Dong Geum Shin1, Soo Min Han2, Doo Il Kim3, Moo-Yong Rhee4, Byoung-Kwon Lee5, Young Keun Ahn6, Byung Ryul Cho7, Jeong-Taek Woo8, Seung-Ho Hur9, Jin-Ok Jeong10, Yangsoo Jang11, Ji Hyun Lee12, Sang-Hak Lee13. 1. Division of Cardiology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. 2. Department of Pharmacology, Pharmacogenomic Research Center for Membrane Transporters, Brain Korea 21 PLUS Project for Medical Sciences, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea. 3. Cardiology Division, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea. 4. Cardiovascular Center, Dongguk University Ilsan Hospital, Goyang, Republic of Korea. 5. Division of Cardiology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. 6. Heart Center of Chonnam, National University Hospital, Gwangju, Republic of Korea. 7. Cardiology Division, Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University College of Medicine, Chuncheon, Republic of Korea. 8. Endocrinology Division, Department of Internal Medicine, Kyunghee University School of Medicine, Seoul, Republic of Korea. 9. Cardiology Division, Department of Internal Medicine, Keimyung University Dongsan Medical Center, Daegu, Republic of Korea. 10. Cardiology Division, Department of Internal Medicine, School of Medicine, Chungnam National University, Chungnam National University Hospital, Daejeon, Republic of Korea. 11. Division of Cardiology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; Cardiovascular Research Institute, Yonsei University Health System, Seoul, Republic of Korea. 12. Department of Oral Biology, College of Dentistry, Yonsei University, Seoul, Republic of Korea. Electronic address: jihyni@yuhs.ac. 13. Division of Cardiology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; Cardiovascular Research Institute, Yonsei University Health System, Seoul, Republic of Korea. Electronic address: shl1106@yuhs.ac.
Abstract
BACKGROUND: Proper screening and diagnosis of familial hypercholesterolemia (FH) is of critical importance for cardiovascular prevention. However, the clinical diagnosis of FH remains difficult partly because its phenotype can vary between different ethnicities. The aim of this study was to determine the clinical features and the best diagnostic approach in Korean FH patients. The predictors of putative pathogenic mutations and coronary artery disease (CAD) were also identified. METHODS AND RESULTS: Ninety-seven patients with low-density lipoprotein-cholesterol >190 mg/dL and xanthoma or FH-compatible family history were included. Putative pathogenic mutations in LDLR, APOB, or PCSK9 genes were identified in 32% of the enrolled patients. The subjects were classified according to four sets of clinical criteria (Simon Broome, Dutch, MEDPED, Japanese). The mutation rates in definite type FH of Simon Broome or Dutch criteria were 35%-37% and lower in our patients than in those of other countries. The mutation detection rate by MEDPED criteria was 67%-75% and higher than those based on other criteria. The best low-density lipoprotein-cholesterol (LDL-C) threshold for predicting mutations was 225 mg/dL. LDL-C was found to be the only independent predictor of mutation carriers, while hypertension and low high-density lipoprotein-cholesterol were predictive of CAD. CONCLUSIONS: The conventional clinical criteria showed limited mutation detection power and low specificities in Korean FH patients, in whom the best LDL-C threshold for putative mutation was 225 mg/dL. Traditional cardiovascular risk factors were also significantly associated with CAD risk in this population.
BACKGROUND: Proper screening and diagnosis of familial hypercholesterolemia (FH) is of critical importance for cardiovascular prevention. However, the clinical diagnosis of FH remains difficult partly because its phenotype can vary between different ethnicities. The aim of this study was to determine the clinical features and the best diagnostic approach in Korean FHpatients. The predictors of putative pathogenic mutations and coronary artery disease (CAD) were also identified. METHODS AND RESULTS: Ninety-seven patients with low-density lipoprotein-cholesterol >190 mg/dL and xanthoma or FH-compatible family history were included. Putative pathogenic mutations in LDLR, APOB, or PCSK9 genes were identified in 32% of the enrolled patients. The subjects were classified according to four sets of clinical criteria (Simon Broome, Dutch, MEDPED, Japanese). The mutation rates in definite type FH of Simon Broome or Dutch criteria were 35%-37% and lower in our patients than in those of other countries. The mutation detection rate by MEDPED criteria was 67%-75% and higher than those based on other criteria. The best low-density lipoprotein-cholesterol (LDL-C) threshold for predicting mutations was 225 mg/dL. LDL-C was found to be the only independent predictor of mutation carriers, while hypertension and low high-density lipoprotein-cholesterol were predictive of CAD. CONCLUSIONS: The conventional clinical criteria showed limited mutation detection power and low specificities in Korean FHpatients, in whom the best LDL-C threshold for putative mutation was 225 mg/dL. Traditional cardiovascular risk factors were also significantly associated with CAD risk in this population.