Background: Familial hypercholesterolemia (FH) has been associated with early coronary artery disease (CAD) and increased risk of atherosclerotic cardiovascular disease. However, the prevalence of FH and its long-term outcomes in a CAD-high-risk cohort, defined as patients with hypercholesteremia who underwent coronary angiography, remains unknown. Besides, studies regarding the impact of genetic variations in FH on long-term cardiovascular (CV) outcomes are scarce. Methods and Results: In total, 285 patients hospitalized for coronary angiography with blood low-density lipoprotein cholesterol (LDL-C) levels ≥ 160 mg/dL were sequenced to detect FH genetic variations in LDL receptors apolipoprotein B and proprotein convertase subtilisin/kexin type 9. Risk factors associated with long-term CV outcomes were evaluated. The prevalence of FH was high (14.4%). CAD and early CAD were significantly more prevalent among FH variation carriers than non-carriers, despite comparable blood LDL-C levels. Moreover, the FH variation carriers also underwent more revascularization after a mean follow-up of 6.1 years. Multivariate logistic regression demonstrated that FH genetic variation was associated with increased incidence of cardiovascular disease and mortality (odds ratio = 3.17, p = 0.047). Two common FH variants, LDLR c.986G>A and LDLR c.268G>A, showed the most significant impacts on high blood LDL-C levels and early-onset CAD. Conclusions: Our results indicate that FH genetic variants may exhibit differential effects on early-onset CAD and revascularization risks in patients undergoing coronary angiography. FH genetic information might help identify high-risk patients with typical CAD symptoms for appropriate intervention.

中文翻译：

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接受冠状动脉造影的高胆固醇血症患者的家族性高胆固醇血症遗传变异和长期心血管结局

背景：家族性高胆固醇血症（FH）与早期冠状动脉疾病（CAD）和动脉粥样硬化性心血管疾病风险增加有关。然而，在 CAD 高风险队列（定义为接受冠状动脉造影的高胆固醇血症患者）中，FH 的患病率及其长期结果仍然未知。此外，关于 FH 遗传变异对长期心血管（CV）结果影响的研究很少。方法和结果：共对 285 例因血液低密度脂蛋白胆固醇 (LDL-C) ≥ 160 mg/dL 住院接受冠状动脉造影的患者进行测序，以检测 LDL 受体载脂蛋白 B 和前蛋白转化酶枯草杆菌蛋白酶 / kexin 型的 FH 遗传变异。 9. 评估了与长期 CV 结果相关的风险因素。FH 的患病率很高（14. 4%）。尽管血液 LDL-C 水平相当，但 FH 变异携带者中 CAD 和早期 CAD 的患病率明显高于非携带者。此外，FH 变异携带者在平均随访 6.1 年后也接受了更多的血运重建。多变量逻辑回归表明，FH 遗传变异与心血管疾病发病率和死亡率增加相关（优势比 = 3.17，p = 0.047）。两种常见的 FH 变异，LDLR c.986G>A 和LDLR c.268G>A，对高血 LDL-C 水平和早发性 CAD 的影响最为显着。结论：我们的结果表明，FH 基因变异可能对接受冠状动脉造影的患者的早发 CAD 和血运重建风险表现出不同的影响。FH 遗传信息可能有助于识别具有典型 CAD 症状的高危患者以进行适当干预。