Clinical significance of remnant lipoproteinemia as a therapeutic target of cardiovascular diseases

本研究旨在确定残脂蛋白(一种富含甘油三酯的致动脉粥样硬化的脂蛋白)水平升高是否与冠状动脉疾病(CAD)、内皮血管运动功能障碍和代谢综合征中未来的中风有关。用免疫分离法测定了210例符合ATPIII标准的代谢综合征患者的空腹血清残余脂蛋白(残留样脂蛋白颗粒胆固醇；RLP-C)水平。应用高分辨率超声技术检测反应性充血时肱动脉血流介导的内皮依赖性扩张(FMD)。这项研究发现，RLP-C水平升高是FMD受损和经血管造影术证实的冠心病的重要和独立的危险因素。Kaplan-Meier分析显示，RLP-C水平越高，发生缺血性卒中的概率越高(经对数等级检验，P=0.02)。多变量COX风险分析显示，高RLP-C水平是独立于代谢综合征成分和其他传统动脉粥样硬化危险因素的未来缺血性卒中的显著预测因素(优势比3.2，95%可信区间1.2-8.1，P&lt；0.01)。此外，高RLP-C水平是颈动脉斑块回声透明的显著危险因素，颈动脉超声结合背向散射积分(IBS)分析(内膜-中层IBS值减外膜IBS[小于或等于]-16分贝)独立于代谢综合征和其他传统的动脉粥样硬化危险因素(优势比4.3，95%可信区间1.6-6.7，P&lt；0.01)。苯扎贝特(n=20)或阿托伐他汀(n=20)治疗4周可显著降低RLP-C水平，并伴随FMD的改善。因此，在代谢综合征中，RLP-C水平升高是冠心病、内皮血管运动功能障碍、冠状动脉事件和中风的危险因素。测定RLP-C有助于评估代谢综合征的心血管疾病风险和治疗效果。

This study aimed to determine whether elevated levels of remnant lipoprotein, an atherogenic triglyceride-rich lipoprotein, might be associated with coronary artery disease (CAD), endothelial vasomotor dysfunction, and future stroke in metabolic syndrome. The fasting serum levels of remnant lipoproteins (remnant-like lipoprotein particles cholesterol ; RLP-C) were measured by an immunoseparation method in 210 patients with metabolic syndrome meeting ATP III criteria. Flow-mediated endothelium-dependent dilatation (FMD) in the brachial artery during reactive hyperemia was examined by high-resolution ultrasound technique. This study found that elevated RLP-C levels were a significant and independent risk factor for impaired FMD and angiographically proven CAD. Kaplan-Meier analysis demonstrated that higher RLP-C levels resulted in a higher probability of ischemic stroke (P=0.02 by log-rank test). A multivariate Cox hazard analysis showed that high RLP-C levels were a significant predictor of a future ischemic stroke that was independent of components of the metabolic syndrome and other traditional atherosclerotic risk factors (odds ratio 3.2, 95% CI 1.2-8.1, P<0.01). Furthermore, high RLP-C levels were a significant risk of echolucent carotid plaques, assessed by carotid ultrasound with the integrated backscatter (IBS) analysis (intima-media IBS value minus adventitia IBS【less than or equal】-16 dB) that was independent of components of metabolic syndrome and other traditional atherosclerotic risk factors (odds ratio 4.3, 95% CI 1.6-6.7, P<0.01). Treatment with bezafibrate (n=20) or atorvastatin (n=20) for 4 weeks significantly reduced RLP-C levels, with a concomitant improvement in FMD. Thus, elevated levels of RLP-C are a risk factor for CAD, endothelial vasomotor dysfunction, a predictor of coronary events, and stroke in metabolic syndrome. Measurement of RLP-C is useful for assessment of risk of cardiovascular diseases and therapeutic effects in metabolic syndrome.