Molnar Stefan, Scharnagl Hubert, Delgado Graciela E, Krämer Bernhard K, Laufs Ulrich, März Winfried, Kleber Marcus E, Katzmann Julius L
Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology, Pneumology), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
Eur Heart J Qual Care Clin Outcomes. 2024 Nov 5;10(7):632-640. doi: 10.1093/ehjqcco/qcad075.
To investigate the prevalence of familial hypercholesterolaemia (FH) and compare the performance of clinical criteria and genetic testing in patients undergoing coronary angiography.
The prevalence of FH was determined with the Dutch Lipid Clinical Network (DLCN), US 'Make Early Diagnosis to Prevent Early Death' (US-MEDPED), Simon Broome (SB) criteria, the 'familial hypercholesterolaemia case ascertainment tool' (FAMCAT), and a clinical algorithm. Genetic screening was conducted with a custom array from Affymetrix (CARRENAL array) harbouring 944 FH mutations.The study cohort consisted of 3267 patients [78.6% with coronary artery disease (CAD)]. FH was diagnosed in 2.8%, 2.2%, 3.9%, and 7.9% using the DLCN, US-MEDPED, SB criteria, and the FAMCAT. The clinical algorithm identified the same patients as the SB criteria. Pathogenic FH mutations were found in 1.2% (1.2% in patients with CAD, 1.0% in patients without CAD). FH was more frequently diagnosed in younger patients. With genetic testing as reference, the clinical criteria achieved areas under the ROC curve [area under the curves (AUCs)] in the range of 0.56-0.68. Using only low-density lipoprotein cholesterol (LDL-C) corrected for statin intake, an AUC of 0.68 was achieved.
FH is up to four-fold more prevalent in patients undergoing coronary angiography than in contemporary cohorts representing the general population. Different clinical criteria yield substantially different diagnosis rates, overestimating the prevalence of FH compared with genetic testing. LDL-C testing alone may be sufficient to raise the suspicion of FH, which then needs to be corroborated by genetic testing.
In this study, we investigated the frequency of familial hypercholesterolaemia-a common genetic condition leading to markedly elevated low-density lipoprotein (LDL) cholesterol and increased risk of atherosclerosis-in 3267 patients undergoing coronary angiography according to commonly used diagnostic scoring systems and genetic testing.
调查家族性高胆固醇血症（FH）的患病率，并比较临床标准和基因检测在接受冠状动脉造影患者中的表现。
使用荷兰脂质临床网络（DLCN）、美国“早诊断防早死”（US-MEDPED）、西蒙·布鲁姆（SB）标准、“家族性高胆固醇血症病例确定工具”（FAMCAT）和一种临床算法来确定FH的患病率。使用来自Affymetrix的包含944个FH突变的定制芯片（CARRENAL芯片）进行基因筛查。研究队列由3267名患者组成[78.6%患有冠状动脉疾病（CAD）]。使用DLCN、US-MEDPED、SB标准和FAMCAT诊断出的FH患病率分别为2.8%、2.2%、3.9%和7.9%。临床算法识别出的患者与SB标准相同。在1.2%的患者中发现了致病性FH突变（CAD患者中为1.2%，无CAD患者中为1.0%）。FH在年轻患者中更常被诊断出。以基因检测为参考，临床标准的ROC曲线下面积[曲线下面积（AUC）]在0.56 - 0.68范围内。仅使用根据他汀类药物摄入量校正的低密度脂蛋白胆固醇（LDL-C），AUC为0.68。
接受冠状动脉造影的患者中FH的患病率比代表普通人群的当代队列高至多四倍。不同的临床标准产生的诊断率有很大差异，与基因检测相比高估了FH的患病率。仅进行LDL-C检测可能足以引发对FH的怀疑，随后需要通过基因检测来证实。
在本研究中，我们根据常用的诊断评分系统和基因检测，调查了3267名接受冠状动脉造影患者中家族性高胆固醇血症的频率，家族性高胆固醇血症是一种常见的遗传疾病，会导致低密度脂蛋白（LDL）胆固醇显著升高并增加动脉粥样硬化风险。
