Atorvastatin improves endothelial function and cardiac performance in patients with dilated cardiomyopathy: the role of inflammation.
OBJECTIVE
Statins have been demonstrated to significantly affect the prognosis and outcome of patients with cardiac diseases. Several studies have suggested pleiotropic effects of the statins in these patients. The present study was designed to examine the effects of atorvastatin on inflammation, endothelial function, cardiac performance and exercise tolerance in patients with idiopathic dilated cardiomyopathy (IDCM).


METHODS
Sixty-four patients with IDCM were divided randomly into an atorvastatin treatment group (atorvastatin 10 mg/d orally) and a placebo control group. Before and 12 weeks after the treatment, circulating soluble intercellular adhesion molecule-1 (sICAM-1), Von Willebrand factor (vWF) and C-reactive protein (CRP) levels were detected using enzyme-linked immunosorbent assay (ELISA); Flow-mediated dilatation (FMD) of the brachial artery was measured, and left ventricular ejection fraction (LVEF) and the 6-min walk test (6MWT) evaluated.


RESULTS
After atorvastatin treatment, LVEF increased from 34.5 +/- 5.7% to 41.4 +/- 4.5% (P < 0.05), and from 32.8 +/- 4.0% to 36.9 +/- 5.2% (P < 0.05) in the placebo group. Also, the distances covered in the 6MWT increased from 358 +/- 61 m to 431 +/- 66 m in the atorvastatin group, and from 351 +/- 70 m to 382 +/- 74 m in the placebo group (both p < 0.05 vs. baseline). The increases in LVEF and 6MWT distances were significantly greater in the atorvastatin than in the placebo group. sICAM-1, CRP and vWF levels decreased and FMD increased significantly in the atorvastatin group, but not in the control group. Correlation analysis showed that the baseline sICAM-1 level was positively correlated with plasma CRP and vWF levels (r = 0.554 and 0.628, respectively); FMD was inversely correlated with serum sICAM-1 and plasma vWF levels (r = -0.579 and -0.590, respectively) and positively correlated with LVEF and distance attained in 6MWT (r = 0.536 and 0.522, respectively).


CONCLUSIONS
Twelve weeks of treatment with atorvastatin significantly decreased serum sICAM-1, CRP and vWF levels, and improved the FMD, LVEF and 6MWT outcomes. Inhibition of inflammation, alleviating endothelium damage and endothelial dysfunction might comprise part of the underlying mechanisms leading to the improvement of LV function and exercise tolerance in patients with IDCM.
Liu
Miao
M
Department of paediatrics, Wuhan Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China.
Wang
Fang
F
Wang
Yanrong
Y
Jin
Runming
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000069059:Atorvastatin; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000473:pathology*; D002784:Cholesterol / Q000097:blood; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D015444:Exercise / Q000502:physiology; D005080:Exercise Test; D005260:Female; D006334:Heart Function Tests; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007249:Inflammation / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D014664:Vasodilation / Q000502:physiology; D016277:Ventricular Function, Left / Q000187:drug effects; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D018799:Intercellular Adhesion Molecule-1; D002784:Cholesterol; D000069059:Atorvastatin