ABC | Volume 110, Nº2, February 2018

Original Article Lorenzo et al Clinical characterization of patients with HF Arq Bras Cardiol. 2018; 110(2):119-123 Discussion FH is a disorder of cholesterol metabolism and indeed one of the most common inherited disorders. 2,10 Rates of premature cardiovascular disease are much higher in patients with FH, but long-termdrug therapy has the potential to lower cardiovascular event rates in patients with FH, leading to similar rates to those found in the general population. 11 Since effective primary prevention in the setting of FH requires its early diagnosis, the largest knowledge we have on this disease, the best we may recognize it and accomplish adequate patient management. In this study, patients with genetically confirmed FH had, as expected, a higher clinical score for FH. In addition, they had more clinical evidence of severe hypercholesterolemia such as xanthelasma, possibly since the monogenic group have had severely elevated LDL-C level since birth, and thus, a greater cumulative “LDL-C burden”. 12 Finally, LDL-C and Apo B levels were higher than in those patients with negative genetic testing, as previously demonstrated. 13,14 ApoB is themainprotein constituent of lipoproteins such as VLDL and LDL, and concentrations of Apo B tend tomirror those of LDL-C. 15 Plasma levels of apolipoprotein B represent all atherogenic lipoproteins in the circulation; however, because every atherogenic particle contains a single apolipoprotein Bmolecule, Apo B levels also provide an accurate reflection of the number of atherogenic particles. 16 Of note, LDL-C levels were 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. This might suggest that the former might have less severe forms of FH related to other mutations, or severe hypercholesterolemia due to other etiologies, and in those cases the level of LDL-C would be also associated with modifiable or environmental factors. In contrast, in patients with FH, the severity of the derangements caused by the mutations would be the predominant factor determining LDL-C levels, what would turn other correlations with anthropometric or biochemical variables less significant. This study is limited by the small sample size, which turns the results hypothesis-generating. Importantly, it may be possible that a proportion of the patients have a mutation in whomever as a yet unidentified gene. With standard molecular diagnostic techniques, a known mutation can be detected in 20–30% of patients with possible FH and 60–80% of patients with definite FH. 17,18 Since approximately 2/3 of patients have possible FH, no mutations are detected in about 60% of tested patients with this disorder 17 what has led to a search for additional FH-causing genes. However, some clinically diagnosed cases of FH may be polygenic, due to the inheritance of a greater than average number of common LDL-C raising alleles (each causing a slight effect) leading to an increase in LDL-C above the diagnostic cut off. 19 Conclusions The present results suggest that in patients with severe hypercholesterolemia and the FH phenotype, even in the absence of genetic confirmation of FH, patient management should have special attention directed towards modifiable factors associated with LDL-C, as body fat. A decrease in body fat might determine a reduction of LDL-C, what is known to decrease cardiovascular risk. 20 Author contributions Conception and design of the research: Lorenzo A, James CE, Pereira AC, Moreira ASB; Acquisition of data: Silva JDL, James CE, Pereira AC; Analysis and interpretation of the data: Lorenzo A; Statistical analysis: Silva JDL; Obtaining financing: Moreira ASB; Writing of the manuscript: Lorenzo A, Silva JDL; Critical revision of the manuscript for intellectual content: Lorenzo A, Moreira ASB. Potential Conflict of Interest No potential conflict of interest relevant to this article was reported. Sources of Funding This study was funded by FAPERJ. Study Association This article is part of the thesis of master submitted by Juliana Duarte Lopes da Silva, from Universidade Federal do Rio de Janeiro. Ethics approval and consent to participate This study was approved by the Ethics Committee of the Instituto Nacional de Cardiologia under the protocol number #26802514.4.0000.5272. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study. 122