Impact of the clinical diagnostic strata of familial hypercholesterolemia on risk stratification among patients with hypercholesterolemia

Background and Aims In 2022, the Japan Atherosclerosis Society (JAS) revised clinical diagnostic criteria of familial hypercholesterolemia (FH), adopting the use of definite, probable, possible, and unlikely FH categories following the Dutch Lipid Clinic Network (DLCN) FH criteria. However, whether these strata would be useful for the risk stratification of coronary artery disease (CAD) events among patients with hypercholesterolemia is unclear. Methods We retrospectively reviewed the data of patients with hypercholesterolemia (LDL cholesterol ≥180 mg/dL) aged ≥15 years (N = 1,273, male = 631) admitted to a university hospital between 2000 and 2022. Using the Cox proportional hazard model, we assessed whether factors, including the diagnostic strata of FH, were associated with CAD events. Results We identified 572, 174, 196, and 331 patients with definite, probable, possible, and unlikely FH, respectively,. The prevalence of the pathogenic variant of FH was 71.0%, 25.9%, 11.7%, and 1.5%, respectively, among patients with definite, probable, possible, and unlikely FH (p < 0.001). We identified 144 CAD events during the 12.4 year median follow-up. Compared with the reference group of unlikely FH, subjects with definite, probable, and possible FH had significantly higher hazard ratios (HRs) of developing CAD events (HR, 6.84; 95% confidence interval [CI], 3.02–10.68; p < 0.001 and HR, 3.11; 95% CI, 1.61–4.61; p < 0.001, and HR, 1.90; 95% CI, 1.10–2.70; p = 0.02, respectively). Conclusion Among patients with hypercholesterolemia, the JAS clinical diagnostic strata of FH are useful for risk discrimination beyond their diagnosis as FH.