Cardiovascular and inflammatory effects of simvastatin therapy in patients with COPD: a randomized controlled trial

Abstract

Michelle E John,1 John R Cockcroft,2 Tricia M McKeever,3 William R Coward,1 Dennis J Shale,2 Simon R Johnson,1 Jim G Thornton,4 Timothy W Harrison,1 Alan J Knox,1 Charlotte E Bolton1 1Nottingham Respiratory Research Unit, School of Medicine, University of Nottingham, Nottingham, UK; 2Wales Heart Research Institute, Cardiff University, Cardiff, UK; 3Division of Epidemiology and Public Health, 4Clinical Trials Unit and Department of Obstetrics and Gynaecology, School of Medicine, University of Nottingham, Nottingham, UK Background: There is excess cardiovascular mortality in patients with chronic obstructive pulmonary disease. Aortic stiffness, an independent predictor of cardiovascular risk, and systemic and airway inflammation are increased in patients with the disease. Statins modulate aortic stiffness and have anti-inflammatory properties. A proof-of-principle, double-blind, randomized trial determined if 6 weeks of simvastatin 20 mg once daily reduced aortic stiffness and systemic and airway inflammation in patients with chronic obstructive pulmonary disease.Methods: Stable patients (n=70) were randomized to simvastatin (active) or placebo. Pre-treatment and post-treatment aortic stiffness, blood pressure, spirometry, and circulating and airway inflammatory mediators and lipids were measured. A predefined subgroup analysis was performed where baseline aortic pulse wave velocity (PWV) was >10 m/sec.Results: Total cholesterol dropped in the active group. There was no significant change in aortic PWV between the active group and the placebo group (-0.7 m/sec, P=0.24). In those with aortic stiffness >10 m/sec (n=22), aortic PWV improved in the active group compared with the placebo group (-2.8 m/sec, P=0.03). Neither systemic nor airway inflammatory markers changed. Conclusion: There was a nonsignificant improvement in aortic PWV in those taking simvastatin 20 mg compared with placebo, but in those with higher baseline aortic stiffness (a higher risk group) a significant and clinically relevant reduction in PWV was shown. Keywords: chronic obstructive pulmonary disease, arterial stiffness, statins