Back to Search Start Over

Atorvastatin restores endothelial function in normocholesterolemic smokers independent of changes in low-density lipoprotein.

Authors :
Beckman JA
Liao JK
Hurley S
Garrett LA
Chui D
Mitra D
Creager MA
Source :
Circulation research [Circ Res] 2004 Jul 23; Vol. 95 (2), pp. 217-23. Date of Electronic Publication: 2004 Jun 03.
Publication Year :
2004

Abstract

Cigarette smoking impairs endothelial function. Hydroxymethylglutaryl (HMG) CoA reductase inhibitors (statins) may favorably affect endothelial function via nonlipid mechanisms. We tested the hypothesis that statins would improve endothelial function independent of changes in lipids in cigarette smokers. Twenty normocholesterolemic cigarette smokers and 20 matched healthy control subjects were randomized to atorvastatin 40 mg daily or placebo for 4 weeks, washed out for 4 weeks, and then crossed-over to the other treatment. Baseline low-density lipoprotein (LDL) levels were similar in smokers and healthy subjects, 103+/-22 versus 95+/-27 mg/dL, respectively (P=NS) and were reduced similarly in smokers and control subjects by atorvastatin, to 55+/-30 and 58+/-20 mg/dL, respectively (P=NS). Vascular ultrasonography was used to determine brachial artery, flow-mediated, endothelium-dependent, and nitroglycerin-mediated, endothelium-independent vasodilation. To elucidate potential molecular mechanisms that may account for changes in endothelial function, skin biopsy specimens were assayed for eNOS mRNA, eNOS activity, and nitrotyrosine. Endothelium-dependent vasodilation was less in smokers than nonsmoking control subjects during placebo treatment, 8.0+/-0.6% versus 12.1+/-1.1%, (P=0.003). Atorvastatin increased endothelium-dependent vasodilation in smokers to 10.5+/-1.3% (P=0.017 versus placebo) but did not change endothelium-dependent vasodilation in control subjects (to 11.0+/-0.8%, P=NS). Endothelium-independent vasodilation did not differ between groups during placebo treatment and was not significantly affected by atorvastatin. Multivariate analysis did not demonstrate any association between baseline lipid levels or the change in lipid levels and endothelium-dependent vasodilation. Cutaneous nitrotyrosine levels and skin microvessel eNOS mRNA, but not ENOS activity, were increased in smokers compared with controls but unaffected by atorvastatin treatment. Atorvastatin restores endothelium-dependent vasodilation in normocholesterolemic cigarette smokers independent of changes in lipids. These results are consistent with a lipid-independent vascular benefit of statins but could not be explained by changes in eNOS message and tissue oxidative stress. These findings implicate a potential role for statin therapy to restore endothelial function and thereby investigate vascular disease in cigarette smokers.

Details

Language :
English
ISSN :
1524-4571
Volume :
95
Issue :
2
Database :
MEDLINE
Journal :
Circulation research
Publication Type :
Academic Journal
Accession number :
15178637
Full Text :
https://doi.org/10.1161/01.RES.0000134628.96682.9b