Short-term statin treatment improves endothelial function and neurohormonal imbalance in normocholesterolaemic patients with non-ischaemic heart failure

• Published in: Heart (British Cardiac Society) 2006-11, Vol.92 (11), p.1603-1609
• Main Authors: Strey, C H, Young, J M, Lainchbury, J H, Frampton, C M, Nicholls, M G, Richards, A M, Scott, R S
• Format: Article
• Language: English
• Subjects: ANP; Atorvastatin; atrial natriuretic peptide; B-type natriuretic peptide; Biological and medical sciences; Biomarkers - blood; BNP; C-type natriuretic peptide; Cardiology. Vascular system; Cardiomyopathy; Cardiovascular disease; Cardiovascular Medicine; CHF; Cholesterol - blood; chronic heart failure; CNP; coefficient of variation; Coronary vessels; Cross-Over Studies; Double-Blind Method; Drug dosages; Echocardiography; EID; Endothelium; Endothelium, Vascular; endothelium-independent dilatation; Female; flow-mediated dilatation; FMD; Heart; Heart failure; Heart Failure - drug therapy; Heart Failure - physiopathology; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Heptanoic Acids - therapeutic use; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; l-NMMA; LDL; low density lipoprotein; Male; Medical sciences; Middle Aged; Natriuretic Peptides - blood; NG-monomethyl-l-arginine; nitric oxide; Plasma; Pyrroles - therapeutic use; Statins; Studies; Ultrasonic imaging; Vascular Resistance - drug effects; Vasodilation - drug effects
• ISSN: 1355-6037; 1468-201X
• DOI: 10.1136/hrt.2005.082560

Objectives: To investigate the effect of short-term statin treatment on impaired endothelium-dependent vasodilatation and haemodynamic abnormalities typically occurring in chronic heart failure (CHF). Methods: In a double-blind, crossover study endothelium-dependent vasodilatation was measured in conduit and resistance vessels of 23 patients with non-ischaemic CHF after 6 weeks of placebo and 40 mg atorvastatin. The haemodynamic impact was assessed by cardioendocrine hormones, echocardiography and clinical indicators of CHF. Results: Cholesterol concentrations were population average (low density lipoprotein 3.56 (SEM 0.16) mmol/l, triglycerides 1.70 (0.20) mmol/l and high density lipoprotein 1.17 (0.07) mmol/l). In resistance vessels, the area under the curve ratio during acetylcholine infusion increased from 9.2 (1.9) with placebo to 12.2 (2.1) with statin (p < 0.01). This improvement was reversed during co-infusion with the nitric oxide antagonist NG-monomethyl-l-arginine. In conduit arteries, flow-mediated dilatation increased from 5.64 (SEM 0.88)% with placebo to 6.83 (0.97)% with statin (p < 0.05). Endothelium-independent vasodilatation did not change (p  =  0.68 for conduit and p  =  0.45 for resistance vessels). Endothelin 1 and atrial natriuretic peptide (ANP) decreased from 1.57 (0.08) and 51.3 (1.0) with placebo to 1.42 (0.09) pg/ml (p < 0.05) and 42.1 (7.5) pmol/l (p < 0.05), respectively, with statin. Conclusions: In patients with non-ischaemic CHF and population-average cholesterol concentrations, short-term statin treatment improves endothelial function in conduit and resistance vessels and lowers plasma endothelin 1 and ANP concentrations.