Cardiovascular Imaging Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
Inova Heart and Vascular Institute, Falls Church, Virginia, USA.
J Infect Dis. 2022 Nov 11;226(10):1809-1822. doi: 10.1093/infdis/jiac196.
People with HIV (PWH) have subclinical coronary artery disease (CAD) despite low traditional atherosclerotic cardiovascular disease (ASCVD) risk scores. Coronary plaque in PWH presents as a unique phenotype, but little is known about the contributions of specific inflammatory pathways to plaque phenotypes in PWH.
The REPRIEVE Mechanistic Substudy enrolled PWH on ART without known cardiovascular disease. We used a targeted discovery proteomics approach to evaluate 246 unique proteins representing cardiovascular, inflammatory, and immune pathways. Proteomic signatures were determined for presence of coronary artery calcium (CAC > 0) and presence of coronary plaque.
Data were available for 662 participants (aged 51 [SD 6] years, ASCVD risk score 4.9% [SD 3.1%]). Among 12 proteins associated with both CAC and presence of coronary plaque, independent of ASCVD risk score, the odds ratios were highest for NRP1: 5.1 (95% confidence interval [CI], 2.3-11.4) for CAC and 2.9 (95% CI, 1.4-6.1) for presence of plaque. Proteins uniquely related to presence of plaque were CST3, LTBR, MEPE, PLC, SERPINA5, and TNFSF13B; in contrast, DCN, IL-6RA, OSMR, ST2, and VCAM1 were only related to CAC.
Distinct immune and inflammatory pathways are differentially associated with subclinical CAD phenotypes among PWH. This comprehensive set of targets should be further investigated to reduce atherosclerosis and ASCVD in PWH.
NCT02344290.
尽管艾滋病毒感染者（PWH）的传统动脉粥样硬化性心血管疾病（ASCVD）风险评分较低，但他们仍存在亚临床冠状动脉疾病（CAD）。PWH 的冠状动脉斑块表现为一种独特的表型，但对于特定炎症途径对 PWH 斑块表型的贡献知之甚少。
REPRIEVE 机制子研究纳入了正在接受抗逆转录病毒疗法（ART）治疗且无已知心血管疾病的 PWH。我们使用靶向发现蛋白质组学方法来评估代表心血管、炎症和免疫途径的 246 种独特蛋白质。根据是否存在冠状动脉钙化（CAC > 0）和是否存在冠状动脉斑块来确定蛋白质组特征。
共有 662 名参与者（年龄 51 [SD 6]岁，ASCVD 风险评分 4.9% [SD 3.1%]）的数据可用。在与 CAC 和冠状动脉斑块均相关的 12 种蛋白中，NRP1 的比值比最高，与 CAC 相关的比值比为 5.1（95%置信区间 [CI]，2.3-11.4），与斑块相关的比值比为 2.9（95% CI，1.4-6.1）。与斑块存在相关的蛋白为 NRP1、CST3、LTBR、MEPE、PLC、SERPINA5 和 TNFSF13B；相反，DCN、IL-6RA、OSMR、ST2 和 VCAM1 仅与 CAC 相关。
在 PWH 中，不同的免疫和炎症途径与亚临床 CAD 表型存在差异相关。应该进一步研究这一全面的靶点集，以减少 PWH 的动脉粥样硬化和 ASCVD。
NCT02344290。
