Association between Estimated Cardiorespiratory Fitness and Abnormal Glucose Risk: A Cohort Study.

BACKGROUND: Cardiorespiratory fitness (CRF) is a predictor of chronic disease that is impractical to routinely measure in primary care settings. We used a new estimated cardiorespiratory fitness (eCRF) algorithm that uses information routinely documented in electronic health care records to predict abnormal blood glucose incidence. METHODS: Participants were adults (17.8% female) 20-81 years old at baseline from the Aerobics Center Longitudinal Study between 1979 and 2006. eCRF was based on sex, age, body mass index, resting heart rate, resting blood pressure, and smoking status. CRF was measured by maximal treadmill testing. Cox proportional hazards regression models were established using eCRF and CRF as independent variables predicting the abnormal blood glucose incidence while adjusting for covariates (age, sex, exam year, waist girth, heavy drinking, smoking, and family history of diabetes mellitus and lipids). RESULTS: Of 8602 participants at risk at baseline, 3580 (41.6%) developed abnormal blood glucose during an average of 4.9 years follow-up. The average eCRF of 12.03 ± 1.75 METs was equivalent to the CRF of 12.15 ± 2.40 METs within the 10% equivalence limit. In fully adjusted models, the estimated risks were the same (HRs = 0.96), eCRF (95% CIs = 0.93-0.99), and CRF (95% CI of 0.94-0.98). Each 1-MET increase was associated with a 4% reduced risk. CONCLUSIONS: Higher eCRF is associated with a lower risk of abnormal glucose. eCRF can be a vital sign used for research and prevention.

A randomized controlled trial of exercise to prevent muscle mass and functional loss in elderly hemodialysis patients: Rationale, study design, and baseline sample.

BACKGROUND: Elderly maintenance hemodialysis (MHD) patients exhibit muscle wasting and impaired physical function. This trial determines whether MHD patients benefit from a 12-week home-based exercise program, protein supplementation, or both. DESIGN: and Methods: This is a randomized, blinded controlled trial involving 60 elderly MHD patients with impaired exercise capacity and function. Patients are randomized into either a homebased exercise program or normal care over a 12-week period. Measures at baseline include peak VO2, strength and body composition as well as cognitive and disease-specific questionnaires. Muscle biopsies are obtained and analyzed for protein signaling, expression of IGF-1, androgen receptors, and myostatin. RESULTS: At baseline, patient characteristics in the exercise and normal care groups were similar by age, gender and anthropomorphic measures. Peak VO2 was impaired (14.7 ±â€¯3.3 ml/kg/min), representing 55 ±â€¯14% of the age-predicted value. Six-minute walk distance was 322 ±â€¯71 m, and the mean 1-min sit to stand test was 18 ±â€¯8 repetitions, representing 69 ±â€¯16% and 55 ±â€¯22% of the age-predicted values, respectively. Indices of muscle function, including upper and lower body and hand grip strength all indicate marked impairment. Quality of life (QoL) using the SF36, the Beeson cognitive test, and KDQOL all suggest marked impairments compared to age-expected reference values for non-MHD patients. CONCLUSIONS: Patients undergoing MHD exhibit markedly reduced physical function and QoL. Thus, there are potentially significant gains to be made through a program of aerobic and resistance exercise. We anticipate this trial will demonstrate that home-based exercise improves cardiopulmonary function, protein signaling and QoL, and increases muscle mass, strength, and body composition.

Impact of Cardiorespiratory Fitness on Mortality in Black Male Veterans With Resistant Systemic Hypertension.

Patients with resistant systemic hypertension have poorer outcomes than nonresistant hypertensives. The purpose of this study was to evaluate the association between cardiorespiratory fitness and all-cause mortality in black male Veterans with resistant systemic hypertension. Patients were identified from a cohort undergoing exercise tolerance test at the department of Veterans Affairs Medical Center in Washington, DC. Patients were divided into 4 cardiorespiratory fitness categories based on age-specific peak metabolic equivalents achieved on a standard Bruce protocol. Multivariate Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality across all fitness categories. A total of 1,276 patients out of 9,068 hypertensives had resistant hypertension defined as systolic and/or diastolic blood pressure >140 and/or >90 mm Hg, respectively, on 3 antihypertensive medications, one of which was a diuretic or use of >4 antihypertensive medications. During a follow-up of 9.5 ± 4.2 years, an inverse association was observed between cardiorespiratory fitness and all-cause mortality in patients with resistant hypertension. Compared with the least-fit group, mortality was reduced by 21% in the low-fit group (HR 0.79, CI 0.60 to 1.05; p value: 0.280), 36% in the moderate-fit group (HR 0.64, CI 0.48 to 0.87; p value 0.001), and 62% in the high-fit group (HR 0.38, CI 0.25 to 0.56; p value <0.001). In conclusion, an inverse association was observed between the level of cardiorespiratory fitness and all-cause mortality in patients with resistant systemic hypertension. Compared with the least-fit referent group, the high-fit group had a significant 62% lower risk of all-cause mortality.

Prehabilitation for kidney transplant candidates: Is it time?

Many patients become frail with diminished cardiorespiratory fitness while awaiting kidney transplantation. Frailty and poor fitness powerfully predict mortality, transplant graft survival, and healthcare utilization after kidney transplantation. Efforts to intervene with post-transplant physical therapy have been met with limited success, in large part due to high study dropout. We reviewed the literature on chronic kidney disease and exercise to propose a clinical framework for physical therapy interventions to improve fitness, scheduled for before the transplant. This framework may lead to better patient retention and compliance, and thus demonstrate better efficacy in mitigating the effects of frailty and poor fitness after kidney transplantation.

Association Between Exercise Capacity and Late Onset of Dementia, Alzheimer Disease, and Cognitive Impairment.

OBJECTIVE: To address the association between exercise capacity and the onset of dementia, Alzheimer disease, and cognitive impairment. PATIENTS AND METHODS: For 6104 consecutive veteran patients (mean ± SD age: 59.2±11.4 years) referred for treadmill exercise testing, the combined end point of dementia, Alzheimer disease, and cognitive impairment was abstracted from the Veterans Affairs computerized patient record system. RESULTS: After mean ± SD follow-up of 10.3±5.5 years, 353 patients (5.8%) developed the composite end point at a mean ± SD age of 76.7±10.3 years. After correction for confounders in multivariate Cox proportional hazards regression, higher age at exercise testing (hazard ratio [HR]=1.08; 95% CI, 1.07-1.09; P<.001), current smoking (HR=1.44; 95% CI, 1.08-1.93; P=.01), and exercise capacity (HR=0.92; 95% CI, 0.89-0.96; P<.001) emerged as predictors of cognitive impairment. Each 1-metabolic equivalent increase in exercise capacity conferred a nearly 8% reduction in the incidence of cognitive impairment. Meeting the recommendations for daily activity was not associated with a delay in onset of cognitive impairment (HR=1.07; 95% CI, 0.86-1.32; P=.55). CONCLUSION: Exercise capacity is strongly associated with cognitive function; the inverse association between fitness and cognitive impairment provides an additional impetus for health care providers to promote physical activity.

The Impact of Fitness on Surgical Outcomes: The Case for Prehabilitation.

In recent years, a growing body of research has demonstrated that an individual's fitness level is a strong and independent marker of risk for cardiovascular and all-cause mortality. In addition, modest improvements in fitness through exercise intervention have been associated with considerable health outcome benefits. These studies have generally assessed fitness as a baseline marker in traditional epidemiological cohorts. However, there has been a recent recognition that fitness powerfully predicts outcomes associated with a wide range of surgical interventions. The concept of 'prehabilitation' is based on the principle that patients with higher functional capability will better tolerate a surgical intervention, and studies have shown that patients with higher fitness have reduced postoperative complications and demonstrate better functional, psychosocial, and surgery-related outcomes. This review focuses on the impact of fitness on surgical outcomes and provides a rationale in support of routine application of prehabilitation in the management of patients undergoing surgery.

Prediction of peak oxygen pulse (O2Ppeak) without exercise testing in older adults.

Peak oxygen pulse has been considered a surrogate of cardiovascular function and an independent predictor of all cause mortality. However, O2P(peak) depends on maximal volitional effort which may limit its utility in older subjects. The aim of this study was to develop a model to estimate O2P(peak) without exercise in an elderly sample. This cross-sectional study enrolled 67 community-dwelling older adults (69.4±7.1 years; 41 men) for the non-exercise model development and 30 community-dwelling older adults (67.7±6.4 years; n=30; 17 men) for cross-validation. The non-exercise model was derived through hierarchical regression model and cross-validated by means of PRESS statistics and comparison against an independent sample. Classification accuracy of the model for tertiles of estimated and actual O2P(peak) was tested by gamma (γ) nonparametric correlation. The following prediction equation was generated: -3.416+0.137 × weight (kg)+1.226 × Veterans Specific Activity Questionnaire (VSAQ) (metabolic equivalents, METs)+1.987 × gender (0=women, 1=men)-2.045 × ß-Blockers use (0=no, 1=yes)-0.044 × resting heart rate (HR) (R(2)=0.83; standard error of estimate (SEE)=1.68 mL beat(-1)). Correlation in cross-validation group was 0.80 (P<0.001). A high probability was observed for the model to rank the values in the same tertile in validation and cross-validation groups (γ=0.98; γ=0.92, respectively, P<0.05). In conclusion, O2P(peak) can be estimated with reasonable precision without exercise testing, providing an alternative for elder subjects not capable to perform maximal effort.

Heart rate response at the onset of exercise in an apparently healthy cohort.

BACKGROUND: The exercise test is a powerful non-invasive tool for risk stratifying patients with or suspected of having cardiovascular disease (CVD). Heart rate (HR) response during and following exercise has been extensively studied. However, the clinical utility of HR response at the onset of exercise is less understood. Furthermore, conflicting reports exist regarding whether a faster vs. slower HR acceleration represents a CVD risk marker. The primary study purpose was to describe HR acceleration early in exercise in apparently healthy individuals. METHODS: Retrospective analyses were performed in a sample (N = 947) representing a range of age and fitness (11-78 years; VO2peak 17-49 mL kg(-1) min(-1)). HR response was defined over the initial 7 min of the protocol. Associations between HR acceleration and CVD risk factors were also assessed. RESULTS: Mean increases in HR were 18 ± 9 and 23 ± 11 beats at minute one, for men and women, respectively (p < 0.05). After adjusting for gender and pre-exercise HR, only modest associations were observed between the change in HR at minute one and body mass index, resting blood pressure, cigarette smoking, physical activity, HR reserve, and cardiorespiratory fitness. CONCLUSION: There was wide variability in HR acceleration at the onset of exercise in this apparently healthy cohort. A lower increase in HR during the first minute of exercise was associated with a better CVD risk profile, including higher cardiorespiratory fitness, in apparently healthy individuals. These data suggest a greater parasympathetic influence at the onset of exercise may be protective in an asymptomatic population.

The obesity paradox and cardiorespiratory fitness.

Cardiorespiratory fitness as an explanation for the obesity paradox warrants further examination. We evaluated independent and joint associations of cardiorespiratory fitness and adiposity with all-cause mortality in 811 middle-aged (age, 53.3 ± 7.2 years) male never smokers without documented cardiopulmonary disease or diabetes from the Veterans Exercise Testing Study (VETS). Cardiorespiratory fitness was quantified in metabolic equivalents (METs) using final treadmill speed and grade achieved on a maximal exercise test. Subjects were grouped for analysis by METs: unfit (lowest third) and fit (upper two-thirds); and by body mass index (kg/m(2)): nonobese (18.5-29.9) and obese (≥30.0). Associations of baseline fitness and adiposity measures with all-cause mortality were determined by Cox proportional hazards analysis adjusted for age, ethnicity, hypertension, hypercholesterolemia, family history of coronary artery disease, and cardiovascular medication use. In multivariate analysis, mortality risk for obese/fit men did not differ significantly from the nonobese/fit reference group. However, compared to the reference group, nonobese and obese unfit men were 2.2 (P = 0.01) and 1.9 (P = 0.03) times more likely to die, respectively. Cardiorespiratory fitness altered the obesity paradox such that mortality risk was lower for both obese and nonobese men who were fit.

The obesity paradox, cardiorespiratory fitness, and coronary heart disease.

OBJECTIVE: To investigate associations of cardiorespiratory fitness (CRF) and different measures of adiposity with cardiovascular disease (CVD) and all-cause mortality in men with known or suspected coronary heart disease (CHD). PATIENTS AND METHODS: We analyzed data from 9563 men (mean age, 47.4 years) with documented or suspected CHD in the Aerobics Center Longitudinal Study (August 13, 1977, to December 30, 2002) using baseline body mass index (BMI) and CRF (quantified as the duration of a symptom-limited maximal treadmill exercise test). Waist circumference (WC) and percent body fat (BF) were measured using standard procedures. RESULTS: There were 733 deaths (348 of CVD) during a mean follow-up of 13.4 years. After adjustment for age, examination year, and multiple baseline risk factors, men with low fitness had a higher risk of all-cause mortality in the BMI categories of normal weight (hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.24-2.05), obese class I (HR, 1.38; 95% CI, 1.04-1.82), and obese class II/III (HR, 2.43; 95% CI, 1.55-3.80) but not overweight (HR, 1.09; 95% CI, 0.88-1.36) compared with the normal-weight and high-fitness reference group. We observed a similar pattern for WC and percent BF tertiles and for CVD mortality. Among men with high fitness, there were no significant differences in CVD and all-cause mortality risk across BMI, WC, and percent BF categories. CONCLUSION: In men with documented or suspected CHD, CRF greatly modifies the relation of adiposity to mortality. Using adiposity to assess mortality risk in patients with CHD may be misleading unless fitness is considered.

Noninvasive measurement of cardiac performance in recovery from exercise in heart failure patients.

OBJECTIVE: To examine the association between cardiac performance during recovery and the severity of heart failure, as determined by clinical and cardiopulmonary exercise test responses. METHODS: As part of a retrospective cohort study, 46 heart failure patients and 13 normal subjects underwent cardiopulmonary exercise testing while cardiac output was measured using a noninvasive device. Cardiac output in recovery was expressed as the slope of a single exponential relationship between cardiac output and time; the recovery-time constant was assessed in relation to indices of cardiac function, along with clinical, functional, and cardiopulmonary exercise responses. RESULTS: The recovery time constant was delayed in patients with heart failure compared with normal subjects (296.7 ± 238 vs. 110.1 ±27 seconds, p <0.01), and the slope of the decline of cardiac output in recovery was steeper in normal subjects compared with heart failure patients (p<0.001). The slope of the decline in cardiac output recovery was inversely related to peak VO(2) (r = -0.72, p<0.001) and directly related to the VE/VCO(2) slope (r = 0.57, p,0.001). Heart failure patients with abnormal recovery time constants had lower peak VO(2), lower VO(2) at the ventilatory threshold, lower peak cardiac output, and a heightened VE/VCO(2) slope during exercise. CONCLUSIONS: Impaired cardiac output recovery kinetics can identify heart failure patients with more severe disease, lower exercise capacity, and inefficient ventilation. Estimating cardiac output in recovery from exercise may provide added insight into the cardiovascular status of patients with heart failure.

Noninvasive measurement of cardiac performance in recovery from exercise in heart failure patients

OBJECTIVE: To examine the association between cardiac performance during recovery and the severity of heart failure, as determined by clinical and cardiopulmonary exercise test responses. METHODS: As part of a retrospective cohort study, 46 heart failure patients and 13 normal subjects underwent cardiopulmonary exercise testing while cardiac output was measured using a noninvasive device. Cardiac output in recovery was expressed as the slope of a single exponential relationship between cardiac output and time; the recovery-time constant was assessed in relation to indices of cardiac function, along with clinical, functional, and cardiopulmonary exercise responses. RESULTS: The recovery time constant was delayed in patients with heart failure compared with normal subjects (296.7 + 238 vs. 110.1 +27 seconds, p <0.01), and the slope of the decline of cardiac output in recovery was steeper in normal subjects compared with heart failure patients (p,0.001). The slope of the decline in cardiac output recovery was inversely related to peak VO2 (r = -0.72, p<0.001) and directly related to the VE/VCO2 slope (r = 0.57, p,0.001). Heart failure patients with abnormal recovery time constants had lower peak VO2, lower VO2 at the ventilatory threshold, lower peak cardiac output, and a heightened VE/VCO2 slope during exercise. CONCLUSIONS: Impaired cardiac output recovery kinetics can identify heart failure patients with more severe disease, lower exercise capacity, and inefficient ventilation. Estimating cardiac output in recovery from exercise may provide added insight into the cardiovascular status of patients with heart failure.

The utility of cardiopulmonary exercise testing to detect and track early-stage ischemic heart disease.

Evidence demonstrating the potential value of noninvasive cardiopulmonary exercise testing (CPET) to accurately detect exercise-induced myocardial ischemia is emerging. This case-based concept report describes CPET abnormalities in an asymptomatic at-risk man with suspected early-stage ischemic heart disease. When CPET was repeated 1 year after baseline assessment, his cardiovascular function had worsened, and an anti-atherosclerotic regimen was initiated. When the patient was retested after 3.3 years, the diminished left ventricular function had reversed with pharmacotherapy directed at decreasing cardiovascular events in patients with coronary artery disease. Thus, in addition to identifying appropriate patients in need of escalating therapy for atherosclerosis, CPET was useful in monitoring progression and reversal of abnormalities of the coronary circulation in a safe and cost-effective manner without the use of radiation. Serial CPET parameters may be useful to track changes marking the progression and/or regression of the underlying global ischemic burden.

Effects of exercise training in patients with abdominal aortic aneurysm: preliminary results from a randomized trial.

OBJECTIVE: No effective medical therapy exists for early abdominal aortic aneurysm (AAA) disease. Lower extremity exercise improves aortic hemodynamics and reduces inflammation, but the safety and efficacy of exercise training in AAA disease is unknown. As an interim analysis of our prospective, randomized, longitudinal trial of exercise for AAA suppression, we investigated whether subjects with early disease could safely achieve target metabolic and hemodynamic goals. METHODS: One hundred eight participants were randomized to exercise training (EX) or usual care (UC). EX subjects participated in a combination of in-house and home exercise training, with efforts directed toward moderate daily exercise participation. Comparisons were made between EX and UC subjects who completed 1 year of follow-up (n = 26 and 31, respectively, mean age 72 ± 8 years). EX and UC groups were compared for safety, cardiopulmonary exercise test responses, weekly energy expenditure, and biometric indices. RESULTS: No paradoxical increase in AAA growth rate or adverse clinical events occurred as a consequence of exercise training. EX participants expended an average of 2269 ± 1207 kcal/wk and increased exercise capacity (42% increase in treadmill time, 24% increase in estimated metabolic equivalents, P = .01 and .08 between groups, respectively). EX participants demonstrated a significant reduction in C-reactive protein and tended to reduce waist circumference and waist-to-hip ratio (P = .06 and .07, respectively). CONCLUSIONS: Preliminary analyses suggest that exercise training is well tolerated and sustainable in small AAA subjects over 1 year. Despite age and comorbidities, exercising AAA subjects achieve meaningful exercise targets and significantly modify activity-dependent variables.

Obesity paradox and cardiorespiratory fitness in 12,417 male veterans aged 40 to 70 years.

OBJECTIVE: To evaluate the influence of cardiorespiratory fitness (fitness) on the obesity paradox in middle-aged men with known or suspected coronary artery disease. PATIENTS AND METHODS: This study consists of 12,417 men aged 40 to 70 years (44% African American) who were referred for exercise testing at the Veterans Affairs Medical Centers in Washington, DC, or Palo Alto, CA (between January 1, 1983, and June 30, 2007). Fitness was quantified as metabolic equivalents achieved during a maximal exercise test and was categorized for analysis as low, moderate, and high (defined as <5, 5-10, and >10 metabolic equivalents, respectively). Adiposity was defined by body mass index (BMI) according to standard clinical guidelines. Separate and combined associations of fitness and adiposity with all-cause mortality were assessed by Cox proportional hazards analyses. RESULTS: We recorded 2801 deaths during a mean+/-SD follow-up of 7.7+/-5.3 years. Multivariate hazard ratios (95% confidence interval) for all-cause mortality, with normal weight (BMI, 18.5-24.9 kg/m2) used as the reference group, were 1.9 (1.5-2.3), 0.7 (0.7-0.8), 0.7 (0.6-0.7), and 1.0 (0.8-1.1) for BMIs of less than 18.5, 25.0 to 29.9, 30.0 to 34.9, and 35.0 or more kg/m2, respectively. Compared with highly fit normal-weight men, underweight men with low fitness had the highest (4.5 [3.1-6.6]) and highly fit overweight men the lowest (0.4 [0.3-0.6]) mortality risk of any subgroup. Overweight and obese men with moderate fitness had mortality rates similar to those of the highly fit normal-weight reference group. CONCLUSION: Fitness altered the obesity paradox. Overweight and obese men had increased longevity only if they registered high fitness.

The joint effects of cardiorespiratory fitness and adiposity on mortality risk in men with hypertension.

BACKGROUND: Whether higher cardiorespiratory fitness (CRF) attenuates the mortality risk associated with higher adiposity in adults with hypertension (HTN) is poorly understood. METHODS: Participants were 13,155 men (mean age, 47.7 (s.d., 9.9) years) who completed a baseline health examination and maximal treadmill exercise test during 1974-2003. All men had HTN at baseline based on resting systolic blood pressure of > or =140 mm Hg or diastolic blood pressure > or =90 mm Hg. CRF was quantified as the duration of a symptom-limited maximal treadmill exercise test, and was grouped for analysis as low (lowest 20%), moderate (middle 40%), and high (upper 40%). Distributions of body mass index (BMI), waist circumference (WC), and percent body fat (%BF) were grouped according to standard clinical guidelines. RESULTS: During a mean follow-up of 12 years, 883 deaths (355 cardiovascular disease (CVD)) were recorded. Multivariate hazard ratios (HRs) (95% confidence interval) for all-cause mortality, using low-fitness as the reference group, were 0.58 (0.48-0.69) and 0.43 (0.35-0.54) for moderate-fit and high-fit groups, respectively. We observed a similar pattern for CVD mortality. High-fit/obese men had no greater risk of all-cause (1.59 (0.95-2.67)) or CVD (1.23 (0.44-3.41)) death, high-fit/abdominal-obese men had no greater risk for all-cause (1.20 (0.80-1.78)) or CVD (0.62 (0.25-1.53)) death, and high-fit/percent body fat (%BF)-obese men had no greater risk for all-cause (1.19 (0.90-1.56)) or CVD (0.86 (0.52-1.43)) death compared with their high-fit/normal counterparts. CONCLUSIONS: Fitness is a powerful effect modifier in the association of adiposity to mortality in men with HTN, negating the all-cause and CVD mortality risk associated with obesity.

Characterizing differences in mortality at the low end of the fitness spectrum.

PURPOSE: A graded nonlinear relationship exists between fitness and mortality with the most remarkable difference in mortality rates observed between the least-fit (first, Q1) and the next-least-fit (second, Q2) quintile of fitness. The purpose of this study was to compare clinical characteristics, exercise test responses, and physical activity patterns in Q1 versus Q2 in apparently healthy individuals. METHODS: A total of 4384 subjects referred for clinical treadmill testing from 1986 to 2006 were followed for a mean +/- SD period of 8.7 +/- 5.3 yr. All subjects had normal exercise ECG responses and no history of cardiovascular disease. Subjects were classified into quintiles of exercise capacity measured in METs. Clinical characteristics, physical activity patterns, and treadmill test results were compared between the first two quintiles (Q1: METs <5.9 (n = 693); Q2: METs 6.0-7.9 (n = 842)). RESULTS: Small differences in age (64 +/- 11 vs 60 +/- 10 yr, P < 0.001), use of antihypertensive medications, prevalence of diabetes (21% vs 16%, P = 0.02), and dyslipidemia (43% vs 49%, P = 0.04) were observed between Q1 and Q2. When the Cox proportional hazards model was adjusted for age and other clinical characteristics, the relative risk of mortality remained almost two times greater in Q1 versus Q2 (cardiovascular mortality: HR: 4.01 vs 2.01, P < 0.001; reference group: fittest subjects (Q5)). In a subset of 802 subjects, recent recreational physical activity was significantly lower in Q1 versus Q2. CONCLUSIONS: Reduced physical activity patterns rather than differences in clinical characteristics contribute to the striking difference in mortality rates between the least-fit and the next-least-fit quintile of fitness in healthy individuals.

Exercise dose-response of the V(E)/VCO(2) slope in postmenopausal women in the DREW study.

PURPOSE: Being overweight/obese, having hypertension, and being postmenopausal are risk factors for the development of congestive heart failure (CHF). A characteristic of CHF is an abnormal V(E)/VCO(2) slope, which is predictive of mortality in patients with CHF. Although the V(E)/VCO(2) slope is well established in CHF patients, little is known regarding interventions for "at-risk" populations. METHODS: We examined the V(E)/VCO(2) slope in 401 sedentary, overweight, moderately hypertensive women randomized to 6 m of nonexercise (control) or 4 kcal x kg(-1) x wk(-1) (KKW), 8 KKW, or 12 KKW of exercise at an intensity corresponding to 50% of baseline VO(2max). We examined trends in exercise treatment dose versus change in mean V(E)/VCO(2) slope using a linear regression model (KKW vs V(E)/VCO(2) slope) and a linear mixed model. RESULTS: Regression analysis showed a significant trend for a reduction in the V(E)/VCO(2) slope from baseline (mean +/- SD: 32.6 +/- 6.3; P < 0.004). When expressed as mean change (95% confidence interval (CI)) from baseline, we observed significant reductions in the V(E)/VCO(2) slope for the 8-KKW (-1.14; 95% CI, -1.5 to -0.2) and 12-KKW (-1.67; 95% CI, -2.3 to -0.3) groups. No significant effect was noted for the 4-KKW (-0.4; 95% CI, -1.2 to 0.15) group. CONCLUSION: Moderate-intensity aerobic exercise at doses of 8 KKW or greater seems to present an adequate dose of exercise to promote small but significant reductions in the V(E)/VCO(2) slope in postmenopausal women who exhibit risk factors associated with the development of CHF.

Prediction of cardiovascular death using a novel heart rate recovery parameter.

INTRODUCTION: Reassertion of vagal tone after exercise is an important component in mediating heart rate recovery (HRR), and both vagal tone and HRR have been associated with mortality. HRR is strongly related to the increase in HR from resting to peak exercise. We hypothesized that a score normalized for HR increase would better isolate the vagal influences in recovery from the sympathetic influences supporting maximal exercise. METHODS: HRR data from 1959 veterans were analyzed. During a mean follow-up of 5.3 years, 187 (9.5%) subjects died-70 (37%) due to cardiovascular (CV) causes. A method was developed to compare HRR curve shapes normalized for differences in HR increase. Differences in the slopes of the normalized curves over the range 50-70 s were observed between the survivors and nonsurvivors, and a prognostic measurement, HRRS50-70, was developed. The incremental increases in predictive power and discriminative accuracy provided by Duke Treadmill Score (DTS), clinical parameters, HR increase, recovery variables, and HRRS50-70 were assessed. RESULTS: In the age-adjusted Cox analysis, the only significant exercise indices associated with CV mortality were HR increase (P < 0.0001), HRRS50-70 (P = 0.01), and DTS (P < 0.001). The increased risk for patients in the lowest tertile for all three indices, relative to those with normal scores, was 22 (95% CI, 7.9-63; P < 0.0001). CONCLUSIONS: HRRS50-70 is independent of and complementary to HR increase and DTS. Patients with abnormal HRRS50-70 and abnormal DTS and/or HR increase are at substantially increased risk of CV mortality.

Exercise capacity and body mass as predictors of mortality among male veterans with type 2 diabetes.

OBJECTIVE: To demonstrate the relation of exercise capacity and BMI to mortality in a population of male veterans with type 2 diabetes. RESEARCH DESIGN AND METHODS: After excluding two underweight patients (BMI <18.5 kg/m2), the study population comprised 831 consecutive patients with type 2 diabetes (mean age 61 +/- 9 years) referred for exercise testing for clinical reasons between 1995 and 2006. Exercise capacity was determined from a maximal exercise test and measured in metabolic equivalents (METs). Patients were classified both according to BMI category (18.5-24.9, 25.0-29.9, and > or =30 kg/m2) and by exercise capacity (<5.0 or > or =5.0 maximal METs). The association among exercise capacity, BMI, other clinical variables, and all-cause mortality was assessed by Cox proportional hazards. Study participants were followed for mortality up to 30 June 2006. RESULTS: During a mean follow-up of 4.8 +/- 3.0 years, 112 patients died, for an average annual mortality rate of 2.2%. Each 1-MET increase in exercise capacity conferred a 10% survival benefit (hazard ratio 0.90 [95% CI 0.82-0.98]; P = 0.01), but BMI was not significantly associated with mortality. After adjustment for age, ethnicity, examination year, BMI, presence of cardiovascular disease (CVD), and CVD risk factors, diabetic patients achieving <5 maximal METs were 70% more likely to die (1.70 [1.13-2.54]) than those achieving > or =5 maximal METs. CONCLUSIONS: There was a strong inverse association between exercise capacity and mortality in this cohort of men with documented diabetes, and this relationship was independent of BMI.