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

Atherosclerosis. 2022 Jun:350:102-108. doi: 10.1016/j.atherosclerosis.2022.03.006. Epub 2022 Mar 11.


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.

Keywords: Cardiovascular events; Low-density lipoprotein cholesterol; Polygenic risk score; Secondary prevention; Systolic blood pressure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Pressure / genetics
  • Cardiovascular Diseases* / diagnosis
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / genetics
  • Cholesterol, LDL
  • Humans
  • Myocardial Infarction*
  • Risk Factors


  • Cholesterol, LDL