Endothelium-ameliorating effects of statin therapy and coenzyme Q10 reductions in chronic heart failure

Although not currently indicated for chronic heart failure (CHF), statins have been associated with improved outcome in retrospective analysis. However, statin therapy reduces plasma levels of coenzyme Q(10) (ubiquinone), which may have adverse effects on heart failure states. We hypothesized that atorvastatin treatment improves endothelial function in patients with chronic heart failure independent of LDL-cholesterol alterations. Furthermore, we assessed how reductions in coenzyme Q10 levels impact on potentially improved endothelial function. Twenty-four patients with stable, symptomatic heart failure (New York Heart Association Class 11 or III) and a left ventricular ejection fraction < 40% were randomised to 40 mg atorvastatin or placebo for 6 weeks and crossed over to the other treatment arm for a further 6 weeks, after a 2-week wash out. Forearm resistance vessel function was assessed by venous occlusion plethysmography during infusion of acetylcholine (ACh), sodium nitroprusside (SNP), and N-G-monomethyl-(L)-arginine ((L)-NMMA) into the brachial artery. Atorvastatin treatment lowered triglycerides, LDL-cholesterol and coenzyme Q(10) levels (all p < 0.001) and improved endothelium-dependent vasodilatation during acetylcholine infusion (p = 0.015). Endothelium-dependent forearm blood flow improvements correlated with reductions in coenzyme Q(10) levels (p = 0.011), but not with LDL-cholesterol levels (p = 0.084). Coenzyme Q10 remained the significant variable predicting improvement in NO dependent endothelial function after adjusting for LDL-cholesterol levels (p = 0.041). In conclusion, short-term atorvastatin therapy improved endothelial function in chronic heart failure patients. Further studies are required to determine whether coenzyme Q10 reductions are limiting the maximum favourable effects of statin therapy on the microcirculation. (c) 2004 Elsevier Ireland Ltd. All rights reserved.