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首页> 外文期刊>Circulation. Genomic and precision medicine. >Genetic Determinants of Lipids andCardiovascular Disease Outcomes A Wide-Angled Mendelian Randomization Investigation
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Genetic Determinants of Lipids andCardiovascular Disease Outcomes A Wide-Angled Mendelian Randomization Investigation

机译：脂质基因因素的建议追根溯源的孟德尔疾病的结果随机调查

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BACKGROUND: Evidence from randomized trials has shown that therapies that lower LDL (low-density lipoprotein)-cholesterol and triglycerides reduce coronary artery disease (CAD) risk. However, there is still uncertainty about their effects on other cardiovascular outcomes. We therefore performed a systematic investigation of causal relationships between circulating lipids and cardiovascular outcomes using a Mendelian randomization approach. METHODS: In the primary analysis, we performed 2-sample multivariable Mendelian randomization using data from participants of European ancestry. We also conducted univariable analyses using inverse-variance weighted and robust methods, and gene-specific analyses using variants that can be considered as proxies for specific lipid-lowering medications. We obtained associations with lipid fractions from the Global Lipids Genetics Consortium, a meta-analysis of 188 577 participants, and genetic associations with cardiovascular outcomes from 367 703 participants in UK Biobank. RESULTS: For LDL-cholesterol, in addition to the expected positive associations with CAD risk (odds ratio [OR] per 1 SD increase, 1.45 [95% CI, 1.35-1.57]) and other atheromatous outcomes (ischemic cerebrovascular disease and peripheral vascular disease), we found independent associations of genetically predicted LDL-cholesterol with abdominal aortic aneurysm (OR, 1.75 [95% CI, 1.40-2.17]) and aortic valve stenosis (OR, 1.46 [95% CI, 1.25-1.70]). Genetically predicted triglyceride levels were positively associated with CAD (OR, 1.25 [95% CI, 1.12-1.40]), aortic valve stenosis (OR, 1.29 [95% CI, 1.04-1.61]), and hypertension (OR, 1.17 [95% CI, 1.07-1.27]), but inversely associated with venous thromboembolism (OR, 0.79 [95% CI, 0.67-0.93]) and hemorrhagic stroke (OR, 0.78 [95% CI, 0.62-0.98]). We also found positive associations of genetically predicted LDL-cholesterol and triglycerides with heart failure that appeared to be mediated by CAD. CONCLUSIONS: Lowering LDL-cholesterol is likely to prevent abdominal aortic aneurysm and aortic stenosis, in addition to CAD and other atheromatous cardiovascular outcomes. Lowering triglycerides is likely to prevent CAD and aortic valve stenosis but may increase thromboembolic risk.
机译：背景:证据来自随机试验显示疗法降低LDL(低密度脂蛋白胆固醇和甘油三酯降低冠状动脉疾病(CAD)的风险。对他们的影响仍然存在不确定性其他心血管疾病的结果。因果关系进行了系统的调查脂质和循环之间的关系使用孟德尔心血管结果随机化的方法。分析,我们执行2-sample多变量使用数据从孟德尔随机化参与者的欧洲血统。进行单变量分析使用反变量加权和健壮的方法,gene-specific使用变体,可以分析认为是代表特定的降脂的药物。分数从全球脂质基因财团,荟萃分析188 577参与者,和遗传关联从367年703名参与者心血管结果英国生物库。除了预期的积极关联与CAD的风险(优势比[或]每1 SD增加,1.45 (95% CI, 1.35 - -1.57))和其他动脉粥样硬化结果(缺血性脑血管疾病周围性血管疾病),我们发现独立的关联基因预测低密度脂蛋白胆固醇与腹主动脉瘤(或1.75 (95% CI, 1.40 - -2.17))和主动脉瓣狭窄(或者1.46 (95% CI, 1.25 - -1.70))。基因预测的甘油三酸酯水平积极与CAD(或者,1.25(95%可信区间,1.12 - -1.40]),主动脉瓣狭窄(或者1.29 [95%CI, 1.04 - -1.61)和高血压(或1.17 (95%CI, 1.07 - -1.27),但与成负相关静脉血栓栓塞(或者,0.79(95%可信区间,0.67 - -0.93])、出血性中风(或,0.78 [95%CI, 0.62 - -0.98])。关联的基因预测低密度脂蛋白胆固醇和甘油三酯的心这似乎是由CAD失败。结论:降低低密度脂蛋白胆固醇是可能的为了防止腹主动脉瘤和主动脉狭窄,除了CAD及其他动脉粥样硬化心血管结果。甘油三酸酯可能防止CAD和主动脉瓣膜狭窄,但可能会增加血栓栓塞风险。

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