ABC | Volume 111, Nº4, Octuber 2018

Original Article Predictors of Family Enrollment in a Genetic Cascade Screening Program for Familial Hypercholesterolemia Pãmela Rodrigues de Souza Silva, 1 Cinthia Elim Jannes, 1 Theo G. M. Oliveira, 1 Luz Marina Gómez Gómez, 1 José E. Krieger, 1 Raul D. Santos, 2 Alexandre Costa Pereira 1 Laboratório de Genética e Cardiologia Molecular do Instituto do Coração (InCor) da Faculdade de Medicina da Universidade de São Paulo, 1 São Paulo, SP – Brazil Clínica de Lípides do Instituto do Coração (InCor) da Faculdade de Medicina da Universidade de São Paulo, 2 São Paulo, SP – Brazil Mailing Address: Pãmela Rodrigues de Souza Silva • Av. Dr. Enéas de Carvalho Aguiar, 44. Postal Code 05403-900, Cerqueira César, São Paulo, SP – Brazil E-mail: pam_r_s@usp.br, pam_r_s@hotmail.com Manuscript received December 05, 2017, revised manuscript April 18, 2018, accepted April 25, 2018 DOI: 10.5935/abc.20180156 Abstract Background: Genetic cascade screening is the most cost-effective method for the identification of individuals with familial hypercholesterolemia (FH), but the best strategies for the enrollment of at-risk individuals in a FH screening program are not fully known. Objective: The aim of this study is to identify the best predictors of familial enrollment into genetic screening, using features derived from tested probands. Methods: One hundred and eighty-three index-cases (ICs) with a positive genetic result that had relatives screened from 01/2011 to 07/2015 were included. The response variable was the number of relatives for each enrolled IC. All variables in the study were based on ICs’ derived clinical and socioeconomical features. The effect size of predictor variables were obtained through a general linear model using a negative binomial regression link function. Significance was considered with a p < 0.05. Results: Mean IC age when enrolling into the program was 50 years old; 78.1% of individuals reported knowledge of relatives with dyslipidemia. Mean baseline LDL-cholesterol level was 316 ± 90 mg/dL. Referral origin through the cascade program website vs. tertiary care, IC LDL‑cholesterol and familial history of high LDL-cholesterol levels were independent predictors associated with a higher number of enrolled relatives. Conclusions: Our data suggest that FH cascade screening programs can predict family enrollment based on IC features. This information may be useful for devising better and more effective screening approaches for at-risk individuals. (Arq Bras Cardiol. 2018; 111(4):578-584) Keywords: Hypelipoproteinemia Type II/genetics; Mass Screening; Dyslipidemias/genetics; Hypercholesterolemia; Genetic Testing; Cholesterol. Introduction Familial hypercholesterolemia (FH) is a genetic disease characterized by elevated blood LDL cholesterol (LDL-C) levels. FH is usually caused by mutations in the gene encoding the LDL receptor ( LDLR ) and less frequently (~5% of cases) by mutations in genes coding for apolipoprotein-B ( APOB ) or proprotein convertase subtilisin/kexin type 9 ( PCSK9 ). Individuals carrying these mutations are exposed to high lipid levels and, thus, have a higher risk of developing early atherosclerotic cardiovascular disease and mortality. 1,2 The worldwide prevalence of heterozygous FH ranges between 1:200 and 1:500 individuals, varying in a few countries. 3,4 FH is an underdiagnosed disease and, therefore, most affected individuals do not have access to proper treatment until later in life. 5 FH diagnosis usually involves the identification of typical clinical signs of the disease such as high levels of LDL-C (> 190 mg/dL), tissue cholesterol deposition (e.g. tendon xanthomas and corneal arcus when detected in individuals less than 45 years old), a family history of high blood cholesterol and or early atherosclerotic disease. 6 In many instances, a typical FH index case (IC) is clinically diagnosed after the onset of an atherosclerotic cardiovascular event. Due to its autosomal dominant transmission, FH can and must be diagnosed early in asymptomatic relatives to start LDL-C lowering treatment with the aim of preventing cardiovascular disease onset. Genetic testing is important not only for diagnostic confirmation of index cases and in relatives, but also as a prognostic tool since recent evidence confirmed that the presence of FH-causing mutations implicates in higher cardiovascular risk even in comparison with other hypercholesterolemic individuals. 7,8 578