Impact of hyperlipoproteinemia(a) on the diagnosis of familial hypercholesterolemia and cardiovascular risk assessment

Aim. To assess the contribution of extremely elevated Lipoprotein(a) [Lp(a)] level to cardiovascular risk stratification using the SCORE-2 scale and the likelihood of familial hypercholesterolemia (FH) diagnosis. Material and methods. A retrospective cohort study included 45 patients (25 men) with hyperlipoproteinemia(a) from the federal registry "RENESSANS." Participants were over 40 years old and had Lp(a) levels ≥180 mg/dL. The diagnosis of heterozygous FH was confirmed using the Dutch Lipid Clinic Network (DLCN) criteria. Low-density lipoprotein cholesterol (LDL-C) levels were adjusted using Friedewald formula modified by Dahlen. Cardiovascular risk (SCORE-2) was calculated considering LDL-C levels before and after adjustment. Results. Among the 45 patients, the LDL-C level calculated using Friedewald formula was 5.1 [3.17; 7.19] mmol/L. After adjustment with Dahlen’s modification, the LDL-C level decreased to 3.03 [1.54; 4.96] mmol/L, representing a significant reduction (by 2.07 mmol/L or 40.6 %, p < 0.001). Adjusted LDL-C levels affected the FH diagnosis in 8 (26 %) out of 31 patients. Incorporating Lp(a) into the SCORE-2 risk assessment significantly increased cardiovascular risk estimates. The median SCORE-2 value initially was 14 % [7; 20], which increased to 27.2 % [13.6; 54.5] after adjustment, representing a 94 % increase (p < 0.005). Conclusion. Including Lp(a) in routine cardiovascular risk assessment and FH diagnosis is an important addition for more accurate risk stratification and appropriate pharmacological management. In patients with extreme hyperlipoproteinemia(a), LDL-C levels may be overestimated compared to true values, potentially affecting the accuracy of FH diagnosis and treatment strategies. Future multicenter studies should include larger and more diverse populations to validate these findings.