title: Endothelium-ameliorating effects of statin therapy and coenzyme Q10 reductions in chronic heart failure.
abstract: 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 Q(10) levels impact on potentially improved endothelial function. Twenty-four patients with stable, symptomatic heart failure (New York Heart Association Class II 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 Q(10) 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 Q(10) reductions are limiting the maximum favourable effects of statin therapy on the microcirculation.
authors.affiliation: Lipid and Diabetes Research Group, Christchurch Hospital, Christchurch, New Zealand.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Strey
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Young
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Molyneux
authors.forename: Peter M
authors.initials: PM
authors.lastname: George
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Florkowski
authors.forename: Russell S
authors.initials: RS
authors.lastname: Scott
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Frampton
mesh_terms: D000069059:Atorvastatin; D002908:Chronic Disease; D003067:Coenzymes; D018592:Cross-Over Studies; D004730:Endothelium, Vascular / Q000187:drug effects*; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000097:blood*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D003067:Coenzymes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D014451:Ubiquinone; D000069059:Atorvastatin; C024989:coenzyme Q10