用于预测人类免疫缺陷病毒（HIV）感染者亚临床冠状动脉疾病的多基因风险评分：瑞士HIV队列研究

Polygenic Risk Scores for Prediction of Subclinical Coronary Artery Disease in Persons With Human Immunodeficiency Virus (HIV): The Swiss HIV Cohort Study.

作者信息

Schoepf Isabella C, Thorball Christian W, Kovari Helen, Ledergerber Bruno, Buechel Ronny R, Calmy Alexandra, Weber Rainer, Kaufmann Philipp A, Nkoulou René, Schwenke Johannes M, Braun Dominique L, Fellay Jacques, Tarr Philip E

机构信息

Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.

Hepatology, Department for Visceral Surgery and Medicine, Bern University Hospital, University of Bern, Bern, Switzerland.

出版信息

Clin Infect Dis. 2023 Jan 6;76(1):48-56. doi: 10.1093/cid/ciac758.

DOI:10.1093/cid/ciac758

PMID:36097729

Abstract

BACKGROUND

In people with human immunodeficiency virus (HIV) (PWH), individual polygenic risk scores (PRSs) are associated with coronary artery disease (CAD) events. Whether PRSs are associated with subclinical CAD is unknown.

METHODS

In Swiss HIV Cohort Study participants of European descent, we defined subclinical CAD as presence of soft, mixed, or high-risk plaque (SMHRP) on coronary computed tomography (CT) angiography, or as participants in the top tertile of the study population's coronary artery calcium (CAC) score, using noncontrast CT. We obtained univariable and multivariable odds ratios (ORs) for subclinical CAD endpoints based on nongenetic risk factors, and validated genome-wide PRSs built from single nucleotide polymorphisms associated with CAD, carotid intima-media thickness (IMT), or longevity in the general population.

RESULTS

We included 345 genotyped participants (median age, 53 years; 89% male; 96% suppressed HIV RNA); 172 and 127 participants had SMHRP and CAC, respectively. CAD-associated PRS and IMT-associated PRS were associated with SMHRP and CAC (all P < .01), but longevity PRS was not. Participants with unfavorable CAD-PRS (top quintile) had an adjusted SMHRP OR = 2.58 (95% confidence interval [CI], 1.18-5.67), and a CAC OR = 3.95 (95% CI, 1.45-10.77) vs. bottom quintile. Unfavorable nongenetic risk (top vs. bottom quintile) was associated with adjusted SMHRP OR = 24.01 (95% CI, 9.75-59.11), and a CAC-OR = 65.07 (95% CI, 18.48-229.15). Area under the receiver operating characteristic curve increased when we added CAD-PRS to nongenetic risk factors (SMHRP: 0.75 and 0.78, respectively; CAC: 0.80 and 0.83, respectively).

CONCLUSIONS

In Swiss PWH, subclinical CAD is independently associated with an individual CAD-associated PRS. Combining nongenetic and genetic cardiovascular risk factors provided the most powerful subclinical CAD prediction.

摘要

背景

在人类免疫缺陷病毒（HIV）感染者（PWH）中，个体多基因风险评分（PRS）与冠状动脉疾病（CAD）事件相关。PRS是否与亚临床CAD相关尚不清楚。

方法

在瑞士HIV队列研究中具有欧洲血统的参与者中，我们将亚临床CAD定义为冠状动脉计算机断层扫描（CT）血管造影显示存在软斑块、混合斑块或高危斑块（SMHRP），或使用非增强CT检查时处于研究人群冠状动脉钙化（CAC）评分最高三分位数的参与者。我们基于非遗传风险因素获得了亚临床CAD终点的单变量和多变量比值比（OR），并验证了由与CAD、颈动脉内膜中层厚度（IMT）或一般人群寿命相关的单核苷酸多态性构建的全基因组PRS。

结果

我们纳入了345名基因分型参与者（中位年龄53岁；89%为男性；96%的HIV RNA得到抑制）；分别有172名和127名参与者有SMHRP和CAC。CAD相关的PRS和IMT相关的PRS与SMHRP和CAC相关（所有P <.01），但寿命相关的PRS则不然。CAD-PRS不利（最高五分位数）的参与者与最低五分位数相比，调整后的SMHRP OR = 2.58（95%置信区间[CI]，1.18 - 5.67），CAC OR = 3.95（95% CI，1.45 - 10.77）。非遗传风险不利（最高与最低五分位数）与调整后的SMHRP OR = 24.01（95% CI，9.75 - 59.11）和CAC-OR = 65.07（95% CI，18.48 - 229.15）相关。当我们将CAD-PRS添加到非遗传风险因素中时，受试者工作特征曲线下面积增加（SMHRP：分别为0.75和0.78；CAC：分别为0.80和0.83）。