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.
Atherosclerosis. 2010 Jul;211(1):271-7. doi: 10.1016/j.atherosclerosis.2010.01.014. Epub 2010 Jan 21.
Recent guidelines recommend more aggressive lipid-lowering in secondary prevention protocols. We examined whether this resulted in improved endothelial function.
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.
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.
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.
最近的指南建议在二级预防方案中更积极地降低血脂。我们研究了这是否导致内皮功能得到改善。
我们研究了 2007 年接受冠状动脉旁路移植术的患者的隐静脉标本，并将结果与 2003 年检查的患者进行了比较。通过钙载体 A23187 松弛评估内皮依赖性血管舒张，通过荧光素增强化学发光评估血管超氧化物产生。
他汀类药物剂量从 2003 年的 26+/-16mg/d 增加到 2007 年的 37+/-17mg/d（P<0.001），总胆固醇（4.0+/-0.9mmol/L 对 4.8+/-1.0mmol/L）和 LDL 胆固醇水平（2.0+/-0.7mmol/L 对 3.0+/-0.9mmol/L）在 2007 年比 2003 年低（P<0.001；n=90 例）。2007 年内皮依赖性血管舒张（44+/-15%）比 2003 年（28+/-12%；n=36 例；P<0.001）更大。来自内皮一氧化氮合酶（eNOS）的血管超氧化物在 2007 年比 2003 年少（NG-硝基-L-精氨酸甲酯的减少，0.29+/-0.21nmol/（mg min）对 0.09+/-0.20nmol/（mg min）；P=0.002）。在线性回归分析中，LDL 胆固醇水平被证明是 2003 年和 2007 年合并队列内皮功能的主要决定因素。
强化降脂与内皮功能改善和 eNOS 产生的超氧化物减少有关。通过靶向包括黄嘌呤氧化酶在内的其他超氧化物源，血管功能可能会进一步改善。
