Table1_Genetic testing for familial hypercholesterolemia in a Finnish cohort of patients with premature coronary artery disease and elevated LDL-C levels.docx

BackgroundBased on Finnish LDLR-founder variations, the prevalence of familial hypercholesterolemia (FH) in Finland is estimated to be at least 1:600. Patients with FH have increased risk of premature coronary artery disease (CAD) and thus the prevalence of FH is expected to be higher in this subgroup.
ObjectiveTo assess the prevalence of monogenic FH in a Finnish cohort of patients with premature CAD and elevated low-density lipoprotein cholesterol (LDL-C) levels.
MethodsAmong 28,295 patients undergoing angiography at Heart Hospital at Tampere University Hospital between 2007 and 2017, we identified 162 patients diagnosed with premature CAD (men aged <55 years and women aged <60 years) and history of high LDL-C (≥5 mmol/L) levels without secondary causes of hypercholesterolemia. Clinical probability of FH was estimated, and genetic testing of FH was carried out in 80 patients with informed consent.
ResultsOf the 80 patients with premature CAD and history of high LDL-C levels, 70% were men; the age at diagnosis of CAD for male and female patients was 48 and 53 years, respectively. In total, 58 (73%) patients had probable (n = 54) or definite (n = 4) FH based on Dutch Lipid Clinic Network criteria. A pathogenic variant of FH was found in five (6%) patients. Prevalence of the genetically verified FH was 1:16. The FH variant was found in 75% of patients with definite FH.
ConclusionsThe prevalence of genetically verified FH was 1:16 among patients with premature CAD and elevated LDL-C level, which is 38 times higher than the estimated prevalence of 1:600 in the general Finnish population.

背景 基于芬兰人群低密度脂蛋白受体（low-density lipoprotein receptor, LDLR）奠基者变异，芬兰家族性高胆固醇血症（familial hypercholesterolemia, FH）的患病率估计至少为1:600。家族性高胆固醇血症患者发生早发性冠状动脉疾病（coronary artery disease, CAD）的风险升高，因此该亚组人群的FH患病率预计更高。
目的 评估芬兰早发性冠状动脉疾病且低密度脂蛋白胆固醇（low-density lipoprotein cholesterol, LDL-C）水平升高的患者队列中单基因家族性高胆固醇血症的患病率。
方法 2007年至2017年间，在坦佩雷大学医院心脏医院接受血管造影的28295例患者中，我们筛选出162例确诊早发性冠状动脉疾病（男性年龄<55岁、女性年龄<60岁）且有低密度脂蛋白胆固醇≥5 mmol/L升高史、无继发性高胆固醇血症病因的患者。对FH的临床患病概率进行评估，并对80例签署知情同意书的患者开展FH基因检测。
结果 在80例早发性冠状动脉疾病且有低密度脂蛋白胆固醇升高史的患者中，70%为男性；男性和女性患者的冠状动脉疾病确诊年龄分别为48岁和53岁。根据荷兰脂质诊所网络标准，共计58例（73%）患者符合可能（n=54）或确诊（n=4）家族性高胆固醇血症判定标准。5例（6%）患者检出FH致病变异。基因验证的家族性高胆固醇血症患病率为1:16。在确诊家族性高胆固醇血症的患者中，75%检出FH致病变异。
结论 在早发性冠状动脉疾病且低密度脂蛋白胆固醇水平升高的患者中，基因验证的家族性高胆固醇血症患病率为1:16，较芬兰普通人群估计的1:600患病率高出38倍。