Abstract
Aims: The aim of this study is to assess whether the family cascade screening strategy for identifying patients with heterozygous familial hypercholesterolaemia (HeFH) is associated with a reduction in cardiovascular events compared with opportunistic screening strategies.Methods and results: We retrospectively included 3232 patients, from the French FH registry, REFERCHOL, with a molecular diagnosis. We compared patients according to their screening strategy for HeFH: index cases (opportunistic screening) and cascade screening cases (patients diagnosed by cascade screening) on clinical and biological characteristics. We first compared patients according to screening modality using χ² and Student’s t-tests and performed multivariate logistic regression to assess the association between screening strategy and the risk of cardiovascular events. We finally performed the same tests in an age- and sex-matched subpopulation. Compared with index cases (2106 patients), cascade screening cases (1126 patients) started statin use 14 years earlier [18.1 (interquartile range 12.5–29.1) years vs. 31.8 (19.7–42.4) years, P < 0.001] and 8.3% had a cardiovascular event prior to the first visit, vs. 26.5% in the index cases group (P < 0.001). In multivariate logistic regression, the cascade screening was independently associated with 51% less atherosclerotic cardiovascular disease (ASCVD) than the opportunistic screening. Age at statin initiation was also associated with ASCVD, with a higher adjusted odd ratio for higher age categories. In an age- and sex-matched analysis, cascade screening was no longer associated with ASCVD, but age at statin initiation remained.Conclusion The cascade screening strategy for familial hypercholesterolaemia is associated with 51% fewer cardiovascular events in genetically confirmed heFH probably due to an earlier age at treatment initiation.