Effectiveness of cascade testing strategies in relatives for familial hypercholesterolemia: A systematic review and meta-analysis

Leonardi-Bee J, Boateng C, Faria R, et al.



First published: December 1, 2021  DOI: 10.1016/j.atherosclerosis.2021.09.014


Background and aims

Cascade testing in relatives of index cases is the most cost-effective approach to identifying people with familial hypercholesterolemia (FH); however, it is currently unclear which strategy to contact relatives would be the most effective. A systematic review was performed to quantify the effectiveness of different strategies in cascade testing of FH.


Comprehensive searches of three electronic databases and grey literature sources were done (from inception to May 2020). Screening, data extraction and assessments of methodological quality were made independently by two reviewers. Meta-analyses of proportions were performed using random effects models. Effect measures are reported as percentages with 95% confidence intervals.


24 non-comparative studies were included, of which 11 used a direct, 8 used an indirect, and 5 used a combination of both direct and indirect cascade strategies. The median number of new relatives with FH per known index case was approximately 1. The combination strategy resulted in the largest yields of relatives tested for FH out of those contacted (40%, 95% CI 37%–42%, 1 study) and relatives responding to testing out of those contacted (54%, 1 study); however, the direct strategy had the largest yield of index cases participating in cascade testing out of those with FH confirmed (94%, 8 studies) compared to other strategies (p ≤ 0.01 for all comparisons).


Evidence is limited; however, a combination strategy, which allows the index case to decide on method of contacting relatives, appears to lead to better yields compared to using the direct or indirect strategy.

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