Familial hypercholesterolemia (FH) is an autosomal dominant inherited disorder characterized by severe hypercholesterolemia and significantly elevated levels of serum low-density lipoprotein cholesterol (LDL-C). Patients with FH are at an increased risk of premature atherosclerotic cardiovascular disease, and early detection and treatment can improve their survival rates.

This study aims to explore the clinical value and significance of screening for FH among patients with hypercholesterolemia in community populations.

During the period from July to December 2023, a total of 164 patients diagnosed with hyperlipidemia and exhibiting LDL-C levels ≥4.90 mmol/L underwent gene sequencing at Department of Cardiology, the Affiliated Suzhou Hospital of Nanjing Medical University and its 5 community health centers within the medical alliance. Based on quartile intervals of LDL-C levels, the patients were stratified into four groups: Q1 group (LDL-C ≤5.10 mmol/L, n=43), Q2 group (5.10 mmol/L≤LDL-C≤5.32 mmol/L, n=40), Q3 group (5.32 mmol/L≤LDL-C≤5.67 mmol/L, n=41), and Q4 group (LDL-C≥5.67 mmol/L, n=40). Baseline data and laboratory test results of the patients were collected.

A total of 164 patients with hypercholesterolemia were included, with a prevalence of awareness of dyslipidemia at 39.02% (64/164), and 21.95% (36/164) of the patients had previously taken lipid-lowering medications. The comparison of total cholesterol (TC) and LDL-C among Q1 to Q4 groups showed statistically significant differences (P<0.05). Physical examinations of the patients in all groups revealed no tendon xanthomas or corneal arcus, but one case in Q4 had a family history of premature coronary heart disease. The comparison of Dutch Clinical Lipid Network criteria scores and the proportion of suspected FH among Q1 to Q4 groups showed statistically significant differences (P<0.05). The main results of genetic sequencing in all groups were the diagnosis of FH, with a detection rate of FH gene mutations at 14.6% (24/164), including LDL receptor (LDLR) mutations accounting for 11.0% (18/164), apolipoprotein B (ApoB) mutations accounting for 3.1% (5/164), and proprotein convertase subtilisin/kexin type 9 (PCSK9) mutations accounting for 0.6% (1/164). The comparison of FH gene mutation detection rates, pathogenic, likely pathogenic, heterozygous genotypes, and LDLR proportions among Q1 to Q4 groups showed statistically significant differences (P<0.05). The secondary results of genetic sequencing, defined as suspected FH and other primary lipid metabolism abnormalities, showed a mutation rate of 70.12% (115/164). The comparison of secondary results of genetic sequencing among Q1 to Q4 groups showed no statistically significant differences (P>0.05) .

In community populations with hypercholesterolemia and LDL-C ≥ 4.9 mmol/L, the rate of FH gene mutations is relatively high, and the rate of other primary (genetic) lipid metabolism gene mutations is also high. Screening for FH among patients with hypercholesterolemia in community populations has significant clinical importance and value.

家族性高胆固醇血症（FH）是一种常染色体（共）显性遗传病，是严重的高胆固醇血症，血清低密度脂蛋白胆固醇（LDL-C）水平明显升高，这部分患者早发动脉粥样硬化性心血管疾病风险明显增加，早发现和尽早接受治疗可改善患者的存活率。

在高胆固醇血症患者中筛查FH，探讨社区人群筛查FH的临床价值、意义。

2023年7—12月纳入南京医科大学附属苏州医院心血管病中心及下属医联体5个社区卫生中心LDL-C≥4.90 mmol/L并完成基因测序的高胆固醇血症患者164例，根据LDL-C水平的四分位间距，分为Q1组（4.90 mmol/L≤LDL-C<5.10 mmol/L，n=43）、Q2组（5.10 mmol/L≤LDL-C<5.32 mmol/L，n=40）、Q3组（5.32 mmol/L≤LDL-C<5.67 mmol/L，n=41）、Q4组（5.67 mmol/L≤LDL-C<11.06 mmol/L，n=40）。收集患者基线资料和实验室检查结果。

共纳入高胆固醇血症患者164例，血脂异常知晓率为39.02%（64/164），21.95%（36/164）的患者既往服用降脂药，Q1~Q4组患者总胆固醇（TC）、LDL-C比较，差异有统计学意义（P<0.05）。各组患者体格检查，均未发现腱黄素瘤、脂性角膜弓，Q4组有1例患者有早发冠心病家族史。Q1~Q4组患者荷兰临床脂质网络标准评分、疑似FH比例比较，差异有统计学意义（P<0.05）。各组患者基因测序主要结果为确诊FH，FH基因变异检出率14.6%（24/164），其中低密度脂蛋白受体（LDLR）变异占11.0%（18/164），载脂蛋白B（ApoB）变异占3.1%（5/164），前蛋白转化酶枯草溶菌素9（PCSK9）变异占0.6%（1/164）。Q1~Q4组FH基因变异检出率、致病、可能致病、杂合基因型、LDLR比例比较，差异有统计学意义（P<0.05）。各组受试者基因测序次要结果定义为疑似FH及其他原发性脂代谢异常，疑似FH及其他脂代谢相关基因变异率为70.12%（115/164），Q1~Q4组基因测序次要结果比较，差异无统计学意义（P>0.05）。

社区人群高胆固醇血症LDL-C≥4.9 mmol/L的患者中，FH基因变异率较高，同时其他原发性（遗传性）脂代谢基因变异率较高，在社区人群高胆固醇血症患者中筛查FH有重要临床意义和价值。