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

本研究旨在确定残余脂蛋白（一种致动脉粥样硬化的富含磷脂的脂蛋白）水平升高是否与代谢综合征患者的冠状动脉疾病（CAD）、内皮血管功能障碍和未来卒中相关。采用免疫分离法测定了210例符合ATP Ⅲ标准的代谢综合征患者空腹血清残余脂蛋白（残粒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舒张功能（FMD）。这项研究发现，RLP-C水平升高是FMD受损和经血管造影证实的CAD的一个重要和独立的风险因素。Kaplan-Meier分析表明，RLP-C水平越高，缺血性卒中的概率越高（对数秩检验P=0.02）。多变量考克斯风险分析显示，高RLP-C水平是未来缺血性卒中的重要预测因子，独立于代谢综合征和其他传统动脉粥样硬化危险因素（优势比3.2，95%CI 1.2-8.1，P<0.01）。此外，高RLP-C水平是回声斑块的显著风险，通过颈动脉超声和背向散射积分（IBS）分析（内膜-中膜IBS值减去外膜IBS[小于或等于]-16 dB）进行评估，与代谢综合征和其他传统动脉粥样硬化风险因素的成分无关（比值比4.3，95% CI 1.6-6.7，P<0.01）。用苯扎贝特（n=20）或阿托伐他汀（n=20）治疗4周显著降低了RLP-C水平，同时改善了FMD。因此，RLP-C水平升高是代谢综合征中CAD、内皮血管功能障碍、冠状动脉事件和卒中的预测因子。RLP-C的测定有助于评估代谢综合征患者心血管疾病的危险性和治疗效果。

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.