Polygenic risk, aspirin and primary prevention of coronary artery disease.

Autor:	Yu C; School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia., Natarajan P; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA; Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, ; Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Patel AP; Simches Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA., Bhatia HS; Division of Cardiovascular Medicine, Department of Medicine, University of California San Diego, La Jolla, California, USA., Khera AV; Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA; Verve Therapeutics, Boston, Massachusetts  USA., Neumann JT; School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.; Department of Cardiology, University Heart & Vascular Center (UHZ), Hamburg, Germany.; German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany., Tsimikas S; Division of Cardiovascular Medicine, Department of Medicine, University of California San Diego, La Jolla, California, USA., Wolfe R; School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia., Nicholls SJ; School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.; Victorian Heart Institute, Monash University, Clayton, Victoria, Australia., Reid CM; School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.; School of Population Health, Curtin University, Perth WA, Australia., Zoungas S; School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia., Tonkin AM; School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia., McNeil JJ; School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia., Lacaze P; School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
Jazyk:	angličtina
Zdroj:	European heart journal. Cardiovascular pharmacotherapy [Eur Heart J Cardiovasc Pharmacother] 2024 Oct 25. Date of Electronic Publication: 2024 Oct 25.
DOI:	10.1093/ehjcvp/pvae085
Abstrakt:	Aims: Recent aspirin primary prevention trials failed to identify a net benefit of aspirin for preventing cardiovascular disease versus the harms of bleeding. This study aimed to investigate whether a high-risk subgroup, individuals with elevated genetic predisposition to coronary artery disease (CAD), might derive more benefit than harm with aspirin, compared to those with lower genetic risk. Methods and Results: We performed genetic risk stratification of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized controlled trial using a CAD polygenic risk score (GPSMult). For 12,031 genotyped participants (5,974 aspirin, 6,057 placebo) overall, we stratified them by GPSMult quintiles (q1-5), then examined risk of CAD (composite of myocardial infarction and coronary heart disease death) and bleeding events using Cox models. During a median 4.6 years of follow-up with randomization to 100 mg/day aspirin versus placebo, 234 (1.9%) participants had CAD and 373 (3.1%) had bleeding events. In the overall cohort, aspirin resulted in higher bleeding risk (adjusted Hazard Ratio [aHR]=1.30 [1.06-1.61], P=0.01) but no significant CAD reduction (aHR=0.84 [0.64-1.09], P=0.19). However, among the highest quintile of polygenic risk (q5, top 20% of the GPSMult distribution), there was a 47% reduction in risk of CAD events with aspirin (aHR=0.53 [0.31-0.90], P=0.02) without increased bleeding risk (aHR=1.05 [0.60-1.82], P=0.88). Interaction between the GPSMult and aspirin was significant for CAD (q5 versus q1, P=0.02) but not bleeding (P=0.80). Conclusion: The balance between net benefit and harm on aspirin in the primary prevention setting shifts favourably in individuals with an elevated genetic predisposition. (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)
Databáze:	MEDLINE
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