Cardiorespiratory Fitness and the Paradoxical BMI-Mortality Risk Association in Male Veterans

ObjectiveTo assess the effect of fitness status on the paradoxical body mass index (BMI)-mortality risk association.Patients and MethodsFrom February 1, 1986, through December 30, 2011, we assessed fitness and BMI in 18,033 male veterans (mean age, 58.4±11.4 years) in 2 Veterans Affairs Medical centers. We established 3 fitness categories on the basis of peak metabolic equivalents achieved during an exercise test as well as 5 BMI categories. The primary outcome was all-cause mortality.ResultsDuring the follow-up period (median, 10.8 years, comprising a total of 207,168 person-years), 5070 participants (28%) died. After adjusting for age, risk factors, muscle-wasting diseases, medications, and year of entry, mortality risk was higher for individuals with a BMI of 20.1 to 23.9 kg/m² (hazard ratio [HR], 1.21; 95% CI, 1.12-1.30) and 18.5 to 20.0 kg/m² (HR, 1.56; 95% CI, 1.37-1.77) than for those with a BMI of 24.0 to 27.9 kg/m²; mortality risk was not increased for those with a BMI of 28.0 kg/m² or greater. When stratified by fitness, the trend was similar for low-fit and moderate-fit individuals. However, mortality risk was not increased for high-fit individuals across BMI categories. When fitness status was considered within each BMI category, mortality risk increased progressively with decreased fitness and was more pronounced for moderate-fit (HR, 2.52; 95% CI, 2.06-3.08) and low-fit (HR, 2.48; 95% CI, 2.0-3.06) individuals with a BMI of 18.5-20.0 kg/m². Mortality risk was not significantly increased for high-fit individuals (HR, 1.17; 95% CI, 0.78-1.78; P=.45).ConclusionA high mortality risk associated with low BMI levels was observed only in moderate-fit and low-fit individuals, and not in high-fit individuals. Thus, fitness greatly affects the paradoxical BMI-mortality risk association. Furthermore, our findings indicate that lower BMI levels do not increase the risk for premature death as long as they are associated with high fitness. Thus, the paradoxically higher mortality risk observed with lower body weight as represented by lower BMI is likely the result of unhealthy reduction in body weight and, perhaps most importantly, considerable loss of lean body mass.     

Association of Multiple Adiposity Exposures and Cardiorespiratory Fitness With All-Cause Mortality in Men: The Cooper Center Longitudinal Study

ObjectiveTo examine the additive effects of an increased number of positive adiposity exposures on all-cause mortality in men before and after stratification by cardiorespiratory fitness (CRF) level.Patients and MethodsA total of 36,836 men underwent a physical examination at the Cooper Clinic from January 1, 1971, through December 31, 2006. Exposures included body mass index, waist circumference, percentage of body fat, and CRF as determined by duration of a maximal exercise test. Participants were identified as being either obese (positive) or nonobese (negative) for each adiposity exposure and then grouped into 4 categories: group 1, negative for all adiposity exposures; group 2, positive for any 1 exposure; group 3, positive for any 2 exposures; and group 4, positive for all exposures. Then CRF was grouped as fit or unfit on the basis of the upper 80% and lower 20% of the age-standardized CRF distribution as previously reported in the Cooper Center Longitudinal Study. Hazard ratios were computed with Cox regression analysis.ResultsA total of 2294 deaths occurred during a mean ± SD of 15.5±8.1 years of follow-up. Adjusted hazard ratios across adiposity groups were 1.0 (referent), 1.05, 1.37, and 1.87 for groups 1 through 4, respectively (P for trend <.001). Mortality rates were significantly lower within each of the first 3 adiposity groups in fit compared with unfit men (P<.009 for all comparisons).ConclusionAn increasing number of positive adiposity exposures were associated with increased mortality in men. Because moderate to high CRF attenuated mortality rates in all adiposity groups, measurement of CRF should be included for identifying men at increased risk for all-cause mortality.     

Resting Heart Rate in First Year Survivors of Myocardial Infarction and Long-term Mortality: A Community Study

ObjectiveTo evaluate the long-term prognostic effect of resting heart rate (HR) at index myocardial infarction (MI) and during the first year after MI among 1-year survivors.Patients and MethodsThe community-based cohort consisted of 1571 patients hospitalized with an incident MI from January 1, 1983, through December 31, 2007, in Olmsted County, Minnesota, who were in sinus rhythm at index MI and had HR measurements on electrocardiography at index and during the first year after MI. Outcomes were all-cause and cardiovascular deaths.ResultsDuring a median follow-up of 7.0 years, 627 deaths and 311 cardiovascular deaths occurred. Using patients with HRs of 60/min or less as the referent, this study found that long-term all-cause mortality risk increased progressively with increasing HR at index (hazard ratio, 1.62; 95% CI, 1.25-2.09) and even more with increasing HR during the first year after MI (hazard ratio, 2.16; 95% CI, 1.64-2.84) for patients with HRs greater than 90/min, adjusting for clinical characteristics and β-blocker use. Similar results were observed for cardiovascular mortality (adjusted hazard ratio, 1.66; 95% CI, 1.14-2.42; and adjusted hazard ratio, 1.93; 95% CI, 1.27-2.94; for HR at index and within 1 year after MI, respectively).ConclusionThese data from a large MI community cohort indicate that HR is a strong predictor of long-term all-cause and cardiovascular mortality not only at initial presentation of MI but also during the first year of follow-up.     

Use of Functional Aerobic Capacity Based on Stress Testing to Predict Outcomes in Normal,Overweight, and Obese Patients

ObjectiveTo determine the poorly studied relationship between functional aerobic capacity (FAC) as measured by treadmill stress testing and mortality in normal, overweight, and obese patients.Patients and MethodsPatients were identified retrospectively from the stress testing database at Mayo Clinic in Rochester, Minnesota. We selected 5328 male nonsmokers (mean ± SD age, 51.8±11.5 years) without baseline cardiovascular disease who were referred for treadmill exercise testing between January 1, 1986, and December 31, 1991, and classified them by body mass index (BMI) into normal-weight (18.5-24.9 kg/m²), overweight (25.0-29.9 kg/m²), and obese (≥30 kg/m²) categories. Functional aerobic capacity was assessed by maximal exercise test results based on age- and sex-specific metabolic equivalents, and patients were stratified into fitness quintiles. Cox proportional hazards analysis was used to determine the relationship of all-cause mortality to fitness in each BMI category.ResultsThere were 322 deaths during 14 years of follow-up. After adjustment for age and exercise confounders, FAC predicted mortality in the 3 BMI groups. Hazard ratios for FAC less than 80% of predicted vs a reference group with normal BMI and fitness (FAC ≥100%) were 1.754 (95% CI, 0.874-3.522), 1.962 (1.356-2.837), and 1.518 (1.056-2.182) for the normal, overweight, and obese groups, respectively. The CIs of the hazard ratios overlapped with no statistically significant differences (P>.05).ConclusionA significant increase in mortality occurs with FAC below 80% of predicted for overweight and obese subjects and below 70% for normal weight subjects. Our results suggest that clinicians need not adjust the standard for low fitness in obese patients.     

The Effect of Resistance Exercise on All-Cause Mortality in Cancer Survivors

ObjectiveTo examine the independent associations of leisure-time aerobic physical activity (PA) and resistance exercise (RE) on all-cause mortality in cancer survivors.Patients and MethodsPatients included 2863 male and female cancer survivors, aged 18 to 81 years, who received a preventive medical examination between April 8, 1987, and December 27, 2002, while enrolled in the Aerobics Center Longitudinal Study in Dallas, Texas. Physical activity and RE were assessed by self-report at the baseline medical examination. Cox proportional hazards regression analysis was performed to determine the independent associations of PA and RE with all-cause mortality in participants who had a history of cancer.ResultsPhysical activity in cancer survivors was not associated with a lower risk of all-cause mortality. In contrast, RE was associated with a 33% lower risk of all-cause mortality (95% CI, 0.45-0.99) after adjusting for potential confounders, including PA.ConclusionIndividuals who participated in RE during cancer survival had a lower risk for all-cause mortality. The present findings provide preliminary evidence for benefits of RE during cancer survival. Future randomized controlled trials examining RE and its effect on lean body mass, muscular strength, and all-cause mortality in cancer survivors are warranted.     

Association Between Alcohol Consumption and Risk of Cardiovascular Disease and All-Cause Mortality in Patients With Hypertension: A Meta-Analysis of Prospective Cohort Studies

ObjectiveTo conduct a meta-analysis summarizing the risk of cardiovascular disease (CVD) and all-cause mortality (ACM) in relation to alcohol consumption in patients with hypertension, focusing on clarifying dose-response associations.Patients and MethodsPubMed and EMBASE were searched for eligible prospective cohort studies from December 3, 1949, through January 18, 2014. The semi-parameter method and dose-response analysis were used.ResultsNine studies (11 cohorts) were included in the meta-analysis. Compared with the lowest alcohol level (abstainers/occasional drinkers), the pooled relative risk (RR) was 0.72 (95% CI, 0.68-0.77) for the third highest category (median, 10 g/d), 0.81 (95% CI, 0.71-0.93) for the second highest category (median, 20 g/d), and 0.60 (95% CI, 0.54-0.67) for the highest category (median, 30 g/d). A J-shaped relationship between alcohol use and ACM was observed, and the nadir (RR, 0.82; 95% CI, 0.76-0.88) was found to be at a dose of 8 to 10 g of alcohol consumption per day.ConclusionFindings of this meta-analysis suggest that low-to-moderate alcohol consumption was inversely significantly associated with the risk of CVD and ACM in patients with hypertension.     

Increased Cardiovascular Disease Mortality Associated With Excessive Exercise in Heart Attack Survivors

ObjectiveTo test whether greater exercise is associated with progressively lower mortality after a cardiac event.Patients and MethodsWe used Cox proportional hazard analyses to examine mortality vs estimated energy expended by running or walking measured as metabolic equivalents (3.5 mL O₂/kg per min per day or metabolic equivalent of task-h/d [MET-h/d]) in 2377 self-identified heart attack survivors, where 1 MET-h/d is the energy equivalent of running 1 km/d. Mortality surveillance via the National Death Index included January 1991 through December 2008.ResultsA total of 526 deaths occurred during an average prospective follow-up of 10.4 years, 376 (71.5%) of which were related to cardiovascular disease (CVD) (International Statistical Classification of Diseases, 10th Revision codes I00-I99). CVD-related mortality compared with the lowest exercise group decreased by 21% for 1.07 to 1.8 MET-h/d of running or walking (P=.11), 24% for 1.8 to 3.6 MET-h/d (P=.04), 50% for 3.6 to 5.4 MET-h/d (P=.001), and 63% for 5.4 to 7.2 MET-h/d (P<.001) but decreased only 12% for ≥7.2 MET-h/d (P=.68). These data represent a 15% average risk reduction per MET-h/d for CVD-related mortality through 7.2 MET-h/d (P<.001) and a 2.6-fold risk increase above 7.2 MET-h/d (P=.009). Relative to the risk reduction at 7.2 MET-h/d, the risk for ≥7.2 MET-h/d increased 3.2-fold (P=.006) for all ischemic heart disease (IHD)–related mortalities but was not significantly increased for non–IHD-CVD, arrhythmia-related CVD, or non–CVD-related mortalities.ConclusionRunning or walking decreases CVD mortality risk progressively at most levels of exercise in patients after a cardiac event, but the benefit of exercise on CVD mortality and IHD deaths is attenuated at the highest levels of exercise (running: above 7.1 km/d or walking briskly: 10.7 km/d).     

Association of Dysglycemia and All-Cause Mortality Across the Spectrum of Coronary Artery Disease

ObjectiveTo assess the association between fasting plasma glucose (FPG) and all-cause mortality across the spectrum of coronary artery disease (CAD).Patients and MethodsThe study included 18,999 patients during a study period of April 1, 2004, through October 31, 2010. The primary end points were in-hospital and follow-up all-cause mortality. According to the quartiles of FPG levels, patients were categorized into 4 groups: quartile 1, less than 5.1 mmol/L; quartile 2, 5.1 to less than 5.9 mmol/L; quartile 3, 5.9 to less than 7.5 mmol/L; and quartile 4, 7.5 mmol/L or greater. The conversion factor for units of plasma glucose is 1.00 mmol/L equals 18 mg/dL. Presented as mg/dL, the 4 quartile ranges of plasma glucose concentrations used in our data analysis are ≤90.0 mg/dL, 90.1-106.0 mg/dL, 106.1 mg/dL-135.0 mg/dL and ≥135.1 mg/dL. Quartile 1 was recognized as the lower glycemic group, quartiles 2 and 3 as the normoglycemic groups, and quartile 4 as the higher glycemic group.ResultsIn patients with acute myocardial infarction, all-cause mortality for the dysglycemic groups was higher than for the normoglycemic groups: in-hospital mortality for quartiles 1, 2, 3, and 4 was 1.0%, 0.9%, 0.2%, and 1.5%, respectively (P=.001); follow-up mortality for quartiles 1, 2, 3, and 4 was 1.7%, 0.9%, 0.3%, and 1.8%, respectively (P<.001). In patients with stable CAD, no significant differences in mortality were found among groups. However, in patients with unstable angina pectoris, the normoglycemic groups had lower follow-up mortality and roughly equal in-hospital mortality compared with the dysglycemic groups. After adjusting for confounding factors, this observation persisted.ConclusionThe association between lower FPG level and mortality differed across the spectrum of CAD. In patients with acute myocardial infarction, there was a U-shaped relationship. In patients with stable CAD or unstable angina pectoris, mildly to moderately decreasing FPG level was associated with neither higher nor lower all-cause mortality.     

Association of Coffee Consumption With All-Cause and Cardiovascular Disease Mortality

ObjectiveTo evaluate the association between coffee consumption and mortality from all causes and from cardiovascular disease.Patients and MethodsData from the Aerobics Center Longitudinal Study representing 43,727 participants with 699,632 person-years of follow-up were included. Baseline data were collected by an in-person interview on the basis of standardized questionnaires and a medical examination, including fasting blood chemistry analysis, anthropometry, blood pressure, electrocardiography, and a maximal graded exercise test, between February 3, 1971, and December 30, 2002. Cox regression analysis was used to quantify the association between coffee consumption and all-cause and cause-specific mortality.ResultsDuring the 17-year median follow-up, 2512 deaths occurred (804 [32%] due to cardiovascular disease). In multivariate analyses, coffee intake was positively associated with all-cause mortality in men. Men who drank more than 28 cups of coffee per week had higher all-cause mortality (hazard ratio [HR], 1.21; 95% CI, 1.04-1.40). However, after stratification based on age, younger (<55 years old) men and women showed a significant association between high coffee consumption (>28 cups per week) and all-cause mortality after adjusting for potential confounders and fitness level (HR, 1.56; 95% CI, 1.30-1.87 for men; and HR, 2.13; 95% CI, 1.26-3.59 for women).ConclusionIn this large cohort, a positive association between coffee consumption and all-cause mortality was observed in men and in men and women younger than 55 years. On the basis of these findings, it seems appropriate to suggest that younger people avoid heavy coffee consumption (ie, averaging >4 cups per day). However, this finding should be assessed in future studies of other populations.     

Characteristics and Outcomes of Patients Who Achieve High Workload (≥10 Metabolic Equivalents) During Treadmill Exercise Echocardiography

ObjectiveTo determine the frequency and prognostic significance of abnormal exercise echocardiographic results for patients achieving a workload of 10 or more metabolic equivalents during treadmill exercise echocardiography.Patients and MethodsPatients who underwent treadmill exercise echocardiography from November 1, 2003, through December 31, 2008, and exercised for 9 or more minutes using the Bruce protocol (N=7236) were included. Clinical and exercise echocardiographic characteristics and outcomes were evaluated. Variables associated with abnormal exercise echocardiographic results and mortality were identified.ResultsExercise echocardiographic results were positive for ischemia in 862 patients (12%). Extensive ischemia developed in 265 patients (4%). For patients with normal exercise echocardiographic results, all-cause and cardiovascular mortality rates were 0.30% and 0.05% per person-year of follow-up, respectively. For patients who had extensive ischemia, all-cause and cardiovascular mortality rates were 0.84% and 0.25% per person-year of follow-up, respectively. Patients at highest risk were those who had extensive and severe regional wall motion abnormalities at rest (n=58), and their all-cause and cardiovascular mortality rates were 2.65% and 0.76% per person-year of follow-up. Exercise echocardiographic variables did not identify sizable patient subgroups at risk for death and did not provide incremental prognostic information (C statistic was 0.74 compared with 0.73 for the clinical plus exercise electrocardiography model).ConclusionPatients achieving a workload of 10 or more metabolic equivalents during treadmill exercise testing do not often have extensive ischemic abnormalities on exercise echocardiography. Although exercise echocardiographic results provide some prognostic information, it is not of incremental value for these patients, whose short-term and medium-term prognosis is excellent.     

Elite Athletes Live Longer Than the General Population: A Meta-Analysis

ObjectiveTo perform a meta-analysis of cohort studies aimed at providing an accurate overview of mortality in elite athletes.Patients and MethodsWe reviewed English-language scientific articles available in Medline and Web of Science databases following the recommendations of the Meta-analyses Of Observational Studies in Epidemiology group. We searched for publications on longevity and professional or elite athletes (with no restriction on the starting date and up to March 31, 2014).ResultsTen studies, including data from a total of 42,807 athletes (707 women), met all inclusion criteria. The all-cause pooled standard mortality ratio (SMR) was 0.67 (95% CI, 0.55-0.81; P<.001) with no evidence of publication bias (P=.24) but with significant heterogeneity among studies (I²=96%; Q=224.46; P<.001). Six studies provided data on cardiovascular disease (CVD) and 5 on cancer (in a total of 35,920 and 12,119 athletes, respectively). When only CVD was considered as a cause of mortality, the pooled SMR was 0.73 (95% CI, 0.65-0.82; P<.001) with no evidence of bias (P=.68) or heterogenity among studies (I²=38%; Q=8.07; P=.15). The SMR for cancer was 0.60 (95% CI, 0.38-0.94; P=.03) with no evidence of bias (P=.20) despite a significant heterogeneity (I²=91%; Q=44.21; P<.001).ConclusionThe evidence available indicates that top-level athletes live longer than the general population and have a lower risk of 2 major causes of mortality, namely, CVD and cancer.     

Prognostic Value of Exercise Capacity in Patients With Coronary Artery Disease: The FIT (Henry Ford ExercIse Testing) Project

ObjectiveTo examine the prognostic value of exercise capacity in patients with nonrevascularized and revascularized coronary artery disease (CAD) seen in routine clinical practice.Patients and MethodsWe analyzed 9852 adults with known CAD (mean ± SD age, 61±12 years; 69% men [n=6836], 31% black race [n=3005]) from The Henry Ford ExercIse Testing (FIT) Project, a retrospective cohort study of patients who underwent physician-referred stress testing at a single health care system between January 1, 1991, and May 31, 2009. Patients were categorized by revascularization status (nonrevascularized, percutaneous coronary intervention [PCI], or coronary artery bypass graft [CABG] surgery) and by metabolic equivalents (METs) achieved on stress testing. Using Cox regression models, hazard ratios for mortality, myocardial infarction (MI), and downstream revascularizations were calculated after adjusting for potential confounders, including cardiac risk factors, pertinent medications, and stress testing indication.ResultsThere were 3824 all-cause deaths during median follow-up of 11.5 years. In addition, 1880 MIs, and 1930 revascularizations were ascertained. Each 1-MET increment in exercise capacity was associated with a hazard ratio (95% CI) of 0.87 (0.85-0.89), 0.87 (0.85-0.90), and 0.86 (0.84-0.89) for mortality; 0.98 (0.96-1.01), 0.88 (0.84-0.92), and 0.93 (0.90-0.97) for MI; and 0.94 (0.92-0.96), 0.91 (0.88-0.95), and 0.96 (0.92-0.99) for downstream revascularizations in the nonrevascularized, PCI, and CABG groups, respectively. In each MET category, the nonrevascularized group had similar mortality risk as and higher MI and downstream revascularization risk than the PCI and CABG surgery groups (P<.05).ConclusionExercise capacity was a strong predictor of mortality, MI, and downstream revascularizations in this cohort. Furthermore, patients with similar exercise capacities had an equivalent mortality risk, irrespective of baseline revascularization status.     

Hemoglobin A1c in Nondiabetic Patients: An Independent Predictor of Coronary Artery Disease and Its Severity

ObjectiveTo examine the association between hemoglobin A_1c (HbA_1c) and the presence, severity, and complexity of angiographically proven coronary artery disease (CAD) in nondiabetic patients.Patients and MethodsWe performed a single-center, observational, cross-sectional study of 1141 consecutive nondiabetic patients who underwent coronary angiography from January 1, 2011, through December 31, 2011. The study population was divided into 4 interquartiles according to HbA_1c levels (<5.5%, 5.5%-5.7%, 5.8%-6.1%, and >6.1%).ResultsPatients with higher HbA_1c levels tended to be older, overweight, and hypertensive, had higher blood glucose levels, and had lower glomerular filtration rates. Higher HbA_1c levels were associated in a graded fashion with the presence of CAD, disease severity (higher number of diseased vessels and presence of left main and/or triple vessel disease), and disease complexity (higher SYNTAX score, higher number of patients in intermediate or high SYNTAX tertiles, coronary calcium, and chronic total occlusions). After adjustment for major conventional cardiovascular risk factors, compared with patients with HbA_1c levels less than 5.5%, the odds ratios of occurrence of CAD in the HbA_1c quartiles of 5.5% to 5.7%, 5.8% to 6.1%, and greater than 6.1% were 1.8 (95% CI, 1.2-2.7), 3.5 (95% CI, 2.3-5.3), and 4.9 (95% CI, 3.0-8.1), respectively.ConclusionThe HbA_1c level has a linear incremental association with CAD in nondiabetic individuals. The HbA_1c level is also independently correlated with disease severity and higher SYNTAX scores. Thus, HbA_1c measurement could be used to improve cardiovascular risk assessment in nondiabetic individuals.     

Association Between Cardiorespiratory Fitness and Accelerometer-Derived Physical Activity and Sedentary Time in the General Population

ObjectiveTo determine the association between cardiorespiratory fitness and sedentary behavior, independent of exercise activity.Patients and MethodsWe included 2223 participants (aged 12-49 years; 1053 females [47%]) without known heart disease who had both cardiovascular fitness testing and at least 1 day of accelerometer data from the National Health and Nutrition Examination Survey 2003-2004. From accelerometer data, we quantified bouts of exercise as mean minutes per day for each participant. Sedentary time was defined as less than 100 counts per minute in mean minutes per day. Cardiorespiratory fitness was derived from a submaximal exercise treadmill test. Multivariable-adjusted linear regression analyses were performed with fitness as the dependent variable. Models were stratified by sex, adjusted for age, body mass index, and wear time, and included sedentary and exercise time.ResultsAn additional hour of daily exercise activity time was associated with a 0.88 (0.37-1.39; P<.001) metabolic equivalent of task (MET) higher fitness for men and a 1.37 (0.43-2.31; P=.004) MET higher fitness for women. An additional hour of sedentary time was associated with a −0.12 (−0.02 to −0.22; P=.03) and a −0.24 (−0.10 to −0.38; P<.001) MET difference in fitness for men and women, respectively.ConclusionAfter adjustment for exercise activity, sedentary behavior appears to have an inverse association with fitness. These findings suggest that the risk related to sedentary behavior might be mediated, in part, through lower fitness levels.     

Sedentary Behavior,Cardiorespiratory Fitness,Physical Activity,and Cardiometabolic Risk in Men: The Cooper Center Longitudinal Study

ObjectiveTo examine the association between sedentary behavior and cardiometabolic risk, while taking into account cardiorespiratory fitness (fitness) and physical activity.Participants and MethodsWe examined the association of sedentary behavior, physical activity, and fitness (exposure variables) to cardiometabolic biomarkers and metabolic syndrome (outcome measures) among a historic cohort (January 2, 1981, through October 16, 2012) of men. First, we estimated the association (cross-sectionally and longitudinally) of sedentary behavior along with physical activity and fitness to lipids and lipoproteins, glucose, blood pressure, and markers of adiposity, including body mass index, waist circumference, and body fat percentage. We then prospectively examined the effects of baseline sedentary time on the incidence of metabolic syndrome, while adjusting for physical activity, fitness, and other covariates in multivariate models.ResultsMultivariate analysis of baseline data revealed that in comparison with the reference group (≤9 h/wk of sedentary time), more sedentary behavior was significantly associated with a higher triglyceride level, a higher triglycerides–high-density lipoprotein cholesterol ratio, and a higher body mass index, waist circumference, and body fat percentage (P<.05 for trend), after adjusting for physical activity and covariates. When adjusting for fitness and covariates, prolonged sedentary time was only associated with a higher triglyceride–high-density lipoprotein cholesterol ratio (P=.02 for trend). Sedentary time was not associated with the incidence of metabolic syndrome in multivariate models. Longitudinal analyses revealed that a 1–metabolic equivalent increase in fitness was significantly (P<.05) associated with almost all biomarkers when adjusting for sedentary behavior, with little moderation observed.ConclusionThe association between prolonged sedentary time and cardiometabolic biomarkers is markedly less pronounced when taking fitness into account. Further exploration of the effects of sedentary behavior on cardiometabolic risk is warranted in cohorts with available fitness data. Furthermore, our findings underscore the need to encourage achieving higher fitness levels through meeting physical activity guidelines to decrease disease risk factors.     

Association of Exercise Heart Rate Response and Incidence of Hypertension in Men

ObjectiveTo examine the association of heart rate (HR) responses at rest, during exercise, and after exercise with incident hypertension (HTN) in men.Participants and MethodsA total of 10,418 healthy normotensive men without abnormalities on electrocardiography or a history of myocardial infarction, stroke, cancer, or diabetes underwent a maximal exercise test and were followed up for incidence of HTN. Heart rate reserve was defined as the maximal HR minus resting HR. Heart rate recovery was defined as HR 5 minutes after the exercise test.ResultsDuring a mean follow-up of 6 years, there were 2831 cases of HTN. Compared with men who had lower HR reserve, the risk of incident HTN was significantly lower for men with higher HR reserve (hazard ratio, 0.84; 95% CI, 0.74-0.95 for the highest quartile vs the lowest quartile of HR reserve; P=.002) when adjusted for age, baseline examination year, smoking, heavy drinking, body mass index, resting blood pressure, cholesterol and glucose levels, and cardiorespiratory fitness. Compared with men who had higher HR recovery, the risk of incident HTN was significantly lower for men with lower HR recovery (hazard ratio, 0.90; 95% CI, 0.80-0.99 for quartile 3 vs highest quartile; P=.04) after adjusting for the aforementioned confounders. However, the overall linear trend for HR recovery was not significant (P=.26).ConclusionThe risk of HTN decreased in men with higher HR reserve. Therefore, HR reserve may be considered as a useful exercise parameter for predicting the risk of HTN in men.     

Relationship of Body Mass Index With Total Mortality,Cardiovascular Mortality,and Myocardial Infarction After Coronary Revascularization: Evidence From a Meta-analysis

ObjectiveTo investigate the relationship of body mass index (BMI) with total mortality, cardiovascular (CV) mortality, and myocardial infarction (MI) after coronary revascularization procedures (coronary artery bypass grafting [CABG] and percutaneous coronary intervention [PCI]).Patients and MethodsSystematic search of studies was conducted using PubMed, CINAHL, Cochran CENTRAL, Scopus, and the Web of Science databases. We identified studies reporting the rate of MI, CV mortality, and total mortality among coronary artery disease patients' postcoronary revascularization procedures in various BMI categories: less than 20 (underweight), 20-24.9 (normal reference), 25-29.9 (overweight), 30-34.9 (obese), and 35 or more (severely obese). Event rates were compared using a random effects model assuming interstudy heterogeneity.ResultsA total of 36 studies (12 CABG; 26 PCI) were selected for final analyses. The risk of total mortality (relative risk [RR], 2.59; 95% CI, 2.09-3.21), CV mortality (RR, 2.67; 95% CI, 1.63-4.39), and MI (RR, 1.79; 95% CI, 1.28-2.50) was highest among patients with low BMI at the end of a mean follow-up period of 1.7 years. The risk of CV mortality was lowest among overweight patients (RR, 0.81; 95% CI, 0.68-0.95). Increasing degree of adiposity as assessed by BMI had a neutral effect on the risk of MI for overweight (RR, 0.92; 95% CI, 0.84-1.01), obese (RR, 0.99; 95% CI, 0.85-1.15), and severely obese (RR, 0.93; 95% CI, 0.78-1.11) patients.ConclusionAfter coronary artery disease revascularization procedures (PCI and CABG), the risk of total mortality, CV mortality, and MI was highest among underweight patients as defined by low BMI and CV mortality was lowest among overweight patients.     

A Pooled Analysis of Waist Circumference and Mortality in 650,000 Adults

ObjectivesTo assess the independent effect of waist circumference on mortality across the entire body mass index (BMI) range and to estimate the loss in life expectancy related to a higher waist circumference.Patients and MethodsWe pooled data from 11 prospective cohort studies with 650,386 white adults aged 20 to 83 years and enrolled from January 1, 1986, through December 31, 2000. We used proportional hazards regression to estimate hazard ratios (HRs) and 95% CIs for the association of waist circumference with mortality.ResultsDuring a median follow-up of 9 years (maximum, 21 years), 78,268 participants died. After accounting for age, study, BMI, smoking status, alcohol consumption, and physical activity, a strong positive linear association of waist circumference with all-cause mortality was observed for men (HR, 1.52 for waist circumferences of ≥110 vs <90 cm; 95% CI, 1.45-1.59; HR, 1.07 per 5-cm increment in waist circumference; 95% CI, 1.06-1.08) and women (HR, 1.80 for waist circumferences of ≥95 vs <70 cm; 95% CI, 1.70-1.89; HR, 1.09 per 5-cm increment in waist circumference; 95% CI, 1.08-1.09). The estimated decrease in life expectancy for highest vs lowest waist circumference was approximately 3 years for men and approximately 5 years for women. The HR per 5-cm increment in waist circumference was similar for both sexes at all BMI levels from 20 to 50 kg/m², but it was higher at younger ages, higher for longer follow-up, and lower among male current smokers. The associations were stronger for heart and respiratory disease mortality than for cancer.ConclusionsIn white adults, higher waist circumference was positively associated with higher mortality at all levels of BMI from 20 to 50 kg/m². Waist circumference should be assessed in combination with BMI, even for those in the normal BMI range, as part of risk assessment for obesity-related premature mortality.     

Serum Polyclonal Immunoglobulin Free Light Chain Levels Predict Mortality in People With Chronic Kidney Disease

ObjectiveTo determine whether elevated serum polyclonal free light chain (FLC) levels predict mortality in a population of individuals with chronic kidney disease (CKD).Patients and MethodsFrom January 2, 2006, through July 31, 2007, we recruited a cohort of 848 people with CKD who were not receiving renal replacement therapy and did not have monoclonal gammopathy. We measured serum kappa FLC and lambda FLC isotype levels to determine combined FLC (cFLC) levels. The cohort was prospectively followed up for a median of 63 months (interquartile range, 0-93 months). Cox regression analysis was performed to determine variables predictive of mortality.ResultsHigh cFLC levels were an independent risk factor for death (hazard ratio [HR], 2.71; 95% CI, 1.98-3.70; P<.001). Other independent risk factors were age (HR, 1.79; 95% CI, 1.52-2.10; P<.001), South Asian ethnicity (HR, 0.33; 95% CI, 0.14-0.64; P=.02), preexisting cardiovascular disease (HR, 1.59; 95% CI, 1.09-2.31; P=.02), and high-sensitivity C-reactive protein (HR, 1.13; 95% CI, 1.00-1.28; P=.04). Neither estimated glomerular filtration rate nor albuminuria was an independent risk factor for death.ConclusionHigh cFLC levels independently predict mortality in people with CKD.     

Reference Fitness Values in the Untrained Spinal Cord Injury Population

ObjectiveEstablish reference values of cardiorespiratory fitness applicable to the general, untrained spinal cord injury (SCI) population.DesignData were retroactively obtained from 12 studies (May 2004 to May 2012).SettingAn institution-affiliated applied physiology research laboratory.ParticipantsA total of 153 men and 26 women (age, 18–55y) with chronic SCI (N=179) were included. Participants were not involved in training activities for 1 or more months before testing and were able to complete a progressive resistance exercise test to determine peak oxygen consumption (Vo₂peak).InterventionsNot applicable.Main Outcome MeasurePercentile ranking (poor<20%; fair; 20%–40%; average, 40%–60%; good, 60%–80%; excellent, 80%–100%) used to establish reference values.ResultsReference cardiorespiratory fitness values based on functional classification as paraplegic or tetraplegic were established (paraplegic: median, 16.0mL·kg⁻¹·min⁻¹; range, 1.4–35.2mL·kg⁻¹·min⁻¹; tetraplegic: median, 8.8mL·kg⁻¹·min⁻¹; range, 1.5–21.5mL·kg⁻¹·min⁻¹) for untrained men and women. For the primary outcome measure (Vo₂peak), persons with paraplegia had significantly higher values than did persons with tetraplegia (P<.001). Although men had higher values than did women, these differences did not reach significance (P=.256). Regression analysis revealed that motor level of injury was associated with 22.3% of the variability in Vo₂peak (P<.001), and an additional 8.7% was associated with body mass index (P<.001). No other measure accounted for additional significant variability.ConclusionsEstablished reference fitness values will allow investigators/clinicians to stratify the relative fitness of subjects/patients from the general SCI population. Key determinants are motor level of injury and body habitus, yet most variability in aerobic capacity is not associated with standard measures of SCI status or demographic characteristics.