Cardiorespiratory Fitness Is an Independent Predictor of Cardiovascular Morbidity and Mortality and Improves Accuracy of Prediction Models

Background: Although cardiorespiratory fitness (CRF) is a strong independent predictor of adverse cardiovascular outcomes, it is not considered as a risk enhancer by current guidelines. Methods: We evaluated asymptomatic self-referred adults aged 40 to 79 years of age, free of cardiovascular disease at baseline, who were screened annually and completed baseline exercise stress test. Baseline CRF was dichotomized into 2 groups: low (metabolic equivalents < 8) and high. The primary endpoint was the composite of death, nonfatal acute coronary syndrome, and stroke after excluding subjects diagnosed with metastatic cancer during follow-up. Results: Study population included 15,445 subjects with median age of 49 years (interquartile range: 44-55). During median follow-up of 8 years 1362 (9%) subjects developed the study endpoint. Kaplan-Meier survival analysis showed that both fitness and atherosclerotic cardiovascular disease (ASCVD) were associated with developing of the study endpoint (P < 0.001 for both). Cox regression model with adjustment for ASCVD risk consistently showed that lower fitness was associated with a significant 23% higher risk to develop the study endpoint (P = 0.001). Continuous net reclassification improvement analysis showed an overall improvement of 11.4% (95% confidence interval, 8%-14.6%; P value < 0.001) in the accuracy of classification when fitness was added to the ASCVD model. Conclusions: Low CRF is a strong independent predictor of the cardiovascular morbidity and mortality in asymptomatic adults. Addition of fitness to the pooled cohort ASCVD risk significantly improves the accuracy of the model.