Usefulness of C-reactive protein and interleukin-6 as predictors of outcomes in patients with chronic obstructive pulmonary disease receiving pravastatin.

Inflammation is increased in chronic obstructive pulmonary disease (COPD) and plays a role in exercise intolerance. We investigated whether pravastatin administration is effective in improving exercise capacity in patients with COPD, and whether baseline or serial changes in high-sensitivity C-reactive protein (hs-CRP) over time are associated with corresponding changes in exercise capacity. In a randomized, double-blinded, and parallel design, 125 patients with clinically stable COPD were randomly assigned to receive placebo or pravastatin (40 mg/day) over a period of 6 months. Plasma hs-CRP levels were measured before randomization and during follow-up. Baseline characteristics were similar in the 2 groups. Exercise time remained stable throughout the study in the placebo group. Exercise time increased by 54% from 599 +/- 323 seconds at baseline to 922 +/- 328 seconds at the end (p <0.0001) in pravastatin-treated patients. A decrease in hs-CRP over baseline values was observed in 79% of patients (42 of 53) treated with pravastatin. Pravastatin-treated patients with a greater percent decrease in hs-CRP had a significant improvement in exercise time compared with those without hs-CRP decrease. A significant correlation was found in univariate analysis between decrease of log-transformed hs-CRP and increase of exercise time. Baseline hs-CRP and change of hs-CRP were significantly correlated with exercise time, even after adjustment for lipid profiles and hemodynamics. In conclusion, these data reinforce hs-CRP as a significant surrogate marker in COPD and underscore an important guide to the efficacy of treatment in COPD trials.