Work

Clinical and genetic predictors of LDL-C reduction during atorvastatin therapy after ST-elevation myocardial infarction

Year: 2026

Type: article

Abstract: Dyslipidemia and elevated low-density lipoprotein cholesterol (LDL-C) are major drivers of atherosclerotic cardiovascular disease, yet response to statin therapy varies between patients. We investigated clinical and genetic factors associated with LDL-C response to atorvastatin in patients with ST-elevation myocardial infarction (STEMI). A total of 93 patients underwent targeted next-generation sequencing of a pharmacogene panel, and LDL-C was measured at baseline and after 6 months. The mean ΔLDL-C was − 1.46 ± 0.97 mmol/L. After exclusion of singleton variants, 176 variants remained for analysis, including 68 rare variants (minor allele frequency < 0.05). In single-variant analyses adjusted for age, sex, smoking status, and baseline LDL-C, the CYP2C19 phenotype showed the strongest nominal association with ΔLDL-C, followed by KIF6 rs20455, ABCB1 rs3842, and APOB rs72654423; however, none remained significant after false discovery rate correction. Exploratory aggregate analyses showed associations between the transport pathway score and the weighted polygenic risk score and LDL-C response. In the burden model, CYP2C19 phenotype, transport gene variation, age, and baseline LDL-C were associated with ΔLDL-C. For the binary treatment endpoint, the full model combining clinical and genetic variables showed higher apparent in-sample discrimination than the genetic-only model (AUC 0.829 vs. 0.710; DeLong test p = 0.0044). These exploratory findings require independent validation before clinical application.

Source: Scientific Reports

DOI: 10.1038/s41598-026-68422-9