Relation of gemfibrozil treatment and high-density lipoprotein subpopulation profile with cardiovascular events in the Veterans Affairs High-Density Lipoprotein Intervention Trial
Relation of gemfibrozil treatment and high-density lipoprotein subpopulation profile with cardiovascular events in the Veterans Affairs High-Density Lipoprotein Intervention Trial
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DOI：
10.1016/j.metabol.2007.08.009
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发表时间：
2008-01-01
影响因子：
9.8
通讯作者：
Schaefer, Ernst J.
中科院分区：
文献类型：
--
作者：
Asztalos, Bela F.;Collins, Dorothea;Schaefer, Ernst J.
在退伍军人事务部高密度脂蛋白干预试验（VA-HIT）中，高密度脂蛋白（HDL）胆固醇增加6%不能完全解释贝特吉非罗齐导致的心血管疾病（CVD）事件显著减少。我们研究了HDL亚群的测量是否提供了与CVD风险降低相关的额外信息。在接受吉非罗齐（n = 754）或安慰剂（n = 741）治疗的受试者中，通过二维凝胶电泳表征HDL亚群。在本研究中，使用了3个月访视时获得的样本;并使用5.1年随访期间的CVD事件（冠心病死亡、心肌梗死或卒中）对数据进行了前瞻性分析。吉非罗齐组的分析显示，与未发生此类事件的受试者相比，发生复发性CVD事件的受试者的前β 1水平显著较高，α 1和α 2 HDL水平显著较低。前β-1水平是一个显着的积极预测因子; α-1和α-2水平是未来CVD事件的显着的负风险因素。在对已确定的危险因素进行校正后，在心血管疾病风险评估中，α 2水平上级优于HDL胆固醇水平。吉非罗齐治疗与小的、低脂质的前β-1 HDL以及大的、富含脂质的α-1和α-2 HDL降低3%至6%相关，并且与小的α-3（3%）和前α-3（16%）HDL增加相关。尽管吉非罗齐的使用与VA-HIT中CVD事件的减少相关，但HDL亚群分析表明吉非罗齐介导的CVD风险改善可能不是其对HDL影响的结果。吉非罗齐的心血管获益很可能是由于对代谢过程的更广泛影响，而这并不反映在血脂和HDL亚群的变化上。(C)2008年爱思唯尔公司All rights reserved.
The significant cardiovascular disease (CVD) event reduction in the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) could not be fully explained by the 6% increase in high-density lipoprotein (HDL) cholesterol with the fibrate gemfibrozil. We examined whether measurement of HDL subpopulations provided additional information relative to CVD risk reduction. The HDL subpopulations were characterized by 2-dimensional gel electrophoresis in subjects who were treated with gemfibrozil (n = 754) or placebo (n = 741). In this study, samples obtained at the 3-month visit were used; and data were analyzed prospectively using CVD events (coronary heart disease death, myocardial infarction, or stroke) during the 5.1 years of follow-up. Analyses in the gemfibrozil arm showed that subjects with recurrent CVD events had significantly higher pre beta-1 and had significantly lower alpha-1 and alpha-2 HDL levels than those without such events. Pre beta-1 level was a significant positive predictor; alpha-1 and alpha-2 levels were significant negative risk factors for future CVD events. alpha-2 level was superior to HDL cholesterol level in CVD-risk assessment after adjustment for established risk factors. Gemfibrozil treatment was associated with 3% to 6% decreases in the small, lipid-poor pre beta-1 HDL and in the large, lipid-rich alpha-1 and alpha-2 HDL and with increases in the small alpha-3 (3%) and pre alpha-3 (16%) HDLs. Although the use of gemfibrozil has been associated with reduction in CVD events in VA-HIT, HDL subpopulation analysis indicates that gemfibrozil-mediated improvement in C VD risk might not be the result of its effects on HDL. It is quite possible that much of the cardiovascular benefits of gemfibrozil are due to a much wider spectrum of effects on metabolic processes that is not reflected by changes in blood lipids and HDL subpopulations. (C) 2008 Elsevier Inc. All rights reserved.