The Genetic Risk Score with Variants in PDGFs and PDGFRB for the Risk of Major Cardiovascular Adverse Events in Patients with Coronary Artery Disease.

Aims: Previous studies have linked platelet-derived growth factors (PDGFs) and their receptor beta (PDGFRB) genetic variants to coronary artery disease (CAD), but their impact on major adverse cardiovascular events (MACEs) remains unclear.

Methods: A cohort study of 3139 patients with CAD followed up until December 1, 2022 (median 5.42 years), genotyped 13 tagSNPs in PDGFs/PDGFRB pathway genes to establish weighted genetic risk scores (wGRS). Multiple Cox regression models analyzed the association of SNPs and wGRS with MACE outcomes using hazard ratios (HRs) and 95% confidence intervals (CIs). The wGRS improvement on traditional risk factors (TRFs) and the Global Registry of Acute Coronary Events (GRACE) score for MACEs were assessed using the C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI).

Results: Compared to low MACE-GRS (Q1 of quintile), high MACE-GRS (Q5 of quintile) had an increased risk of MACEs, with an adjusted HRs of 1.441 (P = 0.006). Compared to the TRF prediction model, the addition of MACE-GRS showed an improved discrimination with an NRI of 5.1% (95% CI, 0.7%-9.5%, P＜0.001) and IDI of 0.3% (95% CI, 0.0%-0.6%, P＜0.001). In addition, compared to the TRFs and GRACE score model, the addition of MACE-GRS showed an improved discrimination with an NRI of 5.1% (95% CI, 0.7%-9.6%, P＜0.001) and IDI of 0.3% (95% CI, 0.0%-0.5%, P＜0.001).

Conclusions: Variants in the PDGF-PDGFRB pathway genes contribute to the risk of MACEs after CAD, and the wGRS might be able to serve as a risk predictor of MACEs in addition to TRFs.