Hussain Aliza, Sun Caroline, Selvin Elizabeth, Nambi Vijay, Coresh Josef, Jia Xiaoming, Ballantyne Christie M, Hoogeveen Ron C
Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, 6565 Fannin Street, MS F701, Houston, TX 77030, USA.
Department of Medicine, Center for Cardiometabolic Disease Prevention, Baylor College of Medicine, 6565 Fannin Street, MS F701, Houston, TX 77030, USA.
Eur J Prev Cardiol. 2022 Mar 11;29(2):e53-e64. doi: 10.1093/eurjpc/zwaa152.
Despite statin and antihypertensive therapies, older Americans have high atherosclerotic cardiovascular disease (ASCVD) risk. Novel measures of triglyceride-rich lipoproteins, low-density lipoprotein triglycerides (LDL-TG), and remnant-like particle cholesterol (RLP-C), are associated with ASCVD in middle-aged adults. Polymorphisms in genes encoding angiopoietin-related protein 3 (ANGPTL3) and apolipoprotein C-III (apoC-III), two proteins involved in triglyceride catabolism, are associated with increased risk for hypertriglyceridaemia and ASCVD and are potential therapeutic targets. We examined associations of LDL-TG, RLP-C, apoC-III, and ANGPTL3 levels with ASCVD events in older adults in the Atherosclerosis Risk in Communities (ARIC) study.
In 6359 participants (mean age 75.8 ± 5.3 years) followed for ASCVD events [coronary heart disease (CHD) or ischaemic stroke] up to 6 years, associations between LDL-TG, RLP-C, apoC-III, and ANGPTL3 and ASCVD events were assessed using Cox regression. With adjustment for age, sex, and race, RLP-C, LDL-TG, apoC-III, and ANGPTL3 (as continuous variables) were significantly associated with CHD. However, after adjustment for traditional risk factors and lipid-lowering medications, only LDL-TG and ANGPTL3 were significantly associated with ASCVD events [hazard ratio (HR) 1.72, 95% confidence interval (CI) 1.25-2.37 per log unit increase in LDL-TG; HR 1.63, 95% CI 1.17-2.28 per log unit increase in ANGPTL3].
In older adults, LDL-TG, RLP-C, apoC-III, and ANGPTL3 were associated with CHD events in minimally adjusted models; LDL-TG and ANGPTL3 remained independent predictors of ASCVD events with further adjustment. Future studies should assess potential benefit of lowering hepatic apoC-III or ANGPTL3 expression in patients with elevated triglyceride-rich lipoproteins.
尽管接受了他汀类药物和抗高血压治疗，但美国老年人仍有较高的动脉粥样硬化性心血管疾病（ASCVD）风险。富含甘油三酯的脂蛋白、低密度脂蛋白甘油三酯（LDL-TG）和残粒样颗粒胆固醇（RLP-C）的新指标与中年成年人的ASCVD相关。编码血管生成素相关蛋白3（ANGPTL3）和载脂蛋白C-III（apoC-III）的基因多态性与甘油三酯分解代谢有关，这两种蛋白与高甘油三酯血症和ASCVD风险增加相关，是潜在的治疗靶点。我们在社区动脉粥样硬化风险（ARIC）研究中，研究了老年人中LDL-TG、RLP-C、apoC-III和ANGPTL3水平与ASCVD事件的关联。
在6359名参与者（平均年龄75.8±5.3岁）中随访长达6年的ASCVD事件[冠心病（CHD）或缺血性中风]，使用Cox回归评估LDL-TG、RLP-C、apoC-III和ANGPTL3与ASCVD事件之间的关联。在调整年龄、性别和种族后，RLP-C、LDL-TG、apoC-III和ANGPTL3（作为连续变量）与CHD显著相关。然而，在调整传统危险因素和降脂药物后，只有LDL-TG和ANGPTL3与ASCVD事件显著相关[LDL-TG每增加一个对数单位，风险比（HR）为1.72，95%置信区间（CI）为1.25-2.37；ANGPTL3每增加一个对数单位，HR为1.63，95%CI为1.17-2.28]。
在老年人中，在最小调整模型中，LDL-TG、RLP-C、apoC-III和ANGPTL3与CHD事件相关；进一步调整后，LDL-TG和ANGPTL3仍然是ASCVD事件的独立预测因素。未来的研究应评估降低富含甘油三酯脂蛋白升高患者肝脏apoC-III或ANGPTL3表达的潜在益处。
