ABC | Volume 111, Nº4, Octuber 2018

Original Article Silva et al Predictors of family enrollment Arq Bras Cardiol. 2018; 111(4):578-584 Table 3 – Parameters associated with relatives’ inclusion in the cascade screening according to multiple negative binomial regression analysis Predictors Estimate Std. Error p value * Origin (website) † -0.846 0.339 0.012 Family history of increased LDL-C levels 0.565 0.210 0.007 LDL-C 0.002 0.000 0.004 * p value < 0.05. † IC origin was defined according to whom or from where the patient was referred to the program. Website: by the patient itself via the program website. LDL-C: Low-density lipoprotein cholesterol. Once enrolled in the program, ICs are provided with systematic recommendations about the importance of family screening, mainly due to the possible identification of at-risk individuals, which makes genetic testing of great importance. Genetic testing not only confirms the ICs’ clinical diagnosis, but also elucidates the family history of dyslipidemia and the existence of at-risk relatives. 15 Relatives frequently underestimate the disease risks and are not aware of their condition, increasing the chance of early atherosclerotic cardiovascular event onset. 16–18 Sometimes, even though embodied with knowledge of the importance of genetic testing, they remain reluctant to participate due to the lack of motivation. 19 The cascade effectiveness depends on the ICs’ agreement to recruit relatives through the program and on the actual enrollment of these relatives, so that the ideal scenario is the enrolment of all eligible individuals. 20,21 To find the best strategy for familial enrollment in a cascade screening program is relevant and impacts the overall cascade’s cost-effectiveness. The Dutch FH cohort reported the obstacles in recruiting relatives after 5 years of cascade screening, 22 even with a relatively efficient rate of enrollment. Some of the most important raised points are the social and ethical questions surrounding genetic testing, but also the fact that many participants died before having the chance to enroll in the cascade. Many countries have already implemented this form of detection, revealing its feasibility 9,13,14,22 which is considered the gold-standard method referred by the NICE guidelines. 16 Recruiting ICs via website was a factor that decreased the chance of familial enrollment when compared to ICs referred from the Lipid Clinic of the Heart Institute, a tertiary referral center. This result is probably related to both the amount of information that ICs receive and the severity of the ICs’ condition. Those recruited by specialists of tertiary health centers are more conscious about their risks as well as for their relatives. On the other hand, those recruited via website are only guided by the screening program. Therefore, the amount of information delivered by the screening program only might not be enough for the ICs to understand the importance of family enrollment, suggesting that awareness should be emphasized even after several visits. Unexpectedly, we did not observe a significant effect of the educational level on family enrollment prediction. This observation deserves further study, since it may suggest new ways for educational and awareness programs to be developed. One limitation of our study is that it is based on a genetic- screening cascade and that the identified predictors may not apply to biochemical-based cascades, since the genetic cascade is only performed for those individuals with a pathogenic variant of FH. Conclusions Early diagnosis through cascade screening is important for the prevention of risk factors, because over time individuals would be diagnosed early in their lives or even in childhood, thus allowing adequate treatment and prevention of additional risks. With cascade screening, the relatives are diagnosed at a younger age, which is the main factor that characterizes the effectiveness of this diagnostic method. We conclude that after four years of screening, family history of dyslipidemia, as well as high LDL-C levels are the factors that most influenced the inclusion of relatives in the genetic cascade. A professional approach certainly plays an important role in family adherence and our results laid the foundations for the planning of specific intervention trials designed to test new approaches for increasing family enrollment. The funding of SociedadeHospital Samaritano andMinistério da Saúde (PROADI-SUS; SIPAR: 25000.180.672/2011-81) and FAPESP (grant n. 2013/17368-0) are gratefully acknowledged. Acknowledgments The authors would like to thank all the patients who participated in the cohort and  the entire professional staff of Laboratory of Genetics and Molecular Cardiology of the Heart Institute (InCor)/University of São Paulo Medical School Hospital. Author contributions Conception and design of the research: Souza Silva PR, Gómez LMG, Krieger JE, Santos RD, Pereira AC; acquisition of data and obtaining financing: Souza Silva PR, Jannes CE, Krieger JE, Santos RD, Pereira AC; analysis and interpretation of the data: Souza Silva PR, Oliveira TGM, Gómez LMG, Santos RD, Pereira AC; statistical analysis: Souza Silva PR, Gómez LMG, Pereira AC; writing of themanuscript: Souza Silva PR, Jannes CE, Oliveira TGM, Santos RD, Pereira AC; critical revision of the manuscript for intellectual contente: Souza Silva PR, Jannes CE, Oliveira TGM, Krieger JE, Pereira AC. Potential Conflict of Interest No potential conflict of interest relevant to this article was reported. 582