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.