Criterios predictores en el diagnóstico de la hipercolesterolemia familiar / Predictive criteria in the diagnosis of familial hypercholesterolemia

Introducción: La hipercolesterolemia familiar es una enfermedad con alta prevalencia, no tratada acorta la esperanza de vida, por lo que el diagnóstico a edades tempranas resulta fundamental. Las pruebas genéticas constituyen el gold standard para el diagnóstico de hipercolesterolemia familiar, sin embargo, la no disponibilidad del test genético no debe constituir un impedimento para la adecuada conducta en estos casos. Objetivo: Identificar criterios clínicos predictores en el diagnóstico por pesquisa de la hipercolesterolemia familiar. Métodos: Se realizó un estudio descriptivo prospectivo a partir de una muestra de 393 pacientes (casos índices) de HF en el Hospital Clínico Quirúrgico Hermanos Ameijeiras; durante el período 2008-2018. Resultados: En la pesquisa familiar fueron identificados 177 (15,66 por ciento) nuevos casos de hipercolesterolemia familiar, de ellos se clasifican como casos positivos 35 (19,77 por ciento), casos probables 58 (32,77 por ciento) y casos posibles 84 (47,46 por ciento). Las categorías del estrato Make early diagnosis to prevent early death MEDPED y la edad del caso índice resultaron ser las variables clínicas de interés con mayor probabilidad para identificar nuevos casos de hipercolesterolemia familiar. Conclusiones: los criterios clínicos estandarizados de la escala make early diagnosis to prevent early death P y la edad del caso índice resultaron ser indicadores predictivos de gran valor para identificar y estratificar casos con variantes fenotípicas de hipercolesterolemia familiar(AU)

Introduction: Familial hypercholesterolemia is a disease with high prevalence; it shortens life expectancy if it is not treated, so early diagnosis is essential. Genetic tests are the gold standard for the diagnosis of familial hypercholesterolemia, however, the unavailability of the genetic test should not be an obstacle to proper conduct in these cases. Objective: To identify predictive clinical criteria in the diagnosis by screening of familial hypercholesterolemia. Methods: A prospective descriptive study was carried out from a sample of 393 patients (index cases) of FH at Hermanos Ameijeiras Surgical Clinical Hospital from 2008 to 2018. Results: In the family investigation, 177 (15.66 percent) new cases of familial hypercholesterolemia were identified, 35 of them (19.77 percent) are classified as positive cases, 58 (32.77 percent) as probable cases and 84 as possible cases (47.46 percent)The stratum categories of Make Early Diagnosis to Prevent Early Death (MEDPED) and the age of the index case turned out to be the clinical variables of interest with the greatest probability to identify new cases of familial hypercholesterolemia. Conclusions: The standardized clinical criteria of the make early diagnosis to prevent early death P scale and the age of the index case turned out to be highly valuable predictive indicators to identify and stratify cases with phenotypic variants of familial hypercholesterolemia(AU)

Identificación de variantes genéticas asociadas a hipercolesterolemia familiar en niños y adolescentes de la Región del Biobío, Chile / Identification of genetic variants associated with familial hypercholesterolemia in Chilean children and adolescents

Background: Familial hypercholesterolemia (FH) is commonly associated with mutations in-LDL receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9). Aim: To identify genetic variants associated with FH in a population of children and adolescents with hypercholesterolemia or a family history of-demonstrated early CVD. Material and Methods: Clinical and biochemical parameters were evaluated, and nine genes related to FH were sequenced namely LDLR, APOB, PCSK9, LDLRAP1, LIPA, APOE, ABCG5, ABCG8 and STAP1, in 55 children and adolescents aged 1 to 18 years old, from non-consanguineous families. Results: Mutations associated with FH were found in 17 children and adolescents, corresponding to p.Asp47Asn, duplication of exons 13-15 and p.Ser326Cys of the LDLR gene; p.Glu204* and Ile268Met of the APOE gene. Thirteen patients were heterozygous, two homozygous, two compound heterozygous, and one double heterozygous. Conclusions: Children and adolescents carrying mutations associated with FH were found by selective screening, which constitutes the first stage in the identification of genetic variants in our country.

Cross sectional study of familial hypercholesterolemia in dyslipidemia patients receiving lipid-lowering therapy: DYSIS-China subgroup analysis / 中华心血管病杂志

Objectives: To analyze the incidence, blood lipid levels and cardiovascular disease of familial hypercholesterolemia (FH) in dyslipidemia patients receiving lipid-lowing therapy from the DYSIS-China. Methods: Dyslipidemia International Study-China (DYSIS-China) database was re-analyzed according to the criteria of "Chinese guidelines for prevention and treatment of dyslipidemia in adults-2016 version". DYSIS-China database included 25 317 dyslipidemia out-patients who received at least one lipid-lowering drug for at least three months. All the patients were divided into three groups: unlikely HF, possible FH and definite FH according to the Dutch Lipid Clinic Network diagnostic criteria. Age, gender, lipids levels, drug use and complications were compared among the three groups. Factors were compared between Possible FH group and definite FH group in terms of age stratification. Results: A total of 23 973 patients with dyslipidemia were included. The average age was (64.8±9.9) years, 11 757 patients were females (49.0%). The proportion of unlikely FH in the total population was 20 561 (85.7%), possible FH was 3294 (13.7%), and the definite FH was 118(0.5%). Patients in the definite FH group (58.3±8.5 years) was younger than in unlikely HF(65.3±9.8 years) and possible FH(61.8±9.9 years) group. LDL-C ((5.6±1.9) mmol/L) levels were significantly higher in definite FH group than in unlikely HF ((2.5±0.9) mmol/L) and possible FH ((4.3±1.0) mmol/L) group. TC ((7.4±1.8) mmol/L) levels were also significantly higher in definite FH group than in unlikely HF ((4.3±1.0) mmol/L) and possible FH ((6.0±1.0) mmol/L) group. Percent of female sex, sedentary lifestyle and systolic blood pressure value were significantly higher in definite FH group than in other two groups (all P<0.05). Statin use was similar among the 3 groups. Prevalence of ischemic cardiomyopathy (70(59.3%)) was significantly higher in the definite FH group than in unlikely FH group7519 (36.6%) and possible FH group1149 (34.9%). The rate of hypertension (82 (69.5%)) was also significantly higher in the definite FH group than in unlikely FH group (2 063 (62.6%) and in possible FH group (13 928 (67.7%)). The possible FH group had the highest proportion of patients aged 55-64 years (1 146 (34.8%)), and the prevalence of hypertension 358 (76.8%), diabetes 189 (40.6%), ischemic heart disease 186 (39.9%), cerebrovascular disease 149 (32.0%) and heart failure 28 (6.0%) was the highest in patients over 75 years old. The definite FH group had the highest proportion of patients aged 55-64 years (49 (41.52%)), and the prevalence of ischemic heart disease (70 (59.3%)) was the highest in patients aged 45-54 years old group, there was no significant difference in the prevalence of diabetes,hypertension,heart failure,peripheral artery disease and cerebrovascular disease among different age groups. Conclusion: The detection rate of FH in Chinese patients with dyslipidemia is not low, the blood lipid level is poorly controlled, and the risk of cardiovascular disease is high in Chinses FH patients.