@article {850, title = {Alcohol use and risk of ischemic stroke among older adults: the cardiovascular health study.}, journal = {Stroke}, volume = {36}, year = {2005}, month = {2005 Sep}, pages = {1830-4}, abstract = {

BACKGROUND AND PURPOSE: The association of light to moderate alcohol consumption with risk of ischemic stroke remains uncertain, as are the roles of potentially mediating factors and modification by apolipoprotein E (apoE) genotype.

METHODS: We studied the prospective association of alcohol consumption and risk of ischemic stroke among 4410 participants free of cardiovascular disease at baseline in the Cardiovascular Health Study, a population-based cohort study of older adults from 4 US communities. Participants reported their consumption of alcoholic beverages yearly.

RESULTS: During an average follow-up period of 9.2 years, 434 cases of incident ischemic stroke occurred. Compared with long-term abstainers, the multivariate relative risks of ischemic stroke were 0.85 (95\% CI, 0.63 to 1.13), 0.75 (95\% CI, 0.53 to 1.06), 0.82 (95\% CI, 0.51 to 1.30), and 1.03 (95\% CI, 0.68 to 1.57) among consumers of <1, 1 to 6, 7 to 13, and > or =14 drinks per week (P quadratic trend 0.06). ApoE genotype appeared to modify the alcohol-ischemic stroke relationship (P interaction 0.08), with generally lower risks among drinkers than abstainers in apoE4-negative participants but higher risks among drinkers than abstainers among apoE4-positive participants. We could not identify candidate mediators among lipid, inflammatory, and prothrombotic factors.

CONCLUSIONS: In this study of older adults, the association of alcohol use and risk of ischemic stroke was U-shaped, with modestly lower risk among consumers of 1 to 6 drinks per week. However, apoE genotype may modify this association, and even moderate alcohol intake may be associated with an increased risk of ischemic stroke among apoE4-positive older adults.

}, keywords = {Aged, Alcohol Drinking, Apolipoproteins E, Brain Infarction, Brain Ischemia, Cohort Studies, Female, Follow-Up Studies, Genetic Predisposition to Disease, Genotype, Humans, Hypertension, Inflammation, Ischemia, Lipids, Male, Middle Aged, Multivariate Analysis, Myocardial Infarction, Prospective Studies, Risk, Risk Factors, Stroke, Substance-Related Disorders, Thrombosis, Time Factors, Vascular Diseases}, issn = {1524-4628}, doi = {10.1161/01.STR.0000177587.76846.89}, author = {Mukamal, Kenneth J and Chung, Hyoju and Jenny, Nancy S and Kuller, Lewis H and Longstreth, W T and Mittleman, Murray A and Burke, Gregory L and Cushman, Mary and Beauchamp, Norman J and Siscovick, David S} } @article {881, title = {Alcohol consumption and risk of coronary heart disease in older adults: the Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {54}, year = {2006}, month = {2006 Jan}, pages = {30-7}, abstract = {

OBJECTIVES: To evaluate several aspects of the relationship between alcohol use and coronary heart disease in older adults, including beverage type, mediating factors, and type of outcome.

DESIGN: Prospective cohort study.

SETTING: Four U.S. communities.

PARTICIPANTS: Four thousand four hundred ten adults aged 65 and older free of cardiovascular disease at baseline.

MEASUREMENTS: Risk of incident myocardial infarction or coronary death according to self-reported consumption of beer, wine, and spirits ascertained yearly.

RESULTS: During an average follow-up period of 9.2 years, 675 cases of incident myocardial infarction or coronary death occurred. Compared with long-term abstainers, multivariate relative risks of 0.90 (95\% confidence interval (CI)=0.71-1.14), 0.93 (95\% CI=0.73-1.20), 0.76 (95\% CI=0.53-1.10), and 0.58 (95\% CI=0.39-0.86) were found in consumers of less than one, one to six, seven to 13, and 14 or more drinks per week, respectively (P for trend=.007). Associations were similar for secondary coronary outcomes, including nonfatal and fatal events. No strong mediators of the association were identified, although fibrinogen appeared to account for 9\% to 10\% of the relationship. The associations were statistically similar for intake of wine, beer, and liquor and generally similar in subgroups, including those with and without an apolipoprotein E4 allele.

CONCLUSION: In this population, consumption of 14 or more drinks per week was associated with the lowest risk of coronary heart disease, although clinicians should not recommend moderate drinking to prevent coronary heart disease based on this evidence alone, because current National Institute on Alcohol Abuse and Alcoholism guidelines suggest that older adults limit alcohol intake to one drink per day.

}, keywords = {Aged, Alcohol Drinking, Apolipoproteins E, Beer, Cohort Studies, Coronary Disease, Female, Genotype, Health Behavior, Humans, Incidence, Male, Residence Characteristics, Risk Assessment, Socioeconomic Factors, United States, Wine}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2005.00561.x}, author = {Mukamal, Kenneth J and Chung, Hyoju and Jenny, Nancy S and Kuller, Lewis H and Longstreth, W T and Mittleman, Murray A and Burke, Gregory L and Cushman, Mary and Psaty, Bruce M and Siscovick, David S} } @article {932, title = {Association of polymorphisms in the CRP gene with circulating C-reactive protein levels and cardiovascular events.}, journal = {JAMA}, volume = {296}, year = {2006}, month = {2006 Dec 13}, pages = {2703-11}, abstract = {

CONTEXT: C-reactive protein (CRP) is an inflammation protein that may play a role in the pathogenesis of cardiovascular disease (CVD).

OBJECTIVE: To assess whether polymorphisms in the CRP gene are associated with plasma CRP, carotid intima-media thickness (CIMT), and CVD events.

DESIGN, SETTING, AND PARTICIPANTS: In the prospective, population-based Cardiovascular Health Study, 4 tag single-nucleotide polymorphisms (SNPs) (1919A/T, 2667G/C, 3872G/A, 5237A/G) were genotyped in 3941 white (European American) participants and 5 tag SNPs (addition of 790A/T) were genotyped in 700 black (African American) participants, aged 65 years or older, all of whom were without myocardial infarction (MI) or stroke before study entry. Median follow-up was 13 years (1989-2003).

MAIN OUTCOME MEASURES: Baseline CIMT; occurrence of MI, stroke, and CVD mortality during follow-up.

RESULTS: In white participants, 461 incident MIs, 491 incident strokes, and 490 CVD-related deaths occurred; in black participants, 67 incident MIs, 78 incident strokes, and 75 CVD-related deaths occurred. The 1919T and 790T alleles were associated with higher CRP levels in white and black participants, respectively. The 3872A allele was associated with lower CRP levels in both populations, and the 2667C allele was associated with lower CRP levels in white participants only. There was no association between CIMT and any CRP gene polymorphism in either population. In white participants, the 1919T allele was associated with increased risk of stroke for TT vs AA (hazard ratio [HR], 1.40; 95\% confidence interval [CI], 1.06-1.87) and for CVD mortality (HR, 1.40; 95\% CI, 1.10-1.90). In black participants, homozygosity for the 790T allele was associated with a 4-fold increased risk of MI compared with homozygosity for the 790A allele (95\% CI, 1.58-10.53). The minor alleles of the 2 SNPs associated with lower plasma CRP concentration in white participants (2667C and 3872A) were associated with decreased risk of CVD mortality.

CONCLUSIONS: Genetic variation in the CRP gene is associated with plasma CRP levels and CVD risk in older adults.

}, keywords = {African Continental Ancestry Group, Aged, C-Reactive Protein, Cardiovascular Diseases, Carotid Arteries, European Continental Ancestry Group, Female, Genotype, Humans, Male, Myocardial Infarction, Polymorphism, Single Nucleotide, Proportional Hazards Models, Risk, Stroke, Tunica Intima}, issn = {1538-3598}, doi = {10.1001/jama.296.22.2703}, author = {Lange, Leslie A and Carlson, Christopher S and Hindorff, Lucia A and Lange, Ethan M and Walston, Jeremy and Durda, J Peter and Cushman, Mary and Bis, Joshua C and Zeng, Donglin and Lin, Danyu and Kuller, Lewis H and Nickerson, Deborah A and Psaty, Bruce M and Tracy, Russell P and Reiner, Alexander P} } @article {959, title = {Alcohol consumption and lipoprotein subclasses in older adults.}, journal = {J Clin Endocrinol Metab}, volume = {92}, year = {2007}, month = {2007 Jul}, pages = {2559-66}, abstract = {

CONTEXT: Limited evidence suggests that alcohol intake may be associated with lipoprotein subclass distribution, which could mediate its relationship with coronary heart disease.

OBJECTIVES: The objective was to determine the relationship of alcohol intake with lipoprotein particle subclasses.

DESIGN, SETTING, AND PARTICIPANTS: The study included a cross-sectional analysis of 1850 participants of the Cardiovascular Health Study aged 65 yr and older and free of clinical cardiovascular disease.

MAIN OUTCOME MEASURE: Lipoprotein subclass distribution was measured with nuclear magnetic resonance spectroscopy, according to self-reported alcohol intake.

RESULTS: Alcohol intake was associated with total low-density lipoprotein (LDL) particles in a U-shaped manner. Consumers of one or more drinks per week had the highest number of large LDL particles, whereas consumers of 7-13 drinks per week had the lowest number of small LDL particles. Alcohol intake was strongly positively associated with large- and medium-sized high-density lipoprotein (HDL) particles but had an inverse relationship with concentrations of small HDL particles and small- and medium-sized very-low-density lipoprotein particles. Average particle sizes of all three lipoproteins were positively associated with alcohol intake. Associations were generally stronger among women than men but in similar directions. Beverage type did not consistently modify these findings.

CONCLUSIONS: Alcohol intake is associated with less total LDL particles, lower levels of small LDL, HDL, and very-low-density lipoprotein particles, and higher levels of large LDL and medium- and large-sized HDL particles in older adults free of prevalent clinical cardiovascular disease.

}, keywords = {Aged, Alcohol Drinking, Cholesterol, Cholesterol, HDL, Cholesterol, LDL, Cholesterol, VLDL, Coronary Disease, Cross-Sectional Studies, Female, Humans, Magnetic Resonance Spectroscopy, Male, Prevalence, Risk Factors}, issn = {0021-972X}, doi = {10.1210/jc.2006-2422}, author = {Mukamal, Kenneth J and Mackey, Rachel H and Kuller, Lewis H and Tracy, Russell P and Kronmal, Richard A and Mittleman, Murray A and Siscovick, David S} } @article {939, title = {Alcohol consumption and risk and prognosis of atrial fibrillation among older adults: the Cardiovascular Health Study.}, journal = {Am Heart J}, volume = {153}, year = {2007}, month = {2007 Feb}, pages = {260-6}, abstract = {

BACKGROUND: The relationship of alcohol consumption with risk of atrial fibrillation (AF) is inconsistent in previous studies, and its relationship with prognosis of AF is undetermined.

METHODS: As part of the Cardiovascular Health Study, a population-based cohort of adults 65 years and older from 4 US communities, 5609 participants reported their use of beer, wine, and spirits yearly. We identified cases of AF with routine study electrocardiograms and validated discharge diagnoses from hospitalizations.

RESULTS: A total of 1232 cases of AF were documented during a mean of 9.1 years of follow-up. Compared with long-term abstainers, the multivariable-adjusted hazard ratios were 1.25 (95\% CI, 1.02-1.54) among former drinkers, 1.09 (95\% CI, 0.94-1.28) among consumers of less than 1 drink per week, 1.00 (95\% CI, 0.84-1.19) among consumers of 1 to 6 drinks per week, 1.06 (95\% CI, 0.82-1.37) among consumers of 7 to 13 drinks per week, and 1.09 (95\% CI, 0.88-1.37) among consumers of 14 or more drinks per week (P trend = 0.64). In analyses of mortality among participants with AF, the hazard ratios were 1.27 (95\% CI, 1.06-1.52) among former drinkers, 0.94 (95\% CI, 0.76-1.18) among consumers of less than 1 drink per week, 0.98 (95\% CI, 0.78-1.23) among consumers of 1 to 6 drinks per week, 0.73 (95\% CI, 0.51-1.03) among consumers of 7 to 13 drinks per week, and 0.81 (95\% CI, 0.59-1.11) among consumers of 14 or more drinks per week (P trend = 0.12).

CONCLUSIONS: Current moderate alcohol consumption is not associated with risk of AF or with risk of death after diagnosis of AF, but former drinking identifies individuals at higher risk.

}, keywords = {Aged, Alcohol Drinking, Atrial Fibrillation, Female, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Male, Prognosis, Risk Factors}, issn = {1097-6744}, doi = {10.1016/j.ahj.2006.10.039}, author = {Mukamal, Kenneth J and Psaty, Bruce M and Rautaharju, Pentti M and Furberg, Curt D and Kuller, Lewis H and Mittleman, Murray A and Gottdiener, John S and Siscovick, David S} } @article {967, title = {Association of carotid artery intima-media thickness, plaques, and C-reactive protein with future cardiovascular disease and all-cause mortality: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {116}, year = {2007}, month = {2007 Jul 03}, pages = {32-8}, abstract = {

BACKGROUND: Carotid atherosclerosis, measured as carotid intima-media thickness or as characteristics of plaques, has been linked to cardiovascular disease (CVD) and to C-reactive protein (CRP) levels. We investigated the relationship between carotid atherosclerosis and CRP and their joint roles in CVD prediction.

METHODS AND RESULTS: Of 5888 participants in the Cardiovascular Health Study, an observational study of adults aged > or = 65 years, 5020 without baseline CVD were included in the analysis. They were followed up for as long as 12 years for CVD incidence and all-cause mortality after baseline ultrasound and CRP measurement. When CRP was elevated (> 3 mg/L) among those with detectable atherosclerosis on ultrasound, there was a 72\% (95\% CI, 1.46 to 2.01) increased risk for CVD death and a 52\% (95\% CI, 1.37 to 1.68) increased risk for all-cause mortality. Elevated CRP in the absence of atherosclerosis did not increase CVD or all-cause mortality risk. The proportion of excess risk attributable to the interaction of high CRP and atherosclerosis was 54\% for CVD death and 79\% for all-cause mortality. Addition of CRP or carotid atherosclerosis to conventional risk factors modestly increased in the ability to predict CVD, as measured by the c statistic.

CONCLUSIONS: In older adults, elevated CRP was associated with increased risk for CVD and all-cause mortality only in those with detectable atherosclerosis based on carotid ultrasound. Despite the significant associations of CRP and carotid atherosclerosis with CVD, these measures modestly improve the prediction of CVD outcomes after one accounts for the conventional risk factors.

}, keywords = {African Americans, Aged, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Carotid Artery Diseases, Cohort Studies, Comorbidity, Diabetes Mellitus, European Continental Ancestry Group, Female, Follow-Up Studies, Humans, Hyperlipidemias, Hypertension, Incidence, Inflammation, Kaplan-Meier Estimate, Male, Mass Screening, Mortality, Myocardial Infarction, Obesity, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, ROC Curve, Smoking, Stroke, Survival Analysis, Tunica Intima, Tunica Media, Ultrasonography, United States}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.106.645606}, author = {Cao, Jie J and Arnold, Alice M and Manolio, Teri A and Polak, Joseph F and Psaty, Bruce M and Hirsch, Calvin H and Kuller, Lewis H and Cushman, Mary} } @article {940, title = {Association of total insulin-like growth factor-I, insulin-like growth factor binding protein-1 (IGFBP-1), and IGFBP-3 levels with incident coronary events and ischemic stroke.}, journal = {J Clin Endocrinol Metab}, volume = {92}, year = {2007}, month = {2007 Apr}, pages = {1319-25}, abstract = {

CONTEXT: Prior observational studies have demonstrated that the GH/IGF axis is associated with cardiovascular disease. However, this association has not been extensively studied among older adults.

OBJECTIVE: The objective of this study was to assess the association between levels of total IGF-I and IGF binding proteins (IGFBP-1, IGFBP-3) and risk of incident coronary events and ischemic stroke.

DESIGN AND PARTICIPANTS: A case-cohort analysis was conducted among adults 65 yr and older in the Cardiovascular Health Study.

MAIN OUTCOME MEASURES: A total of 534 coronary events [316 nonfatal myocardial infarctions (MIs), 48 fatal MIs, and 170 fatal coronary heart disease events] and 370 ischemic strokes were identified on follow-up. Comparison subjects were 1122 randomly selected participants from the Cardiovascular Health Study.

RESULTS: Mean follow-up time was 6.7 yr for coronary events, 5.6 yr for strokes, and 9.3 yr for comparison subjects. Hazard ratios (95\% confidence intervals) associated with baseline levels of total IGF-I and IGFBPs were estimated using multivariate adjusted Cox proportional hazards models. Neither IGF-I nor IGFBP-1 levels predicted risk of incident coronary events or stroke. IGFBP-3 had an inverse association with risk of coronary events [adjusted hazard ratio per sd=0.88 (0.78-1.00), P=0.05] but was not associated with stroke. Exploratory analyses suggested that low IGF-I and low IGFBP-3 levels were significantly associated with higher risk of nonfatal MI (P<0.05) but not with risk of fatal MI or fatal coronary heart disease.

CONCLUSION: Circulating levels of total IGF-I or IGFBP-1 were not associated with risk of total coronary events or ischemic stroke among older adults, whereas low IGFBP-3 level was associated with increased risk of incident coronary events.

}, keywords = {Aged, Cardiovascular Diseases, Case-Control Studies, Cohort Studies, Coronary Disease, Female, Humans, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Male, Multivariate Analysis, Risk Factors, Stroke}, issn = {0021-972X}, doi = {10.1210/jc.2006-1631}, author = {Kaplan, Robert C and McGinn, Aileen P and Pollak, Michael N and Kuller, Lewis H and Strickler, Howard D and Rohan, Tom E and Cappola, Anne R and Xue, XiaoNan and Psaty, Bruce M} } @article {1017, title = {Abdominal aortic aneurysms, increasing infrarenal aortic diameter, and risk of total mortality and incident cardiovascular disease events: 10-year follow-up data from the Cardiovascular Health Study.}, journal = {Circulation}, volume = {117}, year = {2008}, month = {2008 Feb 26}, pages = {1010-7}, abstract = {

BACKGROUND: Long-term data describing small abdominal aortic aneurysms (AAAs) and increasing infrarenal aortic diameters and their relationship to future surgical repair, total mortality, and incident cardiovascular disease (CVD) events, particularly among women, are sparse.

METHODS AND RESULTS: In 1992 to 1993, 4734 Cardiovascular Health Study participants > or = 65 years old had an abdominal aortic ultrasound evaluation. Of those screened, 416 had an AAA (infrarenal aortic diameter > or = 3.0 cm or an infrarenal/suprarenal ratio > or = 1.2). By 2002, there were 56 surgical AAA repairs and 10 AAA-related deaths. A single ultrasound screening demonstrated that aneurysm dilation > or = 3 cm identified 68\% of all AAA repairs over the next 10 years and 6 of the 10 AAA-related deaths in 4\% of the total population and that a > or = 2.5-cm dilation identified 91\% of all AAA repairs and 9 of the 10 deaths in 10\% of the total population. With adjusted Cox proportional hazard models, AAAs were associated with a higher risk of total mortality (hazard ratio 1.44, 95\% confidence interval 1.25 to 1.66) and incident CVD events (hazard ratio 1.52, 95\% confidence interval 1.25 to 1.85). Compared with diameters < 2.0 cm, infrarenal aortic diameters 2.0 to < 3.0 cm were associated with increased risk of incident CVD events in women and total mortality in men.

CONCLUSIONS: This study suggests that a 1-time screening of the abdominal aorta can acceptably identify individuals with a clinically significant AAA. Infrarenal aortic diameters > 2.0 cm are associated with a significantly increased risk of future CVD events and total mortality.

}, keywords = {Aged, Aged, 80 and over, Aorta, Abdominal, Aortic Aneurysm, Abdominal, Cause of Death, Female, Follow-Up Studies, Humans, Incidence, Intermittent Claudication, Kidney, Male, Prospective Studies, Risk Factors, Sex Distribution, Ultrasonography}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.107.720219}, author = {Freiberg, Matthew S and Arnold, Alice M and Newman, Anne B and Edwards, Matthew S and Kraemer, Kevin L and Kuller, Lewis H} } @article {1005, title = {Abnormal regional cerebral blood flow in cognitively normal elderly subjects with hypertension.}, journal = {Stroke}, volume = {39}, year = {2008}, month = {2008 Feb}, pages = {349-54}, abstract = {

BACKGROUND AND PURPOSE: The purpose of this study was to examine regional cerebral blood flow (rCBF) in normal cognitive-performing subjects with hypertension (HTN) using continuous arterial spin-labeled MRI. The most common explanation for the effect of blood pressure on cognition is that HTN increases the risk of cerebrovascular disease, and it may increase the risk for Alzheimer disease possibly through small vessel disease, ischemia, oxidative stress, and inflammation. However, few studies to date have examined the rCBF of cognitively normal subjects with HTN in population-based cohorts, and none have used continuous arterial spin-labeled MRI. This is a noninvasive technique that does not require either injections or ionizing radiation and can measure absolute rCBF rates over the entire brain.

METHODS: rCBF was measured at 1.5 T using continuous arterial spin-labeled MRI in 41 cognitively normal subjects who were participating in the Cardiovascular Health Study Cognition Study. A deformable atrophy-corrected registration method was used to warp the rCBF maps to the standard colin27 brain space. Image and cluster-based statistical analyses were performed between subject groups.

RESULTS: Cognitively normal subjects with HTN (n=19) had decreased rCBF in the putamen, globus pallidus, bilaterally, and in the left hippocampus compared with normotensives (n=22). In addition, decreased rCBF was observed in the right and left anterior cingulate gyrus with extension to the subcallosal region, left posterior cingulate gyrus and medial precuneus, left lateral inferior and superior frontal, and inferior parietal, left orbitofrontal, and left superior temporal cortices.

CONCLUSIONS: rCBF is affected in normal subjects with HTN, not only in the subcortical regions, but also in limbic and paralimbic structures. We hypothesize that the HTN creates a vulnerability state for the development of neurodegenerative disorders, especially Alzheimer disease.

}, keywords = {Aged, Aged, 80 and over, Cerebral Cortex, Cerebrovascular Circulation, Cognition, Cognition Disorders, Female, Globus Pallidus, Gyrus Cinguli, Humans, Hypertension, Magnetic Resonance Imaging, Male, Putamen, Spin Labels}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.107.495457}, author = {Dai, Weiying and Lopez, Oscar L and Carmichael, Owen T and Becker, James T and Kuller, Lewis H and Gach, H Michael} } @article {1038, title = {Adiponectin and risk of coronary heart disease in older men and women.}, journal = {J Clin Endocrinol Metab}, volume = {93}, year = {2008}, month = {2008 Sep}, pages = {3357-64}, abstract = {

CONTEXT: Despite established insulin-sensitizing and antiatherogenic preclinical effects, epidemiological investigations of adiponectin have yielded conflicting findings, and its relationship with coronary heart disease (CHD) remains uncertain.

OBJECTIVE: Our objective was to investigate the relationship between adiponectin and CHD in older adults.

DESIGN, SETTING, AND PARTICIPANTS: This was a case-control study (n = 1386) nested within the population-based Cardiovascular Health Study from 1992--2001. Controls were frequency-matched to cases by age, sex, race, subclinical cardiovascular disease, and center.

MAIN OUTCOME MEASURES: Incident CHD was defined as angina pectoris, percutaneous or surgical revascularization, nonfatal myocardial infarction (MI), or CHD death. A more restrictive CHD endpoint was limited to nonfatal MI and CHD death.

RESULTS: Adiponectin exhibited significant negative correlations with baseline adiposity, insulin resistance, dyslipidemia, inflammatory markers, and leptin. After controlling for matching factors, adjustment for waist to hip ratio, hypertension, smoking, alcohol, low-density lipoprotein cholesterol, creatinine, and leptin revealed a modestly increased risk of incident CHD with adiponectin concentrations at the upper end [odds ratio = 1.37 (quintile 5 vs. 1-4), 95\% confidence interval 1.02-1.84]. This association was stronger when the outcome was limited to nonfatal MI and fatal CHD (odds ratio = 1.69, 95\% confidence interval 1.23-2.32). The findings were not influenced by additional adjustment for weight change, health status, or cystatin C, nor were they abolished by adjustment for potential mediators.

CONCLUSIONS: This study shows an association between adiponectin and increased risk of first-ever CHD in older adults. Further research is needed to elucidate the basis for the concurrent beneficial and detrimental aspects of this relationship, and under what circumstances one or the other may predominate.

}, keywords = {Adiponectin, Age Factors, Aged, Aged, 80 and over, Body Weight, Case-Control Studies, Cohort Studies, Coronary Disease, Female, Humans, Longitudinal Studies, Male, Odds Ratio, Risk Factors}, issn = {0021-972X}, doi = {10.1210/jc.2008-0640}, author = {Kizer, Jorge R and Barzilay, Joshua I and Kuller, Lewis H and Gottdiener, John S} } @article {1032, title = {Albuminuria and dementia in the elderly: a community study.}, journal = {Am J Kidney Dis}, volume = {52}, year = {2008}, month = {2008 Aug}, pages = {216-26}, abstract = {

BACKGROUND: Dementia is associated with microvascular disease of the retina. In this study, we examine whether cognitive status (normal cognition, mild cognitive impairment, and dementia) is associated with albuminuria, a microvascular disorder of the kidney.

STUDY DESIGN: Cross-sectional analysis.

SETTING \& PARTICIPANTS: 2,316 participants from the Cardiovascular Health Cognition Study who underwent brain magnetic resonance imaging and testing for albuminuria.

PREDICTOR: Doubling of albuminuria.

OUTCOME: Dementia defined according to neuropsychological and clinical evaluation.

MEASUREMENTS: Multinomial logistic modeling was used to estimate odds ratios (ORs) and 95\% confidence intervals (CIs) of dementia and mild cognitive impairment with doubling of albuminuria compared with the odds with normal cognition.

RESULTS: 283 participants (12.2\%) had dementia, 344 (14.9\%) had mild cognitive impairment, and 1,689 (72.9\%) had normal cognition. Compared with participants with normal cognition, doubling of albuminuria was associated with increased odds of dementia (OR, 1.22; 95\% CI, 1.15 to 1.29). Adjustment for prevalent cardiovascular disease and cardiovascular risk factors, lipid levels, C-reactive protein level, estimated glomerular filtration rate, and apolipoprotein E-4 genotype attenuated this association, but it remained statistically significant (OR, 1.12; 95\% CI, 1.03 to 1.22). Mild cognitive impairment was associated with albuminuria on unadjusted analysis, but not with adjustment for other factors.

LIMITATIONS: Results are cross-sectional; causality cannot be imputed.

CONCLUSIONS: The odds of dementia increased in the presence of albuminuria. These findings suggest a role of shared susceptibility for microvascular disease in the brain and kidney in older adults.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Albuminuria, Brain, Cognition, Cross-Sectional Studies, Dementia, Female, Humans, Incidence, Magnetic Resonance Imaging, Male, Odds Ratio, Population Surveillance, Prognosis, Retrospective Studies, Risk Factors}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2007.12.044}, author = {Barzilay, Joshua I and Fitzpatrick, Annette L and Luchsinger, Jose and Yasar, Sevil and Bernick, Charles and Jenny, Nancy S and Kuller, Lewis H} } @article {994, title = {Alcohol consumption and lower extremity arterial disease among older adults: the cardiovascular health study.}, journal = {Am J Epidemiol}, volume = {167}, year = {2008}, month = {2008 Jan 01}, pages = {34-41}, abstract = {

Few studies of the relation of alcohol intake to lower-extremity arterial disease (LEAD) have included clinical events and objective measurements repeated longitudinally. As part of the Cardiovascular Health Study, a study of older adults from four US communities, 5,635 participants reported their use of beer, wine, and spirits yearly. Incident LEAD was identified by hospitalization surveillance. Technicians measured ankle-brachial index 6 years apart in 2,298 participants. A total of 172 cases of LEAD were documented during a mean of 7.5 years of follow-up between 1989 and 1999. Compared with abstention, the multivariable-adjusted hazard ratios were 1.10 (95\% confidence interval (CI): 0.71, 1.71) for <1 alcoholic drink per week, 0.56 (95\% CI: 0.33, 0.95) for 1-13 drinks per week, and 1.02 (95\% CI: 0.53, 1.97) for > or =14 drinks per week (p for quadratic trend = 0.04). These relations were consistent within strata of sex, age, and apolipoprotein E genotype, and neither lipids nor inflammatory markers appeared to be important intermediates. Change in ankle-brachial index showed a similar relation (p for quadratic trend = 0.01). Alcohol consumption of 1-13 drinks per week in older adults may be associated with lower risk of LEAD, but heavier drinking is not associated with lower risk.

}, keywords = {Aged, Alcohol Drinking, Female, Follow-Up Studies, Health Surveys, Humans, Intermittent Claudication, Male, Prevalence, Prospective Studies, Risk Factors, Surveys and Questionnaires, Time Factors, United States}, issn = {1476-6256}, doi = {10.1093/aje/kwm274}, author = {Mukamal, Kenneth J and Kennedy, Margaret and Cushman, Mary and Kuller, Lewis H and Newman, Anne B and Polak, Joseph and Criqui, Michael H and Siscovick, David S} } @article {1049, title = {Association between lower digit symbol substitution test score and slower gait and greater risk of mortality and of developing incident disability in well-functioning older adults.}, journal = {J Am Geriatr Soc}, volume = {56}, year = {2008}, month = {2008 Sep}, pages = {1618-25}, abstract = {

OBJECTIVES: To determine whether, in well-functioning older adults, a lower score on the Digit Symbol Substitution Test (DSST) and slower gait are associated with greater risk of mortality and of developing incident disability independent of other risk factors, including brain structural abnormalities (white matter hyperintensities, brain infarcts, ventricular enlargement) and whether the combination of varying levels of DSST score and gait speed are associated with a greater risk of mortality and disability than low DSST or slow gait alone.

DESIGN: Observational cohort study.

SETTING: Community.

PARTICIPANTS: Three thousand one hundred fifty-six (43\% men, 29\% black, mean age 70.4) participants in the Cardiovascular Health Study (CHS), free from stroke and physical disability and with a modified Mini-Mental State Examination (3MS) score of 80 or higher.

MEASUREMENTS: Total mortality and incident disability (self-report of any difficulty performing one or more of the six activities of daily living) ascertained over a median follow-up time of 8.4 years.

RESULTS: By the end of follow-up, 704 participants had died and 1,096 had incident disability. In Cox proportional hazards models adjusted for age, sex, race, education, cardiovascular disease, and brain magnetic resonance imaging abnormalities, lower DSST score and slower gait remained significantly associated with greater risk of mortality and of incident disability. Mortality rates were higher in those who had both low DSST score (<27 points) and slow gait (speed <1.0 m/s) than in those who had only low DSST score, only slow gait, or neither (rates per 1,000 person years (p-y): 61.2, 42.8, 20.8, and 16.3, respectively). A similar risk gradient was observed for incident disability (82.0, 57.9, 47.9, and 36.0/1,000 p-y, respectively).

CONCLUSION: In well-functioning older adults, low DSST score and slow gait, alone or in combination, could be risk factors for mortality and for developing disability, independent of other risk factors, including measures of brain integrity.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Analysis of Variance, Atrophy, Brain, Brain Diseases, Cause of Death, Cohort Studies, Disability Evaluation, Discrimination Learning, Female, Gait, Humans, Male, Memory, Short-Term, Mobility Limitation, Neuropsychological Tests, Pattern Recognition, Visual, Psychometrics, Psychomotor Performance, Risk Factors}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2008.01856.x}, author = {Rosano, Caterina and Newman, Anne B and Katz, Ronit and Hirsch, Calvin H and Kuller, Lewis H} } @article {1063, title = {Agreement between nosologist and cardiovascular health study review of deaths: implications of coding differences.}, journal = {J Am Geriatr Soc}, volume = {57}, year = {2009}, month = {2009 Jan}, pages = {133-9}, abstract = {

OBJECTIVES: To compare nosologist coding of underlying cause of death according to the death certificate with adjudicated cause of death for subjects aged 65 and older in the Cardiovascular Health Study (CHS).

DESIGN: Observational.

SETTING: Four communities: Forsyth County, North Carolina (Wake Forest University); Sacramento County, California (University of California at Davis); Washington County, Maryland (Johns Hopkins University); and Pittsburgh, Pennsylvania (University of Pittsburgh).

PARTICIPANTS: Men and women aged 65 and older participating in CHS, a longitudinal study of coronary heart disease and stroke, who died through June 2004.

MEASUREMENTS: The CHS centrally adjudicated underlying cause of death for 3,194 fatal events from June 1989 to June 2004 using medical records, death certificates, proxy interviews, and autopsies, and results were compared with underlying cause of death assigned by a trained nosologist based on death certificate only.

RESULTS: Comparison of 3,194 CHS versus nosologist underlying cause of death revealed moderate agreement except for cancer (kappa=0.91, 95\% confidence interval (CI)=0.89-0.93). kappas varied according to category (coronary heart disease, kappa=0.61, 95\% CI=0.58-0.64; stroke, kappa=0.59, 95\% CI=0.54-0.64; chronic obstructive pulmonary disease, kappa=0.58, 95\% CI=0.51-0.65; dementia, kappa=0.40, 95\% CI=0.34-0.45; and pneumonia, kappa=0.35, 95\% CI=0.29-0.42). Differences between CHS and nosologist coding of dementia were found especially in older ages in the sex and race categories. CHS attributed 340 (10.6\%) deaths due to dementia, whereas nosologist coding attributed only 113 (3.5\%) to dementia as the underlying cause.

CONCLUSION: Studies that use only death certificates to determine cause of death may result in misclassification and potential bias. Changing trends in cause-specific mortality in older individuals may be a function of classification process rather than incidence and case fatality.

}, keywords = {Aged, Aged, 80 and over, Cause of Death, Coronary Disease, Death Certificates, Female, Forms and Records Control, Humans, Longitudinal Studies, Male, Stroke}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2008.02056.x}, author = {Ives, Diane G and Samuel, Paulraj and Psaty, Bruce M and Kuller, Lewis H} } @article {1072, title = {Associations of pentraxin 3 with cardiovascular disease and all-cause death: the Cardiovascular Health Study.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {29}, year = {2009}, month = {2009 Apr}, pages = {594-9}, abstract = {

OBJECTIVE: We examined associations of pentraxin 3 (PTX3), a vascular inflammation marker, with incident cardiovascular disease (CVD) and all-cause death.

METHODS AND RESULTS: 1583 Cardiovascular Health Study participants free of prevalent CVD were included. Nonexclusive case groups were angina (n=476), myocardial infarction (MI; n=237), stroke (n=310), CVD death (n=282), and all-cause death (n=772). 535 participants had no events. PTX3 levels were higher in those with subclinical CVD (1.90+/-1.89 ng/mL) than those without (1.71+/-1.88 ng/mL; P=0.001). Using Cox regression adjusted for age, sex, and ethnicity, a standard deviation increase in PTX3 (1.89 ng/mL) was associated with CVD death (hazard ratio 1.11; 95\% confidence interval 1.02 to 1.21) and all-cause death (1.08; 1.02 to 1.15). PTX3 was not associated with angina (1.09; 0.98 to 1.20), MI (0.96; 0.81 to 1.12), or stroke (1.06; 0.95 to 1.18). Adding C-reactive protein (CRP) or CVD risk factors to the models had no significant effects on associations.

CONCLUSIONS: In these older adults, PTX3 was associated with CVD and all-cause death independent of CRP and CVD risk factors. PTX3 likely reflects different aspects of inflammation than CRP and may provide insight into vascular health in aging and chronic diseases of aging that lead to death.

}, keywords = {Aged, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Case-Control Studies, Female, Health Surveys, Humans, Inflammation Mediators, Linear Models, Male, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Serum Amyloid P-Component, Time Factors, United States, Up-Regulation}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.108.178947}, author = {Jenny, Nancy Swords and Arnold, Alice M and Kuller, Lewis H and Tracy, Russell P and Psaty, Bruce M} } @article {6811, title = {Association of Cardiometabolic Multimorbidity With Mortality.}, journal = {JAMA}, volume = {314}, year = {2015}, month = {2015 Jul 7}, pages = {52-60}, abstract = {

IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing.

OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity.

DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates.

EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI).

MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy.

RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95\% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95\% CI, 2.0-2.2) in those with stroke, 2.0 (95\% CI, 1.9-2.2) in those with MI, 3.7 (95\% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95\% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95\% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95\% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy.

CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

}, keywords = {Adult, Aged, Comorbidity, Diabetes Mellitus, Female, Humans, Life Expectancy, Male, Middle Aged, Mortality, Myocardial Infarction, Risk Factors, Stroke}, issn = {1538-3598}, doi = {10.1001/jama.2015.7008}, author = {Di Angelantonio, Emanuele and Kaptoge, Stephen and Wormser, David and Willeit, Peter and Butterworth, Adam S and Bansal, Narinder and O{\textquoteright}Keeffe, Linda M and Gao, Pei and Wood, Angela M and Burgess, Stephen and Freitag, Daniel F and Pennells, Lisa and Peters, Sanne A and Hart, Carole L and H{\r a}heim, Lise Lund and Gillum, Richard F and Nordestgaard, B{\o}rge G and Psaty, Bruce M and Yeap, Bu B and Knuiman, Matthew W and Nietert, Paul J and Kauhanen, Jussi and Salonen, Jukka T and Kuller, Lewis H and Simons, Leon A and van der Schouw, Yvonne T and Barrett-Connor, Elizabeth and Selmer, Randi and Crespo, Carlos J and Rodriguez, Beatriz and Verschuren, W M Monique and Salomaa, Veikko and Sv{\"a}rdsudd, Kurt and van der Harst, Pim and Bj{\"o}rkelund, Cecilia and Wilhelmsen, Lars and Wallace, Robert B and Brenner, Hermann and Amouyel, Philippe and Barr, Elizabeth L M and Iso, Hiroyasu and Onat, Altan and Trevisan, Maurizio and D{\textquoteright}Agostino, Ralph B and Cooper, Cyrus and Kavousi, Maryam and Welin, Lennart and Roussel, Ronan and Hu, Frank B and Sato, Shinichi and Davidson, Karina W and Howard, Barbara V and Leening, Maarten J G and Leening, Maarten and Rosengren, Annika and D{\"o}rr, Marcus and Deeg, Dorly J H and Kiechl, Stefan and Stehouwer, Coen D A and Nissinen, Aulikki and Giampaoli, Simona and Donfrancesco, Chiara and Kromhout, Daan and Price, Jackie F and Peters, Annette and Meade, Tom W and Casiglia, Edoardo and Lawlor, Debbie A and Gallacher, John and Nagel, Dorothea and Franco, Oscar H and Assmann, Gerd and Dagenais, Gilles R and Jukema, J Wouter and Sundstr{\"o}m, Johan and Woodward, Mark and Brunner, Eric J and Khaw, Kay-Tee and Wareham, Nicholas J and Whitsel, Eric A and Nj{\o}lstad, Inger and Hedblad, Bo and Wassertheil-Smoller, Sylvia and Engstr{\"o}m, Gunnar and Rosamond, Wayne D and Selvin, Elizabeth and Sattar, Naveed and Thompson, Simon G and Danesh, John} } @article {6931, title = {APOL1 Genotype, Kidney and Cardiovascular Disease, and Death in Older Adults.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {36}, year = {2016}, month = {2016 Feb}, pages = {398-403}, abstract = {

OBJECTIVE: We sought to evaluate the cardiovascular impact of coding variants in the apolipoprotein L1 gene APOL1 that protect against trypanosome infection but have been associated with kidney disease among African Americans.

APPROACH AND RESULTS: As part of the Cardiovascular Health Study, a population-based cohort of Americans aged >=65 years, we genotyped APOL1 polymorphisms rs73885319 and rs71785153 and examined kidney function, subclinical atherosclerosis, and incident cardiovascular disease and death over 13 years of follow-up among 91 African Americans with 2 risk alleles, 707 other African Americans, and 4964 white participants. The high-risk genotype with 2 risk alleles was associated with 2-fold higher levels of albuminuria and lower ankle-brachial indices but similar carotid intima-media thickness among African Americans. Median survival among high-risk African Americans was 9.9 years (95\% confidence interval [CI], 8.7-11.9), compared with 13.6 years (95\% CI, 12.5-14.3) among other African Americans and 13.3 years (95\% CI, 13.0-13.6) among whites (P=0.03). The high-risk genotype was also associated with increased risk for incident myocardial infarction (adjusted hazard ratio 1.8; 95\% CI, 1.1-3.0) and mortality (adjusted hazard ratio 1.3; 95\% CI 1.0-1.7). Albuminuria and risk for myocardial infarction and mortality were nearly identical between African Americans with 0 to 1 risk alleles and whites.

CONCLUSIONS: APOL1 genotype is associated with albuminuria, subclinical atherosclerosis, incident myocardial infarction, and mortality in older African Americans. African Americans without 2 risk alleles do not differ significantly in risk of myocardial infarction or mortality from whites. APOL1 trypanolytic variants may account for a substantial proportion of the excess risk of chronic disease in African Americans.

}, keywords = {African Americans, Age Factors, Aged, Albuminuria, Apolipoproteins, Atherosclerosis, Cardiovascular Diseases, Cause of Death, European Continental Ancestry Group, Female, Gene Frequency, Genetic Predisposition to Disease, Health Status Disparities, Heterozygote, Homozygote, Humans, Incidence, Kaplan-Meier Estimate, Kidney Diseases, Lipoproteins, HDL, Male, Myocardial Infarction, Phenotype, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.115.305970}, author = {Mukamal, Kenneth J and Tremaglio, Joseph and Friedman, David J and Ix, Joachim H and Kuller, Lewis H and Tracy, Russell P and Pollak, Martin R} } @article {6997, title = {Associations of insulin resistance, inflammation and liver synthetic function with very low-density lipoprotein: The Cardiovascular Health Study.}, journal = {Metabolism}, volume = {65}, year = {2016}, month = {2016 Mar}, pages = {92-9}, abstract = {

INTRODUCTION: Production of very low-density lipoprotein (VLDL) is increased in states of metabolic syndrome, leading to hypertriglyceridemia. However, metabolic syndrome is often associated with non-alcoholic fatty liver disease, which leads to liver fibrosis and inflammation that may decrease VLDL production. In this study, we aim to determine the interactive impact on VLDL profiles from insulin resistance, impairment in liver synthetic function and inflammation.

METHODS: We examined cross-sectional associations of insulin sensitivity, inflammation, and liver synthetic function with VLDL particle (VLDL-P) concentration and size among 1,850 older adults in the Cardiovascular Health Study.

RESULTS: Indices for high insulin sensitivity and low liver synthetic function were associated with lower concentrations of VLDL-P. In addition, insulin resistance preferentially increased concentration of large VLDL and was associated with mean VLDL size. Indices for inflammation however demonstrated a nonlinear relationship with both VLDL-P concentration and VLDL size. When mutually adjusted, one standard deviation (SD) increment in Matsuda index and C-reactive protein (CRP) were associated with 4.9 nmol/L (-8.2 to -1.5, p=0.005) and 6.3 nmol/L (-11.0 to -1.6, p=0.009) lower VLDL-P concentration respectively. In contrast, one-SD increment in factor VII, a marker for liver synthetic function, was associated with 16.9 nmol/L (12.6-21.2, p<0.001) higher VLDL-P concentration. Furthermore, a one-SD increment in the Matsuda index was associated with 1.1 nm (-2.0 to -0.3, p=0.006) smaller mean VLDL size, whereas CRP and factor VII were not associated with VLDL size.

CONCLUSION: Insulin sensitivity, inflammation and markers for liver synthetic function differentially impact VLDL-P concentration and VLDL size. These results underscore the complex effects of insulin resistance and its complications on VLDL production.

}, keywords = {Aged, Aged, 80 and over, C-Reactive Protein, Cross-Sectional Studies, Factor VII, Female, Humans, Inflammation, Insulin Resistance, Lipoproteins, VLDL, Liver, Liver Function Tests, Male, Risk Factors, Socioeconomic Factors}, issn = {1532-8600}, doi = {10.1016/j.metabol.2015.10.017}, author = {Jiang, Z Gordon and de Boer, Ian H and Mackey, Rachel H and Jensen, Majken K and Lai, Michelle and Robson, Simon C and Tracy, Russell and Kuller, Lewis H and Mukamal, Kenneth J} } @article {7912, title = {Aortic Stiffness is Associated with Increased Risk of Incident Dementia in Older Adults.}, journal = {J Alzheimers Dis}, volume = {66}, year = {2018}, month = {2018}, pages = {297-306}, abstract = {

Cardiovascular disease risk factors, including age, hypertension, and diabetes, contribute to aortic stiffness and subclinical cardiovascular and brain disease, increasing dementia risk. Aortic stiffness, measured by carotid-femoral pulse wave velocity (cfPWV), reduces the buffering of pulsatile blood flow, exposing cerebral small arteries to microvascular damage. High cfPWV is related to white matter hyperintensities and brain amyloid deposition, and to cognitive decline, but it is unclear whether cfPWV independently predicts incident dementia. Therefore, we tested the hypothesis that cfPWV predicts incident dementia in older adults, independent of potential confounders. The Cardiovascular Health Study Cognition Study followed 532 non-demented older adults with annual cognitive exams from 1998-99 through 2013. CfPWV was measured on 356 (mean age = 78, 59\% women) between 1996-2000. Over 15 years, 212 (59.6\%) developed dementia (median time from cfPWV measurement = 4 years). In age and sex-adjusted Cox models, cfPWV was significantly associated with increased risk of dementia, but systolic blood pressure, mean arterial pressure and pulse pressure were not. CfPWV (transformed as - 1/cfPWV) remained significantly associated with dementia risk when further adjusted for education, race, APOEɛ4, diabetes, body mass index, mean arterial pressure, and anti-hypertensive medication (hazard ratio = 1.60, 95\% CI = 1.02, 2.51). Results were similar when further adjusted for baseline global cognition, subclinical brain measures, and coronary artery calcification. Finally, higher cfPWV was related to lower physical activity intensity and higher systolic blood pressure, heart rate, and waist circumference measured 5 years prior. An important unanswered question is whether interventions to slow arterial stiffening can reduce the risk of dementia.

}, issn = {1875-8908}, doi = {10.3233/JAD-180449}, author = {Cui, Chendi and Sekikawa, Akira and Kuller, Lewis H and Lopez, Oscar L and Newman, Anne B and Kuipers, Allison L and Mackey, Rachel H} } @article {8512, title = {APOL1 gene variants and kidney disease in whites: the cardiovascular health study.}, journal = {Nephrol Dial Transplant}, volume = {34}, year = {2019}, month = {2019 12 01}, pages = {2155-2156}, issn = {1460-2385}, doi = {10.1093/ndt/gfz186}, author = {Drury, Erika R and Friedman, David J and Pollak, Martin R and Ix, Joachim H and Kuller, Lewis H and Tracy, Russell P and Mukamal, Kenneth J} } @article {8437, title = {Associations of body composition with incident dementia in older adults: Cardiovascular Health Study-Cognition Study.}, journal = {Alzheimers Dement}, year = {2020}, month = {2020 Aug 17}, abstract = {

INTRODUCTION: A body of literature reported associations between late-life general adiposity measures (eg, body mass index) and dementia. Little is known about the association of late-life body composition with dementia risk.

METHODS: We determined this association among cognitively normal participants from the Cardiovascular Health Study- Cognition Study. Body composition was assessed by dual-energy x-ray absorptiometry in 1994-1995. Dementia was ascertained at annual follow-up from 1998-1999 to 2013. Associations of body composition with incident dementia were assessed by the Fine-Gray model.

RESULT: Among 344 participants (mean age 78, 62.2\% women), body composition was significantly different between men and women, despite similar body mass indexes (BMIs). Increased dementia risk was significantly associated with lower lean mass in men and marginally with low appendicular lean mass in women.

DISCUSSION: Decreased lean mass was an indicator of increased dementia risk in older adults. Studies should test whether preventing lean mass loss in older adults reduces dementia risk.

}, issn = {1552-5279}, doi = {10.1002/alz.12125}, author = {Cui, Chendi and Mackey, Rachel H and Shaaban, C Elizabeth and Kuller, Lewis H and Lopez, Oscar L and Sekikawa, Akira} } @article {9087, title = {The Association of Lipids and Lipoproteins with Hip Fracture Risk the Cardiovascular Health Study.}, journal = {Am J Med}, year = {2022}, month = {2022 Jun 06}, abstract = {

BACKGROUND: It is uncertain if lipids or lipoproteins are associated with osteoporotic fractures. In this study, incident hip fracture risk according to conventional lipid levels and lipoprotein levels and sizes was examined.

METHODS: We followed 5832 participants aged >=65 years from the Cardiovascular Health Study for hip fracture for a mean of 13.5 (SD 5.7) years. Standard enzymatic methods were used to determine lipid levels (HDL-c, LDL-c, triglycerides). Nuclear magnetic resonance spectroscopy was used to measure lipoprotein fractions (VLDL-P, LDL-P, HDL-P) in a subset of 1849 participants.

RESULTS: We documented 755 incident hip fractures among women (1.19 fractures per 100 participant years [95\% CI, 1.04, 1.35]) and 197 among men (0.67 fractures per 100 participant years [95\% CI, 0.41, 1.10]) over an average follow-up. HDL-c and LDL-c levels had statistically significant non-linear U-shaped relationships with hip fracture risk (HDL-c, p=0.009; LDL-c, p=0.02). Triglyceride levels were not significantly associated with hip fracture risk. In fully adjusted conjoint models, higher VLDL-P concentration [HR per 1-standard (SD) increment 1.47 (1.13, 1.91)] and size [HR per 1-SD increment 1.24 [1.05, 1.46]) and higher HDL-P size (HR per 1-SD increment 1.81 [1.25, 2.62]) were all associated with higher hip fracture risk.

CONCLUSIONS: Lipids and lipoproteins are associated with hip fracture risk in older adults. The associations are complex. Mechanistic studies are needed to understand these findings.

}, issn = {1555-7162}, doi = {10.1016/j.amjmed.2022.05.024}, author = {Barzilay, Joshua I and B{\r u}zkov{\'a}, Petra and Kuller, Lewis H and Cauley, Jane A and Fink, Howard A and Sheets, Kerry and Robbins, John A and Carbone, Laura D and Elam, Rachel E and Mukamal, Kenneth J} } @article {8990, title = {Association of Serum Neurofilament Light Chain Concentration and MRI Findings in Older Adults: The Cardiovascular Health Study.}, journal = {Neurology}, volume = {98}, year = {2022}, month = {2022 Mar 01}, pages = {e903-e911}, abstract = {

BACKGROUND AND OBJECTIVES: Neurofilament light chain (NfL) in blood is a sensitive but nonspecific marker of brain injury. This study sought to evaluate associations between NfL concentration and MRI findings of vascular brain injury in older adults.

METHODS: A longitudinal cohort study included 2 cranial MRI scans performed about 5 years apart and assessed for white matter hyperintensities (WMH) and infarcts. About 1 year before their second MRI, 1,362 participants (median age 77 years, 61.4\% women) without a history of TIA or stroke had measurement of 4 biomarkers: NfL, total tau, glial fibrillary acidic protein (GFAP), and ubiquitin carboxyl-terminal hydrolase L1. Most (n = 1,279) also had the first MRI scan, and some (n = 633) had quantitative measurements of hippocampal and WMH. In primary analyses, we assessed associations of NfL with a 10-point white matter grade (WMG) and prevalent infarcts on second MRI and with worsening WMG and incident infarct comparing the 2 scans. A value <0.0125 (0.05/4) was considered significant for these analyses. We also assessed associations with hippocampal and WMH volume.

RESULTS: In fully adjusted models, log(NfL) concentration was associated with WMG (β = 0.27; = 2.3 {\texttimes} 10) and worsening WMG (relative risk [RR] 1.24; = 0.0022), but less strongly with prevalent brain infarcts (RR 1.18; = 0.013) and not with incident brain infarcts (RR 1.18; = 0.18). Associations were also present with WMH volume (β = 2,242.9, = 0.0036). For the other 3 biomarkers, the associations for log (GFAP) concentration with WMG and worsening WMG were significant.

DISCUSSION: Among older adults without a history of stroke, higher serum NfL concentration was associated with covert MRI findings of vascular brain injury, especially the burden of WMH and its worsening. Whether these results offer opportunities for the use of NfL as a noninvasive biomarker of WMH or to control vascular risk factors remains to be determined.

}, issn = {1526-632X}, doi = {10.1212/WNL.0000000000013229}, author = {Fohner, Alison E and Bartz, Traci M and Tracy, Russell P and Adams, Hieab H H and Bis, Joshua C and Djouss{\'e}, Luc and Satizabal, Claudia L and Lopez, Oscar L and Seshadri, Sudha and Mukamal, Kenneth J and Kuller, Lewis H and Psaty, Bruce M and Longstreth, W T} } @article {9438, title = {Association of a blood-based aging biomarker index with death and chronic disease: Cardiovascular Health Study.}, journal = {J Gerontol A Biol Sci Med Sci}, year = {2023}, month = {2023 Jul 19}, abstract = {

BACKGROUND: A goal of gerontology is to discover phenotypes that reflect biological aging distinct from disease pathogenesis. Biomarkers that are strongly associated with mortality could be used to define such a phenotype. However, the relation of such an index with multiple chronic conditions warrants further exploration.

METHODS: A Biomarker Index (BI) was constructed in the Cardiovascular Health Study (N=3197), with a mean age of 74 years. The BI incorporated circulating levels of new biomarkers, including insulin-like growth factor-1, interleukin-6, amino-terminal pro-B-type natriuretic peptide, cystatin-C, C-reactive protein, tumor necrosis factor-alpha soluble receptor 1, fasting insulin, and fasting glucose, and was built based on their relationships with mortality. Cox proportional hazards models predicting a composite of death and chronic disease involving cardiovascular disease, dementia, and cancer were calculated with 6 years of follow-up.

RESULTS: The hazard ratio (HR, 95\% CI) for the composite outcome of death or chronic disease per category of BI was 1.65 (1.52, 1.80) and 1.75 (1.58, 1.94) in women and men, respectively. The HR (95\% CI) per 5 years of age was 1.57 (1.48, 1.67) and 1.55 (1.44, 1.67) in women and men, respectively. Moreover, BI could attenuate the effect of age on the composite outcome by 16.7\% and 22.0\% in women and men, respectively.

CONCLUSIONS: BI was significantly and independently associated with a composite outcome of death and chronic disease, and attenuated the effect of age. The BI that is composed of plasma biomarkers may be a practical intermediate phenotype for interventions aiming to modify the course of aging.

}, issn = {1758-535X}, doi = {10.1093/gerona/glad172}, author = {Zhang, Xiao and Sanders, Jason L and Boudreau, Robert M and Arnold, Alice M and Justice, Jamie N and Espeland, Mark A and Kuchel, George A and Barzilai, Nir and Kuller, Lewis H and Lopez, Oscar L and Kritchevsky, Stephen B and Newman, Anne B} }