@article {713, title = {In the elderly, interleukin-6 plasma levels and the -174G>C polymorphism are associated with the development of cardiovascular disease.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {22}, year = {2002}, month = {2002 Dec 01}, pages = {2066-71}, abstract = {

OBJECTIVE: Interleukin (IL)-6-mediated inflammation is involved in cardiovascular disease (CVD). We assessed IL-6 levels and the -174G>C genotype in a case-control study of men and women (average age 73 years) within the Cardiovascular Health Study.

METHODS AND RESULTS: Cases included incident angina, myocardial infarction (MI), and stroke (5-year follow-up), prevalent MI, and MRI-detectable infarcts. A control group and a group free of subclinical CVD were used for comparison. The -174C allele was associated with higher C-reactive protein (11\% higher, P=0.02), fibrinogen (3\% higher, P=0.02), and IL-6 (5\% higher; P=0.16). IL-6 was associated with increased atherosclerosis when the control group was compared with the group free of subclinical CVD. No further association with CVD events was found when case groups were compared with the control group. Compared with its absence, presence of the -174C allele was associated with risk of MRI infarcts (odds ratio 1.5).

CONCLUSIONS: IL-6 levels differentiated those with subclinical CVD from those without. Although the -174C allele was not associated with incident events, associations of the genotype with inflammation and MRI infarcts, combined with the plasma IL-6 results, suggest that IL-6 may chronically predispose an individual to develop atherosclerosis.

}, keywords = {Age Factors, Aged, Biomarkers, Cardiovascular Diseases, Case-Control Studies, Cytosine, Female, Follow-Up Studies, Genetic Predisposition to Disease, Genotype, Guanine, Health Surveys, Humans, Inflammation, Interleukin-6, Linear Models, Male, Polymorphism, Genetic, Predictive Value of Tests, Promoter Regions, Genetic}, issn = {1524-4636}, doi = {10.1161/01.atv.0000040224.49362.60}, author = {Jenny, Nancy S and Tracy, Russell P and Ogg, Malcolm S and Luong, Le Ahn and Kuller, Lewis H and Arnold, Alice M and Sharrett, A Richey and Humphries, Steve E} } @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 {1075, title = {Long-term function in an older cohort--the cardiovascular health study all stars study.}, journal = {J Am Geriatr Soc}, volume = {57}, year = {2009}, month = {2009 Mar}, pages = {432-40}, abstract = {

OBJECTIVES: To evaluate shared and unique risk factors for maintaining physical and cognitive function into the ninth decade and beyond.

DESIGN: Longitudinal cohort study.

SETTING: Four U.S. communities.

PARTICIPANTS: One thousand six hundred seventy-seven participants in the Cardiovascular Health Study All Stars Study, assessed in 2005/06. Median age was 85 (range 77-102), 66.5\% were women, and 16.6\% were black.

MEASUREMENTS: Intact function was defined as no difficulty with any activities of daily living and a score of 80 or higher on the Modified Mini-Mental State Examination. Baseline characteristics assessed in 1992/93 included demographics, behavioral health factors, chronic disease history, subclinical disease markers, cardiovascular risk factors, and inflammatory markers. Multinomial logistic regression was used to compare risk for physical disability, cognitive impairment,and combined impairments with no functional impairment.

RESULTS: Of the 1,677 participants evaluated in both domains, 891 (53\%) were functionally intact. Continuous measures of function, including the Digit Symbol Substitution Test and gait speed, showed that all groups, including the most functional, had declined over time. The functional group had less decline but also tended to have higher starting values. Functional individuals had a higher baseline health profile than those with either or cognitive impairment or both impairments combined. Women and individuals with greater weight had higher rates of physical impairment but not cognitive impairment. Risk factors common to both types of impairment included cardiovascular disease and hypertension.

CONCLUSION: Intact function was found in only approximately half of these older adults in the ninth decade and beyond. High baseline function and low vascular disease risk characterized functional aging.

}, keywords = {Activities of Daily Living, Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Attention, Cardiovascular Diseases, Chronic Disease, Cohort Studies, Comorbidity, Cross-Sectional Studies, Female, Follow-Up Studies, Gait, Geriatric Assessment, Hand Strength, Health Surveys, Humans, Male, Memory, Short-Term, Mental Status Schedule, Proportional Hazards Models, Psychometrics, Risk Factors, United States}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2008.02152.x}, author = {Newman, Anne B and Arnold, Alice M and Sachs, Michael C and Ives, Diane G and Cushman, Mary and Strotmeyer, Elsa S and Ding, Jingzhong and Kritchevsky, Stephen B and Chaves, Paulo H M and Fried, Linda P and Robbins, John} } @article {1124, title = {Total and cause-specific mortality in the cardiovascular health study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {64}, year = {2009}, month = {2009 Dec}, pages = {1251-61}, abstract = {

BACKGROUND: Few cohort studies have adequate numbers of carefully reviewed deaths to allow an analysis of unique and shared risk factors for cause-specific mortality. Shared risk factors could be targeted for prevention of premature death and the study of longevity.

METHODS: A total of 5,888 community-dwelling persons aged 65 years or older living in four communities in the United States participated in the Cardiovascular Health Study cohort. Participants were initially recruited from 1989 to 1990; an additional 687 black participants were recruited in 1992-1993. The average length of follow-up was 16 years. Total and cause-specific mortality, including cardiovascular disease, stroke, cancer, dementia, pulmonary disease, infection, and other cause, were examined as outcomes. Variables previously associated with total mortality were examined for each cause of death using Cox proportional hazard models.

RESULTS: Multiple risk factors were related to total mortality. When examining specific causes, many factors were related to cardiovascular death, whereas fewer were related to other causes. For most causes, risk factors were specific for that cause. For example, apolipoprotein E epsilon4 was strongly associated for dementia death and forced vital capacity with pulmonary death. Age, male sex, markers of inflammation, and cognitive function were related to multiple causes of death.

CONCLUSIONS: In these older adults, associations of risk factors with a given cause of death were related to specific deficits in that same organ system. Inflammation may represent a common pathway to all causes of death.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Aging, Cardiovascular Diseases, Cause of Death, Chronic Disease, Cohort Studies, Female, Geriatric Assessment, Health Surveys, Humans, Kaplan-Meier Estimate, Male, Probability, Proportional Hazards Models, Retrospective Studies, Risk Assessment, Severity of Illness Index, Sex Factors, Survival Analysis, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glp127}, author = {Newman, Anne B and Sachs, Michael C and Arnold, Alice M and Fried, Linda P and Kronmal, Richard and Cushman, Mary and Psaty, Bruce M and Harris, Tamara B and Robbins, John A and Burke, Gregory L and Kuller, Lewis H and Lumley, Thomas} } @article {1352, title = {Serum 25-hydroxyvitamin D and physical function in older adults: the Cardiovascular Health Study All Stars.}, journal = {J Am Geriatr Soc}, volume = {59}, year = {2011}, month = {2011 Oct}, pages = {1793-801}, abstract = {

OBJECTIVES: To examine the association between 25-hydroxyvitamin D (25(OH)D) and physical function in adults of advanced age.

DESIGN: Cross-sectional and longitudinal analysis of physical function over 3~years of follow-up in the Cardiovascular Health Study All Stars.

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

PARTICIPANTS: Community-dwelling adults aged 77 to 100 (N~=~988).

MEASUREMENTS: Serum 25-hydroxyvitamin D 25(OH)D), Short Physical Performance Battery (SPPB), and grip and knee extensor strength assessed at baseline. Mobility disability (difficulty walking half a mile or up 10 steps) and activities of daily living (ADLs) disability were assessed at baseline and every 6~months over 3~years of follow-up.

RESULTS: Almost one-third (30.8\%) of participants were deficient in 25(OH)D (<20~ng/mL). SPPB scores were lower in those with deficient 25(OH)D (mean (standard error) 6.53~(0.24)) than in those with sufficient 25(OH)D (>=30~ng/mL) (7.15~(0.25)) after adjusting for sociodemographic characteristics, season, health behaviors, and chronic conditions (P~=~.006). Grip strength adjusted for body size was also lower in those with deficient 25(OH)D than in those with sufficient 25(OH)D (24.7~(0.6)~kg vs 26.0~(0.6)~kg, P~=~.02). Participants with deficient 25(OH)D were more likely to have prevalent mobility (OR~=~1.44, 95\% confidence interval (CI))~=~0.96-2.14) and ADL disability (OR~=~1.51, 95\% CI~=~1.01-2.25) at baseline than those with sufficient 25(OH)D. Furthermore, participants with deficient 25(OH)D were at greater risk of incident mobility disability over 3~years of follow-up (hazard ratio~=~1.56, 95\% CI~=~1.06-2.30).

CONCLUSION: Vitamin D deficiency was common and was associated with poorer physical performance, lower muscle strength, and prevalent mobility and ADL disability in community-dwelling older adults. Moreover, vitamin D deficiency predicted incident mobility disability.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Female, Follow-Up Studies, Geriatric Assessment, Health Surveys, Humans, Male, Mobility Limitation, Muscle Strength, Physical Fitness, Proportional Hazards Models, Reference Values, United States, Vitamin D, Vitamin D Deficiency}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2011.03601.x}, author = {Houston, Denise K and Tooze, Janet A and Davis, Cralen C and Chaves, Paulo H M and Hirsch, Calvin H and Robbins, John A and Arnold, Alice M and Newman, Anne B and Kritchevsky, Stephen B} } @article {1553, title = {Associations of total and high-molecular-weight adiponectin with all-cause and cardiovascular mortality in older persons: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {126}, year = {2012}, month = {2012 Dec 18}, pages = {2951-61}, abstract = {

BACKGROUND: Adiponectin shows opposite associations with adverse outcomes in healthy middle-aged populations (lower risk) and cohorts with prevalent cardiovascular disease, heart failure, or advanced age (higher risk).

METHODS AND RESULTS: In a population-based study of older adults, we examined the relationships of total and high-molecular-weight adiponectin with mortality among subgroups defined by baseline cardiovascular status: No cardiovascular disease, heart failure, or atrial fibrillation (group 1); cardiovascular disease but no heart failure/atrial fibrillation (group 2); and heart failure/atrial fibrillation (group 3). We found significant differences in the associations with all-cause mortality across the groups. The association in group 1 was U-shaped; increasing levels of total adiponectin up to 12.4 mg/L were associated with lower mortality after adjustment for confounders (hazard ratio=0.81 per 1 SD [95\% confidence interval, 0.65-0.95]), but above this cut point, higher levels conferred greater risk (hazard ratio=1.19 [95\% confidence interval, 1.12-1.27]). Further adjustment for diabetes mellitus or insulin resistance, protection against which has been proposed to mediate the beneficial relationships of adiponectin with outcome, attenuated the association in the lower range. There was no significant association in group 2, but in group 3, total adiponectin showed a direct adjusted association. Additional adjustment for putative metabolic/inflammatory intermediates suggested a direct association for group 2, and magnified the one for group 3 (hazard ratio=1.31 [1.15-1.50]). Results were similar for high-molecular-weight adiponectin and for cardiovascular mortality.

CONCLUSIONS: Adiponectin exhibits distinct associations with mortality in elders, which shift from U-shaped to flat to direct with greater baseline cardiovascular dysfunction but become more consistently adverse after accounting for metabolic/inflammatory factors presumed to be favorably regulated by the adipokine. These findings advance understanding of the adiponectin paradox as it relates to older adults.

}, keywords = {Adiponectin, Aged, Aged, 80 and over, Body Mass Index, Cardiovascular Diseases, Female, Health Surveys, Humans, Male, Molecular Weight}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.112.135202}, author = {Kizer, Jorge R and Benkeser, David and Arnold, Alice M and Mukamal, Kenneth J and Ix, Joachim H and Zieman, Susan J and Siscovick, David S and Tracy, Russell P and Mantzoros, Christos S and deFilippi, Christopher R and Newman, Anne B and Djouss{\'e}, Luc} } @article {6932, title = {Study of Cardiovascular Health Outcomes in the Era of Claims Data: The Cardiovascular Health Study.}, journal = {Circulation}, volume = {133}, year = {2016}, month = {2016 Jan 12}, pages = {156-64}, abstract = {

BACKGROUND: Increasingly, the diagnostic codes from administrative claims data are being used as clinical outcomes.

METHODS AND RESULTS: Data from the Cardiovascular Health Study (CHS) were used to compare event rates and risk factor associations between adjudicated hospitalized cardiovascular events and claims-based methods of defining events. The outcomes of myocardial infarction (MI), stroke, and heart failure were defined in 3 ways: the CHS adjudicated event (CHS[adj]), selected International Classification of Diseases, Ninth Edition diagnostic codes only in the primary position for Medicare claims data from the Center for Medicare \& Medicaid Services (CMS[1st]), and the same selected diagnostic codes in any position (CMS[any]). Conventional claims-based methods of defining events had high positive predictive values but low sensitivities. For instance, the positive predictive value of International Classification of Diseases, Ninth Edition code 410.x1 for a new acute MI in the first position was 90.6\%, but this code identified only 53.8\% of incident MIs. The observed event rates for CMS[1st] were low. For MI, the incidence was 14.9 events per 1000 person-years for CHS[adj] MI, 8.6 for CMS[1st] MI, and 12.2 for CMS[any] MI. In general, cardiovascular disease risk factor associations were similar across the 3 methods of defining events. Indeed, traditional cardiovascular disease risk factors were also associated with all first hospitalizations not resulting from an MI.

CONCLUSIONS: The use of diagnostic codes from claims data as clinical events, especially when restricted to primary diagnoses, leads to an underestimation of event rates. Additionally, claims-based events data represent a composite end point that includes the outcome of interest and selected (misclassified) nonevent hospitalizations.

}, keywords = {Blood Glucose, Cardiovascular Diseases, Female, Follow-Up Studies, Health Surveys, Hospitalization, Hospitals, Veterans, Humans, Insurance Claim Review, International Classification of Diseases, Lipids, Male, Managed Care Programs, Medicare, Risk Factors, Sampling Studies, Treatment Outcome, United States}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.115.018610}, author = {Psaty, Bruce M and Delaney, Joseph A and Arnold, Alice M and Curtis, Lesley H and Fitzpatrick, Annette L and Heckbert, Susan R and McKnight, Barbara and Ives, Diane and Gottdiener, John S and Kuller, Lewis H and Longstreth, W T} }