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 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.

Relation of Coronary Artery Diameters With Cardiorespiratory Fitness.

Cardiorespiratory fitness is associated with reduced cardiovascular morbidity and mortality when adjusted for traditional risk factors. Mechanisms by which fitness reduces risk have been studied but remain incompletely understood. We hypothesize that higher fitness is associated with larger coronary artery diameters independent of its effect on traditional risk factors. Two independent measurements of the proximal diameters of the left main, left anterior descending, left circumflex, and right coronary arteries were obtained from gated multidetector computed tomography scans in 500 men from the Cooper Center Longitudinal Study (CCLS). Men with coronary artery calcium scores ≥10 were excluded. Fitness was measured with a maximal exercise treadmill test and reported by quintiles and as a function of METs. We then evaluated the relation between coronary artery diameters and fitness using mixed effect regression models. Higher fitness was associated with larger coronary artery diameters after adjustment for body surface area, smoking status, low-density lipoprotein and high-density lipoprotein cholesterol, resting systolic blood pressure, and serum glucose. When examined continuously, each MET increase in fitness was associated with a mean 0.03 ± 0.01 mm larger diameter of the left main, a 0.04 ± 0.01 mm larger diameter of the left anterior descending, a 0.05 ± 0.01 mm larger diameter of the left circumflex, and a 0.07 ± 0.01 mm larger diameter of the right coronary artery (p = 0.002). This correlation between fitness and coronary artery diameters was most prominent for fitness levels above 10 METs. In conclusion, higher fitness is associated with larger coronary artery diameters.

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 of a favorable cardiovascular health profile with the presence of coronary artery calcification.

BACKGROUND: To examine the association between the American Heart Association's 7 metrics of ideal cardiovascular health (ICH) and the presence of subclinical coronary atherosclerosis as assessed by coronary artery calcification (CAC) using electron-beam computed tomography. METHODS AND RESULTS: This study is a cross-sectional analysis of data obtained on 3121 male and female patients evaluated at the Cooper Clinic in Dallas, Texas, between 1997 and 2007. We included men aged ≥45 and women aged ≥55 without known cardiovascular disease and for whom information on all ICH metrics and a CAC score were available. Patients were grouped into 3 categories according to their number of ICH metrics: favorable (4-7 ICH metrics), intermediate (3 metrics), and unfavorable (0-2 metrics). Patients with favorable ICH profiles had a lower prevalence and severity of subclinical atherosclerosis than those with unfavorable or intermediate ICH profiles as estimated by CAC. This inverse association of CAC with ICH metrics was evident whether the presence of coronary calcium was defined as CAC score>0, CAC score>100, or CAC score>400. Patients with favorable ICH profiles had odds of coronary calcium (CAC>0) less than half of those for patients with unfavorable profiles (odds ratio 0.41; 95% confidence interval, 0.34-0.50) and patients with intermediate ICH profiles had odds of detectable CAC 32% lower (odds ratio 0.68; 95% confidence interval, 0.57-0.82). CONCLUSIONS: A statistically significant association was found between a favorable level of ICH metrics and less or absent subclinical atherosclerosis as measured by CAC underscoring the importance of primordial prevention.

Coronary artery calcium score, risk factors, and incident coronary heart disease events.

BACKGROUND: Whether the absence of coronary artery calcium, or conversely the presence of high volumes of coronary artery calcium, may alter assessment of coronary heart disease risk based on traditional risk factors is uncertain. We sought to identify a potential threshold of coronary artery calcium for clinical use and examine the predictive power of coronary artery calcium in individuals categorized using conventional coronary heart disease risk assessment. METHODS: The study included 10,746 men and women (36.3%) with a mean age of 53.8+/-9.9 years who were either physician- or self-referred for electron beam tomography scanning to a preventive medical clinic. Coronary heart disease risk factors were elicited by use of a questionnaire. RESULTS: During a mean follow-up of 3.5 years, 81 primary events (coronary heart disease death or nonfatal myocardial infarction) occurred. Among individuals with a coronary artery calcium score of zero, the primary event rate was very low (0.4 events per 1000 person-years of observation). When participants were stratified by self-reported coronary heart disease risk factors (0-2, or 3-4), a coronary artery calcium score >or=100 was associated with substantially increased risk of coronary heart disease events within each level of stratification. In a subgroup of participants with available clinical data, similar results were found when participants were categorized by Framingham risk scores. CONCLUSIONS: Coronary artery calcium score can identify individuals at increased risk for coronary heart disease events who otherwise would be considered low-risk based on clinical assessment. A coronary artery calcium score of zero is associated with very low risk for coronary heart disease in the short to intermediate term ( approximately 3.5 years) regardless of the number of risk factors present.

Coronary artery calcium, exercise tolerance, and CHD events in asymptomatic men.

Coronary artery calcium (CAC) scores >/=100 are predictive of CHD events in asymptomatic men. Exercise tolerance of >/=10METs predicts lower event rates in CHD patients; however, its relationship with events in individuals with subclinical atherosclerosis is less known. Participants were 710 asymptomatic men from the Aerobics Center Longitudinal Study whose exercise tolerance (ET) was quantified (<10 or >/=10METs) and whose CAC score was >/=100 as measured by electron beam tomography. During 3.5 years of follow-up 59 CHD events occurred. The age-adjusted hazard ratio (HR) of CHD events was 0.26 (95% CI=0.15-0.45) in men whose ET was >/=10METs compared with men whose ET was <10METs. Adjustment for CHD risk factors and abnormal exercise ECG did not change the association between ET and CHD. The extent of underlying atherosclerosis did not influence the association between ET and CHD; for example, the HR for CHD events in the >/=10MET group among men with CAC scores <400 and >/=400 was 0.16 (95% CI=0.05-0.56) and 0.23 (95% CI=0.11-0.46), respectively. In asymptomatic men with subclinical coronary atherosclerosis, an ET of >/=10METs identifies patients at lower risk for manifest CHD.

Coronary artery calcium score and coronary heart disease events in a large cohort of asymptomatic men and women.

Coronary artery calcium (CAC), a measure of subclinical coronary heart disease (CHD), may be useful in identifying asymptomatic persons at risk of CHD events. The current study included 10,746 adults who were 22-96 years of age, were free of known CHD, and had their CAC quantified by electron-beam tomography at baseline as part of a preventive medical examination at the Cooper Clinic (Dallas, Texas) during 1995-2000. During a mean follow-up of 3.5 years, 81 hard events (CHD death, nonfatal myocardial infarction) and 287 total events (hard events plus coronary revascularization) occurred. Age-adjusted rates (per 1,000 person-years) of hard events were computed according to four CAC categories: no detectable CAC and incremental sex-specific thirds of detectable CAC; these rates were, respectively, 0.4, 1.5, 4.8, and 8.7 (trend p<0.0001) for men and 0.7, 2.3, 3.1, and 6.3 (trend p=0.02) for women. CAC levels also were positively associated with rates of total CHD events for women and men (trend p<0.0001 each). The association between CAC and CHD events remained significant after adjustment for CHD risk factors. CAC was associated with CHD events in persons with no baseline CHD risk factors and in younger (aged <40 years) and older (aged >65 years) study participants. These findings show that CAC is associated with an increased risk of CHD events in asymptomatic women and men.

Effects of cardiorespiratory fitness on healthcare utilization.

BACKGROUND: Prospective study examining the relationship between cardiorespiratory fitness level and incidence of medical treatments during a 1-yr period before each of two examinations. A subset was also evaluated to assess whether improvement in fitness affected incidence of treatments. METHODS AND RESULTS: Part I: Six thousand six hundred seventy-nine healthy male subjects underwent medical examinations on two occasions, including a maximal exercise test. Division of subjects by fitness into quartiles (Q1 = low fitness through Q4 = high fitness) revealed an inverse relationship between fitness and outcome measures. Men in the low-fitness group had more office visits and overnight hospital stays than men in the high-fitness group (3.5% (Q1) vs 1.6% (Q4) men had 10+ office visits, and 10% (Q1) vs 5.0% (Q4) men had overnight hospital stays, P < 0.0001). These differences held after adjustment for potential confounding variables (age, follow-up yr, blood pressure, cholesterol, and smoking). Part II: Subjects in this subset (N = 2974) were evaluated to compare overnight hospital stays between low-fit men who remained low fit at the second examination, and low-fit men who became fit by the second examination. This cohort was divided into fitness tertiles (T1 = low fitness through T3 = high fitness). Those who improved their fitness by the time of the second examination had a decreased number of overnight hospital stays, compared with those who remained unfit at the time of the second examination (10.2% (T1 at second visit) vs 5.9% (T3 at second visit) had overnight hospital stays, P < 0.03). CONCLUSIONS: Men who maintain or become fit are less likely to have physician visits or overnight hospital stays, compared with men who are unfit.

Exercise capacity and body composition as predictors of mortality among men with diabetes.

OBJECTIVE: To quantify the relation of fitness to mortality among men with diabetes, adjusted for BMI and within levels of BMI. RESEARCH DESIGN AND METHODS: In this observational cohort study, we calculated all-cause death rates in men with diabetes across quartiles of fitness and BMI categories. Study participants were 2,196 men with diabetes (average age 49.3 years, SD 9.5) who underwent a medical examination, including a maximal exercise test, during 1970 to 1995, with mortality follow-up to 31 December 1996. RESULTS: We identified 275 deaths during 32,161 person-years of observation. Risk of all-cause mortality was inversely related to fitness. For example, in the fully adjusted model, the risk of mortality was 4.5 (2.6-7.6), 2.8 (1.6-4.7), and 1.6 (0.93-2.76) for the first, second, and third fitness quartiles, respectively, with the fourth quartile (highest fitness level) as the referent (P for trend <0.0001). There was no significant trend across BMI categories for mortality after adjustment for fitness. Similar results were found when the fitness-mortality relation was examined within levels of body composition. In normal-weight men with diabetes, the relative risks of mortality were 6.6 (2.8-15.0), 3.2 (1.4-7.0), and 2.2 (1.1-4.6) for the first, second, and third quartiles of fitness, respectively, as compared with the fourth quartile (P for trend <0.0001). We found similar results in the overweight and obese weight categories. CONCLUSIONS: There was a steep inverse gradient between fitness and mortality in this cohort of men with documented diabetes, and this association was independent of BMI.

Heart rate recovery following maximal exercise testing as a predictor of cardiovascular disease and all-cause mortality in men with diabetes.

OBJECTIVE: Heart rate recovery (HRR) is an independent prognostic indicator for cardiovascular disease (CVD) and all-cause mortality in healthy men. We examined the association of HRR to CVD-related and all-cause mortality in men with diabetes. RESEARCH DESIGN AND METHODS: In this cohort study we examined 2,333 men with documented diabetes (mean age 49.4 years) that had baseline 5-min HRR measurement following maximal exercise (heart rate(peak) - heart rate(5 min of recovery)) at The Cooper Clinic, Dallas, TX. We identified HRR quartiles as quartile 1 <55, quartile 2 55-66, quartile 3 67-75, and quartile 4 >75 bpm. Hazard ratios (HRs) for cardiovascular and all-cause death were adjusted for age, cardiorespiratory fitness, resting heart rate, fasting blood glucose, BMI, smoking habit, alcohol consumption, total cholesterol, triglyceride, and history of CVD at baseline. RESULTS: During a median of 14.9 years follow-up, there were 142 deaths that were considered CVD related and 287 total deaths. Compared with men in the highest quartile of HRR, adjusted HRs in the first, second, and third quartiles were 2.0 (95% CI 1.1-3.8), 1.5 (0.8-2.7), and 1.5 (0.9-2.8), respectively, for cardiovascular death (P for trend < 0.001). Similarly, for all-cause death, adjusted HRs in the first, second, and third quartiles were 2.0 (1.3-3.2), 1.5 (1.0-2.3), and 1.5 (1.1-2.3) (P for trend < 0.001). CONCLUSIONS: Among men with diabetes, a decreased HRR, even measured as long as 5 min after recovery, was independently predictive of cardiovascular and all-cause death.