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.

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.

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.

Increases in erythrocyte DHA are not associated with increases in LDL-cholesterol: Cooper center longitudinal study.

BACKGROUND: The effects of fish oil products containing docosahexaenoic acid (DHA) on LDL-C levels are controversial. OBJECTIVE: To determine if changes in erythrocyte DHA are associated with changes in LDL-C levels. METHODS: In this prospective observational study, erythrocyte DHA levels and LDL-C levels were measured in 9253 individuals who presented for at least two examinations at a medical clinic. Changes in DHA levels and the reported use of omega-3 dietary supplements were correlated with changes in LDL-C in multi-variable adjusted models including the use of LDL-C-lowering drugs. RESULTS: Mean (standard deviation) age at baseline was 52.6 (10.6) years, and the time between exams averaged 1.9 (1.4) years. As a group, erythrocyte DHA increased from 5.0% (1.3) to 5.3% (1.3) (p < 0.001), and LDL-C was not significantly changed (109 (33) to 108 (33) mg/dL, p = 0.875). However, in multivariable-adjusted models of within-participant changes, a 1% increase in erythrocyte DHA was associated with a 1.9 mg/dL reduction in LDL-C (95% confidence interval (1.6, 2.2), p < 0.001). Similar relationships were seen with changes in erythrocyte EPA and EPA + DHA. In adjusted analyses, an increased use of omega-3 supplements was associated with a significant increase in erythrocyte DHA and a decrease in LDL-C in both users and non-users of lipid-lowering drugs. CONCLUSIONS: In a predominantly male, normolipidemic, middle-aged cohort, increases in erythrocyte DHA were associated with decreases in LDL-C, and initiating fish oil supplement use did not increase LDL-C. These findings may serve to reassure individuals who, in adopting a more heart-healthy lifestyle, want to increase their omega-3 fatty acid intake.

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, Serum Vitamin D, and Prevalence of Metabolic Syndrome in Men.

PURPOSE: Low cardiorespiratory fitness (CRF), vitamin D deficiency, and metabolic syndrome (MetSyn) are prevalent among U.S. adults. Joint associations among these variables are not well described. METHODS: Between 2006 and 2018, 14,353 apparently healthy men completed a comprehensive health examination, including CRF based on a maximal treadmill test, components of MetSyn, and serum vitamin D levels [25(OH)D]. Participants were classified into groups of low (category 1), moderate (categories 2-3), and high (categories 4-5) CRF by age-group, as well as by clinical cut points for MetSyn and 25(OH)D. We calculated odds ratios (OR) of MetSyn across levels of CRF and 25(OH)D and also examined joint associations among these three variables. RESULTS: Mean 25(OH)D levels were 30.9 ± 11.6 and 26.3 ± 10.7 ng·mL in men without and with MetSyn, respectively (P < 0.001). The prevalence of MetSyn was inversely associated with ordered categories of CRF and 25(OH)D (Ptrend < 0.001 for both). Men with normal 25(OH)D had significantly lower odds of MetSyn than men who were vitamin D deficient (OR = 0.29, 95% confidence interval = 0.26-0.33). Men with moderate (OR = 0.31, 0.27-0.35) or high CRF (OR = 0.08, 0.07-0.09) had significantly lower odds of MetSyn than men with low CRF. Joint associations between CRF, 25(OH)D, and MetSyn revealed significantly greater prevalence of MetSyn in unfit men compared with fit men within each category of 25(OH)D (P < 0.001). Each 5 ng·mL increment of 25(OH)D and 1 MET increment of CRF was associated with a 16.0% and 31.3% lower prevalence of MetSyn, respectively. CONCLUSION: There are strong individual and joint associations between CRF, 25(OH)D, and MetSyn. Prospective studies are needed to evaluate these joint associations with regard to mortality outcomes.

Higher omega-3 index is associated with more rapid heart rate recovery in healthy men and women.

BACKGROUND: Previous studies have suggested that omega-3 polyunsaturated fatty acids (n-3 PUFA) can favorably influence cardiac autonomic tone. However, data regarding n-3 PUFA status and heart rate recovery (HRR) in healthy adults are sparse. PURPOSE: To examine the association between n-3 PUFA status and HRR. METHODS: Participants included 13,912 patients who underwent a comprehensive examination at the Cooper Clinic, Dallas TX. Fitness was determined from a maximal exercise test. HRR was calculated by subtracting the heart rate at 1, 3, and 5 min of an active recovery period from the maximal heart rate. Participants were categorized as having a low (<4%), normal (4-8%) or optimal (>8%) Omega-3 Index (O3I) (i.e., erythrocyte levels of eicosapentaenoic and docosahexaenoic acids). Multiple linear regression was used to model the association between O3I and HRR adjusting for age, maximal METs, body mass index, and smoking by sex. RESULTS: Higher categories of O3I were associated with greater HRR at 1 min (men: 23.7, 23.9, 24.6 beats/min; women: 23.9, 24.6, 25.9 and 3 min (men: 52.4, 52.9, 53.6 beats/min; women: 51.9, 53.4, 54.6), p trend <0.01 for all. Corresponding HRR at 5 min were (men: 60.0, 60.2, 60.7 beats/min, p trend=0.09; women: 59.4, 60.8, 61.6, p trend <0.001). The HRR gradients across O3I categories were steeper in women than men at 1, 3, and 5 min (p<0.03 for all sex x O3I category interactions with HRR). CONCLUSIONS: A direct relationship between HRR and O3I values was observed in both men and women, with a steeper gradient in women. These findings suggest a potential cardioprotective mechanism for n-3 PUFA.

Relevance of Fitness to Mortality Risk in Men Receiving Contemporary Medical Care.

BACKGROUND: An inverse association between cardiorespiratory fitness and mortality was robustly demonstrated 3 decades ago. OBJECTIVES: The purpose of this study was to determine whether significant advances in disease prevention, detection, and treatment since that time have modified this association. METHODS: A total of 47,862 men completed baseline examinations, including a maximal treadmill test. Cohort 1 (n = 24,475) was examined during 1971 to 1991 and followed for mortality through 1992. Cohort 2 (n = 23,387) was examined during 1992 to 2013 with follow-up through 2014. Men were categorized as low fit, moderate fit, or high fit using Cooper Clinic normative data. Hazard ratios (HRs) for all-cause, cardiovascular disease, and cancer mortality were determined across fitness categories in the 2 cohorts. RESULTS: A significant inverse trend between fitness categories and all-cause (HR: 1.0, 0.60, and 0.53 in cohort 1 and HR: 1.0, 0.76, and 0.52 in cohort 2) and cardiovascular disease mortality (HR: 1.0, 0.55, and 0.43 in cohort 1 and HR: 1.0, 0.84, and 0.52 in cohort 2) was observed (p trend <0.001 for all). The trend across fitness categories and cancer mortality was significant for cohort 1 (HR: 1.0, 0.62, and 0.48; p < 0.001), but not for cohort 2 (HR: 1.0, 1.08, and 0.74; p = 0.19). HRs for all-cause mortality were 0.86 (95% confidence interval: 0.82 to 0.90) and 0.87 (95% confidence interval: 0.83 to 0.91) per 1-MET increment in fitness for cohorts 1 and 2, respectively (p < 0.001 for both). Similar values were seen for cardiovascular disease and cancer mortality. CONCLUSIONS: Despite significant advances in disease prevention, detection, and treatment since fitness was first shown to be associated with mortality, the inverse association between fitness and mortality remains consistent in a contemporary cohort of men.

Cardiorespiratory Fitness, Body Mass Index, and Markers of Insulin Resistance in Apparently Healthy Women and Men.

BACKGROUND: Insulin resistance may be present in healthy adults and is associated with poor health outcomes. Obesity is a risk factor for insulin resistance, but most obese adults do not have insulin resistance. Fitness may be protective, but the association between fitness, weight, and insulin resistance has not been studied in a large population of healthy adults. METHODS: A cross-sectional analysis of cardiorespiratory fitness, body mass index, and markers of insulin resistance was performed. Study participants were enrolled at the Cooper Clinic in Dallas, Texas. The analysis included 19,263 women and 48,433 men with no history of diabetes or cardiovascular disease. Cardiorespiratory fitness was measured using exercise treadmill testing. Impaired fasting glucose (100-125 mg/dL) and elevated fasting triglycerides (≥150 mg/dL) were used as a markers of insulin resistance. RESULTS: Among individuals with normal weight, poor fitness was associated with 2.2-fold higher odds of insulin resistance in women (1.4-3.6; P = .001) and 2.8-fold higher odds in men (2.1-3.6; P <.001). The impact of fitness remained significant for overweight and obese individuals, with the highest risk group being the unfit obese. Among obese women, the odds ratio for insulin resistance was 11.0 for fit women (8.7-13.9; P <.001) and 20.3 for unfit women (15.5-26.5; P <.001). Among obese men, the odds ratio for insulin resistance was 7.4 for fit men (6.7-8.2; P < .001) and 12.9 for unfit men (11.4-14.6; P < .001). CONCLUSIONS: Independent of weight, poor fitness is associated with risk of insulin resistance. Obese individuals, particularly women, may benefit from the greatest absolute risk reduction by achieving moderate fitness.

Cardiorespiratory Fitness, Different Measures of Adiposity, and Cardiovascular Disease Mortality Risk in Women.

Background: Associations among cardiorespiratory fitness (CRF), different adiposity exposures, and cardiovascular disease (CVD) mortality in women are not well defined. Materials and Methods: A total of 19,838 women completed a baseline examination between 1971 and 2013. Measures included body mass index (BMI), waist circumference (WC), waist-to-height (W:HT) ratio, skinfold-derived percent body fat (% Fat), and CRF estimated from a maximal treadmill test. CRF categories were low (quintile 1), moderate (quintiles 2-3), and high (quintiles 4-5); standard cut points were used for adiposity exposures. Hazard ratios (HRs) were estimated using Cox regression. Results: During a mean follow-up period of 19.2 ± 10.3 years, 391 cardiovascular deaths occurred. HRs (95% confidence interval) for CVD in moderate and low CRF groups, using high CRF as the referent, were 1.87 (1.46-2.38) and 2.54 (1.93-3.35), respectively (p trend <0.001). HRs of obese women within each adiposity exposure were higher when compared with normal-weight women (p ≤ 0.03). Joint associations of CRF × adiposity showed a positive trend in CVD mortality across decreasing categories of CRF within each category of W:HT and % Fat, as well as within the normal and overweight BMI categories and the normal WC category (p ≤ 0.03 for each). Conclusion: Higher levels of CRF are associated with lower CVD mortality risk in women, and predict lower risk of CVD mortality in normal-weight women and in obese women. Using different measures of adiposity to predict CVD mortality risk in women may be misleading unless CRF is taken into account. These results support the American Heart Association (AHA) recommendation for including CRF as a clinical vital sign.

Traditional signs and symptoms commonly attributed to hypogonadism do not correlate with testosterone levels: the Cooper Center Longitudinal Study Experience.

Evidence suggests that substantial testosterone therapy is occurring without checking levels of testosterone, presumably based on the presence of symptoms alone. We sought to explore the relationship between total testosterone level and non-specific symptoms, metabolic abnormalities, and sexual dysfunction associated with hypogonadism. This cross-sectional study included 2994 generally healthy men aged 50-79 years examined at a preventive medicine clinic in Dallas, TX from January 2012 to March 2016. Symptoms of hypogonadism were assessed. Screening morning total testosterone levels were measured and categorized into low (<250 ng/dL), low normal (250-399 ng/dL), and normal (≥400 ng/dL). Multiple logistic regression models were used to test the associations between total testosterone and signs and symptoms of hypogonadism. When considering symptoms and signs of hypogonadism, only decreased libido (OR 1.31, 95% CI 1.00 to 1.70), fasting glucose ≥100 mg/dL (OR 1.47, CI 1.15 to 1.88), and hemoglobin A1c over 6% (OR 1.47, 95% CI 1.06 to 2.03) were associated with increased odds of low testosterone after adjustment for age, body mass index, and cardiorespiratory fitness. Testosterone levels were not associated with fatigue, depression, or erectile dysfunction in our study (p>0.6). In this preventive medicine cohort, symptoms commonly attributed to testosterone deficiency were not associated with low total testosterone levels.

Metabolic Syndrome and Cognitive Impairment among High Socioeconomic, Nondemented Older US Adults.

OBJECTIVES: Nondemented cognitive impairment (CI) presents opportunities for early interventions among individuals at risk for dementia. Identification of modifiable determinants is paramount to the development of effective clinical interventions. Metabolic syndrome (MetS) was theorized as a risk factor, but current research yields inconsistent findings. Few studies have examined the association between MetS and CI among US populations, and global results may be ungeneralizable. We investigated the MetS-CI association among high socioeconomic, nondemented older US adults, examining the roles of sociodemographic, clinical, behavioral, and genetic factors. DESIGN: Cross-sectional. SETTING: Cooper Clinic of Dallas, Texas: Cooper Center Longitudinal Study (2009-2017). PARTICIPANTS: A total of 5200 dementia-free older adult Cooper Clinic patients. MEASUREMENTS: CI was detected with a Montreal Cognitive Assessment (MoCA) score lower than 26. MetS was established based on National Cholesterol Education Program Adult Treatment Panel guidelines. Unadjusted and multivariable log-binomial regression were used to assess the MetS-CI association, with modification assessment by age, sex, education, cardiorespiratory fitness (CRF), and apolipoprotein-ε4 carrier status (APOE-ε4). RESULTS: MetS was not associated with CI when adjusting for age, sex, minority status, education, and marital status (prevalence ratio [PR] = 1.09; 95% confidence interval = .97-1.23) or when additionally adjusting for body mass index, CRF, alcohol consumption, current smoking status, and APOE-ε4 (PR = 1.07; 95% confidence interval = .80-1.45). The association was not modified by age, sex, CRF, or APOE-ε4 (P for interaction >.05). CONCLUSION: In contrast with some global and US studies, MetS and CI were not associated among our study population of nondemented older US adults. MetS may not be a suitable intervention target for poor cognitive outcomes among high socioeconomic older US adults, although separate MetS components may have different recommendations. Future studies should explore more diverse older US populations. If replicated, these findings would inform clinical efforts to reduce the burden of poor cognitive outcomes in the United States.

Association of All-Cause and Cardiovascular Mortality With High Levels of Physical Activity and Concurrent Coronary Artery Calcification.

Importance: Few data are available to guide clinical recommendations for individuals with high levels of physical activity in the presence of clinically significant coronary artery calcification (CAC). Objective: To assess the association among high levels of physical activity, prevalent CAC, and subsequent mortality risk. Design, Setting, and Participants: The Cooper Center Longitudinal Study is a prospective observational study of patients from the Cooper Clinic, a preventive medicine facility. The present study included participants seen from January 13, 1998, through December 30, 2013, with mortality follow-up through December 31, 2014. A total of 21 758 generally healthy men without prevalent cardiovascular disease (CVD) were included if they reported their physical activity level and underwent CAC scanning. Data were analyzed from September 26, 2017, through May 2, 2018. Exposures: Self-reported physical activity was categorized into at least 3000 (n = 1561), 1500 to 2999 (n = 3750), and less than 1500 (n = 16 447) metabolic equivalent of task (MET)-minutes/week (min/wk). The CAC scores were categorized into at least 100 (n = 5314) and less than 100 (n = 16 444) Agatston units (AU). Main Outcomes and Measures: All-cause and CVD mortality collected from the National Death Index Plus. Results: Among the 21 758 male participants, baseline mean (SD) age was 51.7 (8.4) years. Men with at least 3000 MET-min/wk were more likely to have prevalent CAC of at least 100 AU (relative risk, 1.11; 95% CI, 1.03-1.20) compared with those accumulating less physical activity. In the group with physical activity of at least 3000 MET-min/wk and CAC of at least 100 AU, mean (SD) CAC level was 807 (1120) AU. After a mean (SD) follow-up of 10.4 (4.3) years, 759 all-cause and 180 CVD deaths occurred, including 40 all-cause and 10 CVD deaths among those with physical activity of at least 3000 MET-min/wk. Men with CAC of less than 100 AU and physical activity of at least 3000 MET-min/wk were about half as likely to die compared with men with less than 1500 MET-min/wk (hazard ratio [HR], 0.52; 95% CI, 0.29-0.91). In the group with CAC of at least 100 AU, men with at least 3000 MET-min/wk did not have a significant increase in all-cause mortality (HR, 0.77; 95% CI, 0.52-1.15) when compared with men with physical activity of less than 1500 MET-min/wk. In the least active men, those with CAC of at least 100 AU were twice as likely to die of CVD compared with those with CAC of less than 100 AU (HR, 1.93; 95% CI, 1.34-2.78). Conclusions and Relevance: This study suggests there is evidence that high levels of physical activity (≥3000 MET-min/wk) are associated with prevalent CAC but are not associated with increased all-cause or CVD mortality after a decade of follow-up, even in the presence of clinically significant CAC levels.

Association of Educational Attainment and Cardiovascular Risk in Hispanic Individuals: Findings From the Cooper Center Longitudinal Study.

Importance: Hispanic individuals are the fastest growing ethnic group in the United States and face lower socioeconomic status compared with non-Hispanic white (NHW) individuals. However, Hispanic individuals tend to experience better health outcomes than expected, a phenomenon known as the Hispanic paradox. Little is known about how higher socioeconomic status is associated with Hispanic cardiovascular risk factor burden and outcomes. Objective: To determine cardiovascular risk and outcomes among highly educated Hispanic vs NHW individuals in a preventive medicine clinic. Design, Settings, and Participants: Retrospective cohort analysis of participants from the Cooper Center Longitudinal Study who underwent preventive medical examinations at the Cooper Clinic in Dallas, Texas, from October 1972 to November 2017. Analysis began April 2018. Exposure: Ethnicity, self-defined as Hispanic or NHW. Main Outcomes and Measures: Prevalence of major metabolic risk factors and cardiorespiratory fitness were compared, as were changes among participants with at least 2 visits. Ethnic differences adjusted for age, examination year, and educational attainment were estimated using regression models. Age-matched comparisons of coronary artery calcium scores were performed. All-cause mortality was summarized using the Kaplan-Meier method. Results: This study included 1351 Hispanic and 43 736 NHW participants aged 20 to 80 years, body mass index between 18.5 and 50.0, and were not missing key cardiometabolic or fitness variables. Both Hispanic and NHW participants had high educational attainment, with a mean of more than 15 years of total education. Hispanic women and men had a higher prevalence of metabolic syndrome (71 of 518 [13.1%] vs 1477 of 13 732 [10.8%] for women and 255 of 833 [30.6%] vs 7902 of 30 004 [26.3%] for men, respectively). Although Hispanic individuals were twice as likely to have diabetes, there was no difference in calculated 10-year atherosclerotic cardiovascular disease risk scores by ethnicity. Both Hispanic and NWH individuals experienced a statistically significant worsening in cardiometabolic parameters during follow-up, although this was not statistically significantly different between groups. In age-matched analyses, there were no significant differences in the prevalence of coronary artery calcium scores between Hispanic and NWH individuals. During a mean (SD) follow-up of 12.9 (7.5) years, there was no difference in mortality between Hispanic and NHW individuals. Conclusions and Relevance: Hispanic and NHW men and women with high educational attainment had similar atherosclerotic cardiovascular disease risk, subclinical coronary atherosclerosis, and mortality during follow-up. These findings do not support the Hispanic paradox in a highly educated Hispanic population.

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 association of cardiorespiratory fitness, body mass index, and age with testosterone levels at screening of healthy men undergoing preventive medical examinations: The Cooper Center Longitudinal Study.

BACKGROUND: Currently, exogenous hormone replacement is used in many men with hypogonadism without clear organic cause. This study examines the contribution of modifiable health behaviors, i.e., physical activity and weight control, to the maintenance of testosterone levels with aging. METHODS: In a cross-sectional study of 2994 healthy men aged 50-79 years examined at a preventive medicine clinic from January 2012 to March 2016, screening morning total testosterone levels were measured and categorized as low (<250 ng/dL), low normal (250-399 ng/dL), and normal (>400 ng/dL). Cardiorespiratory fitness (fitness) was estimated from a maximal exercise treadmill test. Multiple logistic regression models were used to test the associations between low testosterone levels and age, body mass index (BMI), and fitness. FINDINGS: Mean testosterone levels were in the normal range for each age group (50-59, 60-69, and 70-79). There was a similar prevalence of low testosterone in each age group (11·3%, 10%, and 10·5%, respectively). The prevalence of low testosterone was positively associated with BMI and negatively associated with fitness but was not associated with age. INTERPRETATION: This study found no evidence that low testosterone is an inevitable consequence of aging. Maintenance of healthy weight and fitness may help maintain normal testosterone levels.

Association of Midlife Cardiorespiratory Fitness With Incident Depression and Cardiovascular Death After Depression in Later Life.

Importance: Cardiorespiratory fitness (hereinafter referred to as fitness) as estimated by exercise testing is a modifiable risk factor independently associated with chronic diseases, cardiovascular disease (CVD) events, and mortality, but the association of fitness at midlife with incidence of later-life depression and the risk of CVD mortality after a depression diagnosis is unknown. Objective: To determine whether fitness measured in midlife would be inversely associated with later-life CVD mortality with antecedent depression. Design, Setting, and Participants: This retrospective cohort study at a single-center, community-based preventive medicine clinic was performed as part of the Cooper Center Longitudinal Study. Data were collected from January 13, 1971, through December 31, 2009, and analyzed from October 6, 2015, through August 14, 2017. Participants included generally healthy men and women who presented for preventive medicine examinations at midlife and who were eligible for Medicare from 1999 to 2010. Those with a self-reported history of depression, myocardial infarction, or stroke at examination were excluded. Exposures: Objective midlife fitness estimated from results of treadmill exercise testing. Main Outcomes and Measures: Depression diagnosis from Medicare claims files using established algorithms and CVD mortality from National Death Index records. Results: A total of 17 989 participants (80.2% men) with a mean (SD) age of 50.0 (8.7) years were included. After 117 218 person-years of Medicare follow-up, 2701 depression diagnoses, 610 deaths due to CVD without prior depression, and 231 deaths due to CVD after depression were observed. A high level of fitness in midlife was associated with a 16% lower risk of depression (hazard ratio [HR], 0.84; 95% CI, 0.74-0.95) compared with a low level of fitness. A high fitness level was also associated with a 61% lower risk of death due to CVD without depression (HR, 0.39; 95% CI, 0.31-0.48) compared with a low level of fitness. After a diagnosis of depression, a high fitness level was associated with a 56% lower risk of death due to CVD (HR, 0.44; 95% CI, 0.31-0.64) compared with a low fitness level. Conclusions and Relevance: Midlife fitness is associated with a lower risk of later-life depression, CVD mortality, and CVD mortality after incident later-life depression. These findings suggest the importance of midlife fitness in primary prevention of depression and subsequent CVD mortality in older age and should encourage physicians to consider fitness and physical activity in promoting healthy aging.

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.