SAT-250 Impact of Lipoprotein(a) on the Clinical Diagnosis of Familial Hypercholesterolaemia in Chinese

Abstract Disclosure: C. Tang: None. T. Lui: None. C. Lee: None. H. Fong: None. Y. Wong: None. W. Shiu: None. K.C. Tan: None. Introduction: Elevated lipoprotein(a) [Lp(a)] has been shown to affect the diagnosis of familial hypercholesterolaemia (FH) in Caucasians. Since there are differences in Lp(a) levels by race and ethnicity and East Asians tend to have lower levels, we have investigated firstly whether Chinese FH patients have increased Lp(a) levels, and secondly whether the use of Lp(a)-corrected LDL-cholesterol (LDL-C) influences the clinical diagnosis of FH using the Dutch Lipid Clinic Network (DLCN) diagnostic criteria. Method: Adult patients with a clinical diagnosis of FH (defined as DLCN criteria score of ≥3) were recruited from a tertiary lipid clinic. Lp(a) levels were measured by an isoform-insensitive assay (Tina-quant Lipoprotein(a) Gen.2 assay, Roche Diagnostics). The Lp(a) distribution in FH patients was compared with that of the general population from the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS) using Kernel density estimation. LDL-C was adjusted for Lp(a)-cholesterol using the Rosenson-Marcovina formula [Lp(a)-cholesterol, mg/dL = Lp(a), nmol/L * 0.077]. Diagnostic reclassification rates were determined after the adjustments. Results: 151 FH patients were recruited, and genetic testing had been performed in 120 patients. The median Lp(a) level of the FH cohort was significantly higher than that of the CRISPS cohort [54.2 nmol/L (20.0-169.1) vs 31.4 nmol/L (18.8-56.5) respectively, p < 0.001]. Thirty-two percent of the FH subjects had Lp(a) levels ≥125 nmol/L. Using Lp(a)-corrected LDL-C led to a decrease in DLCN score in 15 patients (10%) but resulted in down-classification in only 5 patients (3.3%). Four patients had their DLCN score categories changed from probable FH to possible FH. Only 1 patient was re-classified from possible FH to unlikely FH. The number of patients who were down-classified in mutation-positive FH (n = 94) and mutation-negative FH patients (n = 26) were 1 (1.1%) and 2 (7.7%), respectively. No mutation-positive patient was re-classified to unlikely FH. Conclusion: The use of Lp(a)-corrected LDL-C influences the diagnosis of FH in Chinese using the DLCN criteria, albeit to a smaller degree than in Caucasian patients. This may be due to genetic polymorphisms in apolipoprotein(a), with Chinese individuals having lower Lp(a) concentrations compared to other ethnicities. Presentation: Saturday, July 12, 2025