Division of Biostatistics, University of Minnesota, Minneapolis, Minnesota, USA.
Immunology, Statens Serum Institut, Copenhagen, Denmark.
J Infect Dis. 2023 Apr 18;227(8):951-960. doi: 10.1093/infdis/jiac496.
There is an incompletely understood increased risk for cardiovascular disease (CVD) among people with HIV (PWH). We investigated if a collection of biomarkers were associated with CVD among PWH. Mendelian randomization (MR) was used to identify potentially causal associations.
Data from follow-up in 4 large trials among PWH were used to identify 131 incident CVD cases and they were matched to 259 participants without incident CVD (controls). Tests of associations between 460 baseline protein levels and case status were conducted.
Univariate analysis found CLEC6A, HGF, IL-6, IL-10RB, and IGFBP7 as being associated with case status and a multivariate model identified 3 of these: CLEC6A (odds ratio [OR] = 1.48, P = .037), HGF (OR = 1.83, P = .012), and IL-6 (OR = 1.45, P = .016). MR methods identified 5 significantly associated proteins: AXL, CHI3L1, GAS6, IL-6RA, and SCGB3A2.
These results implicate inflammatory and fibrotic processes as contributing to CVD. While some of these biomarkers are well established in the general population and in PWH (IL-6 and its receptor), some are novel to PWH (HGF, AXL, and GAS6) and some are novel overall (CLEC6A). Further investigation into the uniqueness of these biomarkers in PWH and the role of these biomarkers as targets among PWH is warranted.
HIV 感染者（PWH）心血管疾病（CVD）的风险增加，但这种风险的机制尚不完全清楚。本研究旨在探讨一组生物标志物与 PWH 发生 CVD 的关系。采用孟德尔随机化（MR）方法来识别潜在的因果关联。
本研究使用了 4 项大型临床试验的随访数据，共纳入了 131 例 CVD 事件患者和 259 例无 CVD 事件的对照患者。采用单变量分析和多变量模型分析了基线时 460 种蛋白水平与 CVD 发生的相关性。
单变量分析发现 CLEC6A、HGF、IL-6、IL-10RB 和 IGFBP7 与 CVD 发生相关，多变量模型进一步确定了其中 3 种蛋白：CLEC6A（比值比 [OR] = 1.48，P =.037）、HGF（OR = 1.83，P =.012）和 IL-6（OR = 1.45，P =.016）。MR 方法共鉴定出 5 种与 CVD 显著相关的蛋白：AXL、CHI3L1、GAS6、IL-6RA 和 SCGB3A2。
这些结果提示炎症和纤维化过程可能导致 CVD 的发生。其中一些生物标志物在一般人群和 PWH 中已得到广泛研究（如 IL-6 和其受体），而另一些标志物（如 HGF、AXL 和 GAS6）在 PWH 中是新发现的，还有一些标志物（如 CLEC6A）在总体人群中也是新发现的。需要进一步研究这些标志物在 PWH 中的独特性及其作为 PWH 治疗靶点的作用。
