Assessment of Coronary Artery Disease With Computed Tomography Angiography and Inflammatory and Immune Activation Biomarkers Among Adults With HIV Eligible for Primary Cardiovascular Prevention

Udo Hoffmann,Shaun Barcavage,Thomas Mayrhofer,Connor Reynolds,Joan Gottesman,Romina Chinchay Collahua,Julie Pasternak,Bingxue K Zhai,Shobha Swaminathan,Amy Sbrolla,Dan Berrner,Aleen Khodabakhshian,Cornelius Van Dam,Todd Stroberg,Mark Mall,Christie Lyn Costanza,John Dwyer,David Choi,Emma M Kileel,Moises S Huaman,Júlia Karády ,Jeffrey M Jacobson ,Jorge Santana ,Borek Foldyna,Michelle Floris-Moore,Heather J Ribaudo ,J Németh ,Michael T Lu,Kenneth C Williams ,Claudia Hawkins ,Susan L Koletar,Steven Grinspoon ,Michael C Keefer,Rebecca C Fry ,Markella V Zanni,Cornelius N Van Dam ,John R Koethe ,Carlos Malvestutto,Judith S Currier ,Beverly E Sha ,Judith A Aberg ,Edgar T Overton,Robert T O’donnell ,Carl J Fichtenbaum,Tricia H Burdo ,Roberto C Arduino ,Craig A Sponseller,Kathleen V Fitch,Quynh A Truong ,Ken Ho ,Pamela S Douglas,Magdalena E Sobieszczyk ,Sigrid Pérez-Frontera ,Jana Taron,Kathleen Melbourne

doi:10.1001/jamanetworkopen.2021.14923

Abstract

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. 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.

Highlights

More than 38 000 000 people are infected with HIV worldwide
But higher-risk plaque features, including vulnerable plaque and high Leaman scores, were seen in approximately one-fifth of participants; plaque indices were associated with atherosclerotic cardiovascular disease (ASCVD) risk scores and, independently, indices of inflammation and immune activation. Meaning These findings suggest that people with HIV at low to moderate risk of cardiovascular disease have a significant prevalence of coronary plaque associated with inflammation and immune activation markers
The mechanistic substudy population was generally representative of participants enrolled in REPRIEVE in the US, with similar distributions of age, antiretroviral therapy (ART), CD4 levels, HIV ribonucleic acid (RNA) levels, and ASCVD risk

Summary

Introduction

More than 38 000 000 people are infected with HIV worldwide. People with HIV (PWH) have significantly increased rates of cardiovascular disease (CVD),[1] which may occur at a younger age in the context of lower traditional risk scores.[1]. The Randomized Trial to Prevent Vascular Events (REPRIEVE) will test the hypothesis that statin therapy, with pleiotropic effects on inflammatory and cholesterol pathways, is a potent primary prevention strategy for major adverse cardiovascular events among PWH.[15] The mechanistic substudy was designed to simultaneously assess plaque by coronary computed tomography angiography (CTA) and critical pathways of arterial inflammation and immune activation.[16] In this baseline analysis, our primary objective was to assess the prevalence and composition of CAD, with a focus on the presence of plaque as our main CAD end point. Our secondary objective was to assess immune activation and inflammatory indices in association with plaque

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Discussion

Conclusion