Aim: In 2022, the Japan Atherosclerosis Society (JAS) has revised its clinical diagnostic criteria of familial hypercholesterolemia (FH) and adopted the use of definite, probable, possible, and unlikely FH according to the Dutch Lipid Clinic Network (DLCN) FH criteria. However, these strata have not been validated and their impact on coronary artery disease (CAD) is yet to be elucidated.
Methods: In this study, we retrospectively examined the patients with FH aged ≥ 15 years (N=857, male=431) who were admitted to Kanazawa University Hospital between 2010 and 2022. We assessed the prevalence of patients with a pathogenic variant as FH and odds ratio (OR) of CAD among each group determined by the JAS criteria 2022 for adults.
Results: In total, 414, 128, 142, and 173 patients were found to have definite, probable, possible, and unlikely FH, respectively, in this population. The prevalences of patients with a pathogenic variant as FH were 77.1%, 28.7%, 13.0%, and 1.2 %, respectively, among the definite, probable, possible, and unlikely FH patients (P-trend ＜0.001). Compared with the reference group of unlikely FH, patients with definite, probable, and possible FH were noted to have significantly higher adjusted odds of developing CAD (OR, 9.1; 95% confidence interval [CI], 3.2-12.6; P＜0.001 and OR, 4.2; 95% CI, 1.7-6.4; P＜0.001, and OR, 2.8; 95% CI, 1.2-4.4; P=0.002, respectively).
Conclusion: The new JAS diagnostic criteria for FH have been noted to work well in terms of diagnosing definitive, probable, or possible FH patients. Thus, it is seen to be of great help in terms of risk discrimination.
Keywords: Familial hypercholesterolemia; Genetics; Guideline; LDL cholesterol; LDL receptor.