Jian-Jun Li1, Sha Li2, Cheng-Gang Zhu2, Na-Qiong Wu2, Yan Zhang2, Yuan-Lin Guo2, Ying Gao2, Xiao-Lin Li2, Ping Qing2, Chuan-Jue Cui2, Rui-Xia Xu2, Zheng-Wen Jiang2, Jing Sun2, Geng Liu2, Qian Dong2. 1. From the Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, XiCheng District, Beijing (J.-J.L., S.L., C.-G.Z., N.-Q.W., Y.Z., Y.-L.G., Y.G., X.-L.L., P.Q., C.-J.C., R.-X.X., J.S., G.L., Q.D.); and Genesky Biotechnologies Inc, PuDong New Area, Shanghai, China (Z.-W.J.). lijianjun938@126.com. 2. From the Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, XiCheng District, Beijing (J.-J.L., S.L., C.-G.Z., N.-Q.W., Y.Z., Y.-L.G., Y.G., X.-L.L., P.Q., C.-J.C., R.-X.X., J.S., G.L., Q.D.); and Genesky Biotechnologies Inc, PuDong New Area, Shanghai, China (Z.-W.J.).
Abstract
OBJECTIVE: 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. APPROACH AND RESULTS: 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%. CONCLUSIONS: 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.
OBJECTIVE: 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. APPROACH AND RESULTS: 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%. CONCLUSIONS: 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.
Authors: Mengmeng Shi; Xinyi Leng; Ying Li; Zihan Chen; Ye Cao; Tiffany Chung; Bonaventure Ym Ip; Vincent Hl Ip; Yannie Oy Soo; Florence Sy Fan; Sze Ho Ma; Karen Ma; Anne Y Y Chan; Lisa Wc Au; Howan Leung; Alexander Y Lau; Vincent Ct Mok; Kwong Wai Choy; Zirui Dong; Thomas W Leung Journal: Stroke Vasc Neurol Date: 2021-12-08