Proteomic Signature of Subclinical Coronary Artery Disease in People With HIV: Analysis of the REPRIEVE Mechanistic Substudy

Márton Kolossváry; Chris deFilippi; Michael T Lu; Markella V Zanni; Evelynne S Fulda; Borek Foldyna; Heather Ribaudo; Thomas Mayrhofer; Ann C Collier; Gerald S Bloomfield; Carl Fichtenbaum; Edgar T Overton; Judith A Aberg; Judith Currier; Kathleen V Fitch; Pamela S Douglas; Steven K Grinspoon

doi:10.1093/infdis/jiac196

Proteomic Signature of Subclinical Coronary Artery Disease in People With HIV: Analysis of the REPRIEVE Mechanistic Substudy

J Infect Dis. 2022 Nov 11;226(10):1809-1822. doi: 10.1093/infdis/jiac196.

Authors

Márton Kolossváry¹, Chris deFilippi², Michael T Lu¹, Markella V Zanni³, Evelynne S Fulda³, Borek Foldyna¹, Heather Ribaudo⁴, Thomas Mayrhofer^{1

5}, Ann C Collier⁶, Gerald S Bloomfield⁷, Carl Fichtenbaum⁸, Edgar T Overton⁹, Judith A Aberg¹⁰, Judith Currier¹¹, Kathleen V Fitch³, Pamela S Douglas⁷, Steven K Grinspoon³

Affiliations

¹ Cardiovascular Imaging Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
² Inova Heart and Vascular Institute, Falls Church, Virginia, USA.
³ Metabolism Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
⁴ Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston Massachusetts, USA.
⁵ School of Business Studies, Stralsund University of Applied Sciences, Stralsund, Germany.
⁶ Department of Medicine, University of Washington, Seattle, Washington, USA.
⁷ Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
⁸ Department of Medicine for Translational Research, University of Cincinnati, Cincinnati, Ohio, USA.
⁹ Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.
¹⁰ Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹¹ Division of Infectious Diseases, University of California at Los Angeles, Los Angeles, California, USA.

Abstract

Background: People with HIV (PWH) have subclinical coronary artery disease (CAD) despite low traditional atherosclerotic cardiovascular disease (ASCVD) risk scores. Coronary plaque in PWH presents as a unique phenotype, but little is known about the contributions of specific inflammatory pathways to plaque phenotypes in PWH.

Methods: The REPRIEVE Mechanistic Substudy enrolled PWH on ART without known cardiovascular disease. We used a targeted discovery proteomics approach to evaluate 246 unique proteins representing cardiovascular, inflammatory, and immune pathways. Proteomic signatures were determined for presence of coronary artery calcium (CAC > 0) and presence of coronary plaque.

Results: Data were available for 662 participants (aged 51 [SD 6] years, ASCVD risk score 4.9% [SD 3.1%]). Among 12 proteins associated with both CAC and presence of coronary plaque, independent of ASCVD risk score, the odds ratios were highest for NRP1: 5.1 (95% confidence interval [CI], 2.3-11.4) for CAC and 2.9 (95% CI, 1.4-6.1) for presence of plaque. Proteins uniquely related to presence of plaque were CST3, LTBR, MEPE, PLC, SERPINA5, and TNFSF13B; in contrast, DCN, IL-6RA, OSMR, ST2, and VCAM1 were only related to CAC.

Conclusions: Distinct immune and inflammatory pathways are differentially associated with subclinical CAD phenotypes among PWH. This comprehensive set of targets should be further investigated to reduce atherosclerosis and ASCVD in PWH.

Clinical trials registration: NCT02344290.

Keywords: CTA; HIV; coronary artery disease; plaque; proteomics.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Atherosclerosis*
Cardiovascular Diseases* / complications
Coronary Artery Disease* / complications
HIV Infections* / drug therapy
Humans
Plaque, Atherosclerotic*
Proteomics
Risk Assessment
Risk Factors

Associated data

ClinicalTrials.gov/NCT02344290

Abstract

Publication types

MeSH terms

Associated data

Grants and funding