背景:冠状动脉疾病(CAD)是全球3840万HIV感染者中的主要死亡原因。在非HIV人群中得出的心血管多基因风险评分(PRS)在HIV感染者中的推广程度尚不清楚。
结果:CAD的PRS(GPSMult)和脂质特征是在REPRIEVE(预防HIV血管事件的随机试验)中招募的接受抗逆转录病毒疗法治疗的HIV患者的全球队列中计算的。在4495名基因型参与者中,PRS与基线脂质性状相关,在接受冠状动脉计算机断层扫描血管造影术的662例亚组中,患有亚临床CAD。在接受冠状动脉计算机断层扫描血管造影术的参与者中(平均年龄,50.9[SD,5.8]岁;16.1%的女性;41.8%的非洲人,57.3%欧洲,1.1%亚洲人),GPSMult与斑块的存在相关,GPSMult中每SD的比值比(OR)为1.42(95%CI,1.20-1.68;P=3.8×10-5),狭窄>50%(或,2.39[95%CI,1.48-3.85];P=3.4×10-4),和非钙化/易损斑块(OR,1.45[95%CI,1.23-1.72];P=9.6×10-6)。在年龄亚组的影响是一致的,性别,10年动脉粥样硬化性心血管疾病风险,祖先,和CD4计数。将GPSMult添加到已确定的危险因素中,预测斑块存在的C统计量从0.718增加到0.734(P=0.02)。此外,低密度脂蛋白胆固醇的PRS与斑块的存在相关,OR为1.21(95%CI,1.01-1.44;P=0.04),和部分钙化斑块,每SD的OR为1.21(95%CI,1.01-1.45;P=0.04)。
结论:在接受抗逆转录病毒治疗的HIV患者中,没有记录到动脉粥样硬化性心血管疾病,并且在REPRIEVE中处于低-中度计算风险,外部开发的CADPRS可预测亚临床动脉粥样硬化.低密度脂蛋白胆固醇的PRS也与亚临床动脉粥样硬化有关,支持低密度脂蛋白胆固醇在HIV相关CAD中的作用。
背景:URL:https://www。reprievetrial.org;唯一标识符:NCT02344290。
BACKGROUND: Coronary artery disease (CAD) is a leading cause of death among the 38.4 million people with HIV globally. The extent to which cardiovascular polygenic risk scores (PRSs) derived in non-HIV populations generalize to people with HIV is not well understood.
RESULTS: PRSs for CAD (GPSMult) and lipid traits were calculated in a global cohort of people with HIV treated with antiretroviral therapy with low-to-moderate atherosclerotic cardiovascular disease risk enrolled in REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV). The PRSs were associated with baseline lipid traits in 4495 genotyped participants, and with subclinical CAD in a subset of 662 who underwent coronary computed tomography angiography. Among participants who underwent coronary computed tomography angiography (mean age, 50.9 [SD, 5.8] years; 16.1% women; 41.8% African, 57.3% European, 1.1% Asian), GPSMult was associated with plaque presence with odds ratio (OR) per SD in GPSMult of 1.42 (95% CI, 1.20-1.68; P=3.8×10-5), stenosis >50% (OR, 2.39 [95% CI, 1.48-3.85]; P=3.4×10-4), and noncalcified/vulnerable plaque (OR, 1.45 [95% CI, 1.23-1.72]; P=9.6×10-6). Effects were consistent in subgroups of age, sex, 10-year atherosclerotic cardiovascular disease risk, ancestry, and CD4 count. Adding GPSMult to established risk factors increased the C-statistic for predicting plaque presence from 0.718 to 0.734 (P=0.02). Furthermore, a PRS for low-density lipoprotein cholesterol was associated with plaque presence with OR of 1.21 (95% CI, 1.01-1.44; P=0.04), and partially calcified plaque with OR of 1.21 (95% CI, 1.01-1.45; P=0.04) per SD.
CONCLUSIONS: Among people with HIV treated with antiretroviral therapy without documented atherosclerotic cardiovascular disease and at low-to-moderate calculated risk in REPRIEVE, an externally developed CAD PRS was predictive of subclinical atherosclerosis. PRS for low-density lipoprotein cholesterol was also associated with subclinical atherosclerosis, supporting a role for low-density lipoprotein cholesterol in HIV-associated CAD.
BACKGROUND: URL: https://www.reprievetrial.org; Unique identifier: NCT02344290.