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Background and aims: Familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of LDL-C leading to premature cardiovascular disease (CAD). Only about 40% of individuals with a clinical diagnosis of FH have a causative genetic variant identified, and a proportion of genetically negative cases may have a polygenic cause rather than a still unidentified monogenic cause. This work aims to evaluate and validate the role of a polygenic risk score (PRS) associated with hypercholesterolemia in a Brazilian FH cohort and its clinical implications. Methods: We analyzed a previously derived PRS of 12 and 6 SNPs (Single Nucleotide Polymorphism) in 684 FH individuals (491 mutation-negative [FH/M-], 193 mutation-positive [FH/M+]) and in 1605 controls. Coronary artery calcium (CAC) score was also evaluated. Results: The PRS was independently associated with LDL-C in control individuals (p < 0.001). Within this group, in individuals in the highest quartile of the 12 SNPs PRS, the odds ratio for CAC score >100 was 1.7 (95% CI: 1.01-2.88, p = 0.04) after adjustment for age and sex. Subjects in the FH/M- group had the highest mean score in both 12 and 6 SNPs PRS (38.25 and 27.82, respectively) when compared to the other two groups (p = 2.2 × 10-16). Both scores were also higher in the FH/M+ group (36.48 and 26.26, respectively) when compared to the control group (p < 0.001 for the two scores) but inferior to the FH/M- group. Within FH individuals, the presence of a higher PRS score was not associated with LDL-C levels or with CAD risk. Conclusion: A higher PRS is associated with significantly higher levels of LDL-C and it is independently associated with higher CAC in the Brazilian general population. A polygenic cause can explain a fraction of FH/M- individuals but does not appear to be a modulator of the clinical phenotype among FH individuals, regardless of mutation status.
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ABSTRACT Background: There is no consensus on the ideal size of intestinal loops in gastric bypass of bariatric surgeries. Aim: To evaluate the metabolic outcome of patients submitted to gastric bypass with alimentary and biliopancreatic loops of different sizes. Methods: Was conducted a retrospective cohort study in diabetic obese patients (BMI≥35 kg/m2) with metabolic syndrome submitted to gastric bypass. The patients were divided into three groups according to the size of the intestinal loop: group 1, biliopancreatic limb 50 cm length and alimentary limb 100 cm length; group 2 , biliopancreatic limb 50 cm length and alimentary limb 150 cm length; and group 3, biliopancreatic limb 100 cm length and alimentary limb 150 cm length. The effect of gastric bypass with different sizes of intestinal loops in relation to the parameters that define metabolic syndrome was determined. Results: Sixty-three patients were evaluated, and they had a mean age of 44.7±9.4 years. All were diabetics, with 62 (98.4%) being hypertensive and 51 (82.2%) dyslipidemic. The three groups were homogeneous in relation to the variables. In 24 months, there was a remission of systemic arterial hypertension in 65% of patients in group 1, 62.5% in group 2 and 68.4% in group 3. Remission of diabetes occurred in 85% of patients in group 1, 83% in group 2 and 84% in group 3. There was no statistical difference in %LEW between the groups, and waist measurements decreased in a homogeneous way in all groups. The size of loops also had no influence on the improvement in dyslipidemia. Conclusion: Variation in size of intestinal loops does not appear to influence improvement in metabolic syndrome in this group of patients.
RESUMO Racional: Não há consenso sobre o tamanho ideal das alças intestinais no bypass gástrico em Y-de-Roux em cirurgias bariátricas. Objetivo: Avaliar os desfechos metabólicos de pacientes submetidos ao bypass gástrico com alça intestinal alimentar e biliopancreática de tamanhos diferentes. Métodos: Realizou-se coorte retrospectiva em pacientes obesos (IMC≥35 kg/m2) diabéticos com síndrome metabólica submetidos ao bypass gástrico em Y-de-Roux. Foram divididos em três grupos conforme a dimensão das alças intestinais: grupo 1, alça biliopancreática de 50 cm e alça alimentar de 100 cm; grupo 2, alça biliopancreática de 50 cm e alça alimentar de 150 cm e grupo 3, alça biliopancreática de 100 cm e alça alimentar de 150 cm. Foram avaliados os parâmetros que compõem a síndrome metabólica. Resultados: Incluíram-se 63 pacientes, com média de idade de 44.7±9.4 anos. Todos eram diabéticos, 62 (98.4%) hipertensos e 51 (82.2%) dislipidêmicos. Os três grupos eram homogêneos em relação às variáveis estudadas. Em 24 meses houve remissão da hipertensão arterial sistêmica em 65% do grupo 1, 62.5% no grupo 2 e 68.4% no grupo 3. A remissão do diabete melito tipo 2 ocorreu em 85% dos pacientes do grupo 1, 83% no grupo 2, e 84% no grupo 3. Não houve diferença estatística na porcentagem de perda do excesso de peso entre os grupos e as medidas da cintura abdominal reduziram de forma homogênea em todos os grupos. A dimensão das alças também não influenciou na melhora da dislipidemia. Conclusão: A variação da dimensão das alças intestinais não influenciou na melhora da síndrome metabólica neste grupo de pacientes.
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Introdução: O objetivo do presente estudo foi analisar a eficácia da utilização da Cordia salicifolia em camundongos submetidos a dieta hiperlipidêmica, através do monitoramento dos índices sorológicos de colesterol e triglicerídeos. Metodologia: Para o experimento foram usados camundongos (mus musculus), com peso médio de 54 ± 5 g, e com idade de 50 ± 5 dias, que foram divididos em 4 grupos de 10 animais. Camundongos recebendo água e com dieta normal, camundongos recebendo água e com dieta hiperlipidêmica, camundongos com dieta normal e administração do extrato de Cordia salicifolia e camundongos com dieta hiperlipidêmica e administração do extrato de Cordia salicifolia. Resultados e conclusões: Houve redução nos níveis séricos de colesterol total, tanto no grupo que recebeu dieta normal + extrato como no grupo com dieta hiperlipidêmica + extrato. Também foi significativa a redução nos níveis séricos de triglicerídeos nos animais que receberam dieta hiperlipidêmica + extrato, quando comparados aos camundongos que receberam dieta hiperlipidêmica + água (AU)
Introduction: The present study evaluates the effectiveness of Cordia salicifolia in reducing serum total cholesterol and triglyceride levels in mice on a hyperlipidemic diet. Methodology: 40 specimens of mice (Mus musculus, mean weight 54 ±5 g and mean age 50 ± 5 days) were studied. They were divided into 4 groups of 10 animals each: mice on a normal diet receiving water, mice on a hyperlipidemic diet receiving water, mice on a normal diet receiving Cordia salicifolia extract, and mice on a hyperlipidemic diet receiving Cordia salicifolia extract. Results and conclusion: There was a serum total cholesterol reduction in the normal diet + extract group as well as in the hyperlipidemic diet + extract group. Also, the serum triglyceride reduction observed in animals on the hyperlipidemic diet + extract was significant as compared to mice on the hyperlipidemic diet + water (AU)