Polygenic risk and incident coronary heart disease in a large multiethnic cohort
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-06-01
|
| Series: | American Journal of Preventive Cardiology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666667724000291 |
| _version_ | 1797221691638677504 |
|---|---|
| author | Carlos Iribarren Meng Lu Roberto Elosua Martha Gulati Nathan D. Wong Roger S. Blumenthal Steven Nissen Jamal S. Rana |
| author_facet | Carlos Iribarren Meng Lu Roberto Elosua Martha Gulati Nathan D. Wong Roger S. Blumenthal Steven Nissen Jamal S. Rana |
| author_sort | Carlos Iribarren |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T13:09:28Z |
| format | Article |
| id | doaj.art-4d6efadf5cc94724a96e6b32a43ce67f |
| institution | Directory Open Access Journal |
| issn | 2666-6677 |
| language | English |
| last_indexed | 2024-04-24T13:09:28Z |
| publishDate | 2024-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | American Journal of Preventive Cardiology |
| spelling | doaj.art-4d6efadf5cc94724a96e6b32a43ce67f2024-04-05T04:41:45ZengElsevierAmerican Journal of Preventive Cardiology2666-66772024-06-0118100661Polygenic risk and incident coronary heart disease in a large multiethnic cohortCarlos Iribarren0Meng Lu1Roberto Elosua2Martha Gulati3Nathan D. Wong4Roger S. Blumenthal5Steven Nissen6Jamal S. Rana7Kaiser Permanente Northern California Division of Research, Oakland, CA, USA; Corresponding author at: Division of Research, Kaiser Permanente Northern California, 2000 Broadway, Oakland, CA 94612, USA.Kaiser Permanente Northern California Division of Research, Oakland, CA, USACardiovascular Epidemiology and Genetics, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Spain and CIBER Cardiovascular Diseases (CIBERCV), Barcelona, Spain; Faculty of Medicine, University of Vic-Central University of Catalonia (UVic-UCC), Vic, SpainBarbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USAHeart Disease Prevention Program, Division of Cardiology, Department of Medicine, University of California Irvine, Irvine, CA, USACiccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins School of Medicine, Baltimore, MD, USACardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USAKaiser Permanente Northern California Division of Research, Oakland, CA, USA; Department of Cardiology, The Permanente Medical Group, Kaiser Permanente Oakland Medical Center, Oakland, CA, USAObjective: 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.http://www.sciencedirect.com/science/article/pii/S2666667724000291Polygenic risk scoreCoronary heart diseaseClinical utilityPrimary prevention |
| spellingShingle | Carlos Iribarren Meng Lu Roberto Elosua Martha Gulati Nathan D. Wong Roger S. Blumenthal Steven Nissen Jamal S. Rana Polygenic risk and incident coronary heart disease in a large multiethnic cohort American Journal of Preventive Cardiology Polygenic risk score Coronary heart disease Clinical utility Primary prevention |
| title | Polygenic risk and incident coronary heart disease in a large multiethnic cohort |
| title_full | Polygenic risk and incident coronary heart disease in a large multiethnic cohort |
| title_fullStr | Polygenic risk and incident coronary heart disease in a large multiethnic cohort |
| title_full_unstemmed | Polygenic risk and incident coronary heart disease in a large multiethnic cohort |
| title_short | Polygenic risk and incident coronary heart disease in a large multiethnic cohort |
| title_sort | polygenic risk and incident coronary heart disease in a large multiethnic cohort |
| topic | Polygenic risk score Coronary heart disease Clinical utility Primary prevention |
| url | http://www.sciencedirect.com/science/article/pii/S2666667724000291 |
| work_keys_str_mv | AT carlosiribarren polygenicriskandincidentcoronaryheartdiseaseinalargemultiethniccohort AT menglu polygenicriskandincidentcoronaryheartdiseaseinalargemultiethniccohort AT robertoelosua polygenicriskandincidentcoronaryheartdiseaseinalargemultiethniccohort AT marthagulati polygenicriskandincidentcoronaryheartdiseaseinalargemultiethniccohort AT nathandwong polygenicriskandincidentcoronaryheartdiseaseinalargemultiethniccohort AT rogersblumenthal polygenicriskandincidentcoronaryheartdiseaseinalargemultiethniccohort AT stevennissen polygenicriskandincidentcoronaryheartdiseaseinalargemultiethniccohort AT jamalsrana polygenicriskandincidentcoronaryheartdiseaseinalargemultiethniccohort |