@article {841, title = {Orthostatic hypotension in older adults. The Cardiovascular Health Study. CHS Collaborative Research Group.}, journal = {Hypertension}, volume = {19}, year = {1992}, month = {1992 Jun}, pages = {508-19}, abstract = {

The purpose of the present study was to assess the prevalence of orthostatic hypotension and its associations with demographic characteristics, cardiovascular risk factors and symptomatology, prevalent cardiovascular disease, and selected clinical measurements in the Cardiovascular Health Study, a multicenter, observational, longitudinal study enrolling 5,201 men and women aged 65 years and older at initial examination. Blood pressure measurements were obtained with the subjects in a supine position and after they had been standing for 3 minutes. The prevalence of asymptomatic orthostatic hypotension, defined as 20 mm Hg or greater decrease in systolic or 10 mm Hg or greater decrease in diastolic blood pressure, was 16.2\%. This prevalence increased to 18.2\% when the definition also included those in whom the procedure was aborted due to dizziness upon standing. The prevalence was higher at successive ages. Orthostatic hypotension was associated significantly with difficulty walking (odds ratio, 1.23; 95\% confidence interval, 1.02, 1.46), frequent falls (odds ratio, 1.52; confidence interval, 1.04, 2.22), and histories of myocardial infarction (odds ratio, 1.24; confidence interval, 1.02, 1.50) and transient ischemic attacks (odds ratio, 1.68; confidence interval, 1.12, 2.51). History of stroke, angina pectoris, and diabetes mellitus were not associated significantly with orthostatic hypotension. In addition, orthostatic hypotension was associated with isolated systolic hypertension (odds ratio, 1.35; confidence interval, 1.09, 1.68), major electrocardiographic abnormalities (odds ratio, 1.21; confidence interval, 1.03, 1.42), and the presence of carotid artery stenosis based on ultrasonography (odds ratio, 1.67; confidence interval, 1.23, 2.26). Orthostatic hypotension was negatively associated with weight. We conclude that orthostatic hypotension is common in the elderly and increases with advancing age. It is associated with cardiovascular disease, particularly those manifestations measured objectively, such as carotid stenosis. It is associated also with general neurological symptoms, but this link may not be causal. Differences in prevalence of and associations with orthostatic hypotension in the present study compared with others are largely attributed to differences in population characteristics and methodology.

}, keywords = {Aged, Aging, Dementia, Demography, Female, Health Status, Humans, Hypotension, Orthostatic, Male, Multivariate Analysis, Nervous System Diseases, Prevalence, Risk Factors}, issn = {0194-911X}, doi = {10.1161/01.hyp.19.6.508}, author = {Rutan, G H and Hermanson, B and Bild, D E and Kittner, S J and LaBaw, F and Tell, G S} } @article {590, title = {Oral anticoagulation in patients with atrial fibrillation: adherence with guidelines in an elderly cohort.}, journal = {Am J Med}, volume = {106}, year = {1999}, month = {1999 Feb}, pages = {165-71}, abstract = {

PURPOSE: To determine adherence with practice guidelines in a population-based cohort of elderly persons aged 70 years or older with atrial fibrillation.

SUBJECTS AND METHODS: This was a cross-sectional analysis of a subgroup of participants in the Cardiovascular Health Study, a prospective observational study involving four communities in the United States. Subjects were participants with atrial fibrillation on electrocardiogram at one or more yearly examinations from 1993 to 1995. The outcome measure was self-reported use of warfarin in 1995.

RESULTS: In 1995, 172 (4.1\%) participants had atrial fibrillation together with information regarding warfarin use and no preexisting indication for its use. Warfarin was used by 63 (37\%) of these participants. Of the 109 participants not reporting warfarin use, 92 (84\%) had at least one of the clinical risk factors (aside from age) associated with stroke in patients with atrial fibrillation. Among participants not taking warfarin, 47\% were taking aspirin. Several characteristics were independently associated with warfarin use, including age [odds ratio (OR) = 0.6 per 5-year increment, 95\% CI 0.5-0.9], a modified mini-mental examination score <85 points [OR = 0.3, 95\% confidence interval (CI) 0.1-0.9], and among patients without prior stroke, female sex (OR = 0.5, 95\% CI 0.2-1.0).

CONCLUSIONS: Despite widely publicized practice guidelines to treat patients who have atrial fibrillation with warfarin, most participants who had atrial fibrillation were at high risk for stroke but were not treated with warfarin. More studies are needed to determine why elderly patients with atrial fibrillation are not being treated with warfarin.

}, keywords = {Administration, Oral, Aged, Anticoagulants, Atrial Fibrillation, Cerebrovascular Disorders, Cross-Sectional Studies, Female, Humans, Logistic Models, Male, Odds Ratio, Practice Guidelines as Topic, Prospective Studies, Risk, Risk Factors, Warfarin}, issn = {0002-9343}, doi = {10.1016/s0002-9343(98)00389-1}, author = {White, R H and McBurnie, M A and Manolio, T and Furberg, C D and Gardin, J M and Kittner, S J and Bovill, E and Knepper, L} } @article {651, title = {Orthostatic Hypotension in the Elderly: Contributions of Impaired LV Filling and Altered Sympathovagal Balance.}, journal = {Am J Geriatr Cardiol}, volume = {9}, year = {2000}, month = {2000 Oct}, pages = {273-280}, abstract = {

Orthostatic hypotension, which occurs in 5\%-18\% of the elderly, may contribute to age-related disability. While autonomic dysfunction and alterations of cardiac structure and function likely to impair postural maintenance of blood pressure are common in the elderly, these have not been jointly studied in large cohorts. The authors evaluated the association of orthostatic hypotension with echocardiographic measures of cardiac structure and function, and with autonomic function determined by analysis of heart rate variability, in a large population of community-dwelling elderly. A total of 5201 men and women, aged 65-100 years and living in four geographically separate communities, were recruited from Medicare eligibility lists. In this prospective, observational cohort study, measurements included clinical questionnaires, standing and supine blood pressures, mini-glucose tolerance testing, echocardiography, and 24-hour Holter recording for assessment of heart rate variability. Orthostatic hypotension, defined as a decrease in standing systolic blood pressure of 20 mm Hg or more, was positively associated in bivariate analyses with left ventricular wall thickness, peak velocity of late diastolic filling, vagal tone on heart rate variability analysis, supine systolic pressure, supine diastolic pressure, age, and diabetes, and inversely associated with body weight. After statistical adjustment for the presence of myocardial infarction, stroke, and use of antihypertensive medication, the associations were maintained, and a previous trend toward an association with decreased left ventricular cavity size became statistically significant. The data suggest that in elderly, community-based individuals, orthostatic hypotension is associated with increased blood pressure and decreased weight; it possibly acts mechanistically via altered sympathovagal balance, increased left ventricular wall thickness, decreased left ventricular preload, and alterations of left ventricular diastolic filling. (c) 2000 by CVRR, Inc.

}, issn = {1751-715X}, doi = {10.1111/j.1076-7460.2000.80051.x}, author = {Gottdiener, John S. and Yanez, David and Rautaharju, Penttii and Gardin, Julius M. and Bild, Diane E. and Lima, Joao and Newman, Anne B.} } @article {705, title = {Outcome of congestive heart failure in elderly persons: influence of left ventricular systolic function. The Cardiovascular Health Study.}, journal = {Ann Intern Med}, volume = {137}, year = {2002}, month = {2002 Oct 15}, pages = {631-9}, abstract = {

BACKGROUND: Most persons with congestive heart failure are elderly, and many elderly persons with congestive heart failure have normal left ventricular systolic function.

OBJECTIVE: To evaluate the relationship between left ventricular systolic function and outcome of congestive heart failure in elderly persons.

DESIGN: Population-based longitudinal study of coronary heart disease and stroke.

SETTING: Four U.S. sites: Forsyth County, North Carolina; Sacramento County, California; Allegheny County, Pennsylvania; and Washington County, Maryland.

PARTICIPANTS: 5888 persons who were at least 65 years of age and were recruited from the community.

MEASUREMENTS: Total mortality and cardiovascular morbidity and mortality.

RESULTS: Of 5532 participants, 269 (4.9\%) had congestive heart failure. Among these, left ventricular function was normal in 63\%, borderline decreased in 15\%, and overtly impaired in 22\%. The mortality rate was 25 deaths per 1000 person-years in the reference group (no congestive heart failure and normal left ventricular function at baseline); 154 deaths per 1000 person-years in participants with congestive heart failure and impaired left ventricular systolic function; 87 and 115 deaths per 1000 person-years in participants with congestive heart failure and normal or borderline systolic function, respectively; and 89 deaths per 1000 person-years in persons with impaired left ventricular function but no congestive heart failure. Although the risk for death from congestive heart failure was lower in persons with normal systolic function than in those with impaired function, more deaths were associated with normal systolic function because more persons with heart failure fall into this category.

CONCLUSIONS: Community-dwelling elderly persons, especially those with impaired left ventricular function, have a substantial risk for death from congestive heart failure. However, more deaths occur from heart failure in persons with normal systolic function because left ventricular function is more often normal than impaired in elderly persons with heart failure.

}, keywords = {Aged, Cause of Death, Echocardiography, Female, Heart Failure, Humans, Longitudinal Studies, Male, Myocardial Infarction, Prevalence, Prognosis, Risk Factors, Stroke, Ventricular Dysfunction, Right, Ventricular Function, Left}, issn = {1539-3704}, doi = {10.7326/0003-4819-137-8-200210150-00006}, author = {Gottdiener, John S and McClelland, Robyn L and Marshall, Robert and Shemanski, Lynn and Furberg, Curt D and Kitzman, Dalane W and Cushman, Mary and Polak, Joseph and Gardin, Julius M and Gersh, Bernard J and Aurigemma, Gerard P and Manolio, Teri A} } @article {925, title = {Obstructive sleep apnea and plasma natriuretic peptide levels in a community-based sample.}, journal = {Sleep}, volume = {29}, year = {2006}, month = {2006 Oct}, pages = {1301-6}, abstract = {

STUDY OBJECTIVES: We hypothesized that alterations in cardiac hemodynamics associated with obstructive sleep apnea-hypopnea (OSAH) would be reflected in higher natriuretic peptide levels. We examined the association of OSAH with natriuretic peptides in a community-based sample.

DESIGN: Cross-sectional, retrospective, observational study.

SETTING: Framingham Heart Study Offspring Cohort and Sleep Heart Health Study.

PARTICIPANTS: Community-based sample of 623 individuals.

MEASUREMENTS: Full-montage home polysomnography was used to determine apnea-hypopnea index (AHI) and percentage of time with an oxyhemoglobin saturation < 90\% (PctLt90). Sensitive immunoradiometric assays were used to measure plasma B-type (BNP) and N-terminal pro-atrial natriuretic peptide (NT-ANP). Multivariable regression was used to examine the relations between natriuretic peptides and indicators of OSAH, adjusting for age, sex, body mass index, and clinical covariates.

RESULTS: No statistically significant relations between OSAH indices and BNP were observed in the multivariable model. Compared with an AHI < 5, relative levels of 1.20, 0.88, and 0.91 were observed forAHI categories 5-15, 15-30, >30 events per hour, respectively. For NT-ANP, no significant relations were seen with AHI in the multivariable model (relative levels of 0.98, 0.91, and 0.90). An inverse association was observed between NT-ANP and PctLt90 in age- and sex-adjusted models (relative levels of 0.93, 0.87, and 0.80), although this association became statistically nonsignificant after adjusting for body mass index.

CONCLUSION: Lack of association of natriuretic peptides with OSAH indices suggests that undiagnosed OSAH may not be associated with major alterations in left ventricular function, as reflected in morning natriuretic peptide levels.

}, keywords = {Atrial Fibrillation, Body Mass Index, Cohort Studies, Female, Humans, Hypertension, Male, Middle Aged, Myocardial Infarction, Natriuretic Peptides, Obesity, Polysomnography, Prevalence, Residence Characteristics, Severity of Illness Index, Sleep Apnea, Obstructive}, issn = {0161-8105}, doi = {10.1093/sleep/29.10.1301}, author = {Patwardhan, Anjali A and Larson, Martin G and Levy, Daniel and Benjamin, Emelia J and Leip, Eric P and Keyes, Michelle J and Wang, Thomas J and Gottlieb, Daniel J and Vasan, Ramachandran S} } @article {902, title = {Obstructive sleep apnea-hypopnea and neurocognitive functioning in the Sleep Heart Health Study.}, journal = {Sleep Med}, volume = {7}, year = {2006}, month = {2006 Sep}, pages = {498-507}, abstract = {

BACKGROUND AND PURPOSE: Obstructive sleep apnea-hypopnea (OSAH) is associated with sleep fragmentation and nocturnal hypoxemia. In clinical samples, patients with OSAH frequently are found to have deficits in neuropsychological function. However, the nature and severity of these abnormalities in non-clinical populations is less well defined.

PATIENTS AND METHODS: One hundred and forty-one participants from the Tucson, AZ and New York, NY field centers of the Sleep Heart Health Study completed a battery of neuropsychological tests for 9-40 months (mean=24 months, SD=7 months) after an unattended home polysomnogram. Sixty-seven participants had OSAH (AHI>10) and 74 did not have OSAH (control (CTL), apnea-hypopnea index (AHI)<5). In addition to the individual tests, composite variables representing attention, executive function, MotorSpeed and processing speed were constructed from the neuropsychological test battery.

RESULTS: There were no significant differences in any individual neuropsychological test or composite variable between the OSAH and CTL groups. However, when time spent with O(2) saturations less than 85\% was dichotomized into those participants in the top quartile of the distribution and those in the lower three quartiles, motor speed was significantly impaired in those who were more hypoxemic. In addition, poorer motor speed (model adjusted R(2)=0.242, P<0.001) and processing speed performance (model adjusted R(2)=0.122, P<0.001) were associated with more severe oxygen desaturation even after controlling for degree of daytime sleepiness, age, gender and educational level.

CONCLUSIONS: Mild to moderate OSAH has little impact on the selected measures of attention, executive function, motor speed and processing speed. However, hypoxemia adversely affects both motor and processing speed. These results suggest that in middle-aged to elderly adults the neuropsychological effects of clinically unrecognized mild to moderate OSAH are neither global nor large.

}, keywords = {Brain, Cognition Disorders, Continuous Positive Airway Pressure, Demography, Disorders of Excessive Somnolence, Electromyography, Electrooculography, Female, Health Status, Humans, Hypoxia, Male, Middle Aged, Neuropsychological Tests, Oxygen, Polysomnography, Severity of Illness Index, Sleep Apnea, Obstructive, Surveys and Questionnaires}, issn = {1389-9457}, doi = {10.1016/j.sleep.2006.02.005}, author = {Quan, Stuart F and Wright, Ron and Baldwin, Carol M and Kaemingk, Kristine L and Goodwin, James L and Kuo, Tracy F and Kaszniak, Alfred and Boland, Lori L and Caccappolo, Elise and Bootzin, Richard R} } @article {1131, title = {Obesity and change in estimated GFR among older adults.}, journal = {Am J Kidney Dis}, volume = {54}, year = {2009}, month = {2009 Dec}, pages = {1043-51}, abstract = {

BACKGROUND: The prevalence of chronic kidney disease is growing most rapidly among older adults; however, determinants of impaired kidney function in this population are not well understood. Obesity assessed in midlife has been associated with chronic kidney disease.

STUDY DESIGN: Cohort study.

SETTING \& PARTICIPANTS: 4,295 participants in the community-based Cardiovascular Health Study, aged >or= 65 years.

PREDICTORS: Body mass index, waist circumference, and fat mass measured using bioelectrical impedance.

OUTCOME: Change in glomerular filtration rate (GFR) during 7 years of follow-up.

MEASUREMENTS: Longitudinal estimates of GFR calculated using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation.

RESULTS: Estimated GFR decreased by an average of 0.4 +/- 3.6 mL/min/1.73 m(2)/y, and rapid GFR loss (>3 mL/min/1.73 m(2)/y) occurred in 693 participants (16\%). Baseline body mass index, waist circumference, and fat mass were each associated with increased risk of rapid GFR loss: ORs, 1.19 (95\% CI, 1.09-1.30) per 5 kg/m(2), 1.25 (95\% CI, 1.16-1.36) per 12 cm, and 1.14 (95\% CI, 1.05-1.24) per 10 kg after adjustment for age, sex, race, and smoking. The magnitude of increased risk was larger for participants with estimated GFR < 60 mL/min/1.73 m(2) at baseline (P for interaction < 0.05). Associations were substantially attenuated by further adjustment for diabetes, hypertension, and C-reactive protein level. Obesity measurements were not associated with change in GFR estimated using serum cystatin C level.

LIMITATIONS: Few participants with advanced chronic kidney disease at baseline, no direct GFR measurements.

CONCLUSION: Obesity may be a modifiable risk factor for the development and progression of kidney disease in older adults.

}, keywords = {Aged, Aging, Body Composition, Body Mass Index, Chronic Disease, Cohort Studies, Creatinine, Cystatin C, Female, Glomerular Filtration Rate, Humans, Kidney, Kidney Diseases, Longitudinal Studies, Male, Obesity, Risk Factors}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2009.07.018}, author = {de Boer, Ian H and Katz, Ronit and Fried, Linda F and Ix, Joachim H and Luchsinger, Jose and Sarnak, Mark J and Shlipak, Michael G and Siscovick, David S and Kestenbaum, Bryan} } @article {1208, title = {Obesity is linked with lower brain volume in 700 AD and MCI patients.}, journal = {Neurobiol Aging}, volume = {31}, year = {2010}, month = {2010 Aug}, pages = {1326-39}, abstract = {

Obesity is associated with lower brain volumes in cognitively normal elderly subjects, but no study has yet investigated the effects of obesity on brain structure in patients with mild cognitive impairment (MCI) or Alzheimer{\textquoteright}s disease (AD). To determine if higher body mass index (BMI) is associated with brain volume deficits in cognitively impaired elderly subjects, we analyzed brain magnetic resonance imaging (MRI) scans of 700 MCI or AD patients from 2 different cohorts: the Alzheimer{\textquoteright}s Disease Neuroimaging Initiative (ADNI) and the Cardiovascular Health Study-Cognition Study (CHS-CS). Tensor-based morphometry (TBM) was used to create 3-dimensional maps of regional tissue excess or deficits in subjects with MCI (ADNI, n = 399; CHS-CS, n = 77) and AD (ADNI, n = 188; CHS, n = 36). In both AD and MCI groups, higher body mass index was associated with brain volume deficits in frontal, temporal, parietal, and occipital lobes; the atrophic pattern was consistent in both ADNI and CHS populations. Cardiovascular risk factors, especially obesity, should be considered as influencing brain structure in those already afflicted by cognitive impairment and dementia.

}, keywords = {Aged, Aged, 80 and over, Alzheimer Disease, Atrophy, Body Mass Index, Brain, Cognition Disorders, Cohort Studies, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Obesity, Organ Size, Prospective Studies, Risk Factors}, issn = {1558-1497}, doi = {10.1016/j.neurobiolaging.2010.04.006}, author = {Ho, April J and Raji, Cyrus A and Becker, James T and Lopez, Oscar L and Kuller, Lewis H and Hua, Xue and Lee, Suh and Hibar, Derrek and Dinov, Ivo D and Stein, Jason L and Jack, Clifford R and Weiner, Michael W and Toga, Arthur W and Thompson, Paul M} } @article {1181, title = {Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health study.}, journal = {Am J Respir Crit Care Med}, volume = {182}, year = {2010}, month = {2010 Jul 15}, pages = {269-77}, abstract = {

RATIONALE: Although obstructive sleep apnea is associated with physiological perturbations that increase risk of hypertension and are proatherogenic, it is uncertain whether sleep apnea is associated with increased stroke risk in the general population.

OBJECTIVES: To quantify the incidence of ischemic stroke with sleep apnea in a community-based sample of men and women across a wide range of sleep apnea.

METHODS: Baseline polysomnography was performed between 1995 and 1998 in a longitudinal cohort study. The primary exposure was the obstructive apnea-hypopnea index (OAHI) and outcome was incident ischemic stroke.

MEASUREMENTS AND MAIN RESULTS: A total of 5,422 participants without a history of stroke at the baseline examination and untreated for sleep apnea were followed for a median of 8.7 years. One hundred ninety-three ischemic strokes were observed. In covariate-adjusted Cox proportional hazard models, a significant positive association between ischemic stroke and OAHI was observed in men (P value for linear trend: P = 0.016). Men in the highest OAHI quartile (>19) had an adjusted hazard ratio of 2.86 (95\% confidence interval, 1.1-7.4). In the mild to moderate range (OAHI, 5-25), each one-unit increase in OAHI in men was estimated to increase stroke risk by 6\% (95\% confidence interval, 2-10\%). In women, stroke was not significantly associated with OAHI quartiles, but increased risk was observed at an OAHI greater than 25.

CONCLUSIONS: The strong adjusted association between ischemic stroke and OAHI in community-dwelling men with mild to moderate sleep apnea suggests that this is an appropriate target for future stroke prevention trials.

}, keywords = {Aged, Female, Humans, Longitudinal Studies, Male, Middle Aged, Polysomnography, Proportional Hazards Models, Prospective Studies, Severity of Illness Index, Sex Factors, Sleep Apnea, Obstructive, Stroke}, issn = {1535-4970}, doi = {10.1164/rccm.200911-1746OC}, author = {Redline, Susan and Yenokyan, Gayane and Gottlieb, Daniel J and Shahar, Eyal and O{\textquoteright}Connor, George T and Resnick, Helaine E and Diener-West, Marie and Sanders, Mark H and Wolf, Philip A and Geraghty, Estella M and Ali, Tauqeer and Lebowitz, Michael and Punjabi, Naresh M} } @article {1411, title = {Obesity is associated with a lower resting oxygen saturation in the ambulatory elderly: results from the cardiovascular health study.}, journal = {Respir Care}, volume = {58}, year = {2013}, month = {2013 May}, pages = {831-7}, abstract = {

BACKGROUND: The contribution of obesity to hypoxemia has not been reported in a community-based study. Our hypothesis was that increasing obesity would be independently associated with lower SpO2 in an ambulatory elderly population.

METHODS: The Cardiovascular Health Study ascertained resting SpO2 in 2,252 subjects over age 64. We used multiple linear regression to estimate the association of body mass index (BMI) with SpO2 and to adjust for potentially confounding factors. Covariates including age, sex, race, smoking, airway obstruction (based on spirometry), self reported diagnosis of emphysema, asthma, heart failure, and left ventricular function (by echocardiography) were evaluated.

RESULTS: Among 2,252 subjects the mean and median SpO2 were 97.6\% and 98.0\% respectively; 5\% of subjects had SpO2 values below 95\%. BMI was negatively correlated with SpO2 (Spearman R = -0.27, P < .001). The mean difference in SpO2 between the lowest and highest BMI categories (< 25 kg/m(2) and >= 35 kg/m(2)) was 1.33\% (95\% CI 0.89-1.78\%). In multivariable linear regression analysis, SpO2 was significantly inversely associated with BMI (1.4\% per 10 units of BMI, 95\% CI 1.2-1.6, for whites/others, and 0.87\% per 10 units of BMI, 95\% CI 0.47-1.27, for African Americans).

CONCLUSIONS: We found a narrow distribution of SpO2 values in a community-based sample of ambulatory elderly. Obesity was a strong independent contributor to a low SpO2, with effects comparable to or greater than other factors clinically associated with lower SpO2.

}, keywords = {African Americans, Age Factors, Aged, Aged, 80 and over, Body Mass Index, European Continental Ancestry Group, Female, Humans, Male, Obesity, Oximetry, Oxygen, Smoking, Waist Circumference}, issn = {1943-3654}, doi = {10.4187/respcare.02008}, author = {Kapur, Vishesh K and Wilsdon, Anthony G and Au, David and Avdalovic, Mark and Enright, Paul and Fan, Vincent S and Hansel, Nadia N and Heckbert, Susan R and Jiang, Rui and Krishnan, Jerry A and Mukamal, Kenneth and Yende, Sachin and Barr, R Graham} } @article {6735, title = {Older Adults, "Malignant" Left Ventricular Hypertrophy, and Associated Cardiac-Specific Biomarker Phenotypes to Identify the Differential Risk of New-Onset Reduced Versus Preserved Ejection Fraction Heart Failure: CHS (Cardiovascular Health Study).}, journal = {JACC Heart Fail}, volume = {3}, year = {2015}, month = {2015 Jun}, pages = {445-55}, abstract = {

OBJECTIVES: This study hypothesized that biomarkers of subclinical myocardial injury (high-sensitivity cardiac troponin T [hs-cTnT]) and hemodynamic stress (N-terminal pro-B-type natriuretic peptide [NT-proBNP]) would differentiate heart~failure (HF) risk among older adults with left ventricular hypertrophy (LVH).

BACKGROUND: The natural history of LVH, an important risk factor for HF, is heterogeneous.

METHODS: NT-proBNP and hs-cTnT were measured at baseline and after 2 to 3 years in older adults without prior HF or myocardial infarction in the CHS (Cardiovascular Health Study). LVH and left ventricular ejection fraction were determined by echocardiography. HF events were adjudicated over a median of 13.1 years and classified as preserved or reduced left ventricular ejection fraction (heart failure with preserved ejection fraction or heart failure with reduced ejection fraction [HFrEF]). Adjusted risk of HF by LVH and biomarker tertiles, and by LVH and longitudinal increase in each biomarker was estimated using Cox regression.

RESULTS: Prevalence of LVH was 12.5\% among 2,347 participants with complete measures. Adjusted risk of HF (N~=~643 events) was approximately 3.8-fold higher among participants with LVH and in the highest biomarker tertile, compared with those with low biomarker levels without LVH (NT-proBNP, hazard ratio [HR]: 3.78; 95\% confidence interval [CI]: 2.78 to 5.15 and hs-cTnT, HR: 3.86; 95\% CI: 2.84 to 5.26). The adjusted risk of HFrEF was 7.8 times higher among those with the highest tertile of hs-cTnT and LVH (HR: 7.83; 95\% CI: 4.43 to 13.83). Those with LVH and longitudinal increases in hs-cTnT or NT-proBNP were approximately 3-fold more likely to develop HF, primarily HFrEF, compared with those without LVH and with stable biomarkers.

CONCLUSIONS: The combination of LVH with greater hs-cTnT or NT-proBNP levels, and their longitudinal increase, identifies older adults at highest risk for symptomatic HF, especially HFrEF. These biomarkers may characterize sub-phenotypes in the transition from LVH to HF and suggest modifiable targets for prevention.

}, keywords = {Aged, Biomarkers, Echocardiography, Female, Heart Failure, Humans, Hypertrophy, Left Ventricular, Male, Natriuretic Peptide, Brain, Peptide Fragments, Phenotype, Prospective Studies, Risk Factors, Troponin T}, issn = {2213-1787}, doi = {10.1016/j.jchf.2014.12.018}, author = {Seliger, Stephen L and de Lemos, James and Neeland, Ian J and Christenson, Robert and Gottdiener, John and Drazner, Mark H and Berry, Jarett and Sorkin, John and DeFilippi, Christopher} } @article {6807, title = {Orthostatic Hypotension and Risk of Venous Thromboembolism in 2 Cohort Studies.}, journal = {Am J Hypertens}, volume = {29}, year = {2016}, month = {2016 May}, pages = {634-40}, abstract = {

BACKGROUND: Although venous stasis is a risk factor for venous thromboembolism (VTE) and orthostatic hypotension (OH) can cause venous stasis, to our knowledge no study has examined the relationship between OH and VTE risk. We sought to quantify the association between OH and VTE (deep vein thrombosis or pulmonary embolism) using data from 2 large, prospective cohort studies: the Cardiovascular Health Study (CHS) and the Atherosclerosis Risk in Communities (ARIC) Study. We hypothesized that OH was positively associated with incident VTE.

METHODS: We measured OH-defined as a drop in systolic blood pressure (SBP) of at least 20 mm Hg or diastolic blood pressure (DBP) of at least 10 mm Hg within 3 minutes of standing-in participants aged 45-64 years in ARIC (n = 12,480) and >=65 years in CHS (n = 5,027) at baseline visits (1987-1989 in ARIC; 1989-1990 and 1992-1993 in CHS), and followed participants for incident VTE (n = 568 in ARIC through 2011 and n = 148 in CHS through 2001). We calculated adjusted hazard ratios (HRs) and their 95\% confidence intervals (CIs) for incident VTE in relation to OH status.

RESULTS: In CHS, there was a positive association between OH status and incident VTE (HR for VTE = 1.74 (95\% CI: 1.20-2.51)). In contrast, there was no association between OH and VTE in the ARIC study (HR for VTE = 0.97 (95\% CI: 0.70-1.33)).

CONCLUSIONS: Community-dwelling older adults with OH had a moderately increased risk of VTE. These results were not seen in a population-based middle-aged cohort.

}, issn = {1941-7225}, doi = {10.1093/ajh/hpv151}, author = {Bell, Elizabeth J and Agarwal, Sunil K and Cushman, Mary and Heckbert, Susan R and Lutsey, Pamela L and Folsom, Aaron R} } @article {7490, title = {Omega-3 Fatty Acids and Incident Ischemic Stroke and Its Atherothrombotic and Cardioembolic Subtypes in 3 US Cohorts.}, journal = {Stroke}, volume = {48}, year = {2017}, month = {2017 Oct}, pages = {2678-2685}, abstract = {

BACKGROUND AND PURPOSE: The associations of individual long-chain n-3 polyunsaturated fatty acids with incident ischemic stroke and its main subtypes are not well established. We aimed to investigate prospectively the relationship of circulating eicosapentaenoic acid, docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with risk of total ischemic, atherothrombotic, and cardioembolic stroke.

METHODS: We measured circulating phospholipid fatty acids at baseline in 3 separate US cohorts: CHS (Cardiovascular Health Study), NHS (Nurses{\textquoteright} Health Study), and HPFS (Health Professionals Follow-Up Study). Ischemic strokes were prospectively adjudicated and classified into atherothrombotic (large- and small-vessel infarctions) or cardioembolic by imaging studies and medical records. Risk according to fatty acid levels was assessed using Cox proportional hazards (CHS) or conditional logistic regression (NHS, HPFS) according to study design. Cohort findings were pooled using fixed-effects meta-analysis.

RESULTS: A total of 953 incident ischemic strokes were identified (408 atherothrombotic, 256 cardioembolic, and 289 undetermined subtypes) during median follow-up of 11.2 years (CHS) and 8.3 years (pooled, NHS and HPFS). After multivariable adjustment, lower risk of total ischemic stroke was seen with higher DPA (highest versus lowest quartiles; pooled hazard ratio [HR], 0.74; 95\% confidence interval [CI], 0.58-0.92) and DHA (HR, 0.80; 95\% CI, 0.64-1.00) but not eicosapentaenoic acid (HR, 0.94; 95\% CI, 0.77-1.19). DHA was associated with lower risk of atherothrombotic stroke (HR, 0.53; 95\% CI, 0.34-0.83) and DPA with lower risk of cardioembolic stroke (HR, 0.58; 95\% CI, 0.37-0.92). Findings in each individual cohort were consistent with pooled results.

CONCLUSIONS: In 3 large US cohorts, higher circulating levels of DHA were inversely associated with incident atherothrombotic stroke and DPA with cardioembolic stroke. These novel findings suggest differential pathways of benefit for DHA, DPA, and eicosapentaenoic acid.

}, keywords = {Adult, Aged, Aged, 80 and over, Biomarkers, Brain Ischemia, Cardiovascular Diseases, Case-Control Studies, Cohort Studies, Fatty Acids, Omega-3, Female, Follow-Up Studies, Humans, Incidence, Intracranial Arteriosclerosis, Intracranial Embolism, Intracranial Thrombosis, Male, Middle Aged, Prospective Studies, Random Allocation, Risk Factors, Stroke, United States}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.117.018235}, author = {Saber, Hamidreza and Yakoob, Mohammad Yawar and Shi, Peilin and Longstreth, W T and Lemaitre, Rozenn N and Siscovick, David and Rexrode, Kathryn M and Willett, Walter C and Mozaffarian, Dariush} } @article {7776, title = {Omega-3 Fatty Acids and Genome-wide Interaction Analyses Reveal DPP10-Pulmonary Function Association.}, journal = {Am J Respir Crit Care Med}, year = {2018}, month = {2018 Sep 10}, abstract = {

RATIONALE: Omega-3 poly-unsaturated fatty acids (n-3 PUFAs) have anti-inflammatory properties that could benefit adults with comprised pulmonary health.

OBJECTIVE: To investigate n-3 PUFA associations with spirometric measures of pulmonary function tests (PFTs) and determine underlying genetic susceptibility.

METHODS: Associations of n-3 PUFA biomarkers (alpha-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid [DPA], and docosahexaenoic acid [DHA]) were evaluated with PFTs (forced expiratory volume in the first second [FEV], forced vital capacity [FVC], and [FEV/FVC]) in meta-analyses across seven cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (N=16,134 of European or African ancestry). PFT-associated n-3 PUFAs were carried forward to genome-wide interaction analyses in the four largest cohorts (N=11,962) and replicated in one cohort (N=1,687). Cohort-specific results were combined using joint 2 degree-of-freedom (2df) meta-analyses of single nucleotide polymorphism (SNP) associations and their interactions with n-3 PUFAs.

RESULTS: DPA and DHA were positively associated with FEV1 and FVC (P<0.025), with evidence for effect modification by smoking and by sex. Genome-wide analyses identified a novel association of rs11693320-an intronic DPP10 SNP-with FVC when incorporating an interaction with DHA, and the finding was replicated (P=9.4{\texttimes}10 across discovery and replication cohorts). The rs11693320-A allele (frequency~80\%) was associated with lower FVC (P=2.1{\texttimes}10; β= -161.0mL), and the association was attenuated by higher DHA levels (P=2.1{\texttimes}10; β=36.2mL).

CONCLUSIONS: We corroborated beneficial effects of n-3 PUFAs on pulmonary function. By modeling genome-wide n-3 PUFA interactions, we identified a novel DPP10 SNP association with FVC that was not detectable in much larger studies ignoring this interaction.

}, issn = {1535-4970}, doi = {10.1164/rccm.201802-0304OC}, author = {Xu, Jiayi and Gaddis, Nathan C and Bartz, Traci M and Hou, Ruixue and Manichaikul, Ani W and Pankratz, Nathan and Smith, Albert V and Sun, Fangui and Terzikhan, Natalie and Markunas, Christina A and Patchen, Bonnie K and Schu, Matthew and Beydoun, May A and Brusselle, Guy G and Eiriksdottir, Gudny and Zhou, Xia and Wood, Alexis C and Graff, Mariaelisa and Harris, Tamara B and Ikram, M Arfan and Jacobs, David R and Launer, Lenore J and Lemaitre, Rozenn N and O{\textquoteright}Connor, George and Oelsner, Elizabeth C and Psaty, Bruce M and Ramachandran, Vasan S and Rohde, Rebecca R and Rich, Stephen S and Rotter, Jerome I and Seshadri, Sudha and Smith, Lewis J and Tiemeier, Henning and Tsai, Michael Y and Uitterlinden, Andr{\'e} G and Voruganti, V Saroja and Xu, Hanfei and Zilh{\~a}o, Nuno R and Fornage, Myriam and Zillikens, M Carola and London, Stephanie J and Barr, R Graham and Dupuis, Jos{\'e}e and Gharib, Sina A and Gudnason, Vilmundur and Lahousse, Lies and North, Kari E and Steffen, Lyn M and Cassano, Patricia A and Hancock, Dana B} } @article {7663, title = {Outdoor air pollution and mosaic loss of chromosome Y in older men from the Cardiovascular Health Study.}, journal = {Environ Int}, volume = {116}, year = {2018}, month = {2018 Apr 23}, pages = {239-247}, abstract = {

BACKGROUND: Mosaic loss of chromosome Y (mLOY) can occur in a fraction of cells as men age, which is potentially linked to increased mortality risk. Smoking is related to mLOY; however, the contribution of air pollution is unclear.

OBJECTIVE: We investigated whether exposure to outdoor air pollution, age, and smoking were associated with mLOY.

METHODS: We analyzed baseline (1989-1993) blood samples from 933 men >=65 years of age from the prospective Cardiovascular Health Study. Particulate matter <=10 μm (PM), carbon monoxide, nitrogen dioxide, sulfur dioxide, and ozone data were obtained from the U.S. EPA Aerometric Information Retrieval System for the year prior to baseline. Inverse-distance weighted air monitor data were used to estimate each participants{\textquoteright} monthly residential exposure. mLOY was detected with standard methods using signal intensity (median log-R ratio (mLRR)) of the male-specific chromosome Y regions from Illumina array data. Linear regression models were used to evaluate relations between mean exposure in the prior year, age, smoking and continuous mLRR.

RESULTS: Increased PM was associated with mLOY, namely decreased mLRR (p-trend = 0.03). Compared with the lowest tertile (<=28.5 μg/m), the middle (28.5-31.0 μg/m; β = -0.0044, p = 0.09) and highest (>=31 μg/m; β = -0.0054, p = 0.04) tertiles had decreased mLRR, adjusted for age, clinic, race/cohort, smoking status and pack-years. Additionally, increasing age (β = -0.00035, p = 0.06) and smoking pack-years (β = -0.00011, p = 1.4E-3) were associated with decreased mLRR, adjusted for each other and race/cohort. No significant associations were found for other pollutants.

CONCLUSIONS: PM may increase leukocyte mLOY, a marker of genomic instability. The sample size was modest and replication is warranted.

}, issn = {1873-6750}, doi = {10.1016/j.envint.2018.04.030}, author = {Wong, Jason Y Y and Margolis, Helene G and Machiela, Mitchell and Zhou, Weiyin and Odden, Michelle C and Psaty, Bruce M and Robbins, John and Jones, Rena R and Rotter, Jerome I and Chanock, Stephen J and Rothman, Nathaniel and Lan, Qing and Lee, Jennifer S} } @article {8532, title = {{Omega-3 Fatty Acids and Genome-Wide Interaction Analyses Reveal DPP10-Pulmonary Function Association}, journal = {Am J Respir Crit Care Med}, volume = {199}, year = {2019}, month = {03}, pages = {631{\textendash}642}, abstract = {Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory properties that could benefit adults with comprised pulmonary health.\ To investigate n-3 PUFA associations with spirometric measures of pulmonary function tests (PFTs) and determine underlying genetic susceptibility.\ Associations of n-3 PUFA biomarkers ({\^I}{\textpm}-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid [DPA], and docosahexaenoic acid [DHA]) were evaluated with PFTs (FEV1, FVC, and FEV1/FVC) in meta-analyses across seven cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (N = 16,134 of European or African ancestry). PFT-associated n-3 PUFAs were carried forward to genome-wide interaction analyses in the four largest cohorts (N = 11,962) and replicated in one cohort (N = 1,687). Cohort-specific results were combined using joint 2 degree-of-freedom (2df) meta-analyses of SNP associations and their interactions with n-3 PUFAs.\ DPA and DHA were positively associated with FEV1 and FVC (P < 0.025), with evidence for effect modification by smoking and by sex. Genome-wide analyses identified a novel association of rs11693320-an intronic DPP10 SNP-with FVC when incorporating an interaction with DHA, and the finding was replicated (P2df = 9.4 {\~A}{\textemdash} 10-9 across discovery and replication cohorts). The rs11693320-A allele (frequency, {\^a}{\textasciicircum}{\textonequarter}80\%) was associated with lower FVC (PSNP = 2.1 {\~A}{\textemdash} 10-9; {\^I}{\texttwosuperior}SNP = -161.0 ml), and the association was attenuated by higher DHA levels (PSNP{\~A}{\textemdash}DHA interaction = 2.1 {\~A}{\textemdash} 10-7; {\^I}{\texttwosuperior}SNP{\~A}{\textemdash}DHA interaction = 36.2 ml).\ We corroborated beneficial effects of n-3 PUFAs on pulmonary function. By modeling genome-wide n-3 PUFA interactions, we identified a novel DPP10 SNP association with FVC that was not detectable in much larger studies ignoring this interaction.}, author = {Xu, J. and Gaddis, N. C. and Bartz, T. M. and Hou, R. and Manichaikul, A. W. and Pankratz, N. and Smith, A. V. and Sun, F. and Terzikhan, N. and Markunas, C. A. and Patchen, B. K. and Schu, M. and Beydoun, M. A. and Brusselle, G. G. and Eiriksdottir, G. and Zhou, X. and Wood, A. C. and Graff, M. and Harris, T. B. and Ikram, M. A. and Jacobs, D. R. and Launer, L. J. and Lemaitre, R. N. and O{\textquoteright}Connor, G. T. and Oelsner, E. C. and Psaty, B. M. and Vasan, R. S. and Rohde, R. R. and Rich, S. S. and Rotter, J. I. and Seshadri, S. and Smith, L. J. and Tiemeier, H. and Tsai, M. Y. and Uitterlinden, A. G. and Voruganti, V. S. and Xu, H. and Zilh?o, N. R. and Fornage, M. and Zillikens, M. C. and London, S. J. and Barr, R. G. and Dupuis, J. and Gharib, S. A. and Gudnason, V. and Lahousse, L. and North, K. E. and Steffen, L. M. and Cassano, P. A. and Hancock, D. B.} } @article {8441, title = {Orthostatic Hypotension, Dizziness, Neurology Outcomes, and Death in Older Adults.}, journal = {Neurology}, year = {2020}, month = {2020 Jul 30}, abstract = {

OBJECTIVE: To test the hypothesis that orthostatic hypotension (OH) might cause cerebral hypoperfusion and injury, we examined the longitudinal relationship between orthostatic hypotension (OH) or orthostatic symptoms and incident neurologic outcomes in a community population of older adults.

METHODS: Cardiovascular Health Study (CHS) participants (>=65yrs) without dementia or stroke had blood pressure (BP) measured after lying 20-minutes and after standing 3-minutes. Participants reported dizziness immediately upon standing and any dizziness in the past 2wks. OH was defined as a drop in standing systolic/diastolic BP >=20/>=10mmHg. We determined the association between OH or dizziness with (1) MRI brain findings (ventricular size, white matter hyperintensities, brain infarcts) using linear or logistic regression, (2) cognitive function (baseline and over time) using generalized estimating equations, and (3) prospective adjudicated events (dementia, stroke, death) using Cox models. Models were adjusted for demographic characteristics and OH risk factors. We used multiple imputation to account for missing OH or dizziness (N=534).

RESULTS: Prior to imputation, there were 5,007 participants (mean age 72.7{\textpm}5.5yrs, 57.6\% women, 10.9\% black, 16\% with OH). OH was modestly associated with death (HR=1.11; 95\%CI:1.02,1.20), but not MRI findings, cognition, dementia, or stroke. In contrast, dizziness upon standing was associated with lower baseline cognition (β=-1.20;-1.94,-0.47), incident dementia (HR=1.32;1.04,1.62), incident stroke (HR=1.22;1.06,1.41), and death (HR=1.13; 1.06,1.21). Similarly, dizziness over the past two weeks was associated with higher white matter grade (β=0.16;0.03,0.30), brain infarcts (OR=1.31;1.06,1.63), lower baseline cognition (β=-1.18;-2.01,-0.34), and death (HR=1.13;1.04,1.22).

CONCLUSIONS: Dizziness was more consistently associated with neurologic outcomes than OH 3-minutes after standing. Delayed OH assessments may miss pathologic information related to cerebral injury.

}, issn = {1526-632X}, doi = {10.1212/WNL.0000000000010456}, author = {Juraschek, Stephen P and Longstreth, W T and Lopez, Oscar L and Gottdiener, John S and Lipsitz, Lewis A and Kuller, Lewis H and Mukamal, Kenneth J} } @article {8708, title = {Ophthalmic conditions associated with dementia risk: The Cardiovascular Health Study.}, journal = {Alzheimers Dement}, year = {2021}, month = {2021 Mar 31}, abstract = {

INTRODUCTION: Ophthalmic conditions and dementia appear to overlap and may share common pathways, but research has not differentiated dementia subtypes.

METHODS: Diagnoses of cataracts, age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma were based on medical histories and International Classification of Diseases, Ninth Revision (ICD-9) codes for 3375 participants from the Cardiovascular Health Study. Dementia, including Alzheimer{\textquoteright}s disease (AD) and vascular dementia (VaD), was classified using standardized research criteria.

RESULTS: Cataracts were associated with AD (hazard ratio [HR]~=~1.34; 95\% confidence interval [CI]~=~1.01-1.80) and VaD/mixed dementia (HR~=~1.41; 95\% CI~=~1.02-1.95). AMD was associated with AD only (HR~=~1.87; 95\% CI~=~1.13-3.09), whereas DR was associated with VaD/mixed dementia only (HR~=~2.63; 95\% CI~=~1.10-6.27).

DISCUSSION: Differential associations between specific ophthalmic conditions and dementia subtypes may elucidate pathophysiologic pathways. Lack of association between glaucoma and dementia was most surprising from these analyses.

}, issn = {1552-5279}, doi = {10.1002/alz.12313}, author = {Hwang, Phillip H and Longstreth, Will T and Thielke, Stephen M and Francis, Courtney E and Carone, Marco and Kuller, Lewis H and Fitzpatrick, Annette L} } @article {8982, title = {{Obesity Partially Mediates the Diabetogenic Effect of Lowering LDL Cholesterol}, journal = {Diabetes Care}, volume = {45}, year = {2022}, month = {Jan}, pages = {232{\textendash}240}, abstract = {LDL cholesterol (LDLc)-lowering drugs modestly increase body weight and type 2 diabetes risk, but the extent to which the diabetogenic effect of lowering LDLc is mediated through increased BMI is unknown.\ We conducted summary-level univariable and multivariable Mendelian randomization (MR) analyses in 921,908 participants to investigate the effect of lowering LDLc on type 2 diabetes risk and the proportion of this effect mediated through BMI. We used data from 92,532 participants from 14 observational studies to replicate findings in individual-level MR analyses.\ A 1-SD decrease in genetically predicted LDLc was associated with increased type 2 diabetes odds (odds ratio [OR] 1.12 [95\% CI 1.01, 1.24]) and BMI (β = 0.07 SD units [95\% CI 0.02, 0.12]) in univariable MR analyses. The multivariable MR analysis showed evidence of an indirect effect of lowering LDLc on type 2 diabetes through BMI (OR 1.04 [95\% CI 1.01, 1.08]) with a proportion mediated of 38\% of the total effect (P = 0.03). Total and indirect effect estimates were similar across a number of sensitivity analyses. Individual-level MR analyses confirmed the indirect effect of lowering LDLc on type 2 diabetes through BMI with an estimated proportion mediated of 8\% (P = 0.04).\ These findings suggest that the diabetogenic effect attributed to lowering LDLc is partially mediated through increased BMI. Our results could help advance understanding of adipose tissue and lipids in type 2 diabetes pathophysiology and inform strategies to reduce diabetes risk among individuals taking LDLc-lowering medications.}, author = {Wu, P. and Moon, J. Y. and Daghlas, I. and Franco, G. and Porneala, B. C. and Ahmadizar, F. and Richardson, T. G. and Isaksen, J. L. and Hindy, G. and Yao, J. and Sitlani, C. M. and Raffield, L. M. and Yanek, L. R. and Feitosa, M. F. and Cuadrat, R. R. C. and Qi, Q. and Arfan Ikram, M. and Ellervik, C. and Ericson, U. and Goodarzi, M. O. and Brody, J. A. and Lange, L. and Mercader, J. M. and Vaidya, D. and An, P. and Schulze, M. B. and Masana, L. and Ghanbari, M. and Olesen, M. S. and Cai, J. and Guo, X. and Floyd, J. S. and J{\"a}ger, S. and Province, M. A. and Kalyani, R. R. and Psaty, B. M. and Orho-Melander, M. and Ridker, P. M. and Kanters, J. K. and Uitterlinden, A. and Davey Smith, G. and Gill, D. and Kaplan, R. C. and Kavousi, M. and Raghavan, S. and Chasman, D. I. and Rotter, J. I. and Meigs, J. B. and Florez, J. C. and Dupuis, J. and Liu, C. T. and Merino, J.} }