Abstract

BackgroundFamilial hypercholesterolemia (FH) can elevate serum low-density lipoprotein cholesterol (LDL-C) levels, which can promote the progression of acute coronary syndrome (ACS). However, the effect of FH on the prognosis of ACS remains unclear.MethodsIn this prospective cohort study, 223 patients with ACS having LDL-C ≥ 135.3 mg/dL (3.5 mmol/L) were enrolled and screened for FH using a multiple-gene FH panel. The diagnosis of FH was defined according to the ACMG/AMP criteria as carrying pathogenic or likely pathogenic variants. The clinical features of FH and the relationship of FH to the average 16.6-month risk of cardiovascular events (CVEs) were assessed.ResultsThe prevalence of molecularly defined FH in enrolled patients was 26.9%, and coronary artery lesions were more severe in patients with FH than in those without (Gensini score 66.0 vs. 28.0, respectively; P < 0.001). After lipid lowering, patients with FH still had significantly higher LDL-C levels at their last visit (73.5 ± 25.9 mg/dL vs. 84.7 ± 37.1 mg/dL; P = 0.013) compared with those without. FH increased the incidence of CVEs in patients with ACS [hazard ratio (HR): 3.058; 95% confidence interval (CI): 1.585–5.900; log-rank P < 0.001].ConclusionFH is associated with an increased risk of CVEs in ACS and is an independent risk factor for ACS. This study highlights the importance of genetic testing of FH-related gene mutations in patients with ACS.

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