Abstract
Adverse cardiovascular findings associated with habitual vigorous exercise have raised new questions regarding the benefits of exercise and fitness. To assess the association of all-cause mortality and cardiorespiratory fitness in patients undergoing exercise treadmill testing. This retrospective cohort study enrolled patients at a tertiary care academic medical center from January 1, 1991, to December 31, 2014, with a median follow-up of 8.4 years. Data analysis was performed from April 19 to July 17, 2018. Consecutive adult patients referred for symptom-limited exercise treadmill testing were stratified by age- and sex-matched cardiorespiratory fitness into performance groups: low (<25th percentile), below average (25th-49th percentile), above average (50th-74th percentile), high (75th-97.6th percentile), and elite (≥97.7th percentile). Cardiorespiratory fitness, as quantified by peak estimated metabolic equivalents on treadmill testing. All-cause mortality. The study population included 122 007 patients (mean [SD] age, 53.4 [12.6] years; 72 173 [59.2%] male). Death occurred in 13 637 patients during 1.1 million person-years of observation. Risk-adjusted all-cause mortality was inversely proportional to cardiorespiratory fitness and was lowest in elite performers (elite vs low: adjusted hazard ratio [HR], 0.20; 95% CI, 0.16-0.24; P < .001; elite vs high: adjusted HR, 0.77; 95% CI, 0.63-0.95; P = .02). The increase in all-cause mortality associated with reduced cardiorespiratory fitness (low vs elite: adjusted HR, 5.04; 95% CI, 4.10-6.20; P < .001; below average vs above average: adjusted HR, 1.41; 95% CI, 1.34-1.49; P < .001) was comparable to or greater than traditional clinical risk factors (coronary artery disease: adjusted HR, 1.29; 95% CI, 1.24-1.35; P < .001; smoking: adjusted HR, 1.41; 95% CI, 1.36-1.46; P < .001; diabetes: adjusted HR, 1.40; 95% CI, 1.34-1.46; P < .001). In subgroup analysis, the benefit of elite over high performance was present in patients 70 years or older (adjusted HR, 0.71; 95% CI, 0.52-0.98; P = .04) and patients with hypertension (adjusted HR, 0.70; 95% CI, 0.50-0.99; P = .05). Extreme cardiorespiratory fitness (≥2 SDs above the mean for age and sex) was associated with the lowest risk-adjusted all-cause mortality compared with all other performance groups. Cardiorespiratory fitness is inversely associated with long-term mortality with no observed upper limit of benefit. Extremely high aerobic fitness was associated with the greatest survival and was associated with benefit in older patients and those with hypertension. Cardiorespiratory fitness is a modifiable indicator of long-term mortality, and health care professionals should encourage patients to achieve and maintain high levels of fitness.
Highlights
Riskadjusted all-cause mortality was inversely proportional to cardiorespiratory fitness and was lowest in elite performers
The increase in all-cause mortality associated with reduced cardiorespiratory fitness was comparable to or greater than traditional clinical risk factors
The benefit of elite over high performance was present in patients 70 years or older and patients with hypertension
Summary
The inverse association between cardiorespiratory fitness (CRF) and mortality has been well established and is independent of age,[1,2,3] sex,[4,5,6] race/ethnicity,[7,8] and comorbidities.[9,10,11,12,13] Increased CRF is associated with numerous cardiovascular and noncardiovascular benefits, including reductions in coronary artery disease (CAD),[14] hypertension,[15] diabetes,[16] stroke,[17] and cancer.[18]recent observational studies[19,20,21,22] have described adverse cardiovascular findings associated with habitual vigorous exercise and have raised new questions regarding the benefits of exercise and fitness. The hemodynamic stress of habitual vigorous exercise produces cardiovascular adaptations, including increases in cardiac chamber volumes, a balanced increase in left ventricular mass, and alterations in autonomic tone These adaptations are usually thought of as physiologic and reversible, newer evidence has suggested associations between habitual vigorous exercise and potentially pathologic cardiovascular findings, including atrial fibrillation,[19] coronary artery calcification,[20] myocardial fibrosis,[21] and aortic dilation.[22] These findings have led some to propose a U-shaped dose-response association between exercise and cardiovascular events.[23] In terms of mortality, a large pooled-cohort analysis of physical activity by Arem et al[24] suggested a plateau effect of increasing physical activity volume. Studies[27] linking physical activity levels with outcomes have relied on selfreported data and/or questionnaires; the inferences drawn from these studies are compromised by the limitations of recollection bias
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