Background: Familial hypercholesterolemia (FH) is an autosomal dominant monogenic disease characterized by high low-density lipoprotein cholesterol (LDL-C) levels. Although carrying causative FH variants is associated with coronary heart disease (CHD), it remains unclear whether disclosing its associated cardiovascular risk affects outcomes in patients with FH.
Objective: We aimed to evaluate the efficacy of providing future cardiovascular risk based on genetic testing in addition to a standard FH education program.
Methods: We conducted a randomized, wait-list controlled, open-label, single-center trial. In the intervention group, we reported a future cardiovascular risk based on the genetic testing adding to standard FH education at week 0. In the wait-list control group, we only disseminated standard FH education according to the guidelines at week 0; they later received a genetic testing-based cardiovascular risk assessment at week 24. The primary endpoint of this study was the plasma LDL-C level at week 24.
Results: Fifty eligible patients with clinically diagnosed FH, without a history of CHD, were allocated to the intervention group (n = 24) or the wait-list control group (n = 26). At week 24, the intervention group had a significantly greater reduction in LDL-C levels than the wait-list control group (mean changes, -13.1 mg/dL vs. 6.6 mg/dL; difference, -19.7 mg/dL; 95% confidence interval, -34 to -5.6; p = 0.009). This interventional effect was consistent with FH causative variant carriers but not with non-carriers.
Conclusions: In addition to standard FH care, providing future cardiovascular risk based on genetic testing can further reduce plasma LDL-C levels, particularly among FH causal variant carriers.
Registration: Japan Registry of Clinical Trials (jRCTs04218002). URL: https://jrct.niph.go.jp/latest-detail/jRCTs042180027.
Keywords: Coronary disease; Familial hypercholesterolemia; Genetic risk disclosure; Genomics; Randomized clinical trials.
Copyright © 2023. Published by Elsevier Inc.