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Usefulness of C-Reactive Protein and Interleukin-6 as Predictors of Outcomes in Patients With Chronic Obstructive Pulmonary Disease Receiving Pravastatin

https://doi.org/10.1016/j.amjcard.2007.09.102Get rights and content

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.

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Methods

Patients with COPD in stable condition for ≥3 months, 40 to 80 years of age, and regardless of gender were consecutively recruited into the study. Criteria for diagnosis of COPD was based on standards of the American Thoracic Society6 with forced expiratory volume in 1 second (FEV1) <80% of predicted values and FEV1/forced vital capacity ratio <70%. None had acute exacerbations of COPD, any active infection, or renal disease (serum creatinine concentration ≥1.5 mg/dl or 133 μmol/L) for ≥3

Results

Of the 125 patients enrolled in this study, 18 patients had incomplete data at the end of the study (Figure 1).Table 1 presents baseline and demographic characteristics of patients in each group. Pravastatin was very well tolerated by all patients and none had any significant subjective side effects. Patient compliance with treatment was confirmed by significant effects on blood lipids (Table 2). The drug number of standard therapy for COPD was similar in the 2 groups.

Compared with the placebo

Discussion

Our results demonstrated for the first time that changes in hs-CRP over time and baseline hs-CRP are associated with corresponding changes in exercise tolerance associated with statin therapy. Improvement of exercise tolerance was greater in those with a greater decrease of hs-CRP levels and higher baseline CRP levels, an effect regardless of cholesterol level achieved. This is the first randomized controlled trial to demonstrate that treatment for 6 months with pravastatin caused a significant

Acknowledgment

A special acknowledgment is given to the participants for their cooperation and commitment to the trial.

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This work was supported by Grants CMFHT 9501, CMFHR9502, CMFHR9503, and CM-TMU9601 from the Chi-Mei Medical Center, Tainan, Taiwan; and by Grant NSC 95-2314-B-384-009 from the National Science Council, Taiwan, Republic of China. Pravastatin was in part a generous gift from Sankyo Company, Ltd., Tokyo, Japan.

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