Desenvolvimento de um escore de funcionalidade da lipoproteína de alta densidade (HDL) e sua associação com algoritmos de predição de risco cardiovascular e aterosclerose subclínica em indivíduos brasileiros / Development of a high density-lipoprotein (HDL) functionality score associated with predictive cardiovascular risk algorithms and subclinical atherosclerosis in Brazilian individuals

Introdução: estudos recentes demonstram que o aumento do colesterol na lipoproteína de alta densidade (HDL-C), induzido por medicamentos ou mutações genéticas, não é associado à redução de eventos coronarianos. A lipoproteína de alta densidade (HDL) apresenta aspectos funcionais distintos em relação ao seu papel cardioprotetor. Objetivo: desenvolver um escore de funcionalidade da HDL (EFH) e avaliar a sua associação com algoritmos de predição de risco cardiovascular e aterosclerose subclínica em indivíduos brasileiros. Metodologia: trata-se de um estudo transversal composto por duas etapas. Na 1ª etapa, o EFH preditor de risco cardiovascular (EFH-RCV) foi desenvolvimento e validado a partir de uma subamostra do estudo CARDIONUTRI (n=354). Na 2ª etapa, o EFH preditor de aterosclerose subclínica (EFH-AS) foi desenvolvido e validado com dados de uma subamostra do estudo ELSA-Brasil (n=4549). No estudo CARDIONUTRI foram avaliadas a atividade da paraoxonase 1 (PON1) e da proteína de transferência de ésteres de colesterol (CETP), a concentração da apolipoproteína AI (APOAI), a capacidade antioxidante da HDL (lag time) e as subfrações da HDL pelo método Lipoprint®. O estudo ELSA-Brasil avaliou as subfrações da HDL pelo método Vertical Auto Profile (VAP) e Ressonância Magnética Nuclear (RMN), e a aterosclerose subclínica por tomografia computadorizada, quantificação da calcificação da artéria coronária (CAC) e calculo do escore da CAC. Resultados: no desenvolvimento do EFH-RCV, a HDL grande apresentou maior força de associação com o risco cardiovascular no modelo múltiplo final (OR = 0,797; p <0,001). O EFH-RCV demonstrou bom desempenho em relação ao escore de risco de Framingham (AUC = 0,899; p <0,001), escore de risco de Reynolds (AUC = 0,722; p <0,001) e Adult Treatment Panel III/2013 (AUC = 0,864; p <0,001). Além disso, apresentou boa reprodutibilidade e correlação com aterosclerose subclínica, quando testado na amostra do estudo ELSA-Brasil, utilizando medidas da HDL grande derivadas do método VAP (AUC = 0,864; p <0,001 e r = 0,252 p <0,001) ou do método de RMN (AUC = 0,876; p <0,001 e r = 0,277; p <0,001). O EFH-AS foi desenvolvido a partir do tamanho da HDL (nm), que apresentou a associação mais forte com aterosclerose subclínica no modelo múltiplo final (OR = 0,549; p <0,001) e demonstrou bom desempenho (AUC = 0,769; p <0,001). Conclusão: o EFH apresentou associações mais fortes com o risco cardiovascular e a aterosclerose subclínica, independente do HDL-C, com destaque para a HDL grande. Os resultados controversos entre as subfrações da HDL e o risco cardiovascular parecem manter relação com as metodologias distintas utilizadas nas análises. Portanto, a validação dos métodos e a inclusão do tamanho da HDL como marcador de risco cardiovascular revela um futuro promissor como adjuvante na estimativa do risco cardiovascular, manejo de medicamentos e tomada de decisões na prática clínica.

Introduction: current studies have not presented association between high density-lipoprotein cholesterol (HDL-C) increase, induced by drugs or genetic mutations, and coronary events reduction. HDL plays different functional cardioprotective role. Objective: to develop a HDL functionality score (HFS) and to assessment its association with predictive cardiovascular risk algorithms and subclinical atherosclerosis outcomes in Brazilian subjects. Methods: cross-sectional study based in two steps. In the first step, the HFS predictor of cardiovascular risk disease (HFS-CVR) was developed and validated on CARDIONUTRI study subsample (n=354). In second step the HFS predictor of subclinical atherosclerosis (HFS-SA) was developed and validated on ELSA-Brasil study subsample (n=4549). CARDIONUTRI study evaluated paraoxonase 1(PON1) and cholesterol ester transfer protein (CETP) activity, apolipoprotein AI (APOAI) concentration, HDL antioxidant capacity, and HDL subfractions by standard Lipoprint® method. ELSA-Brasil study evaluated the size of HDL and subfractions by Vertical Auto Profile (VAP) and Nuclear Magnetic Resonance (NMR) method, and the diagnosis of subclinical atherosclerosis by computed tomography, quantifying coronary artery calcification (CAC) and CAC score. Results: in the development of HFS-CVR, the large HDL presented greater strength of association with cardiovascular risk in the multiple final model (OR = 0.797; p <0.001). The HFS-CVR showed satisfactory performance by Framingham risk score (AUC = 0.899; p <0.001), Reynolds risk score (AUC = 0.722; p <0.001) and Adult Treatment Panel III/2013 guidelines (AUC = 0.864; p <0.001). In addition, HFS-CVR presented satisfactory reproducibility and was associated with subclinical atherosclerosis on ELSA-Brasil sample using large HDL measurements derived from the VAP method (AUC = 0.864; p <0.001 and r = 0,252; p <0,001) or the NMR method (AUC = 0.876; p <0.001 and r = 0.277; p <0,001). HFS-AS was developed from the HDL size (nm), because presented greater association with subclinical atherosclerosis in the final multiple model (OR = 0.549; p <0.001). HFS-AS demonstrated satisfactory performance (AUC = 0.769; p <0.001). Conclusion: the HFS demonstrates strong association with cardiovascular risk and subclinical atherosclerosis, independent of HDL-C, with emphasis on large HDL. Controversial results, between HDL subfractions and cardiovascular irsk seem to maintain a relation with the different methodologies used in analysis. Therefore, the validation of the methods and the inclusion of the HDL size as a cardiovascular risk marker reveal a promising future as an adjunct in the estimation of cardiovascular risk, drug management and decision making in clinical practice.

Oxidized and electronegative low-density lipoprotein as potential biomarkers of cardiovascular risk in obese adolescents.

OBJECTIVES: To evaluate biomarkers associated with early cardiometabolic risk in obese adolescents. METHODS: This cross-sectional study included 137 adolescents of both sexes aged 10 to 19 years divided into a normal weight group (NW) (n=69) and an obese group (OB) (n=68). RESULTS: As expected, obesity showed positive associations with homeostatic model assessment for insulin resistance (HOMA-IR), triacylglycerol, insulin, plasma levels of non-esterified fatty acids, and cholesterol ester transfer protein activity and negative associations with plasma antioxidant levels. Plasma oxidized low-density lipoprotein (oxLDL) and electronegative low-density lipoprotein [LDL(-)] levels were significantly higher in the OB group. Higher tertiles of oxLDL were associated with increased values of body mass index; waist circumference; fatty mass percentage (%FM); and the atherogenic lipids non-high-density-lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B and triacylglycerol. Higher tertiles of LDL(-) were robustly associated with body mass index and waist circumference. Logistic regression models (odds ratios) confirmed that increased values of lipids and apolipoprotein B were associated with increased risk of oxLDL. For LDL(-), these associations were not significant, suggesting that another mechanism is involved in generating this particle in obese adolescents. CONCLUSIONS: Obese adolescents showed increased plasma LDL(-) and oxLDL, and obese girls had more LDL(-) than obese boys. Therefore, oxLDL is strongly and independently associated with classical cardiovascular risk factors, while increased levels of LDL(-) were influenced by body mass index, waist circumference and demographic parameters in obese adolescents.

Oxidized and electronegative low-density lipoprotein as potential biomarkers of cardiovascular risk in obese adolescents

OBJECTIVES: To evaluate biomarkers associated with early cardiometabolic risk in obese adolescents. METHODS: This cross-sectional study included 137 adolescents of both sexes aged 10 to 19 years divided into a normal weight group (NW) (n=69) and an obese group (OB) (n=68). RESULTS: As expected, obesity showed positive associations with homeostatic model assessment for insulin resistance (HOMA-IR), triacylglycerol, insulin, plasma levels of non-esterified fatty acids, and cholesterol ester transfer protein activity and negative associations with plasma antioxidant levels. Plasma oxidized low-density lipoprotein (oxLDL) and electronegative low-density lipoprotein [LDL(-)] levels were significantly higher in the OB group. Higher tertiles of oxLDL were associated with increased values of body mass index; waist circumference; fatty mass percentage (%FM); and the atherogenic lipids non-high-density-lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B and triacylglycerol. Higher tertiles of LDL(-) were robustly associated with body mass index and waist circumference. Logistic regression models (odds ratios) confirmed that increased values of lipids and apolipoprotein B were associated with increased risk of oxLDL. For LDL(-), these associations were not significant, suggesting that another mechanism is involved in generating this particle in obese adolescents. CONCLUSIONS: Obese adolescents showed increased plasma LDL(-) and oxLDL, and obese girls had more LDL(-) than obese boys. Therefore, oxLDL is strongly and independently associated with classical cardiovascular risk factors, while increased levels of LDL(-) were influenced by body mass index, waist circumference and demographic parameters in obese adolescents.

Ketogenic food pyramid for patients with refractory epilepsy: From theory to clinical practice / Pirâmide alimentar cetogênica para pacientes com epilepsia refratária: da teoria à prática clínica

ABSTRACT Objective: To develop a graphical representation in the form of a food pyramid for a ketogenic diet for dietary treatment in children and adolescents with refractory epilepsy. Methods: The pyramid was constructed based on: the estimation of energy requirements for different age groups, macronutrient distribution, food groups, and the number of servings and respective amounts of food according to the ketogenic diet. Serving sizes were based on the calculation of energy and macronutrient requirements according to age and nutritional status. Results: The pyramid was divided into three tiers and 5 food groups (fats, proteins, type 1 vegetables, type 2 vegetables, and fruits). Four portion size lists were defined for the following age groups: 1-3 years, 4-6 years, 7-10 years, and 11-19 years. Conclusion: The ketogenic diet food pyramid can be used as nutritional guidance for patients undergoing this dietary therapy by illustrating the variety of foods that can be eaten during the treatment, optimizing adherence to the treatment, and guaranteeing beneficial effects on seizure control.

RESUMO Objetivo: Desenvolver uma representação gráfica sob a forma de pirâmide alimentar para a dieta cetogênica destinada a crianças e adolescentes com indicação de tratamento dietético da epilepsia refratária. Métodos: A construção foi baseada na estimativa da necessidade energética por faixa etária, na distribuição de macronutrientes, nos grupos alimentares, no número de porções e nas respectivas quantidades de alimentos a serem ofertados de forma a atender as recomendações da dieta cetogênica. O porcionamento dos alimentos foi feito baseado no cálculo da necessidade energética e na distribuição de macronutriente segundo a faixa etária e estado nutricional. Resultados: A pirâmide foi dividida em três estratos e em cinco grupos alimentares (gorduras, proteínas, hortaliças tipo 1, hortaliças tipo 2 e frutas). Foram elaboradas quatro listas de porcionamento para as seguintes faixas etárias 1 a 3 anos, 4 a 6 anos, 7 a 10 anos e 11 a 19 anos. Conclusão: A utilização da pirâmide alimentar da dieta cetogênica facilitará a orientação inicial dos pacientes submetidos a essa terapia nutricional, ilustrando a diversidade de alimentos que podem ser ofertados durante o tratamento e otimizando, assim, a aderência ao mesmo e a manutenção dos efeitos benéficos de controle de crises.

Association of the conicity index with diabetes and hypertension in Brazilian women.

OBJECTIVE: The goal of this study was evaluate the conicity index (C index) in women and its association with hypertension (SAH) and diabetes mellitus (DM). SUBJECTS AND METHODS: This was a cross-sectional study, with 573 women between 20 and 59 years of age. After analysis of clinical and demographic characteristics, anthropometric variables were measured and used to calculate the C index. Plasma glucose and lipid profile were evaluated by standard methods. The analysis of the results was based on logistic regression and the odds ratio (OR) was calculated, which was used to assess the association of the variable outcome with the variable exposure using two logistic regression models that tested the possible influence of the C index in the chance of developing SAH or DM. A confidence interval of 95% was used. RESULTS: In the crude and adjusted models, the OR confirmed the association of the C index with DM and SAH. Compared with women that showed C index p < 75, the risk of women with C index (p ≥ 75) developing DM and SAH was 1.72 and 1.75, respectively. Results demonstrated that the negative impact of age on these associations significantly raised the odds of women having DM and SAH. The high C index was also linked to low HDL-C. CONCLUSION: The C index is an important tool in estimating the risk of diabetes and hypertension in women. Besides, high C indexes are negatively associated with HDL-C, an important lipid marker related to cardiovascular risk.

Association of the conicity index with diabetes and hypertension in Brazilian women

ABSTRACT Objective The goal of this study was evaluate the conicity index (C index) in women and its association with hypertension (SAH) and diabetes mellitus (DM). Subjects and methods This was a cross-sectional study, with 573 women between 20 and 59 years of age. After analysis of clinical and demographic characteristics, anthropometric variables were measured and used to calculate the C index. Plasma glucose and lipid profile were evaluated by standard methods. The analysis of the results was based on logistic regression and the odds ratio (OR) was calculated, which was used to assess the association of the variable outcome with the variable exposure using two logistic regression models that tested the possible influence of the C index in the chance of developing SAH or DM. A confidence interval of 95% was used. Results In the crude and adjusted models, the OR confirmed the association of the C index with DM and SAH. Compared with women that showed C index p < 75, the risk of women with C index (p ≥ 75) developing DM and SAH was 1.72 and 1.75, respectively. Results demonstrated that the negative impact of age on these associations significantly raised the odds of women having DM and SAH. The high C index was also linked to low HDL-C. Conclusion The C index is an important tool in estimating the risk of diabetes and hypertension in women. Besides, high C indexes are negatively associated with HDL-C, an important lipid marker related to cardiovascular risk.

Papel do ômega-3 nas características físico-químicas da HDL e LDL e possível associação com medidas Z-scan em indivíduos adultos / Role of omega-3 on HDL and LDL physicochemical characteristics and possible association with Z-scan measurements in adults

Introdução: O aumento na prevalência das doenças cardiovasculares alerta para a necessidade de estratégias eficazes e de baixo custo como medidas preventivas na redução dos fatores de risco, morbidades e óbitos decorrentes de eventos coronarianos. As modificações no estilo de vida são as primeiras alternativas a serem adotadas. Nesse contexto, a dieta ocupa lugar de destaque e os benefícios dos ácidos graxos poli-insaturados ômega-3 na saúde cardiovascular são amplamente reconhecidos. As doenças cardiovasculares são influenciadas por diversos fatores de risco e o desequilíbrio na concentração plasmática das lipoproteínas é um fator de risco independente no desenvolvimento da doença cardiovascular aterosclerótica. Entretanto, há evidências de que as subfrações lipoproteicas podem influenciar o risco cardiovascular de maneira diferenciada, dependendo das características físico-químicas e funcionalidade de cada partícula. O desenvolvimento de novas técnicas, capazes de identificar esses parâmetros, tem sido foco de grande interesse científico. Objetivo: Avaliar o papel do ômega-3 sobre as características físico-químicas da LDL e HDL e possível associação entre medidas Z-scan e marcadores cardiometabólicos em indivíduos adultos. Metodologia: A partir de uma subamostra do estudo CARDIONUTRI (estudo clínico, randomizado, controlado e duplo cego com seguimento de 8 semanas) foram selecionados 36 indivíduos do Grupo Ômega-3 (3,0g/dia de óleo de peixe - 1,11g de EPA + 0,69g de DHA) e 27 do Grupo Placebo (3,0g/dia de óleo mineral). Foram monitorados o perfil clínico, antecedentes familiares, consumo alimentar, atividade física e antropometria. Amostras de sangue foram coletadas após 12 horas de jejum para avaliação das concentrações plasmáticas de CT, TAG, HDL-C, LDL-C, APOAI, APOB, PON1 e glicose. O tamanho da HDL e LDL foi analisado pelo método padronizado Lipoprint®. O conteúdo de LDL(-) foi determinado por ELISA. As medidas Z-scan foram determinadas por meio da difusividade térmica e absorção linear da LDL (1,0 mg/dL de proteína), isolada por ultracentrifugação. Todos as variáveis do estudo foram avaliadas no momento basal e após 8 semanas de intervenção. A adesão à intervenção foi monitorada pela contagem de cápsulas e percentual dos ácidos graxos plasmáticos. Para avaliar a associação das medidas Z-Scan aos marcadores cardiometabólicos, os dados obtidos no momento basal foram submetidos à Análise de Componentes Principais. Resultados: A idade média dos participantes do estudo foi de 51,5 (10,5) anos. A suplementação com ômega-3 promoveu redução significativa de CT, TAG, não-HDL, HDLPEQUENA e LDL(-), além de aumento significativo de HDL-C e HDLGRANDE. O ômega-3 foi mais eficaz na redução dos TAG (29,2 por cento ) quando comparado ao placebo (2,9 por cento ). O Grupo Ômega-3 apresentou aumento de HDLGRANDE (16,9 por cento ) e redução de HDLPEQUENA (-16,3 por cento ) ao final da intervenção, com diferença significativa quando comparado ao Grupo Placebo que apresentou redução de HDLGRANDE (-4,8 por cento ) e aumento de HDLPEQUENA (17,7 por cento ). Não foram observadas diferenças nas medidas Z-scan após a intervenção, porém as medidas se associaram positivamente a Componentes Principais com padrões cardioprotetores da amostra e negativamente a padrões aterogênicos. Conclusão: O ômega-3 demonstrou efeito positivo no perfil lipídico e propriedades aterogênicas das subfrações lipoproteicas. A suplementação com ômega-3 não modificou as medidas Z-scan, no entanto, a técnica demonstrou ser uma ferramenta capaz de se associar a padrões aterogênicos e antiaterogênicos monitorados no presente estudo.

Introduction: The increased of cardiovascular disease prevalence draws attention to the need to adopt effective and inexpensive strategies as preventive measures to reduce risk factors, morbidity and deaths from coronary events. Lifestyle modification is indicated as first alternative to be adopted. In this context the diet stands out and omega-3 polyunsaturated fatty acids benefits on cardiovascular health are largely recognized. Cardiovascular diseases are influenced by several risk factors and the plasma imbalance lipoprotein is considered a crucial independent risk factor. However, there is evidence of the influence of lipoprotein subfractions in cardiovascular risk, based on the physicochemical characteristics of these particles. The development of new techniques able to identify those parameters has been the focus of great scientific interest. Objective: To evaluate the role of omega-3 on HDL and LDL physicochemical characteristics and possible association between Z-scan measurements and cardiometabolic markers in adults. Methods: From a subsample of the study CARDIONUTRI (clinical, randomized, controlled, double blind study with 8-week follow-up) were selected 36 individuals from the Omega-3 Group (3.0g/day of fish oil - 1,11g EPA + 0.69g DHA) and 27 individuals from the Placebo Group (3.0g/day of mineral oil). The clinical profile, family history, dietary intake, physical activity and anthropometry were monitored. Blood samples were collected after 12 hours of fasting to evaluate plasma concentrations of TC, TAG, HDL-C, LDL-C, APOAI, APOB, PON1 and glucose. The HDL and LDL size was analyzed by the standard method Lipoprint®. The levels of LDL (-) was determined by ELISA. The Z-scan measurements were determined by thermal diffusivity and linear absorption of LDL (1.0 mg / dL protein) isolated by ultracentrifugation. All study variables were evaluated at baseline and after 8 weeks of intervention. The intervention accession was monitored by capsule count and percentage of plasma fatty acids. To evaluate the association of the Z-Scan measurements to cardiometabolic markers, the data collected at baseline were subjected to Principal Component Analysis. Results: The average age of individuals were 51.5 (10.5) years. The omega-3 supplementation promoted a significant decreased of TC, TAG, non-HDL, small HDL and LDL(-), and significantly increased HDL-C and large HDL. The omega-3 was more effective in reducing the TAG (29.2 per cent ) when compared to placebo (2.9 per cent ). The Omega-3 Group increased large HDL (16.9 per cent ) and decreased small HDL (-16.3 per cent ) after the intervention, with significant difference when compared to the Placebo Group that decreased large HDL (-4.8 per cent ) and increased small HDL (17.7 per cent ). There were no differences in Z-scan measurements with the interventions, but were observed positively associated the Z-scan measurements with the anti-atherogenic sample patterns and negatively associated with atherogenic sample patterns when the sample was standardized from the Principal Components Analysis. Conclusion: The omega-3 demonstrated positive effect on the lipid profile and atherogenic lipoprotein subfractions. Supplementation with omega-3 did not modify the Z-scan measurements, however, the technique proved to be a tool that can be associated with atherogenic and anti-atherogenic sample patterns monitored in this study.

Associação entre o produto da acumulação lipídica e marcadores aterogênicos é independente do sexo, idade e uso de medicamentos hipolipemiantes / Association between lipid accumulation product and atherogenic markers is sex, age and lipid-lowering drugs use independent

Objective:This study aimed to evaluate the association between Lipid Accumulation Product and biochemical markers and verify how it is affected by sex, age and medication use. Methods:This is a cross-sectional study including biochemical, clinical, demographic and anthropometric data from 617 individuals, both sexes, between 20 and 59 years old, without previous cardiovascular event.Data was collected between 2000 and 2014. The influence of Lipid Accumulation Product on the biochemical variables levels was assessed by multiple linear regression analysis for men and women. Statistical analyzes were performed using SPSS version 20.0 software at significance level of p<0.05. Results:Both sexes presented overweight and increased waist circumference.The median Lipid Accumulation Product was 57.8 and men showed higher values than women. In both sexes, the Lipid Accumulation Product significantly influenced the total cholesterol and high-density lipoprotein levels and these results were adjustment variables (age and hypolipidemic agents) independent. Conclusions:Results showed that Lipid Accumulation Product was associated with low HDL levels and increased concentrations of TC regardless of sexes, age and lipid-lowering drugs

Objetivo: Avaliar a associação do Produto da Acumulação Lipídica com marcadores bioquímicos e verificar a influência do sexo, idade e uso de medicamentos sobre as associações. Métodos: O estudo é de corte transversal com 617 indivíduos de ambos os sexos e idade entre 20 e 59 anos, sem registro de evento cardiovascular prévio. Dados bioquímicos, clínicos, demográficos e antropométricos foram coletados entre os anos de 2000 e 2014. Para avaliar a influência do Produto da Acumulação Lipídica na concentração das variáveis bioquímicas, foram realizadas análises de regressão linear múltipla para homens e mulheres. As análises estatísticas foram feitas no programa SPSS versão 20.0 considerando um valor de significância p<0,05. Resultados: Ambos os sexos apresentaram excesso de peso e circunferência da cintura elevada. A mediana do Produto da Acumulação Lipídica foi 57,8 sendo que os homens apresentaram valores superiores às mulheres. Em ambos os sexos, o Produto da Acumulação Lipídica influenciou de maneira significativa as concentrações de colesterol total e colesterol associado à lipoproteína de alta densidade e estes resultados foram independentes das variáveis de ajuste (idade e medicamentos hipolipemiantes). Conclusão: Os resultados obtidos mostram que o Produto da Acumulação Lipídica se associou com baixos valores de HDL e elevada concentração de CT, independentemente do sexo, idade e medicamentos hipolipemiantes