@article {772, title = {Traditional and novel risk factors in older adults: cardiovascular risk assessment late in life.}, journal = {Am J Geriatr Cardiol}, volume = {13}, year = {2004}, month = {2004 Mar-Apr}, pages = {69-80}, abstract = {

As a population-based, longitudinal study of nearly 6000 older American adults, the Cardiovascular Health Study provides an excellent opportunity to assess the roles of traditional and novel cardiovascular risk factors in the development of coronary heart disease. Cardiovascular Health Study investigators have analyzed both traditional risk factors, such as diabetes, hypertension, and smoking, and new risk factors, such as hemostatic factors, inflammatory markers, exposure to infectious agents, and genetic determinants. These analyses have led to several important conclusions. First, older adults without previous cardiovascular events have a tremendous burden of subclinical vascular disease, which may change how physicians view risk factor modification in this age group. Second, some traditional cardiovascular risk factors lose importance as predictors of cardiovascular disease among older adults. Third, even modest elevations in fasting blood glucose or systolic blood pressure-below the levels used to define diabetes or hypertension-may have prognostic implications. Fourth, novel cardiovascular risk factors may add further information about cardiovascular disease risk in older adults. Promising potential candidates identified in the Cardiovascular Health Study include markers of hemostatic activation, fibrinogen, factor VIII coagulant activity, C-reactive protein, and exposure to herpes simplex virus-1 and possibly chlamydia. Future Cardiovascular Health Study investigations will help to clarify which combination of traditional and newer risk factors provides the best estimate of cardiovascular risk for older adults.

}, keywords = {Aged, Blood Coagulation Factors, Cardiovascular Diseases, Cohort Studies, Diabetes Complications, Female, Genetic Predisposition to Disease, Humans, Hypertension, Infections, Inflammation, Lipids, Longitudinal Studies, Male, Obesity, Predictive Value of Tests, Risk Factors, Smoking, United States}, issn = {1076-7460}, doi = {10.1111/j.1076-7460.2004.02123.x}, author = {Mukamal, Kenneth J and Kronmal, Richard A and Tracy, Russell P and Cushman, Mary and Siscovick, David S} } @article {853, title = {Hospitalization for pneumonia in the Cardiovascular Health Study: incidence, mortality, and influence on longer-term survival.}, journal = {J Am Geriatr Soc}, volume = {53}, year = {2005}, month = {2005 Jul}, pages = {1108-16}, abstract = {

OBJECTIVES: To estimate the rate of hospitalization for pneumonia in community-dwelling older adults and to assess its risk factors and contribution to mortality.

DESIGN: Prospective observational study.

SETTING: The Cardiovascular Health Study (CHS) in four U.S. communities.

PARTICIPANTS: Five thousand eight hundred eighty-eight men and women aged 65 and older who were followed for a median 10.7 years.

MEASUREMENTS: Participants were interviewed about medical history and demographics; evaluated for lung, physical, and cognitive function; and followed for hospitalizations, cardiovascular disease, and death.

RESULTS: Nearly 10\% of the cohort was hospitalized for pneumonia, for a rate of 11.1 per 1,000 person-years (95\% confidence interval (CI)=10.2-12.0). Risk factors included older age, male sex, current and past smoking, poor physical and lung function, and history of cardiovascular disease and chronic obstructive pulmonary disease. Ten percent of participants died during their incident pneumonia hospitalization, and death rates were high in those who survived to discharge. Compared with participants who had not been hospitalized for pneumonia, the relative risk of total mortality was 4.9 (95\% CI=4.1-6.0) during the first year after hospitalization and 2.6 (95\% CI=2.2-3.1) thereafter, adjusted for age, sex, and race. The respective relative risks were 3.9 (95\% CI=3.1-4.8) and 2.0 (95\% CI=1.6-2.4) after further adjustment for baseline history of cardiovascular disease; diabetes mellitus; smoking; and measures of lung, physical, and cognitive function.

CONCLUSION: In older people, hospitalization for pneumonia is common and is associated with an elevated risk of death, as shown in this population-based, prospective cohort.

}, keywords = {Aged, Aged, 80 and over, Cognition, Comorbidity, Diabetes Complications, Female, Hospitalization, Humans, Male, Mortality, Pneumonia, Prospective Studies, Respiratory Physiological Phenomena, Risk Factors, Smoking}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2005.53352.x}, author = {O{\textquoteright}Meara, Ellen S and White, Mark and Siscovick, David S and Lyles, Mary F and Kuller, Lewis H} } @article {6210, title = {The influence of sex on cardiovascular outcomes associated with diabetes among older black and white adults.}, journal = {J Diabetes Complications}, volume = {28}, year = {2014}, month = {2014 May-Jun}, pages = {316-22}, abstract = {

AIMS: It is unknown whether sex differences in the association of diabetes with cardiovascular outcomes vary by race. We examined sex differences in the associations of diabetes with incident congestive heart failure (CHF) and coronary heart disease (CHD) between older black and white adults.

METHODS: We analyzed data from the Cardiovascular Health Study (CHS), a prospective cohort study of community-dwelling individuals aged >=65 from four US counties. We included 4817 participants (476 black women, 279 black men, 2447 white women and 1625 white men). We estimated event rates and multivariate-adjusted hazard ratios for incident CHF, CHD, and all-cause mortality by Cox regression and competing risk analyses.

RESULTS: Over a median follow-up of 12.5years, diabetes was more strongly associated with CHF among black women (HR, 2.42 [95\% CI, 1.70-3.40]) than black men (1.39 [0.83-2.34]); this finding did not reach statistical significance (P for interaction=0.08). Female sex conferred a higher risk for a composite outcome of CHF and CHD among black participants (2.44 [1.82-3.26]) vs. (1.44 [0.97-2.12]), P for interaction=0.03). There were no significant sex differences in the HRs associated with diabetes for CHF among whites, or for CHD or all-cause mortality among blacks or whites. The three-way interaction between sex, race, and diabetes on risk of cardiovascular outcomes was not significant (P=0.07).

CONCLUSIONS: Overall, sex did not modify the cardiovascular risk associated with diabetes among older black or white adults. However, our results suggest that a possible sex interaction among older blacks merits further study.

}, keywords = {African Continental Ancestry Group, Age Factors, Aged, Aged, 80 and over, Cohort Studies, Coronary Disease, Diabetes Complications, European Continental Ancestry Group, Female, Heart Failure, Humans, Incidence, Longitudinal Studies, Male, Prospective Studies, Regression Analysis, Retrospective Studies, Risk Factors, Sex Factors, Survival Rate}, issn = {1873-460X}, doi = {10.1016/j.jdiacomp.2013.12.004}, author = {Vimalananda, Varsha G and Biggs, Mary L and Rosenzweig, James L and Carnethon, Mercedes R and Meigs, James B and Thacker, Evan L and Siscovick, David S and Mukamal, Kenneth J} } @article {6588, title = {Risk factors for cardiovascular disease across the spectrum of older age: the Cardiovascular Health Study.}, journal = {Atherosclerosis}, volume = {237}, year = {2014}, month = {2014 Nov}, pages = {336-42}, abstract = {

OBJECTIVE: The associations of some risk factors with cardiovascular disease (CVD) are attenuated in older age; whereas others appear robust. The present study aimed to compare CVD risk factors across older age.

METHODS: Participants (n~=~4883) in the Cardiovascular Health Study free of prevalent CVD, were stratified into three age groups: 65-74, 75-84, 85+ years. Traditional risk factors included systolic blood pressure (BP), LDL-cholesterol, HDL-cholesterol, obesity, and diabetes. Novel risk factors included kidney function, C-reactive protein (CRP), and N-terminal pro-B-type natriuretic peptide (NT pro-BNP).

RESULTS: There were 1498 composite CVD events (stroke, myocardial infarction, and cardiovascular death) over 5 years. The associations of high systolic BP and diabetes appeared strongest, though both were attenuated with age (p-values for interaction~=~0.01 and 0.002, respectively). The demographic-adjusted hazard ratios (HR) for elevated systolic BP were 1.79 (95\% confidence interval: 1.49, 2.15), 1.59 (1.37, 1.85) and 1.10 (0.86, 1.41) in participants aged 65-74, 75-84, 85+, and for diabetes, 2.36 (1.89, 2.95), 1.55 (1.27, 1.89), 1.51 (1.10, 2.09). The novel risk factors had consistent associations with the outcome across the age spectrum; low kidney function: 1.69 (1.31, 2.19), 1.61 (1.36, 1.90), and 1.57 (1.16, 2.14) for 65-74, 75-84, and 85+ years, respectively; elevated CRP: 1.54 (1.28, 1.87), 1.33 (1.13, 1.55), and 1.51 (1.15, 1.97); elevated NT pro-BNP: 2.67 (1.96, 3.64), 2.71 (2.25, 3.27), and 2.18 (1.43, 3.45).

CONCLUSIONS: The associations of most traditional risk factors with CVD were minimal in the oldest old, whereas diabetes, eGFR, CRP, and NT pro-BNP were associated with CVD across older age.

}, keywords = {Aged, Aged, 80 and over, Blood Pressure, C-Reactive Protein, Cardiovascular Diseases, Cholesterol, HDL, Cholesterol, LDL, Diabetes Complications, Diabetes Mellitus, Female, Humans, Inflammation, Kidney, Kidney Diseases, Lipids, Male, Natriuretic Peptide, Brain, Obesity, Peptide Fragments, Risk Factors}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2014.09.012}, author = {Odden, Michelle C and Shlipak, Michael G and Whitson, Heather E and Katz, Ronit and Kearney, Patricia M and deFilippi, Chris and Shastri, Shani and Sarnak, Mark J and Siscovick, David S and Cushman, Mary and Psaty, Bruce M and Newman, Anne B} } @article {6805, title = {Associations between metabolic dysregulation and circulating biomarkers of fibrosis: the Cardiovascular Health Study.}, journal = {Metabolism}, volume = {64}, year = {2015}, month = {2015 Oct}, pages = {1316-23}, abstract = {

AIM: Fibrosis is one postulated pathway by which diabetes produces cardiac and other systemic complications. Our aim was to determine which metabolic parameters are associated with circulating fibrosis-related biomarkers transforming growth factor-β (TGF-β) and procollagen type III N-terminal propeptide (PIIINP).

METHODS: We used linear regression to determine the cross-sectional associations of diverse metabolic parameters, including fasting glucose, fasting insulin, body mass index, fatty acid binding protein 4, and non-esterified fatty acids, with circulating levels of TGF-β (n = 1559) and PIIINP (n = 3024) among community-living older adults in the Cardiovascular Health Study.

RESULTS: Among the main metabolic parameters we examined, only fasting glucose was associated with TGF-β (P = 0.03). In contrast, multiple metabolic parameters were associated with PIIINP, including fasting insulin, body mass index, and non-esterified fatty acids (P<0.001, P<0.001, P=0.001, respectively). These associations remained statistically significant after mutual adjustment, except the association between BMI and PIIINP.

CONCLUSIONS: Isolated hyperglycemia is associated with higher serum concentrations of TGF-β, while a broader phenotype of insulin resistance is associated with higher serum PIIINP. Whether simultaneous pharmacologic targeting of these two metabolic phenotypes can synergistically reduce the risk of cardiac and other manifestations of fibrosis remains to be determined.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Blood Glucose, Cardiovascular System, Cross-Sectional Studies, Diabetes Complications, Diabetes Mellitus, Fatty Acids, Nonesterified, Female, Fibrosis, Health, Humans, Insulin, Insulin Resistance, Male, Metabolic Diseases, Peptide Fragments, Procollagen, Transforming Growth Factor beta}, issn = {1532-8600}, doi = {10.1016/j.metabol.2015.07.013}, author = {Agarwal, Isha and Glazer, Nicole L and Barasch, Eddy and Djouss{\'e}, Luc and Gottdiener, John S and Ix, Joachim H and Kizer, Jorge R and Rimm, Eric B and Siscovick, David S and King, George L and Mukamal, Ken J} }