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

IF 3 2区医学 Q2 PERIPHERAL VASCULAR DISEASE Journal of atherosclerosis and thrombosis Pub Date : 2025-02-04 DOI:10.5551/jat.65369

Xiaojuan Xu, Wen Li, Fangyuan Liu, Changying Chen, Hankun Xie, Feifan Wang, Xu Han, Qian Zhuang, Xianghai Zhao, Junxiang Sun, Yunjie Yin, Pengfei Wei, Yanchun Chen, Song Yang, Chong Shen

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Abstract

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.

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