Cardiorespiratory Fitness and Atherosclerotic Cardiovascular Outcomes by Levels of Baseline-Predicted Cardiovascular Risk: The Look AHEAD Study

Background: We evaluated the associations of cardiorespiratory fitness with atherosclerotic cardiovascular disease (ASCVD) by levels of baseline-predicted ASCVD risk among adults with type 2 diabetes. Methods: We analyzed data from 4203 adults with type 2 diabetes in the Look AHEAD (Action for Health in Diabetes) study. Cardiorespiratory fitness was assessed using maximal exercise testing and categorized into low, moderate, and high; baseline-predicted. ASCVD risk was calculated using the American College of Cardiology/American Heart Association Pooled Cohort Equation. We used Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for ASCVD events (fatal and nonfatal myocardial infarction and stroke). Results: Over a median of 9.6 years, there were 295 ASCVD events. The effect of fitness on outcomes was different across levels of 10-year predicted ASCVD risk (P for interaction <.001). Among participants with a baseline-predicted risk of 7.5% to 20%, the HR of low (vs high) fitness group was 1.94 (95% CI, 1.12-3.35) for ASCVD events. Fitness was not significantly associated with ASCVD events in the groups with baseline-predicted risk <7.5% (HR 1.53; 95% CI, 0.49-4.76) or ≥20% (HR 1.40; 95% CI, 0.88-2.24). A similar pattern was observed for myocardial infarction and stroke separately. Conclusions: In a large sample of type 2 diabetes individuals, the association of low fitness with incident ASCVD was modified by the baseline-predicted 10-year ASCVD risk. Our findings suggest the utility of assessing fitness in ASCVD risk stratification in type 2 diabetes, especially among those with intermediate predicted 10-year risk of ASCVD.