Centre for Genetic Origins of Health and Disease, School of Biomedical Sciences, University of Western Australia, Perth, Western Australia, Australia.
Centre for Genetic Origins of Health and Disease, School of Biomedical Sciences, Curtin University, Perth, Western Australia, Australia.
Clin Genet. 2020 Feb;97(2):257-263. doi: 10.1111/cge.13648. Epub 2019 Oct 9.
Familial hypercholesterolaemia (FH) is associated with increased risk of coronary artery disease (CAD); however, risk prediction and stratification remain a challenge. Genetic risk scores (GRS) may have utility in identifying FH patients at high CAD risk. The study included 811 patients attending the lipid disorders clinic at Royal Perth Hospital with mutation-positive (n = 251) and mutation-negative (n = 560) FH. Patients were genotyped for a GRS previously associated with CAD. Associations between the GRS, clinical characteristics, and CAD were assessed using regression analyses. The average age of patients was 49.6 years, and 44.1% were male. The GRS was associated with increased odds of a CAD event in mutation-positive [odds ratio (OR) = 3.3; 95% confidence interval (CI) = 1.3-8.2; P = .009] and mutation-negative FH patients (OR = 1.8; 95% CI = 1.0-3.3; P = .039) after adjusting for established predictors of CAD risk. The GRS was associated with greater subclinical atherosclerosis as assessed by coronary artery calcium score (P = .039). A high GRS was associated with CAD defined clinically and angiographically in FH patients. High GRS patients may benefit from more intensive management including lifestyle modification and aggressive lipid-lowering therapy. Further assessment of the utility of the GRS requires investigation in prospective cohorts, including its role in influencing the management of FH patients in the clinic.
家族性高胆固醇血症（FH）与冠心病（CAD）风险增加相关；然而，风险预测和分层仍然是一个挑战。遗传风险评分（GRS）可能有助于识别 CAD 风险高的 FH 患者。该研究纳入了 811 名在皇家珀斯医院脂质疾病诊所就诊的患者，其中突变阳性（n=251）和突变阴性（n=560）FH 患者。对患者进行了先前与 CAD 相关的 GRS 基因分型。使用回归分析评估 GRS 与临床特征和 CAD 之间的关系。患者的平均年龄为 49.6 岁，其中 44.1%为男性。在调整 CAD 风险的既定预测因素后，GRS 与突变阳性（比值比[OR]=3.3；95%置信区间[CI]：1.3-8.2；P=.009）和突变阴性 FH 患者（OR=1.8；95%CI：1.0-3.3；P=.039）的 CAD 事件发生风险增加相关。GRS 与冠状动脉钙评分（P=.039）评估的亚临床动脉粥样硬化程度增加相关。在 FH 患者中，高 GRS 与临床和血管造影定义的 CAD 相关。高 GRS 患者可能受益于更强化的管理，包括生活方式改变和积极的降脂治疗。进一步评估 GRS 的效用需要在前瞻性队列中进行研究，包括其在影响临床 FH 患者管理中的作用。
