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CORONARY ARTERY DISEASE, TRADITIONAL RISK, AND INFLAMMATION AMONG PWH IN REPRIEVE
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"CVD is increased among PWH, in young asymptomatic patients, with lower traditional risk factors"
CROI 2021 March 6-10 Reported by Jules Levin
Udo Hoffmann1, Michael T. Lu1, Borek Foldyna1, Markella V. Zanni1, Tricia H. Burdo2, Carl Fichtenbaum3, E. Turner Overton4, Judith A. Aberg5, Judith S. Currier6, Craig A. Sponseller7, Kathleen Melbourne8, Pamela S. Douglas9, Heather J. Ribaudo10, Thomas Mayrhofer1, Steven Grinspoon1
1Massachusetts General Hospital, Boston, MA, USA, 2Temple University, Philadelphia, PA, USA, 3University of Cincinnati, Cincinnati, OH, USA, 4University of Alabama at Birmingham, Birmingham, AL, USA, 5Icahn School of Medicine at Mt Sinai, New York, NY, USA, 6University of California Los Angeles, Los Angeles, CA, USA, 7Kowa Pharmaceuticals America, Inc, Montgomery, AL, USA, 8Gilead Sciences, Inc, Foster City, CA, USA, 9Duke Clinical Research Institute, Durham, NC, USA, 10Harvard TH Chan School of Public Health, Boston, MA, USA
Background: REPRIEVE is a large ongoing primary prevention trial of people with HIV (PWH), at risk for cardiovascular disease (CVD). The REPRIEVE Mechanistic Substudy, designed to determine unique factors contributing to CVD in PWH, assesses coronary artery disease (CAD) by coronary CTA and critical pathways of arterial inflammation and immune activation. Comprehensive data from the baseline exam establish the plaque phenotype in this key population.
Methods: The study enrolled PWH, 40-75 yrs,without known CVD, on stable ART, with low to moderate risk of atherosclerotic cardiovascular disease (ASCVD) by the 2013 ACC/AHA pooled cohort equation. Coronary CTA data were analyzed across ASCVD risk strata and in regression models including biomarkers: insulin, MCP-1, IL-6, sCD14, sCD163, LpPLA2, oxLDL and hsCRP.
Results: Participants (n=755, 31 US sites) were 51±6 yrs,16% female, 46% non- white, 24% Latinx with CD4 636±275 cells/mm3 and well-controlled viremia (88%0, 23% vulnerable plaque (VP), and 16% high Leaman score >5 (LS). A minority had CAC>400 (2%) or luminal stenosis ≥50% (3%). Overall plaque burden included significant non-calcified plaque. Extent of CAD increased with ASCVD risk (Figure) but plaque (30%) and VP (13%) were seen even among participants with ASCVD risk <2.5%. MCP-1, IL-6, LpPLA2, and oxLDL were higher in those with plaque. hsCRP was higher in those with VP and LS >5. In fully adjusted modeling, including ASCVD risk score, significant associations were: 1) LpPLA2 with presence of plaque, CAC>0 and LS >5, 2) MCP-1 and IL-6 with presence of plaque, 3) hsCRP with LS>5. HIV indices were generally not significant in modeling. In subgroup analyses (< or ≥7.5% ASCVD risk), LpPLA2 associated with CAD in those with lower risk. In contrast, oxLDL and hsCRP most consistently associated with CAD in those with higher risk, with significant interaction terms.
Conclusion: In this primary prevention cohort with well-controlled HIV, we demonstrate a unique CAD phenotype, including a high prevalence of non- calcified non-obstructive and vulnerable plaque, associated with increased immune activation and arterial inflammation, independent of ASCVD risk. These data suggest the importance of developing tailored CVD prevention strategies targeting inflammation and immune activation in addition to traditional risk in this population.
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