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Coronary Artery Disease-associated and Longevity-associated Polygenic Risk Scores for Prediction of Coronary Artery Disease Events in Persons Living with HIV: The Swiss HIV Cohort Study


Schoepf, Isabella C; Thorball, Christian W; Ledergerber, Bruno; Engel, Tanja; Raffenberg, Marieke; Kootstra, Neeltje A; Reiss, Peter; Hasse, Barbara; Marzolini, Catia; Thurnheer, Christine; Seneghini, Marco; Bernasconi, Enos; Cavassini, Matthias; Buvelot, Hélène; Kouyos, Roger; Günthard, Huldrych F; Fellay, Jacques; Tarr, Philip E; Swiss HIV Cohort Study (2021). Coronary Artery Disease-associated and Longevity-associated Polygenic Risk Scores for Prediction of Coronary Artery Disease Events in Persons Living with HIV: The Swiss HIV Cohort Study. Clinical Infectious Diseases:Epub ahead of print.

Abstract

BACKGROUND

Coronary artery disease (CAD) is in part genetically determined. Aging is accentuated in people with HIV (PLWH). It is unknown whether genetic CAD event prediction in PLWH is improved by applying individual polygenic risk scores (PRS) and by considering genetic variants associated with successful aging and longevity.

METHODS

In Swiss HIV Cohort Study participants of self-reported European descent, we determined univariable and multivariable odds ratios (OR) for CAD events, based on traditional CAD risk factors, adverse antiretroviral exposures, and different validated genome-wide PRS. PRS were built from CAD-associated single nucleotide polymorphisms (SNPs), longevity-associated SNPs, or both.

RESULTS

We included 269 cases with CAD events between 2000-2017 (Median age 54 years, 87% male, 82% with suppressed HIV RNA) and 567 event-free controls. Clinical (i.e. traditional and HIV-related) risk factors, and PRS built from CAD-associated SNPs, longevity-associated SNPs, or both, each contributed independently to CAD events (p<0.001). Participants with the most unfavorable clinical risk factor profile (top quintile) had adjusted CAD-OR=17.82 (8.19-38.76), compared to participants in the bottom quintile. Participants with the most unfavorable CAD-PRS (top quintile) had adjusted CAD-OR=3.17 (1.74-5.79), compared to the bottom quintile. After adding longevity-associated SNPs to the CAD-PRS, participants with the most unfavorable genetic background (top quintile) had adjusted CAD-OR=3.67 (2.00-6.73), compared to the bottom quintile.

CONCLUSIONS

In Swiss PLWH, CAD prediction based on traditional and HIV-related risk factors was superior to genetic CAD prediction based on longevity- and CAD-associated PRS. Combining traditional, HIV-related and genetic risk factors provided the most powerful CAD prediction.

Abstract

BACKGROUND

Coronary artery disease (CAD) is in part genetically determined. Aging is accentuated in people with HIV (PLWH). It is unknown whether genetic CAD event prediction in PLWH is improved by applying individual polygenic risk scores (PRS) and by considering genetic variants associated with successful aging and longevity.

METHODS

In Swiss HIV Cohort Study participants of self-reported European descent, we determined univariable and multivariable odds ratios (OR) for CAD events, based on traditional CAD risk factors, adverse antiretroviral exposures, and different validated genome-wide PRS. PRS were built from CAD-associated single nucleotide polymorphisms (SNPs), longevity-associated SNPs, or both.

RESULTS

We included 269 cases with CAD events between 2000-2017 (Median age 54 years, 87% male, 82% with suppressed HIV RNA) and 567 event-free controls. Clinical (i.e. traditional and HIV-related) risk factors, and PRS built from CAD-associated SNPs, longevity-associated SNPs, or both, each contributed independently to CAD events (p<0.001). Participants with the most unfavorable clinical risk factor profile (top quintile) had adjusted CAD-OR=17.82 (8.19-38.76), compared to participants in the bottom quintile. Participants with the most unfavorable CAD-PRS (top quintile) had adjusted CAD-OR=3.17 (1.74-5.79), compared to the bottom quintile. After adding longevity-associated SNPs to the CAD-PRS, participants with the most unfavorable genetic background (top quintile) had adjusted CAD-OR=3.67 (2.00-6.73), compared to the bottom quintile.

CONCLUSIONS

In Swiss PLWH, CAD prediction based on traditional and HIV-related risk factors was superior to genetic CAD prediction based on longevity- and CAD-associated PRS. Combining traditional, HIV-related and genetic risk factors provided the most powerful CAD prediction.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:6 June 2021
Deposited On:14 Oct 2021 07:01
Last Modified:14 Oct 2021 07:02
Publisher:Oxford University Press
ISSN:1058-4838
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/cid/ciab521
PubMed ID:34091660

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