Genetic variants associated with low-density lipoprotein cholesterol and systolic blood pressure and the risk of recurrent cardiovascular disease in patients with established vascular disease

Abstract

Background and aims: Polygenic risk scores (PRSs) can be used to quantify the effect of genetic contribution to LDL-cholesterol (LDL-C) and systolic blood pressure (SBP). Several PRSs for LDL-C and SBP have been shown to be associated with cardiovascular disease (CVD) in the general population. This study aimed to evaluate the effect of an LDL-C PRS and an SBP PRS on the risk of recurrent CVD in patients with CVD. Methods: Genotyping was performed in 4,416 patients included in the UCC-SMART study. Weighted LDL-C PRS (279 LDL-C-related SNPs) and SBP PRS (425 SBP-related SNPs) were calculated. Linear regression models were used to evaluate the relation between both PRSs and LDL-C and SBP. The effects of the LDL-C PRS and SBP PRS, and its combination on the risk of recurrent CVD (stroke, myocardial infarction, and vascular death) were analyzed with Cox proportional-hazard models. Results: Per SD increase in LDL-C PRS, LDL-C increased by 0.18 mmol/L (95%CI 0.15–0.21). Per SD increase in SBP PRS, SBP increased by 3.19 mmHg (95%CI 2.60–3.78). During a follow-up of 11.7 years (IQR 9.2–15.0) 1,198 recurrent events occurred. Neither the LDL-C nor the SBP PRS were associated with recurrent CVD (HR 1.05 per SD increase in LDL-C PRS (95%CI 0.99–1.11) and HR 1.04 per SD increase in SBP PRS (95%CI 0.98–1.10)). The combination of both scores was neither associated with recurrent CVD (HR 1.09; 95%CI 0.93–1.28). Conclusions: In patients with vascular disease, LDL-C PRS and SBP PRS, both separately and in combination, were not significantly associated with recurrent CVD.