Abstract 13328: Impact of Cascade Screening for Familial Hypercholesterolemia on Cardiovascular Events

Abstract

Background: Familial hypercholesterolemia (FH) is an autosomal dominant disorder mainly caused by mutations in the low-density lipoprotein (LDL) receptor or associated genes, resulting in elevated serum cholesterol levels and an increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Early diagnosis and timely treatment can substantially lower the risk of ASCVD. In this sense, cascade screening could be one of the most useful options. However, few data exist regarding the impact of cascade screening for FH on the reduction of risk of ASCVD events. We aimed to evaluate the prognostic impact of cascade screening for FH. Methods: We retrospectively investigated the health records of 1,050 patients with clinically diagnosed FH, including probands and their relatives who were cascade-screened, who were referred to our institute. We used Cox models that were adjusted for established ASCVD risk factors to assess the association between cascade screening and major adverse cardiovascular events (MACE). The median period of follow-up was 12.3 years (interquartile range [IQR] = 9.1-17.5 years), and MACE included death from any causes or hospitalization due to ASCVD events. Results: During the observation period, 246 participants experienced MACE. The mean age of patients identified through cascade screening was 18-years younger than that of the probands (38.7 yr vs. 57.0 yr, P < 2.2 х 10 –16 ), with a lower proportion of ASCVD risk factors. Interestingly, patients identified through cascade screening under milder lipid-lowering therapies were at reduced risk for MACE (hazard ratio [HR] = 0.36; 95%CI = 0.22 to 0.60; P = 6.3 х 10 –5 ) when compared with the probands, even after adjusting for those known risk factors. Conclusions: The identification of patients with FH via cascade screening appeared to result in better prognoses.