Screening for Familial Hypercholesterolemia in Small Towns: Experience from 11 Brazilian Cities at the HipercolBrasil Program

Abstract Background: Familial hypercholesterolemia is an autosomal dominant disease clinically characterized by elevated serum levels of low density lipoprotein-cholesterol (LDL-C) and associated with the occurrence of early atherosclerotic cardiovascular disease. In Brazil, HipercolBrasil, currently the largest screening program underway, exists since 2012 and has already identified more than 2000 individuals with causal genetic variants for FH. The standard approach of HipercolBrasil is based on cascade-screening of refereed index cases, hypercholesterolemic individuals with a clinical suspicion of FH. Methodology: to assess a new methodology for identifying new individuals with genetic alterations for FH we performed a comprehensive city-wide screening in 11 small Brazilian cities (up to 60 thousand inhabitants). The selection of cities occurred in 3 ways: 1) cities with suspicious founder effect (4 cities); 2) Cities in a region with high rates of dyslipidemic individuals as described by the National Health System database (DATASUS) (2 cities); and 3) Cities geographically close to other cities with a high incidence of individuals with FH (5 cities). Results: One-hundred and five (105) index cases and 409 first-degree relatives were enrolled. The yield of such approach was significantly better than the general HipercolBrasil positivity rate in molecular screening. We identified 36 IC with a pathogenic or likely-pathogenic variants for FH and 240 affected first-degree relatives. Conclusion: our data suggest that once detected, specific geographical regions warrant a target approach for the identification of clusters of FH individuals.