Noto Davide, Spina Rossella, Giammanco Antonina, Barbagallo Carlo M, Ganci Antonina, Scrimali Chiara, Brucato Federica, Misiano Gabriella, Ciaccio Marcello, Caldarella Rosalia, Cefalù Angelo B, Averna Maurizio
Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Italy.
Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Italy.
Atherosclerosis. 2022 Apr;347:63-67. doi: 10.1016/j.atherosclerosis.2022.03.012. Epub 2022 Mar 16.
Familial hypercholesterolemia (FH) is the most relevant genetic cause of early cardiovascular disease (CVD). FH is suspected when low density lipoprotein cholesterol (LDL-C) levels exceed the 95th percentile of the population distribution. Different diagnostic scoring systems have been developed, as the Dutch Lipid Clinic Network (DLCN) score, used worldwide. The aim of the study is to describe the characteristics of FH patients of a large cohort of more than eight hundred genotyped subjects enrolled in an Italian Lipid Clinic, and evaluate the DLCN score performance applied retrospectively to the case study.
836 hypercholesterolemic patients with LDL-C > 4.88 mmol/L were genotyped for FH causative gene variants in the LDLR, PCSK and APOB genes. Relatives of mutated patients were also analyzed by cascade screening.
Gene variant carriers were younger, presented higher LDL-C and DLCN score and lower HDL-C levels in comparison with hypercholesterolemic (HC) non-carriers and presented a five-fold higher prevalence of previous CV events. Carotid US data available in 490 subjects showed that variant carriers had an odds ratio of 3.66 (1.43-10.24) for atherosclerotic plaques in comparison with non-carriers. Scoring system were evaluated by ROC analysis in 203 subjects without missing DLCN items and with available pre-therapy LDL-C levels, and LDL-C levels (A.U.C. = 0.737) resulted to be more performing than the DLCN score (A.U.C. = 0.662), even including carotid US data (A.U.C. = 0.641) in a modified DLCN score version.
the DLCN score failed to demonstrate a clear superiority in predicting FH gene variants in comparison with the measure of LDL-C levels in a retrospective case study.
家族性高胆固醇血症（FH）是早期心血管疾病（CVD）最主要的相关遗传病因。当低密度脂蛋白胆固醇（LDL-C）水平超过人群分布的第95百分位数时，怀疑为FH。已开发出不同的诊断评分系统，如在全球范围内使用的荷兰脂质诊所网络（DLCN）评分。本研究的目的是描述在一家意大利脂质诊所登记的800多名基因分型受试者的大型队列中FH患者的特征，并评估回顾性应用于该病例研究的DLCN评分性能。
对836例LDL-C>4.88 mmol/L的高胆固醇血症患者进行FH致病基因变异的基因分型，这些变异存在于LDLR、PCSK和APOB基因中。突变患者的亲属也通过级联筛查进行分析。
与高胆固醇血症（HC）非携带者相比，基因变异携带者更年轻，LDL-C和DLCN评分更高，HDL-C水平更低，既往心血管事件的患病率高出五倍。490名受试者的颈动脉超声数据显示，与非携带者相比，变异携带者出现动脉粥样硬化斑块的优势比为3.66（1.43 - 10.24）。在203例无DLCN项目缺失且有治疗前LDL-C水平可用的受试者中，通过ROC分析评估评分系统，结果显示LDL-C水平（曲线下面积[A.U.C.] = 0.737）比DLCN评分（A.U.C. = 0.662）表现更好，即使在改良的DLCN评分版本中纳入颈动脉超声数据（A.U.C. = 0.641）也是如此。
在一项回顾性病例研究中，与LDL-C水平测量相比，DLCN评分未能显示出在预测FH基因变异方面的明显优势。
