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

Abstract

IMPORTANCE 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. OBJECTIVES 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. EXPOSURE HIV disease. MAIN OUTCOMES AND MEASURESThe 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). RESULTSThe 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 (continued) Key Points Question What is the extent of coronary artery disease among people with well-controlled HIV and low to moderate risk of atherosclerotic cardiovascular disease (ASCVD), and how is coronary artery disease associated with traditional risk, inflammatory, and immune activation indices? Findings In this cohort study of 755 people with HIV, coronary plaque was highly prevalent. Critical stenosis was rare, but higher-risk plaque features, including vulnerable plaque and high Leaman scores, were seen...

Elderly Person with HIV and Antiretroviral Therapy: Prevalence of Dysglycemia and Risk Factors

“…As in our study, Hoffmann et al [30], evaluating a cohort, concluded that there was a robust prevalence of coronary atherosclerosis in HIV patients and that glycemic levels were higher among those with atherosclerotic plaques and in the population with adequately controlled HIV, markers of immune activation were evidenced innate and arterial inflammation related to coronary artery disease (CAD). Endothelial dysfunction is the fundamental element of atherogenesis and represents the confluence of different processes.…”

The Youngbloods. Get Together. Hypercoagulation, Complement, and NET Formation in HIV/SIV Pathogenesis

“…Important insights could be obtained through the large, ongoing REPRIEVE clinical trial that evaluates the efficacy of statins for the primary prevention of cardiovascular events in PWH. This cohort confirmed the high incidence of coronary atherosclerosis in PWH on ART, the presence of plaques being associated with increased immune activation (161). (iii) Angiotensin receptor blockers have also been evaluated in PWH, to assess their potential benefits in reducing endothelial injury.…”

Sex modifies the association between HIV and coronary artery disease among older adults in Uganda

“…1 University Hospitals of Cleveland, Cleveland, Ohio, USA; 2 Case Western Reserve University, Cleveland, Ohio, USA; 3 MetroHealth Medical Center, Cleveland, Ohio, USA; 4 Joint Clinical Research Centre, Kampala, Uganda; 5 University of Sao Paulo, Sao Paulo, Brazil; 6 St. Francis Hospital Nsambya, Kampala, Uganda; 7 Makerere University School of Medicine, Kampala, Uganda; 8 University of Cincinnati College of Medicine, Cincinnati, Ohio, USA; 9 Massachusetts General Hospital, Boston, Massachusetts, USA; 10 Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USA…”

“…The mechanisms of HIV‐associated CVD include higher prevalence of traditional risk factors, HIV‐related factors and ongoing chronic immune dysregulation [ 3 ]. Innate immune mechanisms may be particularly important, as certain subsets of pro‐inflammatory monocytes and soluble markers of monocyte activation have been linked to coronary disease in multiple cohorts [ 4 ], including in a mechanistic sub‐study of the REPREIVE trial [ 5 ]. However, studies have been largely limited to males in high‐income countries (HICs), despite evidence that chronic HIV‐related immune activation is greater among females [ 6 ].…”