Polygenic risk and incident coronary heart disease in a large multiethnic cohort
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- dc.contributor.author Iribarren, Carlos
- dc.contributor.author Lu, Meng
- dc.contributor.author Elosua Llanos, Roberto
- dc.contributor.author Gulati, Martha
- dc.contributor.author Wong, Nathan D.
- dc.contributor.author Blumenthal, Roger S.
- dc.contributor.author Nissen Steven
- dc.contributor.author Rana, Jamal S.
- dc.date.accessioned 2025-02-18T06:18:01Z
- dc.date.available 2025-02-18T06:18:01Z
- dc.date.issued 2024
- dc.description.abstract Objective: Many studies support the notion that polygenic risk scores (PRS) improve risk prediction for coronary heart disease (CHD) beyond conventional risk factors. However, PRS are not yet considered risk-enhancing factor in guidelines. Our objective was to determine the predictive performance of a commercially available PRS (CARDIO inCode-Score®) compared with the Pooled Cohorts Equations (PCE) in a contemporary, multi-ethnic cohort. Methods: Participants (n = 63,070; 67 % female; 18 % non-European) without prior CHD were followed from 2007 through 12/31/2022. The association between the PRS and incident CHD was assessed using Cox regression adjusting for genetic ancestry and risk factors. Event rates were estimated by categories of PCE and by low/intermediate/high genetic risk within PCE categories; risk discrimination and net reclassification improvement (NRI) were also assessed. Results: There were 3,289 incident CHD events during 14 years of follow-up. Adjusted hazard ratio (aHR) for incident CHD per 1 SD increase in PRS was 1.18 (95 % CI:1.14-1.22), and the aHR for the upper vs lower quintile of the PRS was 1.66 (95 % CI:1.49-1.86). The association was consistent in both sexes, in European participants compared with all minority groups combined and was strongest in the first 5 years of follow-up. The increase in the C-statistic was 0.004 (0.747 vs. 0.751; p < 0.0001); the NRI was 2.4 (0.9-3.8) for the entire cohort and 9.7 (7.5-12.0) for intermediate PCE risk individuals. After incorporating high genetic risk, a further 10 percent of participants at borderline/intermediate PCE risk would be candidates for statin therapy. Conclusion: Inclusion of polygenic risk improved identification of primary prevention individuals who may benefit from more intensive risk factor modification.
- dc.format.mimetype application/pdf
- dc.identifier.citation Iribarren C, Lu M, Elosua R, Gulati M, Wong ND, Blumenthal RS, et al. Polygenic risk and incident coronary heart disease in a large multiethnic cohort. Am J Prev Cardiol. 2024 Mar 28;18:100661. DOI: 10.1016/j.ajpc.2024.100661
- dc.identifier.doi http://dx.doi.org/10.1016/j.ajpc.2024.100661
- dc.identifier.issn 2666-6677
- dc.identifier.uri http://hdl.handle.net/10230/69627
- dc.language.iso eng
- dc.publisher Elsevier
- dc.relation.ispartof Am J Prev Cardiol. 2024 Mar 28;18:100661
- dc.rights © 2024 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Clinical utility
- dc.subject.keyword Coronary heart disease
- dc.subject.keyword Polygenic risk score
- dc.subject.keyword Primary prevention
- dc.title Polygenic risk and incident coronary heart disease in a large multiethnic cohort
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion