Physical Activity and Progression of Coronary Artery Calcification in Men and Women.

Importance: Prior cross-sectional studies have suggested that very high levels of physical activity (PA) are associated with a higher prevalence of coronary artery calcium (CAC). However, less is known regarding the association between high-volume PA and progression of CAC over time. Objective: To explore the association between PA (measured at baseline and during follow-up) and the progression of CAC over time. Design, Setting, and Participants: This cohort study included data from 8771 apparently healthy men and women 40 years and older who had multiple preventive medicine visits at the Cooper Clinic (Dallas, Texas), with a mean (SD) follow-up time of 7.8 (4.7) years between the first and last clinic visit. Participants with reported PA and CAC measurements at each visit during 1998 to 2019 were included in the study. Data were analyzed from March 2023 to February 2024. Exposures: PA reported at baseline and follow-up, examined continuously per 500 metabolic equivalent of task minutes per week (MET-min/wk) and categorically: less than 1500, 1500 to 2999, 3000 or more MET-min/wk. Main Outcomes and Measures: Negative binomial regression was used to estimate the rate of mean CAC progression between visits, with potential modification by PA volume, calculated as the mean of PA at baseline and follow-up. In addition, proportional hazards regression was used to estimate hazard ratios for baseline PA as a predictor of CAC progression to 100 or more Agatston units (AU). Results: Among 8771 participants, the mean (SD) age at baseline was 50.2 (7.3) years for men and 51.1 (7.3) years for women. The rate of mean CAC progression per year from baseline was 28.5% in men and 32.1% in women, independent of mean PA during the same time period. That is, the difference in the rate of CAC progression per year was 0.0% per 500 MET-min/wk for men and women (men: 95% CI, -0.1% to 0.1%; women: 95% CI, -0.4% to 0.5%). Moreover, baseline PA was not associated with CAC progression to a clinically meaningful threshold of 100 AU or more over the follow-up period. The hazard ratio for a baseline PA value of 3000 or more MET-min/wk vs less than 1500 MET-min/wk to cross this threshold was 0.84 (95% CI, 0.66 to 1.08) in men and 1.16 (95% CI, 0.57 to 2.35) in women. Conclusions and Relevance: This study found that PA volume was not associated with progression of CAC in a large cohort of healthy men and women who were initially free of overt cardiovascular disease.

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.

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.

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.

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.

The Association of Self-Reported Muscle-Strengthening Activities With Carotid Intima-Media Thickness in Older Adults: Cooper Center Longitudinal Study.

The purpose of the current investigation was to examine the cross-sectional associations of participation in muscle-strengthening activities (MSAs) with carotid intima-media thickness (CIMT) among older adults. The data are from 2,557 older adult participants enrolled in an observational cohort who reported no history of cardiovascular disease. MSA was determined using a questionnaire. Carotid ultrasound was performed to measure the CIMT of the common carotid artery bilaterally. Logistic regression models were constructed to estimate the association of MSA with CIMT after adjustment for potential confounders. The participants were aged 68.6 ± 7.0 years, and the majority were male (71.7%) and White (96.5%); 18% had abnormal CIMT. Meeting the physical activity guidelines for MSA was inversely associated with abnormal CIMT after adjustment for age and sex. However, this observed inverse relation became statistically null after further adjustment for cardiovascular disease risk factors, including aerobic physical activity.

The Association of Physical Activity With Carotid Intima Media Thickening in a Healthy Older Population: Cooper Center Longitudinal Study.

The purpose of this study was to examine the association between self-reported physical activity (PA) and mean common carotid artery intima-media thickness (CCA IMT) among older adults. The data are from 1,811 Cooper Center Longitudinal Study participants, who were aged ≥60 years, with no history of cardiovascular disease. A medical history questionnaire was used to assess PA. Carotid ultrasound was performed to measure CCA IMT and the presence of plaque and stenosis. Logistic regression models were constructed to estimate the association between PA and CCA IMT after adjustment for covariates. The participants were aged 69.2 ± 5.9 years, and the majority were male (73.3%) and White (96.7%). The odds ratio of abnormal thickening of CCA IMT was 0.72 (95% confidence interval [0.54, 0.96]) in physically active participants (≥500 metabolic equivalent·min/week) after adjustment for covariates. In the current study, meeting PA guidelines in older adulthood was associated with lower odds of abnormal thickening of CCA IMT.

The association of midlife cardiorespiratory fitness with later life carotid atherosclerosis: Cooper Center Longitudinal Study.

BACKGROUND AND AIMS: While numerous cross-sectional studies have demonstrated an inverse relationship between cardiorespiratory fitness (CRF) and carotid atherosclerosis in middle age, much less is known about the association of midlife CRF with carotid atherosclerosis in later life. METHODS: We studied 1094 participants, free of cardiovascular disease, who completed a maximal exercise test (GXT) for an objective measure of CRF between ages 40 and 59 and carotid ultrasound after the age of 59, with at least five years between studies. Carotid intima media thickness was measured. Assessments were also made regarding the presence of plaque and percent stenosis in four regions: common carotid, bulb, internal carotid and external carotid arteries. Multivariable logistic regression models were constructed to estimate the association of CRF with carotid artery disease. RESULTS: At the time of GXT and carotid scan, participants were aged 50.7 ±â€¯5.7 years and 69.3 ±â€¯6.4 years, respectively. Almost half of participants had high midlife CRF (48.6%); 41.3% and 10.1% had moderate and low CRF, respectively. Over a mean follow-up period of 18.6 ±â€¯8.5 years, the odds of having carotid artery disease in later life in the high CRF group was 0.50 (95% CI: 0.29-0.87) compared with the low CRF group. Each 1 MET increase in CRF was associated with 10% lower odds of having carotid artery disease (OR = 0.89, 95% CI: 0.80-0.98). CONCLUSIONS: Midlife CRF was inversely associated with carotid artery disease measured almost two decades later. This may represent a mechanistic link between high midlife CRF and reduced risk of stroke in later life.

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.

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.

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.

Association Between Sitting Time and Cardiometabolic Risk Factors After Adjustment for Cardiorespiratory Fitness, Cooper Center Longitudinal Study, 2010-2013.

INTRODUCTION: Objective estimates, based on waist-worn accelerometers, indicate that adults spend over half their day (55%) in sedentary behaviors. Our study examined the association between sitting time and cardiometabolic risk factors after adjustment for cardiorespiratory fitness (CRF). METHODS: A cross-sectional analysis was conducted with 4,486 men and 1,845 women who reported daily estimated sitting time, had measures for adiposity, blood lipids, glucose, and blood pressure, and underwent maximal stress testing. We used a modeling strategy using logistic regression analysis to assess CRF as a potential effect modifier and to control for potential confounding effects of CRF. RESULTS: Men who sat almost all of the time (about 100%) were more likely to be obese whether defined by waist girth (OR, 2.61; 95% CI, 1.25-5.47) or percentage of body fat (OR, 3.33; 95% CI, 1.35-8.20) than were men who sat almost none of the time (about 0%). Sitting time was not significantly associated with other cardiometabolic risk factors after adjustment for CRF level. For women, no significant associations between sitting time and cardiometabolic risk factors were observed after adjustment for CRF and other covariates. CONCLUSION: As health professionals struggle to find ways to combat obesity and its health effects, reducing sitting time can be an initial step in a total physical activity plan that includes strategies to reduce sedentary time through increases in physical activity among men. In addition, further research is needed to elucidate the relationships between sitting time and CRF for women as well as the underlying mechanisms involved in these relationships.

Cardiorespiratory Fitness and Highly Sensitive Cardiac Troponin Levels in a Preventive Medicine Cohort.

BACKGROUND: Cardiorespiratory fitness (CRF) and highly sensitive cardiac troponin T (hs-cTnT) are associated with risk of all-cause and cardiovascular mortality as well as incident heart failure. A link of low CRF to subclinical cardiac injury may explain this association. We hypothesized that CRF would be inversely associated with hs-cTnT measured in healthy adults over age 50. METHODS AND RESULTS: We evaluated 2498 participants (24.7% female, mean age 58.7 years) from the Cooper Center Longitudinal Study between August 2008 and January 2012. Plasma specimens obtained shortly before CRF estimates by Balke treadmill testing were used for hs-cTnT assays. CRF was grouped into low CRF (category 1), moderate CRF (categories 2-3), and high CRF (categories 4-5). Multivariable logistic regression was used to estimate the association of CRF with hs-cTnT. The prevalence of measurable hs-cTnT (≥3 ng/L) was 78.5%. In multivariable analyses, low-fit individuals were significantly more likely than high-fit individuals to have elevated hs-cTnT (≥14 ng/L) (odds ratio 2.47, 95% CI 1.10-5.36). CONCLUSIONS: In healthy older adults, CRF is inversely associated with hs-cTnT level adjusted for other risk factors. Prospective studies are needed to evaluate whether improving CRF is effective in preventing subclinical cardiac injury.

Progression of CAC Score and Risk of Incident CVD.

OBJECTIVES: The authors sought to determine the relative contributions of baseline coronary artery calcification (CAC), follow-up CAC, and CAC progression on incident cardiovascular disease (CVD). BACKGROUND: Repeat CAC scanning has been proposed as a method to track progression of total atherosclerotic burden. However, whether CAC progression is a useful predictor of future CVD events remains unclear. METHODS: This was a prospective observational study of 5,933 participants free of CVD who underwent 2 examinations, including CAC scores, and subsequent CVD event assessment. CAC progression was calculated using the square root method. The primary outcome was total CVD events (CVD death, nonfatal myocardial infarction, nonfatal atherosclerotic stroke, coronary artery bypass surgery, percutaneous coronary intervention). Secondary outcomes included hard CVD events, total coronary heart disease (CHD) events, and hard CHD events. RESULTS: CAC was detected at baseline in 2,870 individuals (48%). The average time between scans was 3.5 ± 2.0 years. After their second scan, 161 individuals experienced a total CVD event during a mean follow-up of 7.3 years. CAC progression was significantly associated with total CVD events (hazard ratio: 1.14, 95% confidence interval: 1.01 to 1.30 per interquartile range; p = 0.042) in the model including baseline CAC, but the contribution of CAC progression was small relative to baseline CAC (chi-square 4.16 vs. 65.92). Furthermore, CAC progression was not associated with total CVD events in the model including follow-up CAC instead of baseline CAC (hazard ratio: 1.05, 95% confidence interval: 0.92 to 1.21; p = 0.475). A model that included follow-up CAC alone performed as well as the model that included baseline CAC and CAC progression. CONCLUSIONS: Although CAC progression was independently, but modestly, associated with CVD outcomes, this relationship was no longer significant when including follow-up CAC in the model. These findings imply that if serial CAC scanning is performed, the latest scan should be used for risk assessment, and in this context, CAC progression provides no additional prognostic information.

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.

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.

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

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