Moving beyond clinical risk factors for diagnosis: The necessity of systematic Lp(a) measurement and familial hypercholesterolemia genetic testing.

Source: PubMed, NCBI / U.S. National Library of Medicine

Elevated lipoprotein(a) [Lp(a)] and familial hypercholesterolemia (FH) are common, underdiagnosed monogenic dyslipidemias that significantly increase cardiovascular risk. We investigated whether standard clinical risk factors-low-density lipoprotein cholesterol (LDL-C), family history, and personal history of premature atherosclerotic cardiovascular disease (pASCVD)-can accurately distinguish these conditions. We analyzed 378 lipid clinic patients receiving Lp(a) screening and FH genetic testing with multinomial logistic regression. we found that while higher LDL-C and younger age were associated with FH, personal/family histories of pASCVD failed to differentiate between FH, elevated Lp(a), or dual diagnoses. Genetic testing for FH and Lp(a) measurement revealed that 22.5% had FH, 35.7% had elevated Lp(a), and 12.7% had both. Despite statistical associations, predicted probabilities for each diagnosis overlapped considerably, and clinical risk factors commonly used in FH clinical diagnostic criteria would insufficiently distinguish these genetic disorders. Results demonstrate that clinical risk factors and scoring systems cannot reliably substitute diagnostic FH genetic testing and Lp(a) measurement-essential for accurate diagnosis and management for these high-risk disorders.