High-sensitivity C-reactive protein (hsCRP) is promoted as an independent predictor of atherosclerotic risk. In addition, cardiorespiratory fitness is inversely related to hsCRP in single-sex cross-sectional analyses. Our objective was to determine if modulating fitness with exercise training imposes changes in high-sensitivity C-reactive protein in a mixed-sex population at risk for cardiovascular disease.

We studied baseline and postintervention plasma hsCRP in 193 sedentary, overweight to mildly obese, dyslipidemic men and women who were randomized to 6 months of inactivity or 1 of 3 aerobic exercise groups: low amount–moderate intensity (energy equivalent of approximately 19.3 km/wk at 40%-55% peak V˙o₂), low amount–high intensity (energy equivalent of approximately 19.3 km/wk at 65%-80% peak V˙o₂), or high amount–high intensity (energy equivalent of approximately 32.2 km/wk at 65%-80% peak V˙o₂).

At baseline, the study population was at intermediate to high cardiovascular risk as defined by hsCRP. Cardiorespiratory fitness was inversely related to hsCRP (P < .001) even after adjusting for significant and expected sex differences. Fitness, hormone replacement therapy use, and high-density lipoprotein cholesterol accounted for the sex difference in baseline hsCRP. Fitness, high-density lipoprotein cholesterol, fasting insulin, hormone replacement therapy, and visceral adiposity were all independent predictors for baseline hsCRP (r² = 0.34 for the entire model, P < .0001). However, despite significant improvements in fitness, visceral adiposity, subcutaneous adiposity, and insulin sensitivity, hsCRP did not change in response to exercise training (P > .20).

Cardiorespiratory fitness is inversely related to hsCRP independent of sex and accounts for most of the large sex disparity in hsCRP. Nonetheless, in the absence of a significant change in diet, 6 months of aerobic exercise training does not produce a significant change in hsCRP in an at-risk population.