Abstract | OBJECTIVE: Recent guidelines recommend more aggressive lipid-lowering in secondary prevention protocols. We examined whether this resulted in improved endothelial function. METHODS: We studied saphenous vein specimens of patients undergoing surgical coronary revascularisation in 2007 and compared results with those of patients examined in 2003. Endothelium-dependent vasodilation was assessed by relaxation to calcium ionophore A23187, and vascular superoxide production by lucigenin enhanced chemiluminescence. RESULTS:
Statin dose increased from 26+/-16 mg/d in 2003 to 37+/-17 mg/d in 2007 (P<0.001), and total (4.0+/-0.9 mmol/L vs 4.8+/-1.0 mmol/L) and LDL-cholesterol levels (2.0+/-0.7 mmol/L vs 3.0+/-0.9 mmol/L) were lower in 2007 compared to 2003 (P<0.001; n=90 each). Endothelium-dependent vasodilation was greater in 2007 (44+/-15%) compared to 2003 (28+/-12%; n=36 each; P<0.001). Vascular superoxide derived from endothelial NO synthase (eNOS) was lower in 2007 than in 2003 (reduction by NG-nitro-L-arginine-methyl ester, 0.29+/-0.21 nmol/(mg min) vs 0.09+/-0.20 nmol/(mg min); P=0.002). In linear regression analysis, LDL-cholesterol levels have been shown to be the major determinant of endothelial function in the combined 2003 and 2007 cohort. CONCLUSION: Intensive lipid-lowering is associated with improved endothelial function and reduced superoxide production from eNOS. Further improvement in vascular function could be achieved by targeting other sources of superoxide including xanthine oxidase.
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Authors | Christian Delles, Jane A Dymott, Ulf Neisius, J Paul Rocchiccioli, Gavin J Bryce, María U Moreno, David M Carty, Geoffrey A Berg, Carlene A Hamilton, Anna F Dominiczak |
Journal | Atherosclerosis
(Atherosclerosis)
Vol. 211
Issue 1
Pg. 271-7
(Jul 2010)
ISSN: 1879-1484 [Electronic] Ireland |
PMID | 20138279
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- Cholesterol, LDL
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Superoxides
- NOS3 protein, human
- Nitric Oxide Synthase Type III
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Topics |
- Aged
- Cholesterol, LDL
(blood)
- Coronary Artery Disease
(blood)
- Endothelium
(physiology)
- Female
- Humans
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
(therapeutic use)
- Male
- Middle Aged
- Nitric Oxide Synthase Type III
(metabolism)
- Superoxides
(blood)
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