Article Impact Level: HIGH Data Quality: STRONG Summary of Annals of Internal Medicine, ANNALS-24-00716. https://doi.org/10.7326/ANNALS-24-00716 Dr. Mohammadreza Naderian et al.
Points
- The study aimed to improve coronary heart disease (CHD) risk prediction by adding a polygenic risk score (PRSCHD) and a polysocial score (PSSCHD) to clinical risk calculators like PCE, PREVENT, and QRISK3.
- PRSCHD and PSSCHD were significantly linked to CHD incidence, with hazard ratios of 1.59 for PRSCHD and 1.43 for PSSCHD, highlighting their predictive value.
- Adding PRSCHD and PSSCHD reclassified 12% of participants at the 7.5% 10-year CHD risk threshold, effectively identifying individuals with nearly twice the risk compared to down-reclassified individuals.
- The integration of PRSCHD and PSSCHD improved the net benefit, calibration, and overall accuracy of clinical risk calculators, outperforming standard models.
- The findings were derived from a predominantly White cohort, which may limit generalizability, and the ecological fallacy could influence the interpretation of social determinants.
Summary
This study aimed to improve coronary heart disease (CHD) risk prediction by incorporating a polygenic risk score (PRS) and a polysocial score (PSS) into clinical risk calculators. The researchers used data from 388,224 UK Biobank participants (mean age 55.5 years; 42.5% male; 94.9% White) recruited between 2006 and 2010. The study included clinical risk models such as pooled cohort equations (PCE), Predicting Risk of Cardiovascular Disease EVENTS (PREVENT), and QRISK3. Additionally, they integrated a polygenic risk score for CHD (PRSCHD) and a polysocial score for CHD (PSSCHD), which incorporated social determinants of health and lifestyle-psychological factors. The main objective was to evaluate whether adding these scores improved the prediction of incident CHD, defined as myocardial infarction or coronary revascularization.
The study found that both PSSCHD and PRSCHD were significantly associated with the incidence of CHD. For every 1 SD increase in PSSCHD, the hazard ratio for incident CHD was 1.43 (95% CI, 1.38–1.49, P < 0.001), and for PRSCHD, the hazard ratio was 1.59 (95% CI, 1.53–1.66, P < 0.001). Adding both scores to the clinical risk calculators led to a 12% reclassification of participants at a 10-year CHD risk threshold of 7.5%. The reclassified individuals had 1.86 times higher CHD risk compared to those who were down-reclassified. Incorporating these scores improved the net benefit of the PCE model, maintained good calibration, and outperformed the standard clinical calculators. These findings were consistent when PSSCHD and PRSCHD were added to the PREVENT and QRISK3 models.
While the study highlights the value of incorporating genetic and social factors into CHD risk prediction, it is limited by the predominantly White cohort and the potential ecological fallacy. Overall, the study suggests that combining PSSCHD with PRSCHD enhances the accuracy of CHD risk prediction and could help improve clinical decision-making and interventions.
Link to the article: https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2826335
References Naderian, M., Norland, K., Schaid, D. J., & Kullo, I. J. (2024). Development and evaluation of a comprehensive prediction model for incident coronary heart disease using genetic, social, and lifestyle–psychological factors: A prospective analysis of the uk biobank. Annals of Internal Medicine, ANNALS-24-00716. https://doi.org/10.7326/ANNALS-24-00716
