Sitting Time, Physical Activity, and Cognitive Impairment in Midlife and Older Adults.

This study cross-sectionally examines the relations of sitting and physical activity (PA) with cognitive impairment in community-dwelling adults aged 55-87 years (n = 3,780). Multivariable logistic regression assessed independent and joint relations of sitting and PA with Montreal Cognitive Assessment scores adjusting for covariates. Sitting ≥75% of the time and not meeting PA guidelines were related to 60% (95% confidence interval [CI] [1.19, 2.17]) and 27% (95% CI [1.06, 1.53]) higher odds for cognitive impairment, respectively. Stratification by age showed that sitting ≥75% of the time was associated with higher cognitive impairment odds in midlife (odds ratio [OR] = 1.86; 95% CI [1.31, 2.65]), but not older adults (OR = 1.06; 95% CI [0.57, 1.95]). Joint association analysis revealed that, overall, the highest odds for cognitive impairment were in those sitting ≥75% of the time while meeting or not meeting PA guidelines (OR = 1.69, 95% CI [1.13, 2.53]; and OR = 1.66, 95% CI [1.19, 2.32], respectively). In conclusion, prolonged sitting and insufficient PA are independent risk markers for cognitive impairment.

Functional Movement Screening Performance and Association With Key Health Markers in Older Adults.

ABSTRACT: Farrell, SW, Pavlovic, A, Barlow, CE, Leonard, D, DeFina, JR, Willis, BL, DeFina, LF, and Haskell, WL. Functional movement screening performance and association with key health markers in older adults. J Strength Cond Res 35(11): 3021-3027, 2021-We examined Functional Movement Screening (FMS) performance and associations with key health markers among adults aged 55 years or older. Apparently healthy men (n = 425) and women (n = 158) completed a preventive medical examination between 2013 and 2018. Subjects were grouped by age and sex to determine mean scores for individual FMS items as well as total FMS score. We examined partial correlations between total FMS score and key health markers. We computed odds ratios (ORs) for having a total FMS score ≤14. The mean FMS scores for men and women were 11.7 ± 2.8 and 11.9 ± 2.3, respectively. Several differences were found between men who participated in FMS (takers) compared with FMS nontakers, whereas women FMS takers were generally similar to women FMS nontakers. After controlling for age, sex, and smoking, FMS scores were directly associated with physical activity (PA), cardiorespiratory fitness, frequency of resistance training, serum vitamin D, omega-3 index, low-density lipoprotein, and high-density lipoprotein (HDL)-cholesterol, and were inversely associated with body mass index (BMI), waist circumference (WC), blood glucose, HbA1c, and metabolic syndrome (p ≤ 0.02 for each). Adjusted OR for scoring ≤14 was significantly greater for those who were BMI and WC-obese, those with metabolic syndrome, those with low HDL-cholesterol, and those not meeting current PA guidelines. This study provides characteristics and mean values for FMS in a large older population and demonstrates that FMS performance is associated with key health markers. Prospective studies of older adults are needed to determine the utility of FMS in predicting future musculoskeletal injury and other chronic disease-related health outcomes.

Cardiorespiratory Fitness, Coronary Artery Calcium, and Cardiovascular Disease Events in a Cohort of Generally Healthy Middle-Age Men: Results From the Cooper Center Longitudinal Study.

BACKGROUND: A robust literature demonstrates that coronary artery calcification (CAC) and cardiorespiratory fitness (CRF) are independent predictors of cardiovascular disease (CVD) events. Much less is known about the joint associations of CRF and CAC with CVD risk. In the setting of high CAC, high versus low CRF has been associated with decreased CVD events. The goal of this study was to assess the effect of continuous levels of CRF on CVD risk in the setting of increasing CAC burden. METHODS: We studied 8425 men without clinical CVD who underwent preventive medicine examinations that included an objective measurement of CRF and CAC between 1998 and 2007. There were 383 CVD events during an average follow-up of 8.4 years. Parametric proportional hazards regression models based on a Gompertz mortality rule were used to estimate total CVD incidence rates at 70 years of age as well as hazard ratios for the included covariates. RESULTS: CVD events increased with increasing CAC and decreased with increasing CRF. Adjusting for CAC level (scores of 0, 1-99, 100-399, and ≥400), for each additional MET of fitness, there was an 11% lower risk for CVD events (hazard ratio, 0.89; 95% confidence interval, 0.84-0.94). When CAC and CRF were considered together, there was a strong association between continuous CRF and CVD incidence rates in all CAC groups. CONCLUSIONS: In a large cohort of generally healthy men, there is an attenuation of CVD risk at all CAC levels with higher CRF.

Long-Term Association of Low-Density Lipoprotein Cholesterol With Cardiovascular Mortality in Individuals at Low 10-Year Risk of Atherosclerotic Cardiovascular Disease.

BACKGROUND: The associations of low-density lipoprotein cholesterol (LDL-C) with cardiovascular disease (CVD) and coronary heart disease mortality in an exclusively low estimated 10-year risk group are not well delineated. We sought to determine the long-term associations of various LDL-C and non-high-density lipoprotein cholesterol (HDL-C) thresholds and CVD and coronary heart disease mortality in a large, low 10-year risk cohort. METHODS: The study sample included participants of the CCLS (Cooper Center Longitudinal Study) without a history of CVD or diabetes mellitus and defined as low risk (<7.5%) for 10-year atherosclerotic CVD events at baseline based on Pooled Cohort Risk Assessment Equations. The associations of fasting LDL-C and non-HDL-C with CVD mortality were tested with Cox proportional hazards models. RESULTS: In 36 375 participants (72% men, median age 42) followed for a median of 26.8 years, 1086 CVD and 598 coronary heart disease deaths occurred. Compared with LDL-C <100 mg/dL, LDL-C categories 100 to 129 mg/dL, 130 to 159 mg/dL, 160 to 189.9 mg/dL, and ≥190 mg/dL were associated with a significantly higher risk of CVD death, with hazard ratios of 1.4 (95% CI, 1.1-1.7), 1.3 (95% CI, 1.1-1.6), 1.9 (95% CI, 1.5-2.4), and 1.7 (95% CI, 1.3-2.3), and mean reductions in years free of CVD death of 1.8, 1.1, 4.3, and 3.9, respectively. After adjustment for atherosclerotic CVD risk factors, LDL-C categories 160 to 189 mg/dL and ≥190 mg/dL remained independently associated with CVD mortality, with hazard ratios of 1.7 (95% CI, 1.4-2.2) and 1.5 (95% CI, 1.2-2.1), respectively. In multivariable-adjusted models using non-HDL-C <130 mg/dL as the reference, non-HDL-C 160 to 189 mg/dL, 190 to 219 mg/dL, and ≥220 mg/dL were significantly associated with CVD death, with hazard ratios of 1.3 (95% CI, 1.1-1.6), 1.8 (95% CI, 1.4-2.2), and 1.5 (95% CI, 1.2-2.0), respectively. Restricting the cohort to those with 10-year risk <5% did not diminish the associations of LDL-C and non-HDL-C with CVD mortality. CONCLUSIONS: In a low 10-year risk cohort with long-term follow-up, LDL-C and non-HDL-C ≥160 mg/dL were independently associated with a 50% to 80% increased relative risk of CVD mortality. These findings may have implications for future cholesterol treatment paradigms.

The Relationship between Cardiorespiratory Fitness and Montreal Cognitive Assessment Scores in Older Adults.

BACKGROUND: Relatively little is known regarding the association between objective measures of physical function such as cardiorespiratory fitness (CRF) and cognitive function tests in healthy older adults. OBJECTIVE: To evaluate the relationship between CRF and cognitive function in adults aged 55 and older. METHODS: Between 2008 and 2017, 4,931 men and women underwent a comprehensive preventive physical exam at the Cooper Clinic in Dallas, Texas. CRF was determined by duration of a maximal treadmill exercise test. Cognitive function was evaluated with the Montreal Cognitive Assessment (MoCA). In a multivariate model, adjusted odds ratios with 95% confidence intervals for MoCA scores < 26 (i.e., cognitive impairment) were determined by using CRF as both a continuous and a categorical variable. RESULTS: The mean age of the sample was 61.0 ± 6.0 years; mean maximal MET values were 10.0 ± 2.2. Mean MoCA scores were 26.9 ± 2.2; 23.4% of the sample had MoCA scores indicative of cognitive impairment. The odds ratio for cognitive impairment was 0.93 (0.88-0.97) per 1-MET increment in CRF. When examined as a categorical variable, and using the lowest CRF quintile as the referent, there was a significantly reduced likelihood for cognitive impairment across the remaining ordered CRF categories (p trend = 0.004). CONCLUSION: The association between CRF and MoCA score in older adults suggests that meeting or exceeding public health guidelines for physical activity is likely to increase CRF in low fit individuals, maintain CRF in those with a moderate to high level of CRF, and thereby help to maintain cognitive function in healthy older adults.

USE OF COMPOSITE MATERIALS AS A COMPONENT OF TUSK FRACTURE MANAGEMENT IN AN ASIAN ELEPHANT (ELEPHAS MAXIMUS) AND AN AFRICAN ELEPHANT (LOXODONTA AFRICANA).

Tusk fractures in Asian (Elephas maximus) and African elephants (Loxodonta africana) can result in damage to the distal end or to longitudinal cracks, potentially progressing to pulpitis. With pulp exposure, endodontic therapy is the treatment of choice, but conservative therapy has sufficed for some elephants. This manuscript describes the use of composite materials as a component of tusk fracture management. A 7-yr-old male Asian elephant fractured the distal end of both tusks with pulp exposure in one. Capping of each tusk with a Kevlar/fiberglass composite prevented further damage, and a modification allowed care of the exposed pulp tissue. A 34-yr-old male African elephant with a longitudinal crack received a carbon fiber/fiberglass composite circumferential wrap to potentially stabilize the crack. Compression of the crack was achieved, but follow-up was truncated due to bacterial pulpitis. Both cases show that composite material allows for lightweight, durable management of tusk fractures with continued radiographic monitoring.

Association Between Midlife Cardiorespiratory Fitness and Risk of Stroke: The Cooper Center Longitudinal Study.

BACKGROUND AND PURPOSE: Low cardiorespiratory fitness (CRF) is associated with an increased risk of stroke. However, the extent to which this association is explained by the development of stroke risk factors such as diabetes mellitus, hypertension, and atrial fibrillation is unknown. We evaluated the relationship between midlife CRF and risk of stroke after the age of 65 years, independent of the antecedent risk factor burden. METHODS: Linking participant data from the Cooper Center Longitudinal Study with Medicare claims files, we studied 19 815 individuals who survived to receive Medicare coverage from 1999 to 2009. CRF estimated at baseline by Balke treadmill time was analyzed as a continuous variable (in metabolic equivalents) and according to age- and sex-specific quintiles (Q1=low CRF). Associations between midlife CRF and stroke hospitalization after the age of 65 years were assessed by applying a proportional hazards recurrent events model to the failure time data with hypertension, diabetes mellitus, and atrial fibrillation as time-dependent covariates. RESULTS: After 129 436 person-years of Medicare follow-up, we observed 808 stroke hospitalizations. After adjustment for baseline risk factors, higher midlife CRF was associated with a lower risk of stroke hospitalization (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.49-0.76; quintiles 4-5 versus 1]. This association remained unchanged after additional adjustment for burden of Medicare-identified stroke risk factors (hypertension, diabetes mellitus, and atrial fibrillation; HR, 0.63; 95% CI, 0.51-0.79; quintiles 4-5 versus 1). CONCLUSIONS: There is a strong, inverse association between midlife CRF and stroke risk in later life independent of baseline and antecedent burden of risk factors, such as hypertension, diabetes mellitus, and atrial fibrillation.

Association between omega-3 fatty acids and serum prostate-specific antigen.

We examined the association between omega-3 fatty acids (O3FAs) and prostate-specific antigen (PSA) in a cross-sectional analysis of 6219 men examined at the Cooper Clinic from 2009 to 2013. We assayed O3FAs from red blood cell membranes and measured PSA levels in study participants. Multiple logistic regression was used to examine the association between O3FAs and PSA. The mean age of study participants was 55.5 years (SD = 9.8) with a mean PSA level of 1.31 ng/mL (SD = 1.5). Unadjusted analyses indicated that there was a slight, direct association with PSA and each of the O3FAs tested. However, after adjusting for age and body mass index (BMI), the associations were reversed but nonsignificant [odds ratio (OR) for PSA > 4 ng/mL: total omega-3 OR = 0.98 per each 1% of total fatty acids, 95% confidence interval (CI) = 0.93-1.03; docosahexaenoic acid OR = 1.01, 95% CI = 0.92-1.11; omega-3 index OR = 0.99, 95% CI = 0.93-1.05). Similar results were obtained after age and BMI adjustment when the omega-3 index was divided into undesirable (0.01-3.99%), intermediate (4.0-7.99%), and desirable ranges ( ≥ 8.0%). Given that the study had >80% power to detect an odds ratio <0.9 or >1.1, we conclude that associations between O3FAs and PSA levels are either nonexistent or quite weak in the population that this healthy sample represents.

The association between midlife cardiorespiratory fitness and later life chronic kidney disease: The Cooper Center Longitudinal Study.

BACKGROUND: Chronic kidney disease (CKD) is a major public health problem, particularly in older age and in those with diabetes mellitus (DM), with high comorbidity and treatment costs. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 17,979 participants, 22% women with a mean age of 50.0 (SD 8.8), in the Cooper Center Longitudinal Study (CCLS) seen initially between 1971 to 2009 who also received Medicare coverage from 1999 to 2009. PREDICTORS: Age, body mass index, blood pressure, cholesterol, glucose levels, current tobacco use, and cardiorespiratory fitness. OUTCOMES: Incident CKD and DM were determined from Medicare administrative claims data. RESULTS: During 116,973person-years of observation, 2022 cases of incident CKD occurred. Multivariable-adjusted proportional hazards models revealed a 24% lower risk of CKD among moderate fit (hazards ratio[HR] 0.76, 95% CI 0.67-0.85 compared to low fit) and a 34% lower risk of CKD among high fit (HR 0.66, 95% CI 0.58-0.76 compared to low fit). Even following the development of DM, fitness was associated with lower risk of CKD (HR 0.94, 95% CI 0.89-0.99) per 1-MET increment. LIMITATIONS: Relatively homogeneous population of well-educated Caucasians. CONCLUSION: Results of the present study suggest that higher fitness is associated with lower risk of CKD decades later even in at-risk populations such as diabetics. The findings support a role for enhancing fitness through regular physical activity in preventive strategies for CKD including those who may develop DM in later life.

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.

The association between midlife cardiorespiratory fitness levels and later-life dementia: a cohort study.

BACKGROUND: Primary prevention of Alzheimer disease and other types of dementia (all-cause dementia) is an important public health goal. Evidence to date is insufficient to recommend any lifestyle change to prevent or delay the onset of dementia. OBJECTIVE: To assess the association between objectively measured midlife cardiorespiratory fitness ("fitness") levels and development of all-cause dementia in advanced age. DESIGN: Prospective, observational cohort study. SETTING: Preventive medicine clinic. PATIENTS: 19 458 community-dwelling, nonelderly adults who had a baseline fitness examination. MEASUREMENTS: Fitness levels, assessed using the modified Balke treadmill protocol between 1971 and 2009, and incident all-cause dementia using Medicare Parts A and B claims data from 1999 to 2009. RESULTS: 1659 cases of incident all-cause dementia occurred during 125 700 person-years of Medicare follow-up (median follow-up, 25 years [interquartile range, 19 to 30 years]). After multivariable adjustment, participants in the highest quintile of fitness level had lower hazard of all-cause dementia than those in the lowest quintile (hazard ratio, 0.64 [95% CI, 0.54 to 0.77]). Higher fitness levels were associated with lower hazard of all-cause dementia with previous stroke (hazard ratio, 0.74 [CI, 0.53 to 1.04]) or without previous stroke (hazard ratio, 0.74 [CI, 0.61 to 0.90]). LIMITATIONS: Dementia diagnoses were based on Medicare claims, and participants generally were non-Hispanic white, healthy, and well-educated and had access to preventive health care. This study evaluated fitness levels, so a specific exercise prescription cannot be generated from results and the findings may not be causal. CONCLUSION: Higher midlife fitness levels seem to be associated with lower hazards of developing all-cause dementia later in life. The magnitude and direction of the association were similar with or without previous stroke, suggesting that higher fitness levels earlier in life may lower risk for dementia later in life, independent of cerebrovascular disease. PRIMARY FUNDING SOURCE: The Cooper Institute; University of Texas Southwestern Medical Center; National Heart, Lung, and Blood Institute; and American Heart Association.

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.

Effect of race and socioeconomic status on cardiovascular risk factor burden: the Cooper Center Longitudinal Study.

OBJECTIVES: This study examines the prevalence of cardiovascular risk factors and chronic disease burden among African Americans compared to Caucasians in a population of higher socioeconomic status. DESIGN: The current study is a cross-sectional, secondary data analysis of the Cooper Center Longitudinal Study. SETTING: Patients with a medical examination from 1970-2010 at the Cooper Clinic. PARTICIPANTS: 762 African Americans and 40,051 Caucasians who met the criteria. OUTCOME MEASURES: Racial differences in cardiovascular risk factors/burden of disease between African Americans and Caucasians. RESULTS: African Americans had higher prevalence of evaluated cardiovascular risk factors than did Caucasians after controlling for obesity, tobacco use, and physical fitness. Caucasians had greater likelihood of no risk factors while African Americans were more likely to have all three risk factors. Race was typically predictive of cardiovascular risk factors in African Americans compared to Caucasians. CONCLUSIONS: Findings suggest that health differences persist despite greater socioeconomic status, and further investigations of biopsychosocial causes are warranted.

The cross-sectional relationship among omega-3 fatty acid levels, cardiorespiratory fitness, and depressive symptoms from the Cooper Center Longitudinal Study.

OBJECTIVE: Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) are implicated in numerous illnesses including depression. The literature is mixed regarding the relationship between n-3 PUFA levels and depression, and studies based on self-reported dietary n-3 PUFA intake may not accurately reflect in vivo levels. METHOD: The current cross-sectional analysis examined the relationship between erythrocyte levels (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and depressive symptoms (Center for Epidemiologic Studies Depression Scale; CESD), adjusting for health-related factors and omega-3 supplement use in 16,398 adults assessed at the Cooper Clinic in Dallas, Texas for preventative medical examinations between April 6, 2009, and September 1, 2020. A three-stage hierarchical linear regression was conducted to examine the EPA and DHA levels on CES-D before and after inclusion of cardiorespiratory fitness (CRF) and high sensitivity C-reactive protein (hs-CRP) in the model. RESULTS: DHA level, but not EPA level, was significantly associated with CES-D scores. Taking omega-3 supplements was associated with lower CES-D scores even when adjusting for CRF, while hs-CRP was non-significantly associated with CES-D scores. These findings suggest that DHA levels are related to depressive symptom severity. Omega-3 PUFA supplement use was associated with lower CES-D scores when controlling for EPA and DHA levels. CONCLUSION: The findings from this cross-sectional study suggest that lifestyle and/or other contextual factors unrelated to EPA and DHA levels may also be associated with depressive symptom severity. Longitudinal studies are needed to evaluate the role of health-related mediators among these relationships.

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.

Mid-Life Cardiorespiratory Fitness, Obesity, and Risk of Atrial Fibrillation: The Cooper Center Longitudinal Study.

Background: Lower cardiorespiratory fitness (CRF) and higher body mass index (BMI) are associated with a higher risk of myocardial infarction and heart failure. However, the independent contribution of these lifestyle factors to the risk of atrial fibrillation (AF) is less well established. Objectives: The purpose of this study was to evaluation the association between midlife CRF, BMI, and risk of AF in older age. Methods: This study included 18,493 participants without AF who underwent assessment of CRF (estimated using the maximal treadmill time) and BMI in middle age and had Medicare coverage after the age of 65 years. The association among midlife CRF, BMI, and risk of AF was assessed by fitting a proportional hazards intensity model to the failure time data with adjustment for potential confounders. The association between changes in CRF and BMI in middle age and the risk of AF was also assessed in the subset of participants with repeat CRF assessments. Results: Among 18,493 participants (79% men), a higher midlife BMI was significantly associated with a higher risk of AF independent of CRF levels and other potential confounders (hazard ratio per 1-kg/m2: 1.05; 95% confidence interval: 1.03-1.06). Lower midlife CRF was also associated with higher risk of AF (hazard ratio per 1 MET higher CRF: 0.98; 95% confidence interval: 0.96-0.99). However, this association was attenuated and not significant after further adjustment for BMI. Change in CRF on follow-up was also not associated with the risk of AF after adjustment for other confounders. Conclusions: The association between low fitness and AF was primarily driven by differences in BMI. In contrast, obesity was independently associated with excess AF risk.

Long-term Cardiovascular Risk in Astronauts: Comparing NASA Mission Astronauts With a Healthy Cohort From the Cooper Center Longitudinal Study.

OBJECTIVE: To determine the long-term cardiovascular disease risk of astronauts with spaceflight exposure compared with a well-matched cohort. METHODS: National Aeronautics and Space Administration (NASA) astronauts are selected into their profession based upon education, unique skills, and health and are exposed to cardiovascular disease risk factors during spaceflight. The Cooper Center Longitudinal Study (CCLS) is a generally healthy cohort from a preventive medicine clinic in Dallas, Texas. Using a matched cohort design, astronauts who were selected beginning April 1, 1959, (and each subsequent selection class through 2009) and exposed to spaceflight were matched to CCLS participants who met astronaut selection criteria; 1514 CCLS participants matched to 303 astronauts in a 5-to-1 ratio on sex, date of birth, and age. The outcome of cardiovascular mortality through December 31, 2016, was determined by death certificate or National Death Index. RESULTS: There were 11 deaths caused by cardiovascular disease (CVD) among astronauts and 46 among CCLS participants. There was no evidence of increased mortality risk in astronauts (hazard ratio [HR]=1.10; 95% confidence interval [CI], 0.50 to 2.45) with adjustment for baseline cardiovascular covariates. However, the secondary outcome of CVD events showed an increased adjusted risk in astronauts (HR=2.41; 95% CI, 1.26 to 4.63). CONCLUSION: No increased risk of CVD mortality was observed in astronauts with spaceflight exposure compared with a well-matched cohort, but there was evidence of increased total CVD events. Given that the duration of spaceflight will increase, particularly on missions to Mars, continued surveillance and mitigation of CVD risk is needed to ensure the safety of those who venture into space.

Midlife Cardiorespiratory Fitness and the Development of Peripheral Artery Disease in Later Life.

Background Data are sparse on the prospective associations between physical activity and incidence of lower extremity peripheral artery disease (PAD). Methods and Results Linking participant data from the CCLS (Cooper Center Longitudinal Study) to Medicare claims files, we studied 19 023 participants with objectively measured midlife cardiorespiratory fitness through maximal effort on the Balke protocol who survived to receive Medicare coverage between 1999 and 2009. The study aimed to determine the association between midlife cardiorespiratory fitness and incident PAD with proportional hazards intensity models, adjusted for age, sex, body mass index, and other covariates, to PAD failure time data. During 121 288 person-years of Medicare follow-up, we observed 805 PAD-related hospitalizations/procedures among 19 023 participants (21% women, median age 50 years). Lower midlife fitness was associated with a higher rate of incident PAD in patients aged 65 years and older (low fit [quintile 1]: 11.4, moderate fit [quintile 2 to 3]: 7.8, and high fit [quintile 4 to 5]: 5.7 per 1000 person years). After multivariable adjustment for common predictors of incident PAD such as age, body mass index, hypertension, and diabetes, these findings persisted. Lower risk for PAD per greater metabolic equivalent task of fitness was observed (hazard ratio [HR], 0.93 [95% CI, 0.90-0.97]; P<0.001). Among a subset of patients with an additional fitness assessment, each 1 metabolic equivalent task increase from baseline fitness was associated with decreased risk of incident PAD (HR, 0.90 [95% CI, 0.82-0.99]; P=0.03). Conclusions Cardiorespiratory fitness in healthy, middle-aged adults is associated with lower risk of incident PAD in later life, independent of other predictors of incident PAD.