The inverse association between cardiorespiratory fitness (CRF) and mortality has been well
established and is independent of age,1-3 sex,4-6 race/ethnicity,7,8 and comorbidities.9-13 Increased
CRF is also associated with numerous cardiovascular and noncardiovascular benefits, including
reductions in coronary artery disease (CAD),14 hypertension,15 diabetes,16 stroke,17 and cancer.18

However, recent observational studies19-22 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. Although 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 al24 suggested a
plateau effect of increasing physical activity volume. Other studies25,26 of self-reported jogging
habits have revealed a dose-response plateau or even harm associated with the most strenuous
jogging habits. However, studies27 linking physical activity levels with outcomes have relied on selfreported
data and/or questionnaires; therefore, the inferences drawn from these studies are
compromised by the limitations of recollection bias.