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.
Keywords: Cardiovascular disease; Cascade screening; Familial hypercholesterolaemia; Familial hypercholesterolaemia screening; Paediatric screening.
Familial hypercholesterolaemia is a genetic disorder characterized by high plasma concentrations of LDL-cholesterol leading to a high or very high risk of atherosclerotic cardiovascular events during life. The first person in a family diagnosed with familial hypercholesterolaemia (mainly by measuring blood cholesterol) is called index case. Practitioners then use cascade screening to detect the disease in relatives of the index case. The aim of this article is to assess whether the cascade screening strategy for familial hypercholesterolemia is associated with less cardiovascular events compared with opportunistic screening. We compared the prevalence of cardiovascular events in patients with heterozygous familial hypercholesterolemia according to method of screening for the disease. We recruited 2106 index cases and 1126 cascade screening cases. Cascade screening cases started statins 14 years earlier (18.1 years vs. 31.8 years, P < 0.001) than index cases. In the cascade screening group, 8.3% had a cardiovascular event before the first visit, compared with 26.5% in the index case group (P < 0.001). Age at statin initiation was also associated with ASCVD, with a higher OR 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.
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