A genetic risk score predicts cardiovascular events in patients with stable coronary artery disease

Background: Genetic risk scores (GRSs) may predict cardiovascular risk in community-based populations. However, studies investigating the association with recurrent cardiovascular events in patients with established coronary artery disease (CAD) are conflicting.

Methods: We genotyped 879 patients with high-risk stable CAD and created a GRS based on 45 single nucleotide polymorphisms previously reported to be associated with CAD in genome-wide association studies. Patients were categorised into high or low GRS according to the median GRS and followed for recurrent cardiovascular events using national Danish registries. The primary endpoint was a composite of myocardial infarction, coronary revascularisation, and cardiovascular death.

Results: Median (interquartile range) follow-up time was 2.8 (2.4-3.8)years. The cumulative incidence proportions of the primary endpoint at 1 and 3years were 6.4% and 11.5% in high-GRS patients vs. 2.5% and 7.3% in low-GRS patients. The corresponding relative risks were 2.56 (95% confidence interval (CI) 1.29-5.07), and 1.57 (95% CI 1.02-2.44). The adjusted hazard ratio (HR) of the primary endpoint was 1.50 (95% CI 1.00-2.25). The most pronounced effect of a high GRS was observed on coronary revascularisations (adjusted HR 2.10 [95% CI 1.08-4.07]). Risks of cardiovascular death (adjusted HR 1.07 [95% CI 0.46-2.48]) and all-cause death (adjusted HR 1.15 [95% CI 0.65-2.03]) were unaffected.

Conclusions: A GRS predicts recurrent cardiovascular events in high-risk stable CAD patients. The observed effect was mainly driven by coronary revascularisations.