ABC | Volume 110, Nº2, February 2018

Original Article Clinical, Anthropometric and Biochemical Characteristics of Patients with or without Genetically Confirmed Familial Hypercholesterolemia Andrea De Lorenzo, 1 Juliana Duarte Lopes da Silva, 1 Cinthia E. James, 2 Alexandre C. Pereira, 2 Annie Seixas Bello Moreira 1 Instituto Nacional de Cardiologia, 1 Rio de Janeiro, RJ; Laboratório de Genética e Cardiologia Molecular, Instituto do Coração (InCor) - Faculdade de Medicina da Universidade de São Paulo, 2 São Paulo, SP – Brazil Mailing Address: Annie Seixas Bello Moreira • Rua das Laranjeiras, 374, 5 andar. CEP 22240-006, Laranjeiras, Rio de Janeiro – Brazil E-mail: anniebello@gmail.com, debora.gapanowicz@gmail.com . Manuscript received May 10, 2017, revised manuscript August 03, 2017, accepted August 07, 2017 DOI: 10.5935/abc.20180005 Abstract Background: Familial hypercholesterolemia (FH) is a common autosomal dominant disorder, characterized by a high level of low-density lipoprotein cholesterol (LDL-C) and a high risk of premature cardiovascular disease. Objective: To evaluate clinical and anthropometric characteristics of patients with the familiar hypercholesterolemia (FH) phenotype, with or without genetic confirmation of FH. Methods: Forty-five patients with LDL-C > 190 mg/dl were genotyped for six FH-related genes: LDLR, APOB, PCSK9, LDLRAP1, LIPA and APOE. Patients who tested positive for any of these mutations were considered to have genetically confirmed FH. The FH phenotype was classified according to the Dutch Lipid Clinic Network criteria. Results: Comparing patients with genetically confirmed FH to those without it, the former had a higher clinical score for FH, more often had xanthelasma and had higher LDL-C and apo B levels. There were significant correlations between LDL-C and the clinical point score for FH (R = 0.382, p = 0.037) and between LDL-C and body fat (R = 0.461, p = 0.01). However, patients with mutations did not have any correlation between LDL-C and other variables, while for those without a mutation, there was a correlation between LDL-C and the clinical point score. Conclusions: LDL-C correlated with the clinical point score and with body fat, both in the overall patient population and in patients without the genetic confirmation of FH. In those with genetically confirmed FH, there were no correlations between LDL-C and other clinical or biochemical variables in patients. (Arq Bras Cardiol. 2018; 110(2):119-123) Keywords: Hyperlipoproteinemia Type II; Body Weights and Measurements, LDL Lipoproteins, Dyslipidemias, Mutation, Phenotype. Introduction Familial hypercholesterolemia (FH) is characterized by a high level of low-density lipoprotein cholesterol (LDL-C) and a high risk of premature cardiovascular disease. 1 It is a common autosomal dominant disorder, affecting up to 1 in 200–250 people in its heterozygous form. 2 According to the Dutch Lipid Clinic Network, the clinical diagnosis of FH (FH phenotype) is based on high LDL-C and a score in which points are assigned for family history of hyperlipidemia or heart disease, clinical characteristics such as tendinous xanthomata, elevated LDL cholesterol, and/or an identified mutation. A total point score greater than eight is considered “definite” FH, 6–8 is “probable” FH, and 3–5 is “possible” FH. 3 Despite being helpful as they provide a standardization of the diagnosis of the FH phenotype, scores may not necessarily result in consistent diagnoses of FH, as cholesterol levels for FH patients overlap with those of the general population. Genetic diagnosis is considered evidence of definite FH according to some criteria. 1 Mutations in 3 genes- the LDL‑receptor gene (LDLR), the gene coding for apolipoprotein B and the gene encoding the proprotein convertase subtilisin/kexin type 9‑are usually responsible for FH. 4-6 However, other mutations have been identified in the LDLR gene, as well as mutations in other genes leading to the clinical FH phenotype, and there is also evidence that some mutations lead to more severe manifestations of FH than others. Additionally, a large proportion of the patients with a clinical diagnosis of FH do not have a detectable mutation in any of these genes. 7,8 In view of the complexity of this scenario, there is continuing need for additional information on the clinical and laboratory profile of patients with either genetically defined FH or with only the phenotype of FH, since such data might help optimize patient management, in the sense of their cardiovascular risk burden. Therefore, this study sought to evaluate clinical and anthropometric characteristics of patients with or without genetic confirmation of FH. Methods Study population This was a cross-sectional study of adult outpatients with severe hypercholesterolemia recruited at the National 119