Coronary Artery Calcification and High-Volume Physical Activity: Role of Lower Intensity versus Longer Duration of Exercise.

AIM: While high-volume physical activity (PA) has been linked to elevated coronary artery calcification (CAC), the role of intensity versus duration of PA has not been investigated. The purpose of the study was to examine the role of intensity versus duration of PA in relation to CAC. METHODS: Data are from 23,383 apparently healthy men who completed a PA questionnaire and underwent CAC scanning as part of a preventive exam. Self-reported PA was categorized into 4 groups of average intensity and weekly duration of PA and (average intensity: 1, 3-5.9, 6-8.9, and 9-12 metabolic equivalents of task [METs]; weekly duration: 0, > 0-<2, 2-<5, and ≥5 hours/week). Mean CAC and CAC ≥ 100 Agatston Units (AU) were regressed separately on continuous or categorical average intensity and weekly duration of PA. RESULTS: The mean and standard deviation (SD) age was 51.7 (8.3) years, and mean CAC was 174.8 (543.6) AU with 23.5% of men presenting with CAC ≥ 100 AU. Higher average intensity of PA was related to lower mean CAC (-3.1%/MET, 95% confidence interval [CI]: -4.6, -1.6%/MET) and lower relative risk (RR) of CAC ≥ 100 AU (RR: 0.99, 95% CI: 0.98, 1.00/MET). Opposite trend was observed for the duration component wherein higher weekly duration of PA was significantly associated with greater mean CAC and RR of CAC ≥ 100 AU. CONCLUSIONS: Elevated CAC was associated with lower average intensity and longer duration of PA in men, providing new insight into the complex relationship between leisure-time PA behaviors and risk of CAC.

Does greater extent of coronary artery calcification observed at high volumes of leisure time physical activity relate more to the intensity or the duration of the activity? Higher average intensity of activity is associated with less coronary artery calcification at any age and weekly duration of activity.Higher weekly duration of activity is associated with more coronary artery calcification at any age and average intensity of activity.

Association between baseline levels of muscular strength and risk of stroke in later life: The Cooper Center Longitudinal Study.

PURPOSE: Muscular strength is an important component of physical fitness. We evaluated the relationship between baseline muscular strength and risk of stroke among adults who were aged ≥65 years during follow-up. METHODS: We included 7627 healthy adults (mean age = 43.9 years, 86.0% male) underwent a baseline physical examination between 1980 and 1989. Muscular strength was determined by 1-repetition maximum measures for bench press and leg press and categorized into age- and sex-specific tertiles for each measure. Cardiorespiratory fitness (CRF) was assessed via a maximal treadmill exercise test. Those enrolled in fee-for-service Medicare from 1999 to 2019 were included in the analyses. Associations between baseline strength and stroke outcomes were estimated using a modified Cox proportional hazards model. In a secondary analysis, we examined stroke risk by categories of CRF where Quintile 1 = low, Quintiles 2-3 = moderate, and Quintiles 4-5 = high CRF based on age and sex. RESULTS: After 70,072 person-years of Medicare follow-up, there were 1211 earliest indications of incident stroke. In multivariable analyses, the hazard ratio (95% confidence interval (95%CI)) for stroke across bench press categories were 1.0 (referent), 0.96 (0.83-1.11), and 0.89 (0.77-1.04), respectively (p trend = 0.14). The trend across categories of leg press was also non-significant (p trend = 0.79). Adjusted hazard ratio (95%CI) for stroke across ordered CRF categories were 1.0 (referent), 0.90 (0.71-1.13), and 0.72 (0.57-0.92) (p trend < 0.01). CONCLUSION: While meeting public health guidelines for muscular strengthening activities is likely to improve muscular strength as well as many health outcomes in older adults, performing such activities may not be helpful in preventing stroke. Conversely, meeting guidelines for aerobic activity is likely to improve CRF and lower stroke risk.

Omega-3 index, cardiorespiratory fitness, and cognitive function in mid-age and older adults.

Higher levels of omega-3 fatty acids in red blood cell membranes (omega-3 index or O3I) and cardiorespiratory fitness (CRF) are each associated with reduced cognitive impairment, but little research has examined the relationship between O3I and cognitive function while accounting for CRF. We analyzed cross-sectional data from 5,464 healthy men and women aged 55-85 years who had preventive medical examinations between 2009 and 2023. Primary exposures included O3I (<4.0%, 4.0-7.9%, or ≥ 8.0%) and age- and sex-based CRF quintile (1 = low, 2-3 = moderate, 4-5 = high). Cognitive impairment was defined as a Montreal Cognitive Assessment score of ≤ 25. We used Poisson regression to estimate relative risks (RR) of cognitive impairment, controlling for covariates. O3I < 4% was associated with increased cognitive impairment relative to ≥ 8.0% (RR, 1.21; 95% CI, 1.01-1.44) in a partially adjusted model. This association did not remain statistically significant in the fully adjusted model which included CRF. Low versus high CRF was associated with cognitive impairment (RR, 1.28; 95% CI, 1.07-1.53), independent of O3I and clinical biomarkers. The interaction between CRF and O3I was not significant (P = 0.8). In joint association analysis, risk of cognitive impairment was elevated with lower omega-3 index or CRF or both. Additional research is needed to fully understand the association between O3I and cognitive function at varying CRF levels.

Cardiorespiratory Fitness and All-Cause Mortality in Women with Metabolic Syndrome.

Purpose: To examine the association between cardiorespiratory fitness (fitness) and all-cause mortality in women with metabolic syndrome (MetSyn). Methods: The sample included 1798 women with MetSyn (mean age 50.2 years) who received a comprehensive preventive baseline examination between 1978 and 2016, with mortality follow-up through December 31, 2017. MetSyn was identified using Adult Treatment Panel-III Guidelines. Fitness was determined by duration of a maximal treadmill exercise test and grouped as fit or unfit on the basis of the upper 80% and lower 20% of the age-standardized fitness distribution. Age- and smoking-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated in a proportional hazards regression model. Results: During a mean follow-up of 16.6 ± 8.7 years, 204 deaths occurred. Crude all-cause mortality rates were 6.8 and 6.9 deaths per 10,000 woman-years in fit and unfit groups, respectively. The adjusted HR (95% CI) for all-cause mortality in unfit versus fit women (referent) with MetSyn was 1.36 (95% CI 1.01-1.83). Conclusions: Higher levels of fitness significantly attenuate the risk of all-cause mortality in women with MetSyn. In accordance with the American Heart Association scientific statement, to more accurately determine mortality risk in this population, health care professionals should measure or estimate fitness and should strongly encourage women to meet current public health guidelines for physical activity with the goal of reaching higher fitness levels.

Associations among cardiorespiratory fitness, C-reactive protein, and all-cause mortality in men and women.

We examined individual and joint associations among high-sensitivity C-reactive protein (CRP), cardiorespiratory fitness (fitness), and mortality in healthy men and women. Between January 1, 2000 and December 31, 2016, 30,077 adults (31.3% women) received a comprehensive physical examination. Fitness was determined from maximal treadmill exercise test duration. Participants were categorized as unfit (Quintile 1) and fit (Quintiles 2-5), and by normal (<2 mg/L) and elevated (≥2 mg/L) CRP categories. Adjusted hazard ratios (HRs) with 95% confidence interval (CI) for all-cause mortality were computed with Cox regression. During an average of 10.1 years of follow-up, 576 deaths occurred. Following adjustment for age, smoking status, sex, exam year, body mass index, systolic blood pressure, total cholesterol, triglyceride:high-density lipoprotein ratio, and fasting glucose, HR (95% CI) for all-cause mortality were 1.0 (referent) and 1.52 (1.14-2.02) for fit and unfit categories, respectively. Corresponding values for normal and elevated CRP categories were 1.0 and 1.50 (1.20-1.89), respectively. When grouped by fitness and CRP category, there was significantly greater mortality risk in the unfit than the fit category within the elevated CRP category (HR = 1.77 (1.14-2.75)), but not in the normal CRP category (HR = 1.38 (0.96-1.98)). Each 1 metabolic equivalent increment in fitness and 1 mg/L increment in CRP were associated with 10.0% (95% CI: 5.1-14.8%) decreased and 7.3% (95% CI: 2.0%-12.9%) increased mortality hazard, respectively. Compared to the unfit, fit individuals have an attenuated mortality risk within each CRP category. Thus, higher fitness appears to provide some protection against all-cause mortality, particularly among those with elevated levels of inflammation.

Examining the Gradient of All-Cause Mortality Risk in Women across the Cardiorespiratory Fitness Continuum.

PURPOSE: Although cardiorespiratory fitness (CRF) is inversely associated with all-cause mortality in women, less is known regarding the gradient of mortality risk in women, particularly at the lower end of the CRF continuum. METHODS: A total of 17,901 healthy women (mean age, 45.9 yr) completed a baseline clinical examination, including a maximal treadmill exercise test at the Cooper Clinic in Dallas, TX, between 1971 and 2016. Participants were placed into CRF quintiles based on age and treadmill time. RESULTS: After a mean follow-up period of 17.9 yr, 1198 all-cause deaths occurred. More favorable cardiometabolic risk factors, smoking status, and physical activity levels were observed across ordered CRF quintiles ( P < 0.001 for all). Adjusted all-cause mortality hazard ratios with 95% confidence intervals were 1.71 (1.40-2.09), 1.55 (1.29-1.87), 1.25 (1.03-1.51), 1.16 (0.97-1.38), and 1.0 (referent), respectively, across CRF quintiles ( P trend ≤ 0.001). When utilizing CRF as a continuous variable in a spline analysis and using 4.5 METs as the referent, we estimate a 10% reduction in mortality risk per 1-MET increment in CRF ( P < 0.001) until a threshold of approximately 11 METs. Mortality risk was approximately 50% lower at the 11-MET threshold when compared with the referent. No further significant reduction in mortality risk was observed beyond the 11-MET threshold. In addition, age-adjusted hemodynamic variables including resting and maximal double product, heart rate reserve, double-product reserve, and 1-min recovery heart rate were more favorable across CRF quintiles ( P < 0.001 for all). CONCLUSIONS: Beginning at a referent value of 4.5 METs, a significant decreasing gradient of all-cause mortality exists across the CRF continuum, until a threshold of approximately 11 METs is reached. Although all women should be encouraged to work toward meeting public health guidelines for physical activity, it is especially important to target those at the low end of the CRF continuum.

Physical Activity, Adiposity, and Serum Vitamin D Levels in Healthy Women: The Cooper Center Longitudinal Study.

Background: Although physical inactivity, obesity, and low serum vitamin D [25-hydroxyvitamin D, 25(OH)D] are common among women, joint associations among these biomarkers are not well-described. Materials and Methods: A total of 7553 healthy women received a comprehensive examination (2006-2018), including self-reported physical activity (PA), body mass index (BMI), waist circumference (WC), waist:height ratio (W:HT), percent body fat (%Fat), and 25(OH)D. Participants were divided into four categories of PA based on current guidelines: <500 (not meeting guidelines), 500-1000 (meeting guidelines), 1001-2500 (>1-2.5 times guidelines), and >2500 (>2.5 times guidelines) metabolic equivalent-minutes/week (MET-Min/wk), and were also classified by clinical cut points for adiposity measures and 25(OH)D. We examined trends of 25(OH)D and adiposity exposures across PA categories and calculated odds ratios (ORs) of vitamin D deficiency across categories of each adiposity exposure. We examined joint associations among PA and adiposity with 25(OH)D. Results: A positive trend was observed for 25(OH)D across PA categories (p < 0.001). Compared with normal weight status, the odds for 25(OH)D deficiency were significantly higher for overweight women within adiposity exposures (p for all <0.001). When examining joint associations, 25(OH)D was higher across PA categories within each stratum of BMI, WC, W:HT, and %Fat (p trend <0.007 for all). When examining PA and BMI as continuous variables, OR for vitamin D deficiency were 0.95 (95% confidence interval [CI]: 0.93-0.96) per 250 MET-minutes/week increment in PA, and 1.20 (95% CI: 1.17-1.23) per 2 kg/m2 increment in BMI. Conclusions: 25(OH)D levels are positively associated with PA and negatively associated with different measures of adiposity. Higher levels of PA attenuate the association between adiposity and 25(OH)D.

Cardiorespiratory fitness, white blood cell count, and mortality in men and women.

BACKGROUND: We examined the associations of cardiorespiratory fitness (CRF) and white blood cell count (WBC) with mortality outcomes. METHODS: A total of 52,056 apparently healthy adults completed a comprehensive health examination, including a maximal treadmill test and blood chemistry analyses. CRF was categorized as high, moderate, or low by age and sex; WBC was categorized as sex-specific quartiles. RESULTS: During 17.8 ± 9.5 years (mean ± SD) of follow-up, a total of 4088 deaths occurred. When regressed jointly, significantly decreased all-cause mortality across CRF categories was observed within each quartile of WBC in men. Within WBC Quartile 1, all-cause mortality hazard ratios (HRs) with a 95% confidence interval (95%CI) were 1.0 (referent), 1.29 (95%CI: 1.06‒1.57), and 2.03 (95%CI: 1.42‒2.92) for high, moderate, and low CRF categories, respectively (p for trend < 0.001). Similar trends were observed in the remaining 3 quartiles. With the exception of cardiovascular disease (CVD) mortality within Quartile 1 (p for trend = 0.743), there were also similar trends across CRF categories within WBC quartiles in men for both CVD and cancer mortality (p for trend < 0.01 for all). For women, there were no significant trends across CRF categories for mortality outcomes within Quartiles 1-3. However, we observed significantly decreased all-cause mortality across CRF categories within WBC Quartile 4 (HR = 1.05 (95%CI: 0.76‒1.44), HR = 1.63 (95%CI:1.20‒2.21), and HR = 1.87 (95%CI:1.29‒2.69) for high, moderate, and low CRF, respectively (p for trend = 0.002)). Similar trends in women were observed for CVD and cancer mortality within WBC Quartile 4 only. CONCLUSION: There are strong joint associations between CRF, WBC, and all-cause, CVD, and cancer mortality in men; these associations are less consistent in women.

Fit and Tipsy? The Interrelationship between Cardiorespiratory Fitness and Alcohol Consumption and Dependence.

PURPOSE: To examine whether higher levels of cardiorespiratory fitness are related to increased alcohol consumption and dependence among a large sample of adults attending a preventive medicine clinic. METHODS: A cross-sectional study of 38,653 apparently healthy patients who visited the Cooper Clinic (Dallas, TX) for preventive medical examinations (1988-2019) and enrolled in the Cooper Center Longitudinal Study. The primary independent variable was cardiorespiratory fitness, based on a maximal treadmill test, and the dependent variables were alcohol consumption and dependence (self-reported). The relations between fitness category (low, moderate, high) and alcohol consumption (low, moderate, heavy) and suggested alcohol dependence (Cut down, Annoyed, Guilty, Eye opener score ≥2) among women and men were estimated via multivariable regression while adjusting for covariates (e.g., age, birth year cohort, marital status, and body mass index). RESULTS: Women within the moderate and high fitness categories had 1.58 (95% confidence interval [CI], 1.32-1.91) and 2.14 (95% CI, 1.77-2.58) greater odds of moderate/heavy alcohol consumption, respectively, in comparison to their low fitness counterparts. Similarly, moderate and high fit men had 1.42 (95% CI, 1.30-1.55) and 1.63 (95% CI, 1.49-1.80) times greater odds of moderate-to-heavy alcohol consumption, respectively, in comparison to the low fitness group. In addition, among men who were heavy drinkers (but not women), higher fitness levels were related to lower rates of suggested alcohol dependence. Specifically, these men had 45.7%, 41.7%, and 34.9% proportions of clinically relevant alcohol problems across low, moderate, and high fitness categories (adjusted P for trend <0.001). CONCLUSIONS: Higher fitness levels are significantly related to greater alcohol consumption among a large cohort of adult patients. Interventions focusing on increasing fitness (via physical activity promotion) might consider concurrently aiming to reduce alcohol consumption.

Body mass, cardiorespiratory fitness, and cardiometabolic risk over time: Findings from the Cooper Center Longitudinal Study.

Few studies have adequately assessed the simultaneous effects of changes in cardiorespiratory fitness (fitness) and body mass on cardiometabolic risk. Hence, the current study's aims were twofold: (1) To determine whether increases in body mass result in higher cardiometabolic risk after controlling for fitness changes; and (2) To assess whether increases in fitness result in lower cardiometabolic risk after controlling for weight changes. The study consisted of 3534 patients who came for preventive medicine visits ≥4 times over any 10-year period (1979-2019). The primary independent variables were body mass and fitness, and the dependent variable was metabolic syndrome (MetS) and its components. Mixed-effects regression was used to model the relationship between changes in body mass, fitness, and MetS. Results indicate that increasing body mass up to a 10-year period was significantly related to increasing risk of MetS while controlling for changes in fitness. Specifically, a 1-kg increase in body mass was associated with a 17% (OR = 1.17; 95% CI 1.15-1.19) increased odds for MetS, while adjusting for fitness changes. A 1-MET increase in fitness was related to a 23% (OR = 0.77; 95% CI 0.70-0.84) decrease in odds for MetS, while adjusting for body mass changes up to 10 years. Moreover, body mass change was significantly related to changes in all cardiometabolic components of MetS. Fitness change was significantly associated with changes in MetS components. Future interventions should focus concurrently on increasing fitness and on body mass loss (or maintenance) to improve cardiometabolic health.

Association of the Omega-3 Index with Incident Prostate Cancer with Updated Meta-Analysis: The Cooper Center Longitudinal Study.

BACKGROUND: The association between long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) and prostate cancer (PC) remains unclear. METHODS: We compared incident PC rates as a function of the Omega-3 Index [O3I, erythrocyte eicosapentaenoic and docosahexaenoic acids (EPA + DHA)] in 5607 men (40-80 years of age) seen at the Cooper Clinic who were free of PC at baseline. The average follow-up was 5.1 ± 2.8 years until censoring or reporting a new PC diagnosis. Proportional hazards regression was used to model the linear association between baseline O3I and the age-adjusted time to diagnosis. A meta-analysis of n-3 PUFA biomarker-based studies and incident PC was updated with the present findings. RESULTS: A total of 116 cases of incident PC were identified. When O3I was examined as a continuous variable, the age-adjusted hazard ratio (HR) (95% CI) was 0.98 (0.89, 1.07; p = 0.25) for each 1% increment in the O3I. The updated meta-analysis with 10 biomarker-based studies found no significant relationship between EPA or DHA levels and risk for PC. CONCLUSIONS: We find no evidence in this study nor in a meta-analysis of similar studies that consuming n-3 PUFA-rich fish or using fish oil supplements affects the risk of PC.

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.

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.

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, 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.

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.

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.