Ricardo B. Oliveira

AGE-RELATED DECLINE IN HANDGRIP STRENGTH DIFFERS ACCORDING TO GENDER

It is well-established that at old age there is a significant decline in muscle strength. Reference values for muscle strength might be useful for assessment of muscle impairment and of physiological adaptations. However, it is still unclear whether gender affects the rate of decline. Therefore, the aim of this study is to investigate the effect of gender and age on handgrip strength and to establish reference values for this variable. Reviewing medical charts collected from 1994 to 2005, a convenience sample of 2,648 subjects (1,787 men and 861 women), aged between 18 and 90 years, was obtained. Our results show higher handgrip strength for men compared with women (36.8 ± 0.20 vs. 21.0 ± 0.18 kg; p ≤ 0.001). The regression analysis with a quadratic model shows that aging accounts for 30% of the variance in handgrip strength (r2 = 0.30; p ≤ 0.001) in men and 28% (r2 = 0.28; p ≤ 0.001) in women. In addition, the bent linear regression with multiple regressors show that a faster decline in handgrip strength occurs at the age of 30 years for men and 50 years for women. We conclude that handgrip strength decline with age differs between genders, making useful the existence of distinct male and female normative age group data.

Maximal exercise oxygen pulse as a predictor of mortality among male veterans referred for exercise testing

Background Maximal oxygen pulse (O2 pulse) mirrors the stroke volume response to exercise, and should therefore be a strong predictor of mortality. Limited and conflicting data are, however, available on this issue. Methods Nine hundred forty-eight participants, classified as those with cardiopulmonary disease (CPD) and those without (non-CPD), underwent cardiopulmonary exercise testing (CPX) for clinical reasons between 1993 and 2003. The ability of maximal O2 pulse and maximal oxygen uptake (peak VO2) to predict mortality was investigated using proportional hazards and Akaike information criterion analyses. All-cause mortality was the endpoint. Results Over a mean follow-up of 6.3 ± 3.2 years, there were 126 deaths. Maximal O2 pulse, expressed in either absolute or relative to age-predicted terms, and peak VO2 were significant and independent predictors of mortality in those with and without CPD (P < 0.04). Akaike information criterion analysis revealed that the model including both maximal O2 pulse and peak VO2 had the highest accuracy for predicting mortality. The optimal cut-points for O2 pulse and peak VO2 (< 12; ≥ 12 ml/beat and < 16; ≥ 16 ml/(kg · min) respectively) were established by the area under the receiver-operating-characteristic curve. The relative risks of mortality were 3.4 and 2.2 (CPD and non-CPD, respectively) among participants with both maximal O2 pulse and peak VO2 responses below these cut-points compared with participants with both responses above these cut-points. Conclusion These results indicate that maximal O2 pulse is a significant predictor of mortality in patients with and without CPD. The addition of absolute and relative O2 pulse data provides complementary information for risk-stratifying heterogeneous participants referred for CPX and should be routinely included in the CPX report.

The Lowest VE/VCO2 Ratio During Exercise as a Predictor of Outcomes in Patients With Heart Failure

BACKGROUND The lowest minute ventilation (VE) and carbon dioxide production (VCO(2)) ratio during exercise has been suggested to be the most stable and reproducible marker of ventilatory efficiency in patients with heart failure (HF). However, the prognostic power of this index is unknown. METHODS AND RESULTS A total of 847 HF patients underwent cardiopulmonary exercise testing (CPX) and were followed for 3 years. The associations between the lowest VE/VCO(2) ratio, maximal oxygen uptake (peak VO(2)), the VE/VCO(2) slope, and major events (death or transplantation) were evaluated using proportional hazards analysis; adequacy of the predictive models was assessed using Akaike information criterion (AIC) weights. There were 147 major adverse events. In multivariate analysis, the lowest VE/VCO(2) ratio (higher ratio associated with greater risk) was similar to the VE/VCO(2) slope in predicting risk (hazard ratios [HR] per unit increment 2.0, 95% CI 1.1-3.4, and 2.2, 95% CI 1.3-3.7, respectively; P < .01), followed by peak VO(2) (HR 1.6, 95% CI 1.1-2.4, P=.01). Patients exhibiting abnormalities for all 3 responses had an 11.6-fold higher risk. The AIC weight for the 3 variables combined (0.94) was higher than any single response or any combination of 2. The model including all 3 responses remained the most powerful after adjustment for beta-blocker use, type of HF, and after applying different cut points for high risk. CONCLUSIONS The lowest VE/VCO(2) ratio adds to the prognostic power of conventional CPX responses in HF.

Validation of a Cardiopulmonary Exercise Test Score in Heart Failure

Background—Cardiopulmonary exercise test (CPX) responses are strong predictors of outcomes in patients with heart failure. We recently developed a CPX score that integrated the additive prognostic information from CPX. The purpose of this study was to validate the score in a larger, independent sample of patients. Methods and Results—A total of 2625 patients with heart failure underwent CPX and were followed for cardiovascular (CV) mortality and major CV events (death, transplantation, left ventricular assist device implantation). Net reclassification improvement (NRI) for the score and each of its components were determined at 3 years. The VE/VCO2 slope was the strongest predictor of risk and was attributed a relative weight of 7, with weighted scores for abnormal heart rate recovery, oxygen uptake efficiency slope, end-tidal CO2 pressure, and peak VO2 having scores of 5, 3, 3, and 2, respectively. A summed score of >15 was associated with an annual mortality rate of 12.2% and a relative risk >9 for total events, whereas a score of <5 was associated with an annual mortality rate of 1.2%. The composite score was the most accurate predictor of CV events among all CPX responses considered (C indexes, 0.70 for CV mortality and 0.72 for the composite outcome). Each component of the score provided significant NRI compared with peak VO2 (category-free NRI, 0.61–0.77), and the score provided significant NRI above clinical risk factors for both CV events and mortality (NRI, 0.63 and 0.65 for CPX score compared with clinical variables alone). Conclusions—These results validate the application of a simple, integrated multivariable score based on readily available CPX responses.

Long-term stability of the oxygen pulse curve during maximal exercise

INTRODUCTION: Exercise oxygen pulse (O2 pulse), a surrogate for stroke volume and arteriovenous oxygen difference, has emerged as an important variable obtained during cardiopulmonary exercise testing. OBJECTIVES: We hypothesized that the O2 pulse curve pattern response to a maximal cycling ramp protocol exhibits a stable linear pattern in subjects reevaluated under the same clinical conditions. METHODS: We retrospectively studied 100 adults (80 males), mean age at baseline of 59 ± 12 years, who performed two cardiopulmonary exercise testings (median interval was 15 months), for clinical and/or exercise prescription reasons. The relative O2 pulse was calculated by dividing its absolute value by body weight. Subjects were classified into quintiles of relative O2 pulse. Cardiopulmonary exercise testing results and the O2 pulse curve pattern, expressed by its slope and intercept, were compared among quintiles of relative O2 pulse at both cardiopulmonary exercise testings. RESULTS: After excluding the first minute of CPX (rest-exercise transition), the relative O2 pulse curve exhibited a linear increase, as demonstrated by high coefficients of determination (R2 from 0.75 to 0.90; p<0.05 for all quintiles). Even though maximum oxygen uptake and relative O2 pulse were significantly higher in the second cardiopulmonary exercise testing for each quintile of relative O2 pulse (p<0.05 for all comparisons), no differences were found when slopes and intercepts were compared between the first and second cardiopulmonary exercise testings (p>0.05 for all comparisons; except for intercept in the 5th quintile). CONCLUSION: Excluding the rest-exercise transition, the relative O2 pulse exhibited a stable linear increase throughout maximal exercise in adults that were retested under same clinical conditions.

Cardiorespiratory fitness and mortality in diabetic men with and without cardiovascular disease

We assessed joint associations of cardiorespiratory fitness and diabetes, cardiovascular disease (CVD), or both with all-cause mortality. High-fitness eliminated mortality risk in diabetes (P<0.001) and halved risk of death in diabetes/CVD (P<0.001). Fitness was a potent effect modifier in the association of diabetes and CVD to mortality.

Effects of High Intensity Interval versus Moderate Continuous Training on Markers of Ventilatory and Cardiac Efficiency in Coronary Heart Disease Patients

Background. We tested the hypothesis that high intensity interval training (HIIT) would be more effective than moderate intensity continuous training (MIT) to improve newly emerged markers of cardiorespiratory fitness in coronary heart disease (CHD) patients, as the relationship between ventilation and carbon dioxide production (VE/VCO2 slope), oxygen uptake efficiency slope (OUES), and oxygen pulse (O2P). Methods. Seventy-one patients with optimized treatment were randomly assigned into HIIT (n = 23, age = 56 ± 12 years), MIT (n = 24, age = 62 ± 12 years), or nonexercise control group (CG) (n = 24, age = 64 ± 12 years). MIT performed 30 min of continuous aerobic exercise at 70–75% of maximal heart rate (HRmax), and HIIT performed 30 min sessions split in 2 min alternate bouts at 60%/90% HRmax (3 times/week for 16 weeks). Results. No differences among groups (before versus after) were found for VE/VCO2 slope or OUES (P > 0.05). After training the O2P slope increased in HIIT (22%, P < 0.05) but not in MIT (2%, P > 0.05), while decreased in CG (−20%, P < 0.05) becoming lower versus HIIT (P = 0.03). Conclusion. HIIT was more effective than MIT for improving O2P slope in CHD patients, while VE/VCO2 slope and OUES were similarly improved by aerobic training regimens versus controls.

Characterizing differences in mortality at the low end of the fitness spectrum in individuals with cardiovascular disease.

Background A graded but nonlinear relationship exists between fitness and mortality, with the greatest mortality differences occurring between the least-fit (first, Q1) and the next-least-fit (second, Q2) quintiles of fitness. The purpose of this study was to compare clinical characteristics, exercise test responses, and physical activity (PA) patterns in Q1 versus Q2 in patients with cardiovascular disease (CVD). Design Observational retrospective study. Methods A total of 5101 patients with a history of CVD underwent clinical treadmill testing and were followed up for 9.1 ± 5.5 years. Patients were classified into quintiles of exercise capacity measured in metabolic equivalents. Clinical characteristics, treadmill test results, and recreational PA patterns were compared between Q1 (n = 923) and Q2 (n = 929). Results Q1 had a nearly two-fold increase in age-adjusted relative risk of cardiovascular mortality compared with Q2 (hazard ratio: 3.79 vs. 2.04, P < 0.05; reference: fittest quintile). Q1 patients were older, had more extensive use of medications, and were more likely to have a history of typical angina (35 vs. 28%), myocardial infarction (30 vs. 24%), chronic heart failure (25 vs. 14%), claudication (15 vs. 9%) and stroke (9 vs. 6%) compared with Q2 (all comparisons: P < 0.05). Recent and lifetime recreational PA was not different between the two groups. Conclusion Greater severity of disease in the least-fit versus the next-least-fit quintile likely contributes to but cannot fully explain marked differences in mortality rates in CVD patients. To achieve potential survival benefits, our results suggest that unfit CVD patients should engage in exercise programs of sufficient volume and intensity to improve fitness. Eur J Cardiovasc Prev Rehabil 17:289-295

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.

Patients With Heart Failure in the "Intermediate Range" of Peak Oxygen Uptake: ADDITIVE VALUE OF HEART RATE RECOVERY AND THE MINUTE VENTILATION/CARBON DIOXIDE OUTPUT SLOPE IN PREDICTING MORTALITY.

PURPOSE: While patients with heart failure who achieve a peak oxygen uptake (peak O2) of 10 mL·kg−1·min−1 or less are often considered for intensive surveillance or intervention, those achieving 14 mL·kg−1·min−1 or more are generally considered to be at lower risk. Among patients in the “intermediate” range of 10.1 to 13.9 mL·kg−1·min−1, optimally stratifying risk remains a challenge. METHODS: Patients with heart failure (N = 1167) referred for cardiopulmonary exercise testing were observed for 21 ± 13 months. Patients were classified into 3 groups of peak o2 (⩽10, 10.1–13.9, and ≥14 mL·kg−1·min−1). The ability of heart rate recovery at 1 minute (HRR1) and the minute ventilation/carbon dioxide output ( E/ co2) slope to complement peak o2 in predicting cardiovascular mortality were determined. RESULTS: Peak o2, HRR1 (<16 beats per minute), and the E/ co2 slope (>34) were independent predictors of mortality (hazard ratio 1.6, 95% CI: 1.2–2.29, P = .006; hazard ratio 1.7, 95% CI: 1.1–2.5, P = .008; and hazard ratio 2.4, 95% CI: 1.6–3.4, P < .001, respectively). Compared with those achieving a peak o2 ≥ 14 mL·kg−1·min−1, patients within the intermediate range with either an abnormal E/ co2 slope or HRR1 had a nearly 2-fold higher risk of cardiac mortality. Those with both an abnormal HRR1 and E/ co2 slope had a higher mortality risk than those with a peak o2 ⩽ 10 mL·kg−1·min−1. Survival was not different between those with a peak o2 ⩽ 10 mL·kg−1·min−1 and those in the intermediate range with either an abnormal HRR1 or E/ co2 slope. CONCLUSIONS: HRR1 and the E/ co2 slope effectively stratify patients with peak o2 within the intermediate range into distinct groups at high and low risk.