A polygenic risk score for coronary heart disease performs well in individuals aged 70 years and older

Background The use of a polygenic risk score (PRS) to predict coronary heart disease (CHD) events has been demonstrated in the general adult population. However, whether predictive performance extends to older individuals is unclear. Aim To evaluate the predictive value of a PRS for incident CHD events in a prospective cohort of individuals aged 70 years and older. Methods We used data from 12,792 genotyped participants of the ASPREE trial, a randomized placebo-controlled trial investigating the effect of daily 100mg aspirin on disability-free survival in healthy older people. Participants had no previous history of diagnosed atherothrombotic cardiovascular events, dementia, or persistent physical disability at enrolment. We calculated a PRS comprising 1.7 million genetic variants (metaGRS). The primary outcome was a composite of incident myocardial infarction or CHD death over 5 years. Results At baseline, the median population age was 73.9 years and 54.9% were female. In total, 254 incident CHD events occurred. When the PRS was added to conventional risk factors, it was independently associated with CHD (hazard ratio 1.24 [95% confidence interval [CI] 1.08-1.42], p=0.002). The AUC of the conventional model was 70.53 (95%CI 67.00-74.06), and after inclusion of the PRS increased to 71.78 (95%CI 68.32-75.24, p=0.019), demonstrating improved prediction. Reclassification was also improved, as the continuous net reclassification index after adding PRS to the conventional model was 0.25 (95%CI 0.15-0.28). Conclusions A PRS for CHD performs well in older people, suggesting that the clinical utility of genomic risk prediction for CHD extends to this distinct high-risk subgroup.