Coronary Artery Disease–Based Polygenic Risk Score in Early-Onset Acute Myocardial Infarction Subtypes

Coronary Artery Disease–Based Polygenic Risk Score in Early-Onset Acute Myocardial Infarction Subtypes

Background: The coronary artery disease–based polygenic risk score (PRS-CAD) estimates risk of acute myocardial infarction (AMI), but its performance across AMI subtypes in younger individuals, especially women, remains uncertain. Objectives: The authors assessed PRS-CAD's performance in AMI su...

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Main Authors: Weilai Dong, MD, PhD, Yuan Lu, ScD, Shu-Xia Li, PhD, Mitsuaki Sawano, MD, PhD, Cesar Caraballo, MD, Yuntian Liu, MPH, Amit Khera, MD, MSc, Anthony Philippakis, MD, PhD, Rachel Dreyer, PhD, Judith Lichtman, PhD, MPH, Gail D'Onofrio, MD, MS, Erica S. Spatz, MD, MHS, David Herrington, MD, MHS, Wendy S. Post, MD, MS, Stephen S. Rich, PhD, Jerome I. Rotter, MD, Harlan M. Krumholz, MD, SM
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:JACC: Advances
Subjects:
acute myocardial infarction
polygenic risk score
subtypes
Online Access:http://www.sciencedirect.com/science/article/pii/S2772963X25004181
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Summary:Background: The coronary artery disease–based polygenic risk score (PRS-CAD) estimates risk of acute myocardial infarction (AMI), but its performance across AMI subtypes in younger individuals, especially women, remains uncertain. Objectives: The authors assessed PRS-CAD's performance in AMI subtypes. Methods: We included 2,079 AMI patients aged 18 to 55 years with a 2:1 female-to-male ratio from the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young Acute Myocardial Infarction Patients) study and 3,761 controls from the MESA (Multi-Ethnic Study of Atherosclerosis) study. AMI subtypes were classified using the VIRGO taxonomy. We evaluated PRS-CAD’s association with AMI subtypes using multinomial logistic regression and with 1-year outcomes in AMI subtypes using Cox regression. Results: PRS-CAD was significantly associated with MI due to coronary artery disease (N = 1,876; OR: 1.82 per 1-SD increase; 95% CI: 1.67-1.97; P < 0.001) but not with MI with nonobstructive coronary artery disease (N = 188; OR: 1.13 per 1-SD increase; 95% CI: 0.96-1.34; P = 0.14). PRS-CAD’s performance did not differ by sex. A 1-SD increase in PRS-CAD was associated with higher risk of 1-year hospitalization or death in patients with MI with nonobstructive coronary artery disease (HR: 1.50; 95% CI: 1.08-2.10; P = 0.02) but not in patients with MI due to coronary artery disease (HR: 0.98; 95% CI: 0.91-1.07; P = 0.67). Conclusions: PRS-CAD’s association with AMI varied by subtype but not by sex in young adults, warranting caution in application.
ISSN:2772-963X

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