Statin treatment reduces protein carbonylation in patients with COPD: A randomized controlled study.

Abstract

Introduction: Protein carbonyl (PC) content, a stable marker of oxidative stress, is increased in chronic obstructive pulmonary disease (COPD) and shows association with cardiovascular events. We investigated prothrombotic effects of increased PC content and its modulation by statin use in COPD.

Materials and methods: We studied 56 patients with stable COPD, who were randomly assigned in an open-label manner to receive simvastatin 40 mg/day (n = 28) or to remain without statin for 3 months (n = 28). Plasma PC levels, along with thrombin generation, fibrin polymerization, clot permeability (K_s), compaction and global fibrinolysis (t50%) were assessed at baseline, at 1 and 3 months.

Results: PC concentration was 4.01 (min 2.20, max 5.43) nM/mg protein and correlated with age (r =.34, p =.0093) and C-reactive protein (CRP) (r =.43, p =.0009). PC was inversely associated with maximum clot absorbance (r = -.27, p =.046) and K_s (r = -.44, p =.0008), but not fibrinolysis or thrombin generation. On statin, PC concentration decreased by 15% after 1 month and by 33% after 3 months compared to baseline, leading to 28.5% lower levels than in controls (p =.0003), with no association with low-density lipoprotein cholesterol or CRP. At 3 months PC showed associations with favourably modified on-treatment K_s (r = -.51, p =.005) and t50% (r =.53, p =.004), but not with lipid profile or inflammation.

Conclusions: This study shows that 3-month simvastatin therapy in COPD patients results in about 30% decrease in PC concentrations, at least in part associated with favourable changes in fibrin clot parameters.