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

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

doi:10.1093/cid/ciac758

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

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

Authors

Isabella C Schoepf^{1

2

3}, Christian W Thorball^{4

5}, Helen Kovari⁶, Bruno Ledergerber⁶, Ronny R Buechel⁷, Alexandra Calmy⁸, Rainer Weber⁶, Philipp A Kaufmann⁷, René Nkoulou⁹, Johannes M Schwenke³, Dominique L Braun⁶, Jacques Fellay^{4

5}, Philip E Tarr³; Swiss HIV Cohort Study

Collaborators

Swiss HIV Cohort Study:
I Abela, K Aebi-Popp, A Anagnostopoulos, M Battegay, E Bernasconi, D L Braun, H C Bucher, A Calmy, M Cavassini, A Ciuffi, G Dollenmaier, M Egger, L Elzi, J Fehr, J Fellay, H Furrer, C A Fux, H F Günthard, A Hachfeld, D Haerry, B Hasse, H H Hirsch, M Hoffmann, I Hösli, M Huber, C R Kahlert, L Kaiser, O Keiser, T Klimkait, R D Kouyos, H Kovari, K Kusejko, G Martinetti, B Martinez de Tejada, C Marzolini, K J Metzner, N Müller, J Nemeth, D Nicca, P Paioni, G Pantaleo, M Perreau, A Rauch, P Schmid, R Speck, M Stöckle, P Tarr, A Trkola, G Wandeler, S Yerly

Affiliations

¹ Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.
² Hepatology, Department for Visceral Surgery and Medicine, Bern University Hospital, University of Bern, Bern, Switzerland.
³ University Department of Medicine and Infectious Diseases Service, Kantonsspital Baselland, University of Basel, Bruderholz, Switzerland.
⁴ Precision Medicine Unit, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁵ School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
⁶ Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁷ Department of Nuclear Medicine, Cardiac Imaging, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁸ Division of Infectious Disease, Geneva University Hospital, Geneva, Switzerland.
⁹ Division of Cardiology, University Hospital Geneva, University of Geneva, Geneva, Switzerland.

PMID: 36097729
DOI: 10.1093/cid/ciac758

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.

Keywords: HIV infection; aging; multivariable analysis; polygenic risk score; subclinical coronary artery disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carotid Intima-Media Thickness
Cohort Studies
Coronary Artery Disease* / complications
Coronary Artery Disease* / epidemiology
Coronary Artery Disease* / genetics
Female
HIV
HIV Infections* / complications
HIV Infections* / epidemiology
Humans
Male
Middle Aged
Risk Factors
Switzerland / epidemiology

Grants and funding

177499/SNSF_/Swiss National Science Foundation/Switzerland