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.
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.


CONCLUSIONS
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.
BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, University of Glasgow, and Department of Vascular Surgery, Gartnavel General Hospital, 126 University Place, Glasgow G12 8TA, Scotland, UK. c.delles@clinmed.gla.ac.uk
Christian
C
Delles
Jane A
JA
Dymott
Ulf
U
Neisius
J Paul
JP
Rocchiccioli
Gavin J
GJ
Bryce
María U
MU
Moreno
David M
DM
Carty
Geoffrey A
GA
Berg
Carlene A
CA
Hamilton
Anna F
AF
Dominiczak
D000368:Aged; D008078:Cholesterol, LDL / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood*; D004727:Endothelium / Q000502:physiology*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D013481:Superoxides / Q000097:blood
D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013481:Superoxides; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III