piecewise constant across the time dimension in the longitudinal problem, with adaptively selected change points (break points). We present an efficient algorithm for computing such estimates, based on proximal gradient descent. We apply our proposed technique to a longitudinal data set on Alzheimer's disease from the Cardiovascular Health Study Cognition Study. Using data analysis and a simulation study, we motivate and demonstrate several practical considerations such as the selection of tuning parameters and the assessment of model stability. While race, gender, vascular and heart disease, lack of caregivers, and deterioration of learning and memory are all important predictors of dementia, we also find that these risk factors become more relevant in the later stages of life.
1 aAdhikari, Samrachana1 aLecci, Fabrizio1 aBecker, James, T1 aJunker, Brian, W1 aKuller, Lewis, H1 aLopez, Oscar, L1 aTibshirani, Ryan, J uhttps://chs-nhlbi.org/node/796602522nas a2200217 4500008004100000022001400041245019500055210006900250260001300319300001200332490000700344520176800351100002102119700002402140700002002164700002102184700002002205700001902225700002402244856003602268 2019 eng d a2048-850500aHigher albumin:creatinine ratio and lower estimated glomerular filtration rate are potential risk factors for decline of physical performance in the elderly: the Cardiovascular Health Study.0 aHigher albumincreatinine ratio and lower estimated glomerular fi c2019 Dec a788-7940 v123 aIntroduction: Mildly reduced renal function and elevated urine protein levels are each prospectively associated with hip fracture risk in older adults. Here we determine whether these markers are associated with reduced appendicular muscle performance.
Methods: We prospectively examined the associations of urine albumin:creatinine ratio (ACR) and reduced estimated glomerular filtration rate (eGFR) with longitudinal changes in grip strength and gait speed >2 years in 2317 older community-dwelling men and women (median age 77 years). The median ACR was 9.8 [interquartile range (IQR) 5.40-21.50] mg/g creatinine and the median eGFR was 71.6 (IQR 59.1-83.56) mL/min/1.73 m. Models were adjusted for demographic factors, clinical history and biochemical measures in four candidate pathways: diabetes, oxidative stress, inflammation and fibrosis.
Results: In demographic- and covariate-adjusted models, a 2-fold higher baseline urine ACR was associated with longitudinal changes of -0.17 kg [95% confidence interval (CI) -0.29 to -0.06) in grip strength and -1.10 cm/s (95% CI -1.67 to -0.53) gait speed per year. Corresponding estimates for a 10 mL/min/1.73 m lower baseline eGFR were -0.13 kg (95% CI -0.23 to -0.04) and -0.89 cm/s (95% CI -1.37 to -0.40), respectively. The associations of a 2-fold higher baseline ACR and a 10 mL/min/1.73 m lower baseline eGFR using cystatin C with grip strength and gait speed were equivalent to ∼1.2-1.9 additional years of age. Adjustment for covariates in candidate pathways did not attenuate these estimates.
Conclusions: In older adults, higher ACR and lower eGFR are potential risk factors for a decline of physical performance >2 years.
1 aBůzková, Petra1 aBarzilay, Joshua, I1 aFink, Howard, A1 aRobbins, John, A1 aCauley, Jane, A1 aIx, Joachim, H1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/825902369nas a2200181 4500008004100000022001400041245009300055210006900148260001600217520178500233100002402018700002102042700002402063700001802087700002202105700002402127856003602151 2020 eng d a1758-535X00aHospitalization Rates in Older Adults with Albuminuria: The Cardiovascular Health Study.0 aHospitalization Rates in Older Adults with Albuminuria The Cardi c2020 Jan 223 aBACKGROUND: Albuminuria is highly prevalent among older adults, especially those with diabetes. It is associated with several chronic diseases, but its overall impact on the health of older adults, as measured by hospitalization, has not been quantified.
METHODS: We followed 3110 adults, mean age 78 years, for a median 9.75 years, of whom 654 (21%) had albuminuria (>30 mg albumin / gram creatinine) at baseline. Poisson regression models, adjusted for cardiovascular, renal and demographic factors, were used to evaluate association of albuminuria with all-cause and cause-specific hospitalizations, as defined by ICD, version 9, categories.
RESULTS: The rates of hospitalization per 100 patient-years were 65.85 for participants with albuminuria and 37.55 for participants without albuminuria. After adjustment for covariates, participants with albuminuria were more likely to be hospitalized for any cause than participants without albuminuria (incident rate ratio [IRR], 1.39 [95% confidence intervals, 1.27. 1.53] and to experience more days in hospital (IRR 1.56 [1.37, 1.76]). The association of albuminuria with hospitalization was similar among participants with and without diabetes (adjusted IRR for albuminuria vs no albuminuria: diabetes 1.37 [1.11, 1.70], no diabetes 1.40 [1.26, 1.55]; p interaction NS). Albuminuria was significantly associated with hospitalization for circulatory, endocrine, genitourinary, respiratory, and injury categories.
CONCLUSIONS: Albuminuria in older adults is associated with an increased risk of hospitalization for a broad range of illnesses. Albuminuria in the presence or absence of diabetes appears to mark a generalized vulnerability to diseases of aging among older adults.
1 aBarzilay, Joshua, I1 aBůzková, Petra1 aShlipak, Michael, G1 aBansal, Nisha1 aGarimella, Pranav1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/828302190nas a2200205 4500008004100000022001400041245014500055210006900200260001600269300002300285520148600308100001601794700002101810700002801831700002001859700002301879700002401902700002201926856003601948 2021 eng d a1524-462800aHDL (High-Density Lipoprotein) Subspecies, Prevalent Covert Brain Infarcts, and Incident Overt Ischemic Stroke: Cardiovascular Health Study.0 aHDL HighDensity Lipoprotein Subspecies Prevalent Covert Brain In c2021 Oct 14 aSTROKEAHA1210342993 aBACKGROUND AND PURPOSE: Whether HDL (high-density lipoprotein) is associated with risk of vascular brain injury is unclear. HDL is comprised of many apo (apolipoprotein) species, creating distinct subtypes of HDL.
METHODS: We utilized sandwich ELISA to determine HDL subspecies from plasma collected in 1998/1999 from 2001 CHS (Cardiovascular Health Study) participants (mean age, 80 years).
RESULTS: In cross-sectional analyses, participants with higher apoA1 in plasma and lower apoE in HDL were less likely to have prevalent covert magnetic resonance imaging-defined infarcts: odds ratio for apoA1 Q4 versus Q1, 0.68 (95% CI, 0.50-0.93), and odds ratio for apoE Q4 versus Q1, 1.36 (95% CI, 1.01-1.84). Similarly, apoA1 in the subspecies of HDL that lacked apoC3, apoJ, or apoE was inversely related to covert infarcts, and apoE in the subspecies of HDL that lacked apoC3 or apoJ was directly related to covert infarcts in prospective analyses. In contrast, the concentrations of apoA1 and apoE in the complementary subspecies of HDL that contained these apos were unrelated to covert infarcts. Patterns of associations between incident overt ischemic stroke and apoA1, apoE, and apoA1 and apoE in subspecies of HDL were similar to those observed for covert infarcts but less pronounced.
CONCLUSIONS: This study highlights HDL subspecies defined by apo content as relevant biomarkers of covert and overt vascular brain injury.
1 aKoch, Manja1 aAroner, Sarah, A1 aFitzpatrick, Annette, L1 aLongstreth, W T1 aFurtado, Jeremy, D1 aMukamal, Kenneth, J1 aJensen, Majken, K uhttps://chs-nhlbi.org/node/891202511nas a2200217 4500008004100000022001400041245010100055210006900156260001600225520182300241100002502064700002102089700002102110700002002131700001702151700001802168700002502186700002402211700002202235856003602257 2021 eng d a1538-783600aHemostatic factor levels and cognitive decline in older adults: The Cardiovascular Health Study.0 aHemostatic factor levels and cognitive decline in older adults T c2021 Mar 163 aBACKGROUND: Hemostasis is a key factor in cerebrovascular disease, but the association of hemostatic factors with cognitive decline is unclear.
OBJECTIVE: To prospectively evaluate associations of 20 hemostatic factor levels with changes in cognition during ≥8 years of follow-up in the Cardiovascular Health Study (CHS) of older adults.
METHODS: We included participants of an existing CHS cross-sectional substudy (n = 400) with hemostatic factors measured in 1989-1990. Between 1989-1990 and 1998-1999, cognitive function was measured using the Modified Mini-Mental State Examination (3MSE) and Digit Symbol Substitution Tests. Mixed-effects linear regression models estimated change in cognitive function over time, adjusting for sociodemographic and clinical factors and APOE genotype, using Bonferroni adjustment. We also derived principal components to account for the interrelationship among factors.
RESULTS: Of 20 factors evaluated individually, only higher levels of plasmin-α -antiplasmin complex (PAP), tissue factor pathway inhibitor (TFPI), and lower factor X (FXc) levels were associated with faster cognitive decline, estimated by annual change in 3MSE points (1 standard deviation PAP β = -0.65, 95% confidence interval [CI]: -1.08 to -0.21; TFPI β = -0.55, 95% CI: -0.90 to -0.19; FXc β = 0.52, 95% CI: 0.21-0.84). One of four principal components, loading positively on D-dimer, prothrombin fragment 1.2 (F1.2), and PAP was significantly associated with change in 3MSE.
CONCLUSIONS: Levels of PAP, TPFI, and FXc and a combination of factors driven by PAP, D-dimer, and F1.2 were associated with cognitive decline. Whether these findings can be used to improve dementia prevention or prediction requires further study.
1 aHarrington, Laura, B1 aEhlert, Alexa, N1 aThacker, Evan, L1 aJenny, Nancy, S1 aLopez, Oscar1 aCushman, Mary1 aFitzpatrick, Annette1 aMukamal, Kenneth, J1 aJensen, Majken, K uhttps://chs-nhlbi.org/node/870603056nas a2200325 4500008004100000022001400041245013200055210006900187260001300256300001400269490000700283520207500290653002402365653002802389653002102417653001102438653001102449653002002460653000902480653002802489653002402517653001702541653001102558100002702569700001702596700002902613700002702642700002502669856003602694 2023 eng d a1468-133100aHigh-risk carotid plaques and incident ischemic stroke in patients with atrial fibrillation in the Cardiovascular Health Study.0 aHighrisk carotid plaques and incident ischemic stroke in patient c2023 Jul a2042-20500 v303 aBACKGROUND AND PURPOSE: Whether carotid artery disease could improve stroke risk stratification tools in patients with atrial fibrillation (AF) remains uncertain. This study was undertaken to investigate the risk of ischemic stroke associated with occlusive and nonocclusive carotid atherosclerotic disease in patients with AF in the prospective population-based Cardiovascular Health Study.
METHODS: We included participants aged ≥65 years with AF. We used multivariable Cox regression analysis to explore the risk of ischemic stroke associated with the percentage of carotid stenosis, plaque irregularity, echogenicity, and vulnerability (markedly irregular, ulcerated, or hypoechoic plaques).
RESULTS: A total of 1398 participants were included (55.2% female, 61.7% aged 65-74 years). The maximum carotid stenosis was <50%, 50%-99%, and 100% in 94.5%, 5%, and 0.5% of participants, respectively. High-risk plaques based on echogenicity and plaque irregularity were found in 25.6% and 8.9% of participants, respectively. After a median follow-up of 10.9 years (interquartile range = 7.5-15.6), 298 ischemic strokes were recorded. There was no difference in the incidence of ischemic stroke according to the degree of carotid artery stenosis (p = 0.44), plaque echogenicity (low vs. high risk, p = 0.68), plaque irregularity (low vs. high risk, p = 0.55), and plaque vulnerability (p = 0.86). The CHA₂DS₂-VASc score was associated with an increased risk of ischemic stroke (adjusted hazard ratio = 1.28, 95% confidence interval = 1.18-1.40, p < 0.001). Both maximum grade of stenosis and plaque vulnerability were not associated with incident ischemic stroke (all p > 0.05).
CONCLUSIONS: Neither the degree of carotid stenosis nor the presence of vulnerable plaques was associated with incident ischemic stroke in this cohort of individuals with AF. This suggests that carotid disease was probably not a significant contributor to ischemic stroke in this population.
10aAtrial Fibrillation10aCarotid Artery Diseases10aCarotid Stenosis10aFemale10aHumans10aIschemic Stroke10aMale10aPlaque, Atherosclerotic10aProspective Studies10aRisk Factors10aStroke1 aNoubiap, Jean, Jacques1 aThomas, Gijo1 aKamtchum-Tatuene, Joseph1 aMiddeldorp, Melissa, E1 aSanders, Prashanthan uhttps://chs-nhlbi.org/node/938302748nas a2200217 4500008004100000022001400041245010600055210006900161260001600230520205100246100001902297700002202316700002102338700002002359700002002379700001902399700002202418700002802440700002602468856003602494 2023 eng d a1421-978600aHospital-Acquired Infection at Time of Stroke and Cognitive Decline: The Cardiovascular Health Study.0 aHospitalAcquired Infection at Time of Stroke and Cognitive Decli c2023 Oct 233 aIntroduction Hospital-acquired infections (HAIs) after stroke are associated with additional morbidity and mortality, but whether HAIs increase long-term cognitive decline in stroke patients is unknown. We hypothesized that older adults with incident stroke with HAI experience faster cognitive decline than those having stroke without HAI and those without stroke. Methods We performed a longitudinal analysis in the population-based prospective Cardiovascular Health Study. Medicare-eligible participants aged >65 years with and without incident stroke had cognition assessed annually. HAIs were assessed by hospital discharge codes. Global cognitive function was assessed annually by Modified Mini-Mental State Examination (3MSE) and executive function by Digit Symbol Substitution Test (DSST). We used linear mixed models to estimate the mean decline and 95% confidence intervals (95% CI) for 3MSE and DSST scores by incident stroke and HAI status, adjusted for demographics and vascular risk factors. Results Among 5,443 participants >65 years without previous history of stroke, 393 participants had stroke with HAI (SI), 766 had a stroke only (SO), and 4,284 had no stroke (NS) throughout a maximum 9-year follow-up. For 3MSE, compared with NS participants, SO participants had a similar adjusted mean decline (additional 0.08 points/year, 95%CI -0.15, 0.31), while SI participants had a more rapid decline (additional 0.28 points/year, 95%CI 0.16, 0.40). Adjusted mean decline was 0.20 points/year faster (95%CI -0.05, 0.45) among SI than SO participants. For DSST, compared with NS participants, SO participants had a faster adjusted mean decline (additional 0.17 points/year (95%CI 0.003, 0.33), as did SI participants (additional 0.27 points/year (95%CI 0.19, 0.35). Conclusion Stroke, when accompanied by HAI, leads to a faster long-term decline in cognitive ability than in those without stroke. The clinical and public health implications of the effect of infection on post-stroke cognitive decline warrant further attention.
1 aCole, Kyril, L1 aBoehme, Amelia, K1 aThacker, Evan, L1 aLongstreth, W T1 aBrown, Bruce, L1 aGale, Shawn, D1 aHedges, Dawson, W1 aAnderson, Jacqueline, K1 aElkind, Mitchell, S V uhttps://chs-nhlbi.org/node/953402608nas a2200541 4500008004100000022001400041245006100055210005800116260001600174300000800190490000700198520111600205653002201321653002601343653001801369653001001387653001301397653001101410100002001421700001701441700001701458700002101475700002101496700002601517700002201543700001901565700002901584700001501613700001801628700002101646700001801667700002001685700002301705700002101728700002001749700002001769700001901789700002101808700002801829700002301857700002101880700002101901700001701922700002801939700001801967710004501985856003602030 2024 eng d a2041-172300aHuman whole-exome genotype data for Alzheimer's disease.0 aHuman wholeexome genotype data for Alzheimers disease c2024 Jan 23 a6840 v153 aThe heterogeneity of the whole-exome sequencing (WES) data generation methods present a challenge to a joint analysis. Here we present a bioinformatics strategy for joint-calling 20,504 WES samples collected across nine studies and sequenced using ten capture kits in fourteen sequencing centers in the Alzheimer's Disease Sequencing Project. The joint-genotype called variant-called format (VCF) file contains only positions within the union of capture kits. The VCF was then processed specifically to account for the batch effects arising from the use of different capture kits from different studies. We identified 8.2 million autosomal variants. 96.82% of the variants are high-quality, and are located in 28,579 Ensembl transcripts. 41% of the variants are intronic and 1.8% of the variants are with CADD > 30, indicating they are of high predicted pathogenicity. Here we show our new strategy can generate high-quality data from processing these diversely generated WES samples. The improved ability to combine data sequenced in different batches benefits the whole genomics research community.
10aAlzheimer Disease10aComputational Biology10aData Accuracy10aExome10aGenotype10aHumans1 aLeung, Yuk, Yee1 aNaj, Adam, C1 aChou, Yi-Fan1 aValladares, Otto1 aSchmidt, Michael1 aHamilton-Nelson, Kara1 aWheeler, Nicholas1 aLin, Honghuang1 aGangadharan, Prabhakaran1 aQu, Liming1 aClark, Kaylyn1 aKuzma, Amanda, B1 aLee, Wan-Ping1 aCantwell, Laura1 aNicaretta, Heather1 aHaines, Jonathan1 aFarrer, Lindsay1 aSeshadri, Sudha1 aBrkanac, Zoran1 aCruchaga, Carlos1 aPericak-Vance, Margaret1 aMayeux, Richard, P1 aBush, William, S1 aDeStefano, Anita1 aMartin, Eden1 aSchellenberg, Gerard, D1 aSan Wang, Li-1 aAlzheimer’s Disease Sequencing Project uhttps://chs-nhlbi.org/node/9577