TY - JOUR
T1 - 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
AU - Groenland, Eline H.
AU - Heidemann, Britt E.
AU - van der Laan, Sander W.
AU - van Setten, Jessica
AU - Koopal, Charlotte
AU - Bots, Michiel L.
AU - Asselbergs, Folkert W.
AU - Visseren, Frank L.J.
AU - Spiering, Wilko
N1 - Funding Information:
Folkert W Asselbergs is supported by UCL Hospitals NIHR Biomedical Research Centre.
Funding Information:
Dr. Sander W. van der Laan is funded through grants from the Netherlands CardioVascular Research Initiative of the Netherlands Heart Foundation ( CVON 2011/B019 and CVON 2017-20 : Generating the best evidence-based pharmaceutical targets for atherosclerosis [GENIUS I&II]). We are thankful for the support of the ERA-CVD program ‘druggable-MI-targets’ (grant number: 01KL1802 ), the EU H2020 TO_AITION (grant number: 848146 ), and the Leducq Fondation ‘PlaqOmics’ .
Funding Information:
The UCC-SMART study was financially supported by a grant of the University Medical Center Utrecht. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Dr. Sander W. van der Laan is funded through grants from the Netherlands CardioVascular Research Initiative of the Netherlands Heart Foundation (CVON 2011/B019 and CVON 2017-20: Generating the best evidence-based pharmaceutical targets for atherosclerosis [GENIUS I&II]). We are thankful for the support of the ERA-CVD program ‘druggable-MI-targets’ (grant number: 01KL1802), the EU H2020 TO_AITION (grant number: 848146), and the Leducq Fondation ‘PlaqOmics’.
Funding Information:
The UCC-SMART study was financially supported by a grant of the University Medical Center Utrecht . The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2022
PY - 2022/6
Y1 - 2022/6
N2 - 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.
AB - 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.
KW - Blood Pressure/genetics
KW - Cardiovascular Diseases/diagnosis
KW - Cholesterol, LDL
KW - Humans
KW - Myocardial Infarction
KW - Risk Factors
UR - http://www.scopus.com/inward/record.url?scp=85126580265&partnerID=8YFLogxK
U2 - 10.1016/j.atherosclerosis.2022.03.006
DO - 10.1016/j.atherosclerosis.2022.03.006
M3 - Article
C2 - 35317921
AN - SCOPUS:85126580265
SN - 0021-9150
VL - 350
SP - 102
EP - 108
JO - Atherosclerosis
JF - Atherosclerosis
ER -