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±16mg/d in 2003 to 37±17mg/d in 2007 (P<0.001), and total (4.0±0.9mmol/L vs 4.8±1.0mmol/L) and LDL-cholesterol levels (2.0±0.7mmol/L vs 3.0±0.9mmol/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±0.21nmol/(mgmin) vs 0.09±0.20nmol/(mgmin); 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. © 2010 Elsevier Ireland Ltd.
Delles, C., Dymott, J. A., Neisius, U., Paul Rocchiccioli, J., Bryce, G. J., Moreno, M. U., … Dominiczak, A. F. (2010). 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. Atherosclerosis, 211(1), 271–277. https://doi.org/10.1016/j.atherosclerosis.2010.01.014