Mariko Harada-Shiba1, Junya Ako2, Atsushi Hirayama3, Masato Nakamura4, Atsushi Nohara5, Kayoko Sato6, Yoshitaka Murakami7, Ryusuke Koshida8, Asuka Ozaki8, Hidenori Arai9. 1. Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center Research Institute. 2. Department of Cardiovascular Medicine, Kitasato University. 3. Cardiovascular Division, Osaka Police Hospital. 4. Division of Cardiovascular Medicine, Toho University Ohashi Medical Center. 5. Department of Clinical Genetics, Ishikawa Prefectural Central Hospital. 6. Department of Cardiology, Tokyo Women's Medical University. 7. Department of Medical Statistics, Toho University. 8. Sanofi K.K. 9. National Center for Geriatrics and Gerontology.
Abstract
AIM: Genetic testing can provide a definitive diagnosis of familial hypercholesterolemia (FH). However, accessibility of genetic testing may be limited in certain countries where it is not considered "standard of care," including Japan. In addition, mutations responsible for FH cannot be identified in approximately 30% of patients. METHODS: EXPLORE-J is a multicenter, prospective, observational study of patients presenting with acute coronary syndrome (ACS). The genetic data were analyzed and adjudicated as pathogenic, indeterminate, or nondetectable pathogenic variant. RESULTS: Of 1,944 patients, 431 underwent genetic screening. Overall, most patients had nonpathogenic variants of LDLR, LDLRAP1, or PCSK9 (n=396, 91.9%). Of the 25 (5.8%) patients with pathogenic variants, variants of the LDLR gene and the PCSK9 gene were seen in 10 and 15 patients, respectively. Indeterminate variants were observed in 10 (2.3%) patients. Of the 431 patients, eight (1.9%) met the criteria for a diagnosis of FH using the Japanese Atherosclerosis Society (JAS) 2017 guidelines. When genetic data were incorporated, 33 (7.7%) patients met the JAS guidelines. No patients with FH pathogenic variants satisfied the JAS clinical criteria for a diagnosis of FH. CONCLUSIONS: The results revealed a higher prevalence of genetic mutations of FH among Japanese patients with ACS and a low sensitivity of the FH diagnostic criteria of the JAS 2017 guidelines. These findings highlight the difficulties of FH diagnosis in patients with ACS in the acute phase and suggest the importance of genetic testing and family history.
AIM: Genetic testing can provide a definitive diagnosis of familial hypercholesterolemia (FH). However, accessibility of genetic testing may be limited in certain countries where it is not considered "standard of care," including Japan. In addition, mutations responsible for FH cannot be identified in approximately 30% of patients. METHODS: EXPLORE-J is a multicenter, prospective, observational study of patients presenting with acute coronary syndrome (ACS). The genetic data were analyzed and adjudicated as pathogenic, indeterminate, or nondetectable pathogenic variant. RESULTS: Of 1,944 patients, 431 underwent genetic screening. Overall, most patients had nonpathogenic variants of LDLR, LDLRAP1, or PCSK9 (n=396, 91.9%). Of the 25 (5.8%) patients with pathogenic variants, variants of the LDLR gene and the PCSK9 gene were seen in 10 and 15 patients, respectively. Indeterminate variants were observed in 10 (2.3%) patients. Of the 431 patients, eight (1.9%) met the criteria for a diagnosis of FH using the Japanese Atherosclerosis Society (JAS) 2017 guidelines. When genetic data were incorporated, 33 (7.7%) patients met the JAS guidelines. No patients with FH pathogenic variants satisfied the JAS clinical criteria for a diagnosis of FH. CONCLUSIONS: The results revealed a higher prevalence of genetic mutations of FH among Japanese patients with ACS and a low sensitivity of the FH diagnostic criteria of the JAS 2017 guidelines. These findings highlight the difficulties of FH diagnosis in patients with ACS in the acute phase and suggest the importance of genetic testing and family history.
Entities:
Keywords:
Acute coronary syndrome; Familial hypercholesterolemia; Genetic testing; Japan
Authors: Sofia G Tsouli; Vasilios Xydis; Maria I Argyropoulou; Alexandros D Tselepis; Moses Elisaf; Dimitrios N Kiortsis Journal: Atherosclerosis Date: 2008-11-11 Impact factor: 5.162