Familial Hypercholesterolemia Phenotype in Chinese Patients Undergoing Coronary Angiography

Familial hypercholesterolemia (FH) is characterized by an elevated low-density lipoprotein cholesterol and increased risk of premature coronary artery disease. However, the general picture and mutational spectrum of FH in China are far from recognized, representing a missed opportunity for the investigation.

A total of 8050 patients undergoing coronary angiography were enrolled. The diagnosis of clinical FH was made using Dutch Lipid Clinic Network criteria, and the information of relatives was obtained by inquiring for the probands or from their own medical records of certain clinics/hospitals. Molecular analysis of FH was performed using target exome sequencing in LDLR (low-density lipoprotein cholesterol receptor gene), APOB (apolipoprotein B gene), and PCSK9 (proprotein convertase subtilisin/kexin type 9 gene). As a result, 3.5% of the patients with definite/probable FH phenotype (definite 1.0% and probable 2.5%) were identified. Women FH had fewer premature coronary artery disease (women <60, or men <55 years of age) when compared with men FH (70.6% versus 82.7%; P<0.001), whereas angiographic extension of coronary artery disease was significantly increased with FH diagnosis in both men and women (P<0.001). Patterns of medication use in definite/probable FH were as follows: nontreated, 20.6%; low intensity, 6.0%; moderate intensity, 68.3%; and high intensity, 5.0%. However, none of them had achieved the low-density lipoprotein cholesterol <100 mg/dL. Additionally, mutational analysis was performed in 245 definite/probable FH cases, and risk variants were identified in 115 patients, giving a detection rate of 46.9%.

We showed firsthand a common identification but poor treatment of patients with FH phenotype in Chinese coronary angiography patients. Genetic data in our FH cases might contribute to update the frequency and spectrum of Chinese FH scenarios.