The aim of the genetic branch of this study is to report the relationship between certain SNPs and the risk of cardiovascular complications in hypertensive patients with coronary artery disease (CAD) confirmed by coronary angiography.Design and method:
In the present study, 1345 subjects with CAD were included. The median follow-up period was 8.6 years (interquartile range 6.1 to 11.1 years). 19 SNPs were investigated for any association with Major Advanced Cardiovascular (CV) Events (MACE), Acute Coronary Syndromes (ACS) and Revascularizations. The SNPs were genotyped using IPLEX reaction. SNPs with a genotyping success rate >90% and those with a minor allele frequency >5%. As a quality control, we re-genotyped a random sample of 20% of the successfully genotyped samples for all genotypes, and the concordance was 99.9%. We modelled the 19 SNPs as a multilocus genetic risk score (GRS19). A logistic regression model was used to examine the association between selected polymorphisms and the risk of MACE, ACS and revascularization. P-values were corrected by Bonferroni's procedure where it was necessary and false discovery rate procedure was performed as a multiple testing correction.Results:
During follow-up period, 245 participants died; 114 due to CV causes. A fatal or non-fatal CV event occurred in 882 participants including 214 ACS, 578 revascularizations and 90 strokes. The alleles of the following SNPs: rs1746048 (CXCL12), rs9818870 (MRAS) and rs17114036 (PPAP2B) were associated with a higher risk of MACE and the alleles of SNPs rs1746048 (CXCL12) and rs1122608 (LDLR) were associated with a higher risk of revascularization. The alleles of rs12190287 (MRAS), rs121902287 (TCF21) and rs2259816 (HNF1a) were associated with a higher risk of ACS. Despite the lack of relationship between significant CAD and GRS19, in the top quartile of GRS19 there was significant relationship between GRS19 and combined endpoint, MACE, ACS, and revascularisation (table).Conclusions:
In the present study, the SNPs of CXCL12 and LDLR were associated with risk of revascularization. The polymorphisms of CXCL12, LPA, MRAS, PPAP2B were associated with the risk of MACE. GRS19 determines CV complications in CAD patients with the highest genetic risk score values.