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.

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.

The History of Aerobics (50 Years and Still Counting).

Looking back over the 50 years since Aerobics was published, I could never have expected for there to have been a major change in physicians' attitudes toward the value of exercise in the practice of medicine. In my lifetime, I never thought I would see a stress test be considered a mandatory component of a complete examination, inactivity classified as importantly as high blood pressure and high cholesterol, and cigarette smoking considered a coronary risk factor. I have tried in this Research Quarterly for Exercise and Sport (RQES) Lecture presentation to document how this slow but gradual transition took place due to my work and the work of many of my colleagues in this field, along with the important work of The Cooper Institute. In June 1970, I chartered the institute 6 months before I saw my first patient at the Cooper Clinic, but now with the Cooper Center Longitudinal Study being the largest database in the world comparing measured levels of fitness, instead of relying only on questionnaires and correlating fitness and health in our more than 700 published peer-review articles, we have proven and can safely say that "exercise is medicine." In greater detail, I want this lecture to present what we and others have done in this scientific endeavor, and even the harshest critics are now saying that "these results are too impressive to be ignored."

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.

Implementing Policies to Enhance Physical Education and Physical Activity in Schools.

The purpose of this commentary is to provide an overview of national physical activity recommendations and policies (e.g., from the Institute of Medicine, National Physical Activity Plan, and Centers for Disease Control and Prevention) and to discuss how these important initiatives can be implemented in local schools. Successful policies are illustrated. Specific strategies and ideas are shared regarding how physical educators can assert themselves and impart their knowledge in an effort to build support for policy implementations that enhance the delivery of physical education and physical activity in their schools and communities.

Cardiorespiratory Fitness in Middle Age and Health Care Costs in Later Life.

BACKGROUND: Low cardiovascular risk factor burdens in middle age are associated with lower health care costs in later life. However, there are few data regarding the effect of cardiorespiratory fitness on health care costs independent of these risk factors. OBJECTIVES: This study sought to evaluate the association of health care costs in later life with cardiorespiratory fitness in midlife after adjustment for cardiovascular risk factors. METHODS: We studied 19,571 healthy individuals in the Cooper Center Longitudinal Study who underwent cardiorespiratory fitness assessment at a mean age of 49 years and received Medicare coverage from 1999 to 2009 at an average age of 71 years. Cardiorespiratory fitness was estimated by maximal metabolic equivalents (METs) calculated from treadmill time. The primary outcome was average annual health care costs obtained from Medicare standard analytical files. RESULTS: Over 126,388 person-years of follow-up, average annual health care costs were significantly lower forparticipants aged 65 years or older with high midlife fitness than with low midlife fitness in both men($7,569 vs. $12,811; p < 0.001) and women ($6,065 vs. $10,029; p < 0.001). [corrected].In a generalized linear model adjusted for cardiovascular risk factors, average annual health care costs in later life were incrementally lower per MET achieved in midlife in men (6.8% decrease in costs per MET achieved; 95% confidence interval: 5.7% to 7.8%; p < 0.001) and women (6.7% decrease in costs per MET achieved; 95% confidence interval: 4.1% to 9.3%; p < 0.001). These associations persisted when participants were separated into those who died during Medicare follow-up and those who survived. CONCLUSIONS: Higher cardiorespiratory fitness in middle age is strongly associated with lower health care costs at an average of 22 years later in life, independent of cardiovascular risk factors. These findings may have important implications for health policies directed at improving physical fitness.

Physical activity versus cardiorespiratory fitness: two (partly) distinct components of cardiovascular health?

Physical activity (PA) and cardiorespiratory fitness (CRF) both have inverse relationships to cardiovascular (CV) morbidity and mortality. Recent position papers and guidelines have identified the important role of both of these factors in CV health. The benefits of PA and CRF in the prevention of CV disease and risk factors are reviewed. In addition, assessment methodology and utilization in the research and clinical arenas are discussed. Finally, the benefits, methodology, and utilization are compared and contrasted to better understand the two (partly) distinct components and their impact on CV health.

Cardiorespiratory fitness and long-term survival in "low-risk" adults.

BACKGROUND: We sought to establish whether cardiorespiratory fitness had important implications for long-term cardiovascular risk among individuals classified as low risk by the Framingham Risk Score (10-year coronary heart disease risk <10%). Prognostic factors of long-term cardiovascular risk are needed for low-risk subjects who make up the largest percentage of the US population. METHODS AND RESULTS: The study population was composed of men and women, 30 to 50 years of age, who had a baseline medical exam at the Cooper Clinic, Dallas, TX, between 1970 and 1983. Eligible individuals were defined as at low risk for coronary heart disease by Framingham Risk Score at the time of study entry and had no history of diabetes (n=11 190). Cardiorespiratory fitness was determined by maximum graded exercise treadmill tests. Over an average 27±2-year period, 15% of low-fit (quintile 1) compared to 6% of high-fit (quintile 5) individuals died (P<0.001). A 1-metabolic equivalent level increase in baseline fitness was associated with an 11% reduction in all-cause deaths and an 18% reduction in deaths due to cardiovascular disease (CVD) after adjustment for age, sex, body mass index, systolic blood pressure, total cholesterol, blood glucose levels, smoking, and early family history of coronary disease. There was an incremental decrease in CVD risk with increasing fitness quintile, such that the high fit had the lowest adjusted 30-year CVD mortality rate (hazard ratio 0.29, 95% CI: 0.16-0.51) compared to the low fit. CONCLUSIONS: Cardiorespiratory fitness is associated with a significant reduction in long-term CVD among individuals identified as low risk by Framingham Risk Score. These data suggest that preventive lifestyle interventions geared to optimize cardiorespiratory fitness, even among a "low-risk" subset, should be considered to improve CVD-free survival. (J Am Heart Assoc. 2012;1:e001354 doi: 10.1161/JAHA.112.001354.).

Accuracy of the Enlite 6-day glucose sensor with guardian and Veo calibration algorithms.

OBJECTIVE: This study investigates the accuracy of a newly developed, next-generation subcutaneous glucose sensor, evaluated for 6-day use. RESEARCH DESIGN AND METHODS: Seventy-nine subjects (53 men, 26 women) with type 1 diabetes and 18 subjects (14 men, four women) with type 2 diabetes completed a three-center, prospective, sensor accuracy study. The mean age for the group was 42.2±15.0 years (mean±SD), ranging from 18 to 71 years, with a mean glycosylated hemoglobin level of 7.6±1.5%, ranging from 5.5% to 14%. Subjects wore Enlite™ sensors (Medtronic Diabetes, Northridge, CA) in the abdominal and buttocks region for two separate 7-day periods and calibrated with a home-use blood glucose meter. Subjects participated in an in-clinic testing day where frequent sampled plasma glucose samples were acquired every 15 min for 10 h. Sensor data was retrospectively processed with Guardian(®) REAL-Time (Medtronic) and Paradigm(®) Veo™ (Medtronic) calibration routines, and accuracy metrics were calculated for each algorithm and sensor location. Physiological time lag for each measurement site was calculated. RESULTS: Based on 6,404 plasma-sensor glucose paired points, the Enlite sensor with Veo calibration algorithm produced a mean absolute relative difference of 13.86% with 97.3% of points within the A+B zones of the Clarke error grid. Threshold-only alarms detected 90.1% of hypoglycemia and 90% of hyperglycemia. Mean time lag measured at the abdominal region was 7.94±6.48 min compared with 11.70±6.71 min (P<0.0001) at the buttocks area. CONCLUSIONS: The Enlite sensor accurately measures glucose when compared with gold standard laboratory measurements over its 6-day use. Sensors placed in the buttocks region exhibited greater time lags than sensors placed in the abdomen.

Secular change in cardiorespiratory fitness of men: Cooper Center Longitudinal Study.

UNLABELLED: Cardiorespiratory fitness (CRF) has been shown to be an independent predictor of all-cause and cardiovascular mortality, as well as health outcomes such as cardiovascular disease, hypertension, diabetes mellitus, and metabolic syndrome. During the last four decades, national guidelines for physical activity and fitness have emerged in an ongoing effort to improve health outcomes through enhanced CRF risk profiles. PURPOSE: The purpose of the study was to describe the secular trend in CRF as a function of decade and age in a large cohort of men during the past 40 yr. METHODS: A cross-sectional analysis of baseline fitness data collected during comprehensive medical examinations of 52,785 men age 20-74 yr evaluated at the Cooper Clinic in Dallas, TX, from 1970 to 2009 who completed a maximum treadmill exercise test for estimation of aerobic capacity was conducted. Comparisons were made between mean fitness levels in each decade stratified by five age groups. RESULTS: Mean CRF in MET from estimated V·O 2max has increased overall approximately 1 MET during a 40-yr period for each of the five age groups (P < 0.0001). The greatest change occurred during the 1970s to 1980s with minimal subsequent increase and a small decline commencing in the last decade especially in younger men. CONCLUSIONS: In a large cohort of men, average CRF has improved during the last 40 yr with a slight decline in the favorable trend notable in the most recent decade.

The association of health-related fitness with indicators of academic performance in Texas schools.

This study examined the associations between indicators of health-related physical fitness (cardiovascular fitness and body mass index) and academic performance (Texas Assessment of Knowledge and Skills). Partial correlations were generally stronger for cardiovascular fitness than body mass index and consistently stronger in the middle school grades. Mixed-model regression analyses revealed modest associations between fitness and academic achievement after controlling for potentially confounding variables. The effects of fitness on academic achievement were positive but small. A separate logistic regression analysis indicated that higher fitness rates increased the odds of schools achieving exemplary/recognized school status within the state. School fitness attainment is an indicator of higher performing schools. Direction of causality cannot be inferred due to the cross-sectional nature of the data.

Reflections on the Texas Youth Evaluation Project and implications for the future.

The passage of Senate Bill 530 in June 2007 increased visibility about the importance of health-related fitness in Texas. As a result of the mandate, more than 2.6 million 3rd- through 12th-grade students from all Texas counties were evaluated between January 1, 2008, and June 1, 2008, using a standardized test of health-related physical fitness (FITNESSGRAM). This number represented 84.8% of all public school districts in Texas. In the subsequent 2 years, 2.8 and 2.9 million children were tested, which represents more than 90% of all public school districts in Texas. This summary provides reflections on the test results and implications for future school-based fitness initiatives, both in Texas and in other states.

Risk of mortality increases with increasing number of abnormal non-ST parameters recorded during exercise testing.

BACKGROUND: Abnormal non-ST segment treadmill parameters are associated with an increased mortality risk. Such measures include fitness, resting heart rate (HR), chronotropic incompetence, and HR recovery. However, whether there is an additive association among these parameters and the risk of mortality is unknown. DESIGN: Prospective observational registry study. METHODS: We assessed the risk of cardiovascular and all-cause mortality in 25 642 individuals as an additive function of the number of these parameters. Abnormal responses were defined as follows: abnormal resting HR as a HR>or=80 bpm, abnormal fitness as an adjusted fitness level in the lowest 20%, chronotropic incompetence as an inability to achieve at least 80% of the predicted HR reserve, and abnormal HR recovery as an HR decline less than 12 bpm 1 min after exercise. RESULTS: During 7.2 years of follow-up, 392 participants died, with 94 from cardiovascular causes. Each parameter was significantly associated with all-cause and cardiovascular mortality (P<0.01) after adjustment for cardiovascular risk factors. There was a significant trend between both all-cause or cardiovascular mortality and the number of abnormal parameters (P<0.05). CONCLUSION: There is a continuum of risk as the number of abnormal parameters increases, suggesting that it may be important to determine their presence and number during exercise testing.

Relation of the number of metabolic syndrome risk factors with all-cause and cardiovascular mortality.

The metabolic syndrome (MS) is a constellation of risk factors associated with diabetes and cardiovascular disease. This syndrome consists of at least 3 parameters assessing central obesity, hypertension, high-density lipoprotein cholesterol, triglycerides, and impaired glucose metabolism. Whether persons with 4 or 5 risk factors are at higher risk than those with 3 risk factors is unclear. Also unclear is whether those without the MS but with 1 or 2 risk factors warrant therapy. We assessed cardiovascular and all-cause mortality as a function of the number of these risk factors. We followed 30,365 men for a median follow-up of 13.6 years. During follow-up, 1,449 participants died, 527 from cardiovascular causes. All of the individual parameters defining the MS were significantly associated with both all-cause and cardiovascular mortality (p <0.001). After adjustment for age and the other MS variables, hypertension was the most potent risk factor whereas central obesity and hypertriglyceridemia remained associated with both all-cause and cardiovascular mortality. A highly significant trend was also noted between both all-cause or cardiovascular mortality and the number of risk factors (p <0.001 for trend). Risk increased incrementally, beginning at 1 risk factor for cardiovascular mortality and at 2 risk factors for all-cause mortality. In conclusion, there is a continuum of risk as the number of metabolic syndrome risk factors increases. These findings add to the growing evidence that central obesity can independently and adversely affect health.

Efficacy of a complex multivitamin supplement.

OBJECTIVES: Multivitamin supplements are often sold to consumers with the claim that supplements modify risk factors associated with disease. Because few products are validated scientifically, we examined the effects of a 24-ingredient multivitamin formula in an open-label pilot investigation. METHODS: We examined 150 subjects for specific endpoints including blood concentrations of selected vitamins, homocysteine, lipids, and low-density lipoprotein (LDL) oxidation indices at baseline and at 12 and 24 wk. RESULTS: One hundred forty-one subjects were successfully assayed for and showed significant time effects for homocysteine and vitamin B6 (as pyridoxal-5'-phosphate), B12, and folic acid concentrations during treatment (P < 0.0001). Vitamin B6, B12, and folic acid concentrations were significantly elevated at weeks 12 and 24 (P < 0.05). Homocysteine concentration decreased significantly during the same periods (7.9 +/- 2.4 versus 6.7 +/- 1.7 versus 6.7 +/- 1.9 mM/mL; P < 0.05). There were correlations relating homocysteine to vitamins B6 (P = 0.001, r(2) = 0.03), B12 (P < 0.001, r(2) = 0.09), and folic acid (P = 0.001, r(2) = 0.10). Significant time effects were noted for 121 subjects successfully assayed for vitamin C, E, beta-carotene, LDL oxidation rate, and LDL lag time (P < 0.0001). Post hoc assessment showed elevations in vitamin C, E, and beta-carotene concentrations at 12 and 24 wk (P < 0.05). LDL oxidation lag time at baseline (57.5 +/- 13.9 min) increased by 12 wk (63.5 +/- 19.0 min; P < 0.05) and 24 wk (63.8 +/- 16.3 min; P < 0.05). LDL oxidation rate at baseline (9.7 +/- 3.0 microM x min(-1). g(-1)) was reduced at 12 wk (7.1 +/- 2.5 microM x min(-1) x g(-1); P < 0.05) and 24 wk (6.0 +/- 2.0 microM x min(-1) x g(-1); P < 0.05). Only vitamin C was significantly correlated with LDL oxidation rate (P = 0.05, r(2) = 0.003). CONCLUSIONS: A multi-ingredient vitamin formula with antioxidant properties has measurable effects on homocysteine and LDL oxidation indices.

GENETIC DETERMINANTS OF PROTANDRIC SEX IN THE PACIFIC OYSTER, CRASSOSTREA GIGAS THUNBERG.

A unique feature of sex in Crassostrea oysters is the coexistence of protandric sex change, dioecy, and hermaphroditism. To determine whether such a system is genetically controlled, we analyzed sex ratios in 86 pair-mated families of the Pacific oyster, Crassostrea gigas Thunberg. The overall female ratios of one-, two-, and three-year-old oysters were 37%, 55%, and 75%, respectively, suggesting that a significant proportion of oysters matured first as males and changed to females in later years. Detailed analysis of sex ratios in factorial and nested crosses revealed significant paternal effects, which corresponded to two types of sires. No major maternal effects on sex were observed. Major genetic control of sex was further indicated by the distribution of family sex ratios in two to four apparently discreet groups. These and other data from the literature are compatible with a single-locus model of primary sex determination with a dominant male allele (M) and a protandric female allele (F), so that MF are true males and FF are protandric females that are capable of sex change. The rate of sex change of FF individuals may be influenced by secondary genes and/or environmental factors. Strong maternal and weak paternal effects on sexual maturation or time of spawning were also suggested.