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

被引:21
作者
Delles, Christian [1 ]
Dymott, Jane A. [1 ]
Neisius, Ulf [1 ]
Rocchiccioli, J. Paul [1 ]
Bryce, Gavin J. [1 ,2 ]
Moreno, Maria U. [1 ]
Carty, David M. [1 ]
Berg, Geoffrey A. [3 ]
Hamilton, Carlene A. [1 ]
Dominiczak, Anna F. [1 ]
机构
[1] Univ Glasgow, Fac Med, BHF Glasgow Cardiovasc Res Ctr, Glasgow G12 8TA, Lanark, Scotland
[2] Gartnavel Royal Hosp, Dept Vasc Surg, Glasgow, Lanark, Scotland
[3] Univ Glasgow, Western Infirm, Dept Cardiothorac Surg, Glasgow G11 6NT, Lanark, Scotland
关键词
Cholesterol; Endothelial function; Coronary disease; Statins; Oxidative stress; LOW-DENSITY-LIPOPROTEIN; NITRIC-OXIDE SYNTHASE; OXIDATIVE STRESS; SUPEROXIDE ANION; VASCULAR ENDOTHELIUM; REDUCTASE INHIBITOR; HEART-DISEASE; DYSFUNCTION; RISK; HYPERCHOLESTEROLEMIA;
D O I
10.1016/j.atherosclerosis.2010.01.014
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 N-G-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. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:271 / 277
页数:7
相关论文
共 31 条
[1]   Low-density lipoprotein cholesterol determines oxidative stress and endothelial dysfunction in saphenous veins from patients with coronary artery disease [J].
Al-Benna, S ;
Hamilton, CA ;
McClure, JD ;
Rogers, PN ;
Berg, GA ;
Ford, I ;
Delles, C ;
Dominiczak, AF .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2006, 26 (01) :218-223
[2]   Renin angiotensin system inhibition is associated with reduced free radical concentrations in arteries of patients with coronary heart disease [J].
Berry, C ;
Anderson, N ;
Kirk, AJB ;
Dominiczak, AF ;
McMurray, JJV .
HEART, 2001, 86 (02) :217-218
[3]   Endothelial dysfunction and cardiovascular risk prediction in peripheral arterial disease - Additive value of flow-mediated dilation to ankle-brachial pressure index [J].
Brevetti, G ;
Silvestro, A ;
Schiano, V ;
Chiariello, M .
CIRCULATION, 2003, 108 (17) :2093-2098
[4]   Allopurinol normalizes endothelial dysfunction in type 2 diabetics with mild hypertension [J].
Butler, R ;
Morris, AD ;
Belch, JJF ;
Hill, A ;
Struthers, AD .
HYPERTENSION, 2000, 35 (03) :746-751
[5]   Chronic treatment with tetrahydrobiopterin reverses endothelial dysfunction and oxidative stress in hypercholesterolaemia [J].
Cosentino, F. ;
Huerlimann, D. ;
Gatti, C. Delli ;
Chenevard, R. ;
Blau, N. ;
Alp, N. J. ;
Channon, K. M. ;
Eto, M. ;
Lerch, P. ;
Enseleit, F. ;
Ruschitzka, F. ;
Volpe, M. ;
Luescher, T. F. ;
Noll, G. .
HEART, 2008, 94 (04) :487-492
[6]   A new approach for extracellular spin trapping of nitroglycerin-induced superoxide radicals both in vitro and in vivo [J].
Fink, B ;
Dikalov, S ;
Bassenge, E .
FREE RADICAL BIOLOGY AND MEDICINE, 2000, 28 (01) :121-128
[7]   Long-term follow-up of the West of Scotland Coronary Prevention Study [J].
Ford, Ian ;
Murray, Heather ;
Packard, Chris J. ;
Shepherd, James ;
Macfarlane, Peter W. ;
Cobbe, Stuart M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2007, 357 (15) :1477-1486
[8]   Coronary artery superoxide production and nox isoform expression in human coronary artery disease [J].
Guzik, TJ ;
Sadowski, J ;
Guzik, B ;
Jopek, A ;
Kapelak, B ;
Przybylowski, P ;
Wierzbicki, K ;
Korbut, R ;
Harrison, DG ;
Channon, KM .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2006, 26 (02) :333-339
[9]   Cholesterol-lowering treatment is associated with improvement in coronary vascular remodeling and endothelial function in patients with normal or mildly diseased coronary arteries [J].
Hamasaki, S ;
Higano, ST ;
Al Suwaidi, J ;
Nishimura, RA ;
Miyauchi, K ;
Holmes, DR ;
Lerman, A .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2000, 20 (03) :737-743
[10]   Systemic endothelial dysfunction as an early predictor of adverse outcome in heart failure [J].
Heitzer, T ;
Baldus, S ;
von Kodolitsch, Y ;
Rudolph, V ;
Meinertz, T .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2005, 25 (06) :1174-1179