Benjamin L. Willis

Cardiorespiratory Fitness and Classification of Risk of Cardiovascular Disease Mortality

Background— Cardiorespiratory fitness (fitness) is associated with cardiovascular disease (CVD) mortality. However, the extent to which fitness improves risk classification when added to traditional risk factors is unclear. Methods and Results— Fitness was measured by the Balke protocol in 66 371 subjects without prior CVD enrolled in the Cooper Center Longitudinal Study between 1970 and 2006; follow-up was extended through 2006. Cox proportional hazards models were used to estimate the risk of CVD mortality with a traditional risk factor model (age, sex, systolic blood pressure, diabetes mellitus, total cholesterol, and smoking) with and without the addition of fitness. The net reclassification improvement and integrated discrimination improvement were calculated at 10 and 25 years. Ten-year risk estimates for CVD mortality were categorized as <1%, 1% to <5%, and ≥5%, and 25-year risk estimates were categorized as <8%, 8% to 30%, and ≥30%. During a median follow-up period of 16 years, there were 1621 CVD deaths. The addition of fitness to the traditional risk factor model resulted in reclassification of 10.7% of the men, with significant net reclassification improvement at both 10 years (net reclassification improvement=0.121) and 25 years (net reclassification improvement=0.041) (P<0.001 for both). The integrated discrimination improvement was 0.010 at 10 years (P<0.001), and the relative integrated discrimination improvement was 29%. Similar findings were observed for women at 25 years. Conclusions— A single measurement of fitness significantly improves classification of both short-term (10-year) and long-term (25-year) risk for CVD mortality when added to traditional risk factors.

Physical activity versus cardiorespiratory fitness: two (partly) distinct components of cardiovascular health?

Physical activity (PA) and cardiorespiratory fitness (CRF) both have inverse relationships to cardiovascular (CV) morbidity and mortality. Recent position papers and guidelines have identified the important role of both of these factors in CV health. The benefits of PA and CRF in the prevention of CV disease and risk factors are reviewed. In addition, assessment methodology and utilization in the research and clinical arenas are discussed. Finally, the benefits, methodology, and utilization are compared and contrasted to better understand the two (partly) distinct components and their impact on CV health.

Lifetime risks for cardiovascular disease mortality by cardiorespiratory fitness levels measured at ages 45, 55, and 65 years in men. The Cooper Center Longitudinal Study.

OBJECTIVES The purpose of this study was to determine the association between fitness and lifetime risk for cardiovascular disease (CVD). BACKGROUND Higher levels of traditional risk factors are associated with marked differences in lifetime risks for CVD. However, data are sparse regarding the association between fitness and the lifetime risk for CVD. METHODS We followed up 11,049 men who underwent clinical examination at the Cooper Institute in Dallas, Texas, before 1990 until the occurrence of CVD death, non-CVD death, or attainment of age 90 years (281,469 person-years of follow-up, median follow-up 25.3 years, 1,106 CVD deaths). Fitness was measured by the Balke protocol and categorized according to treadmill time into low, moderate, and high fitness, with further stratification by CVD risk factor burden. Lifetime risk for CVD death determined by the National Death Index was estimated for fitness levels measured at ages 45, 55, and 65 years, with non-CVD death as the competing event. RESULTS Differences in fitness levels (low fitness vs. high fitness) were associated with marked differences in the lifetime risks for CVD death at each index age: age 45 years, 13.7% versus 3.4%; age 55 years, 34.2% versus 15.3%; and age 65 years, 35.6% versus 17.1%. These associations were strongest among persons with CVD risk factors. CONCLUSIONS A single measurement of low fitness in mid-life was associated with higher lifetime risk for CVD death, particularly among persons with a high burden of CVD risk factors.

Association Between Low Serum 25-Hydroxyvitamin D and Depression in a Large Sample of Healthy Adults: The Cooper Center Longitudinal Study

OBJECTIVE To investigate the association between serum vitamin D levels and depression in a large database of patients from the Cooper Clinic. PATIENTS AND METHODS We conducted a cross-sectional study of 12,594 participants seen at the Cooper Clinic from November 27, 2006, to October 4, 2010. Serum 25-hydroxyvitamin D [25(OH)D] was analyzed, and depression was defined as a Center for Epidemiologic Studies Depression Scale (CES-D) score of 10 or more. Those with and those without a history of depression represented 2 distinct populations with respect to CES-D scores; accordingly, they were analyzed separately. RESULTS In the total sample, higher vitamin D levels were associated with a significantly decreased risk [odds ratio, 0.92 (95% confidence interval, 0.87-0.97)] of current depression based on CES-D scores. The finding was stronger in those with a prior history of depression [odds ratio, 0.90 (95% confidence interval, 0.82-0.98)] and not significant in those without a history of depression [odds ratio, 0.95 (95% confidence interval, 0.89-1.02)]. CONCLUSION We found that low vitamin D levels are associated with depressive symptoms, especially in persons with a history of depression. These findings suggest that primary care patients with a history of depression may be an important target for assessment of vitamin D levels.

Physical Fitness and Risk for Heart Failure and Coronary Artery Disease

Background—Multiple studies have demonstrated strong associations between cardiorespiratory fitness and lower cardiovascular disease mortality. In contrast, little is known about associations of fitness with nonfatal cardiovascular events. Methods and Results—Linking individual participant data from the Cooper Center Longitudinal Study with Medicare claims files, we studied 20 642 participants (21% women) with fitness measured at the mean age of 49 years and who survived to receive Medicare coverage from 1999 to 2009. Fitness was categorized into age- and sex-specific quintiles (Q) according to Balke protocol treadmill time with Q1 as low fitness. Fitness was also estimated in metabolic equivalents according to treadmill time. Associations between midlife fitness and hospitalizations for heart failure and acute myocardial infarction after the age of 65 years were assessed by applying a proportional hazards model to the multivariate failure time data. After 133 514 person-years of Medicare follow-up, we observed 1051 hospitalizations for heart failure and 832 hospitalizations for acute myocardial infarction. Compared with high fitness (Q4–5), low fitness (Q1) was associated with a higher rate of heart failure hospitalization (14.3% versus 4.2%) and hospitalization for myocardial infarction (9.7% versus 4.5%). After multivariable adjustment for baseline age, blood pressure, diabetes mellitus, body mass index, smoking status, and total cholesterol, a 1 unit greater fitness level in metabolic equivalents achieved in midlife was associated with ≈20% lower risk for heart failure hospitalization after the age of 65 years (men: hazard ratio [95% confidence intervals], 0.79 [0.75–0.83]; P<0.001 and women: 0.81 [0.68–0.96]; P=0.01) but just a 10% lower risk for acute myocardial infarction in men (0.91 [0.87–0.95]; P<0.001) and no association in women (0.97 [0.83–1.13]; P=0.68). Conclusions—Fitness in healthy, middle-aged adults is more strongly associated with heart failure hospitalization than acute myocardial infarction outcomes decades later in older age.

Effects of omega-3 supplementation in combination with diet and exercise on weight loss and body composition

BACKGROUND In addition to the metabolic and cardiovascular benefits of omega-3 (n-3) fatty acids, several studies have suggested an added weight loss-enhancing benefit to this supplement. OBJECTIVE The objective was to assess whether supplemental omega-3 fatty acids in conjunction with diet and exercise augment weight loss over a 6-mo period. DESIGN In a single-institution, placebo-controlled, randomized clinical trial, 128 individuals with a body mass index (in kg/m(2)) between 26 and 40 were assigned to receive 5 omega-3 [3.0 g eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) at a 5:1 ratio (EPA:DHA)] or placebo capsules daily in conjunction with lifestyle modification. The primary endpoint was weight loss; secondary endpoints included metabolic and psychometric variables. Analyses were by intention-to-treat. RESULTS Overweight and obese individuals were assigned to the omega-3 arm (n = 64) or to the placebo arm (n = 64). Subjects in both arms received dietary and exercise counseling. Eighty-one individuals completed the 24-wk study, and the dropout rate was 27%. Subjects in both arms lost an average of >5% of their body weight. No significant differences in weight loss were observed between the omega-3 (-5.2 kg; 95% CI: -6.0, -4.4 kg) and placebo (-5.8 kg; 95% CI: -6.7, -5.1 kg) arms. The absolute mean (±SEM) change difference was 0.61 ± 0.58 kg (P = 0.29). In addition, no significant differences in the other factors assessed were observed. CONCLUSION Omega-3 fatty acids were not effective as an adjunct for weight loss in this otherwise healthy, overweight population.

Association Between Family History and Coronary Heart Disease Death Across Long-Term Follow-Up in Men The Cooper Center Longitudinal Study

Background— Family history of coronary heart disease (CHD) has been well studied as an independent risk factor for CHD events in the short term (<10 years). However, data are sparse on the association between family history and risk for CHD across long-term follow-up. Methods and Results— We included 49 255 men from the Cooper Center Longitudinal Study. Premature family history of CHD was defined as the presence of angina, myocardial infarction, angioplasty, or bypass surgery in a relative <50 years of age. Cause-specific mortality was obtained from the National Death Index. The association between premature family history and cardiovascular disease (CVD) or CHD death was compared across 3 unique follow-up periods (0–10, >10–20, and >20 years). Lifetime risk was estimated by use of a modified survival analytic technique adjusted for competing risk with non-CVD death as the competing event. After 811 708 person-years of follow-up, there were 919 CHD deaths and 1456 CVD deaths. After adjustment for traditional risk factors, premature family history was associated with CHD mortality >10 to 20 years (1.59; 95% confidence interval, 1.14–2.22) and >20 years (1.43; 95% confidence interval, 1.05–1.95) with wider confidence intervals at 0 to 10 years (1.32; 95% confidence interval, 0.76–2.31). Similar findings were observed for CVD mortality. Compared with men without a family history of coronary artery disease, premature family history was associated with an ≈50% higher lifetime risk for both CHD and CVD mortality (13.7% versus 8.9% and 21% versus 14.1%, respectively). Conclusion— Premature family history was associated with a persistent increase in both CHD and CVD mortality risk across long-term follow-up, resulting in significantly higher lifetime risk estimates.

Changes in mid-life fitness predicts heart failure risk at a later age independent of interval development of cardiac and noncardiac risk factors: the Cooper Center Longitudinal Study.

AIMS Low mid-life fitness is associated with higher risk for heart failure (HF). However, it is unclear to what extent this HF risk is modifiable and mediated by the burden of cardiac and noncardiac comorbidities. We studied the effect of cardiac and noncardiac comorbidities on the association of mid-life fitness and fitness change with HF risk. METHODS Linking individual subject data from the Cooper Center Longitudinal Study (CCLS) with Medicare claims files, we studied 19,485 subjects (21.2% women) who survived to receive Medicare coverage from 1999 to 2009. Fitness estimated by Balke treadmill time at mean age of 49 years was analyzed as a continuous variable (in metabolic equivalents [METs]) and according to age- and sex-specific quintiles. Associations of mid-life fitness and fitness change with HF hospitalization after age of 65 years were assessed by applying a proportional hazards recurrent events model to the failure time data with each comorbidity entered as time-dependent covariates. RESULTS After 127,110 person years of Medicare follow-up, we observed 1,038 HF hospitalizations. Higher mid-life fitness was associated with a lower risk for HF hospitalization (hazard ratio [HR] 0.82 [0.76-0.87] per MET) after adjustment for traditional risk factors. This remained unchanged after further adjustment for the burden of Medicare-identified cardiac and noncardiac comorbidities (HR 0.83 [0.78-0.89]). Each 1 MET improvement in mid-life fitness was associated with a 17% lower risk for HF hospitalization in later life (HR 0.83 [0.74-0.93] per MET). CONCLUSIONS Mid-life fitness is an independent and modifiable risk factor for HF hospitalization at a later age.

Secular Change in Cardiorespiratory Fitness of Men: Cooper Center Longitudinal Study

UNLABELLED Cardiorespiratory fitness (CRF) has been shown to be an independent predictor of all-cause and cardiovascular mortality, as well as health outcomes such as cardiovascular disease, hypertension, diabetes mellitus, and metabolic syndrome. During the last four decades, national guidelines for physical activity and fitness have emerged in an ongoing effort to improve health outcomes through enhanced CRF risk profiles. PURPOSE The purpose of the study was to describe the secular trend in CRF as a function of decade and age in a large cohort of men during the past 40 yr. METHODS A cross-sectional analysis of baseline fitness data collected during comprehensive medical examinations of 52,785 men age 20-74 yr evaluated at the Cooper Clinic in Dallas, TX, from 1970 to 2009 who completed a maximum treadmill exercise test for estimation of aerobic capacity was conducted. Comparisons were made between mean fitness levels in each decade stratified by five age groups. RESULTS Mean CRF in MET from estimated V·O 2max has increased overall approximately 1 MET during a 40-yr period for each of the five age groups (P < 0.0001). The greatest change occurred during the 1970s to 1980s with minimal subsequent increase and a small decline commencing in the last decade especially in younger men. CONCLUSIONS In a large cohort of men, average CRF has improved during the last 40 yr with a slight decline in the favorable trend notable in the most recent decade.

Midlife Cardiorespiratory Fitness, Incident Cancer, and Survival After Cancer in Men: The Cooper Center Longitudinal Study

IMPORTANCE Cardiorespiratory fitness (CRF) as assessed by formalized incremental exercise testing is an independent predictor of numerous chronic diseases, but its association with incident cancer or survival following a diagnosis of cancer has received little attention. OBJECTIVE To assess the association between midlife CRF and incident cancer and survival following a cancer diagnosis. DESIGN, SETTING, AND PARTICIPANTS This was a prospective, observational cohort study conducted at a preventive medicine clinic. The study included 13 949 community-dwelling men who had a baseline fitness examination. All men completed a comprehensive medical examination, a cardiovascular risk factor assessment, and incremental treadmill exercise test to evaluate CRF. We used age- and sex-specific distribution of treadmill duration from the overall Cooper Center Longitudinal Study population to define fitness groups as those with low (lowest 20%), moderate (middle 40%), and high (upper 40%) CRF groups. The adjusted multivariable model included age, examination year, body mass index, smoking, total cholesterol level, systolic blood pressure, diabetes mellitus, and fasting glucose level. Cardiorespiratory fitness levels were assessed between 1971 and 2009, and incident lung, prostate, and colorectal cancer using Medicare Parts A and B claims data from 1999 to 2009; the analysis was conducted in 2014. MAIN OUTCOMES AND MEASURES The main outcomes were (1) incident prostate, lung, and colorectal cancer and (2) all-cause mortality and cause-specific mortality among men who developed cancer at Medicare age (≥65 years). RESULTS Compared with men with low CRF, the adjusted hazard ratios (HRs) for incident lung, colorectal, and prostate cancers among men with high CRF were 0.45 (95% CI, 0.29-0.68), 0.56 (95% CI, 0.36-0.87), and 1.22 (95% CI, 1.02-1.46), respectively. Among those diagnosed as having cancer at Medicare age, high CRF in midlife was associated with an adjusted 32% (HR, 0.68; 95% CI, 0.47-0.98) risk reduction in all cancer-related deaths and a 68% reduction in cardiovascular disease mortality following a cancer diagnosis (HR, 0.32; 95% CI, 0.16-0.64) compared with men with low CRF in midlife. CONCLUSIONS AND RELEVANCE There is an inverse association between midlife CRF and incident lung and colorectal cancer but not prostate cancer. High midlife CRF is associated with lower risk of cause-specific mortality in those diagnosed as having cancer at Medicare age.