Comparison of the mutation spectrum and association with pre and post treatment lipid measures of children with heterozygous familial hypercholesterolaemia (FH) from eight European countries.

BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) is commonly caused by mutations in the LDLR, APOB or PCSK9 genes, with untreated mean low density lipoprotein-cholesterol (LDL-C) concentrations being elevated in APOB mutation carriers, even higher in LDLR mutation and highest in those with a PCSK9 mutation. Here we examine this in children with FH from Norway, UK, The Netherlands, Belgium, Czech Republic, Austria, Portugal and Greece. METHODS: Differences in characteristics and pre- and post-treatment lipid concentrations in those with different molecular causes were compared by standard statistical tests. RESULTS: Data were obtained from 2866 children, of whom 2531 (88%) carried a reported LDLR/APOB/PCSK9 variant. In all countries, the most common cause of FH was an LDLR mutation (79% of children, 297 different), but the prevalence of the APOB p.(Arg3527Gln) mutation varied significantly (ranging from 0% in Greece to 39% in Czech Republic, p < 2.2 × 10-16). The prevalence of a family history of premature CHD was significantly higher in children with an LDLR vs APOB mutation (16% vs 7% p=0.0005). Compared to the LDLR mutation group, mean (±SD) concentrations of pre-treatment LDL-C were significantly lower in those with an APOB mutation (n = 2260 vs n = 264, 4.96 (1.08)mmol/l vs 5.88 (1.41)mmol/l, p < 2.2 × 10-16) and lowest in those with a PCSK9 mutation (n = 7, 4.71 (1.22)mmol/l). CONCLUSIONS: The most common cause of FH in children from eight European countries was an LDLR mutation, with the prevalence of the APOB p.(Arg3527Gln) mutation varying significantly across countries. In children, LDLR-FH is associated with higher concentrations of LDL-C and family history of CHD compared to those with APOB-FH.

Valor prognóstico da interleucina-6 na evolução de pacientes com síndrome coronariana aguda sem supradesnivelamento de segmento ST / Prognostic value of interleukin-6 in the outcome of patients with acute coronary syndrome without ST-segment elevation

Objetivo: Identificar o valor prognóstico da interleucina-6 (IL-6) em pacientes com síndrome coronariana aguda sem supradesnivelamento de segmento ST internados na Unidade Coronariana do Hospital São Lucas da PUCRS. Métodos: Foram selecionados 90 pacientes consecutivos com síndrome coronariana aguda sem supra-desnivelamento de segmento ST, acompanhados por um período médio de 29,4 meses, em busca de desfechos tais como: óbito, infarto agudo do miocárdio, angina instável e cirurgia de revascularização miocárdica nos períodos de 30 dias, 60 dias, 6 meses, 1 ano e maior que uma ano. Os pacientes foram divididos em 2 grupos, com valores de IL-6 acima ou abaixo do percentil 50, correspondentes a um ponto de corte de 3,7 (unidade de medida conforme a padronização do laboratório DPC-Medlab). Resultados: Através de regressão logística determinado que níveis de IL-6>3,7 estavam associados a um maior risco de infarto agudo do miocárdio após o período total de acompanhamento.