纳入血浆脂蛋白(a)的家族性高胆固醇血症改良诊断模型的探索性研究

目的:本研究旨在建立纳入血浆脂蛋白(a)Lp(a)]的家族性高胆固醇血症(FH)的改良诊断模型,并将其诊断性能与荷兰脂质诊所网络(DLCN)标准、中国人群FH简化诊断标准(CSCFH)进行比较。方法:选取2011年5月至2018年1月期间接受冠状动脉造影的受试者10320例用于FH改良诊断模型的建立(7740例为建模人群,2580例为外部验证人群),在DLCN标准的基础上得到改良诊断模型。结果:FH改良诊断模型的诊断项目包括未经治疗的低密度脂蛋白胆固醇(LDL-C)水平、Lp(a)、早发冠心病、肌腱黄色瘤和早发冠心病家族史或高胆固醇血症家族史,并给以上指标确定分值,将总分≥6分时可诊断为临床FH。改良诊断模型与DLCN标准一致性良好,在建模人群中κ=0.766,在外部验证人群中κ=0.721(P均<0.001),与CSCFH的一致性一般(κ=0.495)。结论:纳入Lp(a)的新型改良诊断模型具有较好的诊断效能,可以为中国人群的FH诊断提供新的见解。

Exploratory Study on a Modified Algorithm Including Lipoprotein(a) for Diagnosis of Familial Hypercholesterolemia

Objectives:We aimed to develop a modified model including lipoprotein(a)Lp(a)]for the diagnosis of familial hypercholesterolemia(FH)and further compared its diagnostic performance with Dutch Lipid Clinic Network(DLCN)criteria and a newly developed Chinese Simplified Criteria for FH(CSCFH).Methods:Data of 10320 individuals,who underwent coronary angiography from May 2011 to January 2018,were utilized for the model establishment(7740 for derivation and 2580 for validation).The novel score model was modified on the basis of DLCN.Major index included:LDL-C level,Lp(a)level,history of premature coronary artery disease,tendon xanthomas,family history of early onset coronary artery disease or FH among primary relatives of the patients.Results:The novel modified model consisted of untreated low-density lipoprotein cholesterol(LDL-C)level,Lp(a),personal premature coronary heart disease(CHD),tendon xanthomas and family history of coronary artery disease and/or hypercholesterolemia.This modified model showed high discrimination efficacy for distinguishing clinical FH from non-FH in derivation population and validation population.Furthermore,a concordance analysis was performed to compare the modified model with DLCN and results showed a good agreement with DLCN(κ=0.766).External validation of the novel model also showed good accordance(κ=0.721).Compared to CSCFH,the agreement of the medified model was fair.Conclusions:The novel modified model,including Lp(a),could provide new insights into FH diagnosis with special adaption in Chinese population.