Massachusetts General Hospital, Boston.
MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
JAMA Netw Open. 2021 Jun 1;4(6):e2114923. doi: 10.1001/jamanetworkopen.2021.14923.
Cardiovascular disease (CVD) is increased among people with HIV (PWH), but little is known regarding the prevalence and extent of coronary artery disease (CAD) and associated biological factors in PWH with low to moderate traditional CVD risk.
To determine unique factors associated with CVD in PWH and to assess CAD by coronary computed tomography angiography (CTA) and critical pathways of arterial inflammation and immune activation.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study among male and female PWH, aged 40 to 75 years, without known CVD, receiving stable antiretroviral therapy, and with low to moderate atherosclerotic cardiovascular disease (ASCVD) risk according to the 2013 American College of Cardiology/American Heart Association pooled cohort equation, was part of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), a large, ongoing primary prevention trial of statin therapy among PWH conducted at 31 US sites. Participants were enrolled from May 2015 to February 2018. Data analysis was conducted from May to December 2020.
HIV disease.
The primary outcome was the prevalence and composition of CAD assessed by coronary CTA and, secondarily, the association of CAD with traditional risk indices and circulating biomarkers, including insulin, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL) 6, soluble CD14 (sCD14), sCD163, lipoprotein-associated phospholipase A2 (LpPLA2), oxidized low-density lipoprotein (oxLDL), and high-sensitivity C-reactive protein (hsCRP).
The sample included 755 participants, with a mean (SD) age of 51 (6) years, 124 (16%) female participants, 267 (35%) Black or African American participants, 182 (24%) Latinx participants, a low median (interquartile range) ASCVD risk (4.5% [2.6%-6.8%]), and well-controlled viremia. Overall, plaque was seen in 368 participants (49%), including among 52 of 175 participants (30%) with atherosclerotic CVD (ASCVD) risk of less than 2.5%. Luminal obstruction of at least 50% was rare (25 [3%]), but vulnerable plaque and high Leaman score (ie, >5) were more frequently observed (172 of 755 [23%] and 118 of 743 [16%], respectively). Overall, 251 of 718 participants (35%) demonstrated coronary artery calcium score scores greater than 0. IL-6, LpPLA2, oxLDL, and MCP-1 levels were higher in those with plaque compared with those without (eg, median [IQR] IL-6 level, 1.71 [1.05-3.04] pg/mL vs 1.45 [0.96-2.60] pg/mL; P = .008). LpPLA2 and IL-6 levels were associated with plaque in adjusted modeling, independent of traditional risk indices and HIV parameters (eg, IL-6: adjusted odds ratio, 1.07; 95% CI, 1.02-1.12; P = .01).
In this study of a large primary prevention cohort of individuals with well-controlled HIV and low to moderate ASCVD risk, CAD, including noncalcified, nonobstructive, and vulnerable plaque, was highly prevalent. Participants with plaque demonstrated higher levels of immune activation and arterial inflammation, independent of traditional ASCVD risk and HIV parameters.
心血管疾病(CVD)在 HIV 感染者(PWH)中较为常见,但对于 CVD 风险低至中度的 PWH 中冠状动脉疾病(CAD)的流行程度和相关生物学因素知之甚少。
确定与 PWH 中 CVD 相关的独特因素,并通过冠状动脉计算机断层血管造影(CTA)和动脉炎症和免疫激活的关键途径评估 CAD。
设计、地点和参与者:这是一项队列研究,纳入了年龄在 40 至 75 岁之间、无已知 CVD、接受稳定抗逆转录病毒治疗且根据 2013 年美国心脏病学会/美国心脏协会 pooled cohort 方程评估的 CVD 风险低至中度的男性和女性 PWH。该研究部分纳入了正在进行的一项大型、针对 CVD 的他汀类药物一级预防试验——预防 HIV 血管事件的随机试验(REPRIEVE),该试验在 31 个美国地点进行。参与者于 2015 年 5 月至 2018 年 2 月入组。数据分析于 2020 年 5 月至 12 月进行。
HIV 疾病。
主要结局是通过冠状动脉 CTA 评估的 CAD 的患病率和构成,其次是 CAD 与传统风险指数和循环生物标志物(包括胰岛素、单核细胞趋化蛋白 1(MCP-1)、白细胞介素(IL)6、可溶性 CD14(sCD14)、sCD163、脂蛋白相关磷脂酶 A2(LpPLA2)、氧化型低密度脂蛋白(oxLDL)和高敏 C 反应蛋白(hsCRP))的相关性。
该样本包括 755 名参与者,平均(SD)年龄为 51(6)岁,124(16%)名女性参与者,267(35%)名黑人和非洲裔美国参与者,182(24%)名拉丁裔参与者,中位(四分位距)ASCVD 风险低(4.5%[2.6%-6.8%]),病毒载量得到良好控制。总体而言,368 名参与者(49%)有斑块,包括 175 名参与者中有 52 名(30%)的 ASCVD 风险低于 2.5%。至少 50%的管腔阻塞较为罕见(25[3%]),但易损斑块和高 Leaman 评分(即>5)更为常见(755 名参与者中有 172 名[23%]和 118 名[16%])。总体而言,718 名参与者中有 251 名(35%)冠状动脉钙评分大于 0。与无斑块者相比,有斑块者的 IL-6、LpPLA2、oxLDL 和 MCP-1 水平更高(例如,中位数[IQR]IL-6 水平分别为 1.71[1.05-3.04]pg/mL 与 1.45[0.96-2.60]pg/mL;P = .008)。在调整后的模型中,LpPLA2 和 IL-6 水平与斑块相关,独立于传统风险指数和 HIV 参数(例如,IL-6:调整后的比值比,1.07;95%CI,1.02-1.12;P = .01)。
在这项针对 CVD 风险低至中度且 HIV 得到良好控制的大型一级预防队列研究中,CAD 包括非钙化、非阻塞性和易损斑块,高度流行。与斑块相关的参与者表现出更高的免疫激活和动脉炎症水平,独立于传统 ASCVD 风险和 HIV 参数。