Department of Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden.
Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
J Intern Med. 2018 Dec;284(6):674-684. doi: 10.1111/joim.12812. Epub 2018 Jul 29.
Familial hypercholesterolemia could be prevalent among patients with acute coronary syndrome.
To investigate both the frequency of causative mutations for familial hypercholesterolemia (FH) and the optimal selection of patients for genetic testing among patients with an acute coronary syndrome (ACS).
One hundred and sixteen patients with an ACS during 2009-2015 were identified through the SWEDEHEART registry. Patients who had either a high total cholesterol level ≥7 mmol L combined with a triglyceride level ≤2.6 mmol L , or were treated with lipid-lowering medication and had a total cholesterol level >4.9 mmol L and a triglyceride level ≤2.6 mmol L were included. Genetic testing was performed first with a regionally designed FH mutation panel (118 mutations), followed by testing with a commercially available FH genetic analysis (Progenika Biopharma).
A total of 6.9% (8/116) patients had a FH-causative mutation, all in the LDL-receptor. Five patients were detected on the panel, and further testing of the remaining 111 patients detected an additional 3 FH-causative mutations. Baseline characteristics were similar in FH-positive and FH-negative patients with respect to age, gender, prior ACS and diabetes. Patients with a FH-causative mutation had higher Dutch Lipid Clinical Network (DLCN) score (5.5 (5.0-6.5) vs 3.0 (2.0-5.0), P < 0.001) and a higher low-density lipoprotein level (5.7 (4.7-6.5) vs 4.9 (3.5-5.4), P = 0.030). The Dutch Lipid Clinical Network (DLCN) score had a good discrimination with an area under the curve of 0.856 (95% CI 0.763-0.949).
Genetic testing for FH should be considered in patients with ACS and high DLCN score.
家族性高胆固醇血症在急性冠脉综合征患者中可能较为常见。
旨在调查急性冠脉综合征（ACS）患者中家族性高胆固醇血症（FH）的致病突变频率以及遗传检测的最佳患者选择。
通过 SWEDEHEART 登记处确定了 2009-2015 年期间的 116 名 ACS 患者。将总胆固醇水平≥7 mmol/L 且甘油三酯水平≤2.6 mmol/L，或正在接受降脂药物治疗且总胆固醇水平>4.9 mmol/L 且甘油三酯水平≤2.6 mmol/L的患者纳入研究。首先进行区域性设计的 FH 突变面板（118 个突变）检测，然后使用商业 FH 遗传分析（Progenika Biopharma）进行检测。
共有 6.9%（8/116）的患者存在 FH 致病突变，均为 LDL 受体突变。8 例患者通过 panel 检测出突变，进一步检测其余 111 例患者发现了另外 3 个 FH 致病突变。FH 阳性和 FH 阴性患者的基线特征在年龄、性别、既往 ACS 和糖尿病方面相似。携带 FH 致病突变的患者具有更高的荷兰脂质临床网络（DLCN）评分（5.5（5.0-6.5）比 3.0（2.0-5.0），P<0.001）和更高的低密度脂蛋白水平（5.7（4.7-6.5）比 4.9（3.5-5.4），P=0.030）。荷兰脂质临床网络（DLCN）评分具有良好的区分度，曲线下面积为 0.856（95%CI 0.763-0.949）。
在 ACS 患者和高 DLCN 评分患者中，应考虑进行 FH 基因检测。
