Residual Inflammatory Risk on Treatment With PCSK9 Inhibition and Statin Therapy
Residual Inflammatory Risk on Treatment With PCSK9 Inhibition and Statin Therapy
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DOI：
10.1161/circulationaha.118.035432
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发表时间：
2018-07-10
期刊：
影响因子：
37.8
通讯作者：
Ridker, Paul M.
中科院分区：
文献类型：
--
作者：
Pradhan, Aruna D.;Aday, Aaron W.;Ridker, Paul M.
背景：尽管低密度脂蛋白（LDL）胆固醇浓度升高与冠状动脉和脑血管疾病的发生存在强烈且一致的前瞻性关联，但外周动脉疾病（PAD）的发生数据却不那么可靠。以小LDL颗粒（LDL- p）浓度升高而非总LDL胆固醇含量升高为特征的致动脉粥样硬化性血脂异常，以及富甘油三酯脂蛋白和低高密度脂蛋白胆固醇（HDL- c）升高，可能是PAD风险的主要脂质驱动因素。方法：研究人群是一项前瞻性队列研究，包括27888名基线时无心血管疾病的45岁女性，随访时间中位数为15.1年。我们测试了标准脂质浓度，以及核磁共振波谱衍生的脂蛋白测量，是否与症状性PAD事件（n=110）相关，这些事件被定义为跛行和/或血运重建。结果：在年龄调整分析中，虽然低密度脂蛋白胆固醇与PAD事件无关，但我们发现总LDL-P浓度、小LDL-P浓度、甘油三酯、非常LDL （VLDL）颗粒（VLDL-P）亚类浓度、总胆固醇（TC）升高、HDL- c、低HDL- c和低HDL-P颗粒（HDL-P）浓度（所有P用于极端五分位数比较）显著相关
Background: Despite strong and consistent prospective associations of elevated low-density lipoprotein (LDL) cholesterol concentration with incident coronary and cerebrovascular disease, data for incident peripheral artery disease (PAD) are less robust. Atherogenic dyslipidemia characterized by increased small LDL particle (LDL-P) concentration, rather than total LDL cholesterol content, along with elevated triglyceride-rich lipoproteins and low high-density lipoprotein (HDL) cholesterol (HDL-C), may be the primary lipid driver of PAD risk.Methods: The study population was a prospective cohort study of 27 888 women 45 years old free of cardiovascular disease at baseline and followed for a median of 15.1 years. We tested whether standard lipid concentrations, as well as nuclear magnetic resonance spectroscopy-derived lipoprotein measures, were associated with incident symptomatic PAD (n=110) defined as claudication and/or revascularization.Results: In age-adjusted analyses, while LDL cholesterol was not associated with incident PAD, we found significant associations for increased total and small LDL-P concentrations, triglycerides, and concentrations of very LDL (VLDL) particle (VLDL-P) subclasses, increased total cholesterol (TC):HDL-C, low HDL-C, and low HDL particle (HDL-P) concentration (all P for extreme tertile comparisons