Reduced LDL-cholesterol levels in patients with coronary artery disease are paralleled by improved endothelial function: An observational study in patients from 2003 and 2007.

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.

• 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)
• 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

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)