• Mohammadreza Naderian, Kristjan Norland, Daniel J Schaid, and Iftikhar J Kullo.
• Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota (M.N., K.N.).
• Ann. Intern. Med. 2024 Dec 10.

BackgroundClinical risk calculators for coronary heart disease (CHD) do not include genetic, social, and lifestyle-psychological risk factors.ObjectiveTo improve CHD risk prediction by developing and evaluating a prediction model that incorporated a polygenic risk score (PRS) and a polysocial score (PSS), the latter including social determinants of health and lifestyle-psychological factors.DesignCohort study.SettingUnited Kingdom.ParticipantsUK Biobank participants recruited between 2006 and 2010.MeasurementsIncident CHD (myocardial infarction and/or coronary revascularization); 10-year clinical risk based on pooled cohort equations (PCE), Predicting Risk of cardiovascular disease EVENTs (PREVENT), and QRISK3; PRS (Polygenic Score Catalog identification: PGS000018) for CHD (PRSCHD); and PSSCHD from 100 related covariates. Machine-learning and time-to-event analyses and model performance indices.ResultsIn 388 224 participants (age, 55.5 [SD, 8.1] years; 42.5% men; 94.9% White), the hazard ratio for 1 SD increase in PSSCHD for incident CHD was 1.43 (95% CI, 1.38 to 1.49; P < 0.001) and for 1 SD increase in PRSCHD was 1.59 (CI, 1.53 to 1.66, P < 0.001). Non-White persons had higher PSSCHD than White persons. The effects of PSSCHD and PRSCHD on CHD were independent and additive. At a 10-year CHD risk threshold of 7.5%, adding PSSCHD and PRSCHD to PCE reclassified 12% of participants, with 1.86 times higher CHD risk in the up- versus down-reclassified persons and showed superior performance compared with PCE as reflected by improved net benefit while maintaining good calibration relative to the clinical risk calculators. Similar results were seen when incorporating PSSCHD and PRSCHD into PREVENT and QRISK3.LimitationA predominantly White cohort; possible healthy participant effect and ecological fallacy.ConclusionA PSSCHD was associated with incident CHD and its joint modeling with PRSCHD improved the performance of clinical risk calculators.Primary Funding SourceNational Human Genome Research Institute.

9 keywords...

hide…