Red Blood Cells' Omega-6 and Omega-3 Polyunsaturated Fatty Acids Have a Distinct Influence on LDL Particle Size and its Structural Modifications. / Os Ácidos Graxos Poli-insaturados Ômega-6 e Ômega-3 Presentes nas Hemácias Exercem uma Influência Distinta sobre o Tamanho das Partículas de LDL e suas Alterações Estruturais.

BACKGROUND: While Omega-3 and omega-6 polyunsaturated fatty acids (n-3 and n-6 PUFAs) have established effects on cardiovascular disease (CVD) risk factors, little is known about their impacts on LDL quality markers. OBJECTIVE: To assess the associations of n-3 and n-6 PUFA within red blood cells (RBC) with LDL particle size, small dense LDL-c (sdLDL-c), and electronegative LDL [LDL(-)] in adults with CVD risk factors. METHODS: Cross-sectional study involving 335 men and women aged 30 to 74 with at least one cardiovascular risk factor. Analyses were conducted on biochemical parameters, such as glucose, insulin, HbA1c, C-reactive protein (CRP), lipid profile, lipoprotein subfractions, electronegative LDL particle [LDL(-)] and its autoantibody, and RBC n-3 and n-6 PUFAs. Independent t-test/Mann-Whitney test, one-way ANOVA/Kruskal-Wallis test, and multiple linear regressions were applied. All tests were two-sided, and a p-value of less than 0.05 was considered statistically significant. RESULTS: The RBC n-6/n-3 ratio was associated with increased LDL(-) (ß = 4.064; 95% CI = 1.381 - 6.748) and sdLDL-c (ß = 1.905; 95% CI = 0.863 - 2.947) levels, and reduced LDL particle size (ß = -1.032; 95% CI = -1.585 - -0.478). Separately, n-6 and n-3 PUFAs had opposing associations with those parameters, reinforcing the protective effects of n-3 and showing the potential negative effects of n-6 on LDL particle quality. CONCLUSION: RBC n-6 PUFA was associated with increased cardiometabolic risk and atherogenicity of LDL particles, while n-3 PUFA was associated with better cardiometabolic parameters and LDL particle quality.

FUNDAMENTO: Embora os ácidos graxos poli-insaturados ômega-3 e ômega-6 (AGPIs n-3 e n-6) tenham efeitos bem conhecidos sobre os fatores de risco de doenças cardiovasculares (DCV), ainda existe um conhecimento limitado sobre como eles afetam os indicadores de qualidade da LDL. OBJETIVO: Avaliar as associações dos AGPIs n-3 e n-6 de hemácias com o tamanho da partícula da LDL, LDL-c pequena e densa (sdLDL-c) e com LDL eletronegativa [LDL(-)] em adultos com fatores de risco para DCV. MÉTODOS: Estudo transversal com 335 homens e mulheres de 30 a 74 anos com, pelo menos, um fator de risco cardiovascular. Foram realizadas análises de parâmetros bioquímicos, como glicose, insulina, HbA1c, proteína C reativa (PCR), perfil lipídico, subfrações de lipoproteínas, partícula eletronegativa de LDL [LDL(-)] e seu autoanticorpo, e os AGPIs n-3 e n- 6 de hemácias. Os testes t independente/teste de Mann-Whitney, ANOVA unidirecional/teste de Kruskal-Wallis e regressões lineares múltiplas foram aplicados. Todos os testes foram bilaterais e um valor de p inferior a 0,05 foi considerado estatisticamente significativo. RESULTADOS: A relação n-6/n-3 de hemácias foi associada ao aumento dos níveis de LDL(-) (ß = 4,064; IC de 95% = 1,381 ­ 6,748) e sdLDL-c (ß = 1,905; IC de 95% = 0,863 ­ 2,947), e redução do tamanho das partículas de LDL (ß = -1,032; IC de 95% = -1,585 − -0,478). Individualmente, os AGPIs n-6 e n-3 apresentaram associações opostas com esses parâmetros, realçando os efeitos protetores do n-3 e evidenciando os possíveis efeitos adversos do n-6 na qualidade das partículas de LDL. CONCLUSÃO: O AGPI n-6, presente nas hemácias, foi associado ao aumento do risco cardiometabólico e à aterogenicidade das partículas de LDL, enquanto o AGPI n-3 foi associado a melhores parâmetros cardiometabólicos e à qualidade das partículas de LDL.

Stearic Acid, but not Palmitic Acid, is Associated with Inflammatory and Endothelial Dysfunction Biomarkers in Individuals at Cardiovascular Risk. / Ácido Esteárico (mas não o Ácido Palmítico) está Associado a Biomarcadores Inflamatórios e de Disfunção Endotelial em Indivíduos em Risco Cardiovascular.

BACKGROUND: Several studies have associated dietary saturated fatty acids (SFAs) with cardiovascular risk but there are still many controversies. Most of these studies have focused on the effects of palmitic acid on circulating lipids. Stearic acid usually shows a neutral effect on blood lipids, however, there is a lack of clinical studies assessing the link with inflammatory and endothelial dysfunction markers. OBJECTIVE: To evaluate the association of red blood cell (RBC) SFA (palmitic and stearic acids) with circulating inflammatory and endothelial dysfunction biomarkers. METHODS: Cross-sectional study of 79 adults of both sexes with at least one cardiovascular risk factor but without previous events (acute myocardial infarction or stroke). Plasma biomarkers - lipids, glucometabolic markers, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) - and RBC palmitic and stearic fatty acids were analyzed. The associations were assessed by correlation and multiple linear regression analyses, with statistical significance set at p < 0.05. RESULTS: Palmitic acid showed no significant associations with traditional cardiovascular risk factors or inflammatory markers. Stearic acid, on the other hand, was inversely correlated with blood cholesterol and triglycerides, but independently associated with hs-CRP, IL-6, and TNF-α. CONCLUSION: Stearic acid is associated with inflammatory and endothelial dysfunction biomarkers in individuals with at least one cardiovascular risk factor.

FUNDAMENTO: Vários estudos têm associado o consumo de ácidos graxos saturados (AGSs) com risco cardiovascular, mas ainda existem muitas controvérsias. A maioria desses estudos avaliou os efeitos do ácido palmítico sobre lipídios circulantes. O ácido esteárico geralmente apresenta um efeito neutro sobre os lipídios sanguíneos, mas faltam estudos clínicos avaliando sua relação com marcadores de inflamação e de disfunção endotelial. OBJETIVOS: Avaliar a associação de AGSs das hemácias (ácido palmítico e ácido esteárico) com biomarcadores inflamatórios e de disfunção endotelial circulantes. MÉTODOS: Estudo transversal que incluiu 79 adultos de ambos os sexos com pelo menos um fator de risco cardiovascular, mas sem eventos prévios (infarto agudo do miocárdio ou acidente vascular cerebral). Biomarcadores plasmáticos ­ lipídios, marcadores glicometabólicos, proteína C ultrassensível (PCR-us), Interleucina 6 (IL-6), Interleucina 10 (IL-10), Fator de Necrose Tumoral-α (TNF-α), Proteína quimioatraente de Monócitos 1 (MCP-1) ­ e ácidos graxos das hemácias (ácidos palmítico e esteárico) foram analisados. As associações foram avaliadas por análises de correlações e regressões lineares múltiplas, com significância estatística estabelecida em p<0,05. RESULTADOS: O ácido palmítico não apresentou associações com fatores de risco cardiovasculares ou com marcadores inflamatórios. Por outro lado, o ácido esteárico foi inversamente correlacionado com PCR-us, IL-6 e TNF-α, mas independentemente associado com PCR-us, IL-6, e TNF-α. CONCLUSÃO: O ácido esteárico está associado com biomarcadores inflamatórios e disfunção endotelial em indivíduos com um ou mais fatores de risco cardiovascular.

Sirtuin 1 and Vascular Function in Healthy Women and Men: A Randomized Clinical Trial Comparing the Effects of Energy Restriction and Resveratrol.

Background: Sirtuin 1 (SIRT1) has been associated with longevity and protection against cardiometabolic diseases, but little is known about how it influences human vascular function. Therefore, this study evaluated the effects of SIRT1 activation by resveratrol and energy restriction on vascular reactivity in adults. Methods: A randomized trial allocated 48 healthy adults (24 women and 24 men), aged 55 to 65 years, to resveratrol supplementation or energy restriction for 30 days. Blood lipids, glucose, insulin, C-reactive protein, noradrenaline, SIRT1 (circulating and gene expression), and flow-mediated vasodilation (FMD) and nitrate-mediated vasodilation (NMD) were measured. Results: Both interventions increased circulating SIRT1 (p < 0.001). Pre- and post-tests changes of plasma noradrenaline were significant for both groups (resveratrol: p = 0.037; energy restriction: p = 0.008). Baseline circulating SIRT1 was inversely correlated with noradrenaline (r = -0.508; p < 0.01), and post-treatment circulating SIRT1 was correlated with NMD (r = 0.433; p < 0.01). Circulating SIRT1 was a predictor of FMD in men (p = 0.045), but not in women. SIRT1 was an independent predictor of NMD (p = 0.026) only in the energy restriction group. Conclusions: Energy restriction and resveratrol increased circulating SIRT1 and reduced sympathetic activity similarly in healthy adults. SIRT1 was independently associated with NMD only in the energy restriction group.

Ácido Esteárico (mas não o Ácido Palmítico) está Associado a Biomarcadores Inflamatórios e de Disfunção Endotelial em Indivíduos em Risco Cardiovascular / Stearic Acid, but not Palmitic Acid, is Associated with Inflammatory and Endothelial Dysfunction Biomarkers in Individuals at Cardiovascular Risk

Resumo Fundamento Vários estudos têm associado o consumo de ácidos graxos saturados (AGSs) com risco cardiovascular, mas ainda existem muitas controvérsias. A maioria desses estudos avaliou os efeitos do ácido palmítico sobre lipídios circulantes. O ácido esteárico geralmente apresenta um efeito neutro sobre os lipídios sanguíneos, mas faltam estudos clínicos avaliando sua relação com marcadores de inflamação e de disfunção endotelial. Objetivos Avaliar a associação de AGSs das hemácias (ácido palmítico e ácido esteárico) com biomarcadores inflamatórios e de disfunção endotelial circulantes. Métodos Estudo transversal que incluiu 79 adultos de ambos os sexos com pelo menos um fator de risco cardiovascular, mas sem eventos prévios (infarto agudo do miocárdio ou acidente vascular cerebral). Biomarcadores plasmáticos - lipídios, marcadores glicometabólicos, proteína C ultrassensível (PCR-us), Interleucina 6 (IL-6), Interleucina 10 (IL-10), Fator de Necrose Tumoral-α (TNF-α), Proteína quimioatraente de Monócitos 1 (MCP-1) - e ácidos graxos das hemácias (ácidos palmítico e esteárico) foram analisados. As associações foram avaliadas por análises de correlações e regressões lineares múltiplas, com significância estatística estabelecida em p<0,05. Resultados O ácido palmítico não apresentou associações com fatores de risco cardiovasculares ou com marcadores inflamatórios. Por outro lado, o ácido esteárico foi inversamente correlacionado com PCR-us, IL-6 e TNF-α, mas independentemente associado com PCR-us, IL-6, e TNF-α. Conclusão O ácido esteárico está associado com biomarcadores inflamatórios e disfunção endotelial em indivíduos com um ou mais fatores de risco cardiovascular.

Abstract Background Several studies have associated dietary saturated fatty acids (SFAs) with cardiovascular risk but there are still many controversies. Most of these studies have focused on the effects of palmitic acid on circulating lipids. Stearic acid usually shows a neutral effect on blood lipids, however, there is a lack of clinical studies assessing the link with inflammatory and endothelial dysfunction markers. Objective To evaluate the association of red blood cell (RBC) SFA (palmitic and stearic acids) with circulating inflammatory and endothelial dysfunction biomarkers. Methods Cross-sectional study of 79 adults of both sexes with at least one cardiovascular risk factor but without previous events (acute myocardial infarction or stroke). Plasma biomarkers - lipids, glucometabolic markers, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) - and RBC palmitic and stearic fatty acids were analyzed. The associations were assessed by correlation and multiple linear regression analyses, with statistical significance set at p < 0.05. Results Palmitic acid showed no significant associations with traditional cardiovascular risk factors or inflammatory markers. Stearic acid, on the other hand, was inversely correlated with blood cholesterol and triglycerides, but independently associated with hs-CRP, IL-6, and TNF-α. Conclusion Stearic acid is associated with inflammatory and endothelial dysfunction biomarkers in individuals with at least one cardiovascular risk factor.

Os Ácidos Graxos Poli-insaturados Ômega-6 e Ômega-3 Presentes nas Hemácias Exercem uma Influência Distinta sobre o Tamanho das Partículas de LDL e suas Alterações Estruturais / Red Blood Cells' Omega-6 and Omega-3 Polyunsaturated Fatty Acids Have a Distinct Influence on LDL Particle Size and its Structural Modifications

Resumo Fundamento Embora os ácidos graxos poli-insaturados ômega-3 e ômega-6 (AGPIs n-3 e n-6) tenham efeitos bem conhecidos sobre os fatores de risco de doenças cardiovasculares (DCV), ainda existe um conhecimento limitado sobre como eles afetam os indicadores de qualidade da LDL. Objetivo Avaliar as associações dos AGPIs n-3 e n-6 de hemácias com o tamanho da partícula da LDL, LDL-c pequena e densa (sdLDL-c) e com LDL eletronegativa [LDL(-)] em adultos com fatores de risco para DCV. Métodos Estudo transversal com 335 homens e mulheres de 30 a 74 anos com, pelo menos, um fator de risco cardiovascular. Foram realizadas análises de parâmetros bioquímicos, como glicose, insulina, HbA1c, proteína C reativa (PCR), perfil lipídico, subfrações de lipoproteínas, partícula eletronegativa de LDL [LDL(-)] e seu autoanticorpo, e os AGPIs n-3 e n- 6 de hemácias. Os testes t independente/teste de Mann-Whitney, ANOVA unidirecional/teste de Kruskal-Wallis e regressões lineares múltiplas foram aplicados. Todos os testes foram bilaterais e um valor de p inferior a 0,05 foi considerado estatisticamente significativo. Resultados A relação n-6/n-3 de hemácias foi associada ao aumento dos níveis de LDL(-) (β = 4,064; IC de 95% = 1,381 - 6,748) e sdLDL-c (β = 1,905; IC de 95% = 0,863 - 2,947), e redução do tamanho das partículas de LDL (β = -1,032; IC de 95% = -1,585 − -0,478). Individualmente, os AGPIs n-6 e n-3 apresentaram associações opostas com esses parâmetros, realçando os efeitos protetores do n-3 e evidenciando os possíveis efeitos adversos do n-6 na qualidade das partículas de LDL. Conclusão O AGPI n-6, presente nas hemácias, foi associado ao aumento do risco cardiometabólico e à aterogenicidade das partículas de LDL, enquanto o AGPI n-3 foi associado a melhores parâmetros cardiometabólicos e à qualidade das partículas de LDL.

Abstract Background While Omega-3 and omega-6 polyunsaturated fatty acids (n-3 and n-6 PUFAs) have established effects on cardiovascular disease (CVD) risk factors, little is known about their impacts on LDL quality markers. Objective To assess the associations of n-3 and n-6 PUFA within red blood cells (RBC) with LDL particle size, small dense LDL-c (sdLDL-c), and electronegative LDL [LDL(-)] in adults with CVD risk factors. Methods Cross-sectional study involving 335 men and women aged 30 to 74 with at least one cardiovascular risk factor. Analyses were conducted on biochemical parameters, such as glucose, insulin, HbA1c, C-reactive protein (CRP), lipid profile, lipoprotein subfractions, electronegative LDL particle [LDL(-)] and its autoantibody, and RBC n-3 and n-6 PUFAs. Independent t-test/Mann-Whitney test, one-way ANOVA/Kruskal-Wallis test, and multiple linear regressions were applied. All tests were two-sided, and a p-value of less than 0.05 was considered statistically significant. Results The RBC n-6/n-3 ratio was associated with increased LDL(-) (β = 4.064; 95% CI = 1.381 - 6.748) and sdLDL-c (β = 1.905; 95% CI = 0.863 - 2.947) levels, and reduced LDL particle size (β = -1.032; 95% CI = -1.585 − -0.478). Separately, n-6 and n-3 PUFAs had opposing associations with those parameters, reinforcing the protective effects of n-3 and showing the potential negative effects of n-6 on LDL particle quality. Conclusion RBC n-6 PUFA was associated with increased cardiometabolic risk and atherogenicity of LDL particles, while n-3 PUFA was associated with better cardiometabolic parameters and LDL particle quality.

The Interplay of Sirtuin-1, LDL-Cholesterol, and HDL Function: A Randomized Controlled Trial Comparing the Effects of Energy Restriction and Atorvastatin on Women with Premature Coronary Artery Disease.

INTRODUCTION: HDL function has gained prominence in the literature as there is a greater predictive capacity for risk in early coronary artery disease when compared to the traditional parameters. However, it is unclear how dietary energy restriction and atorvastatin influence HDL function. METHODS: A randomized controlled trial with 39 women with early CAD divided into three groups (n = 13): energy restriction (30% of VET), atorvastatin (80 mg), and control. Analyses of traditional biochemical markers (lipid and glucose profile), circulating Sirt-1, and HDL function (lipid composition, lipid transfer, and antioxidant capacity). RESULTS: Participants' mean age was 50.5 ± 3.8 years. Energy restriction increased Sirt-1 by 63.6 pg/mL (95%CI: 1.5-125.7; p = 0.045) and reduced BMI by 0.8 kg/m2 (95%CI: -1.349--0.273; p = 0.004) in a manner independent of other cardiometabolic factors. Atorvastatin reduced LDL-c by 40.0 mg/dL (95%CI: -69.910--10.1; p = 0.010). Increased Sirt-1 and reduced BMI were independently associated with reduced phospholipid composition of HDL (respectively, ß = -0.071; CI95%:-0.136--0.006; p = 0.033; ß = 7.486; CI95%:0.350-14.622; p = 0.040). Reduction in BMI was associated with lower HDL-free cholesterol (ß = 0.818; CI95%:0.044-1.593; p = 0.039). LDL-c reduction by statins was associated with reduced maximal lipid peroxide production rate of HDL (ß = 0.002; CI95%:0.000-0.003; p = 0.022) and total conjugated diene generation (ß = 0.001; CI95%:0.000-0.001; p = 0.029). CONCLUSION: This study showed that energy restriction and atorvastatin administration were associated with changes in lipid profile, serum Sirt-1 concentrations, and HDL function.

Sex Differences in Heart Failure Mortality with Preserved, Mildly Reduced and Reduced Ejection Fraction: A Retrospective, Single-Center, Large-Cohort Study.

BACKGROUND: Heart failure (HF) is one of the leading causes of death worldwide. Studies show that women have better survival rates than men despite higher hospitalizations. However, little is known about differences in mortality and predictors of death in women and men with HF with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF). METHODS: From February 2017 to September 2020, mortality and predictors of death were analyzed in women and men with HF. Baseline data included clinical characteristics and echocardiographic findings. RESULTS: A total of 11,282 patients, 63.9 ± 14.4 years, including 6256 (55.4%) males, were studied. Females were older, had a higher baseline mean left ventricular ejection fraction (LVEF) and lower left ventricular diastolic diameter. During follow-ups, 1375 (22%) men and 925 (18.4%) women died. Cumulative incidence of death was higher in men with HFrEF but similar for HFmrEF and HFpEF. Cox regression for death showed renal dysfunction, stroke, diabetes, atrial fibrillation, age, LVEF, valve disease, MI, and hypertensive CMP as independent death predictors for all HF patients. CONCLUSIONS: Women had a better prognosis than men in HFrEF and similar mortality for HFmrEF and HFpEF, but sex was not an independent predictor of death for all HF subtypes.

Effects of Coffee on Sirtuin-1, Homocysteine, and Cholesterol of Healthy Adults: Does the Coffee Powder Matter?

Background: Coffee is one of the most popular beverages globally and contains several bioactive compounds that are relevant to human health. Many nutritional strategies modulate sirtuin-1, thereby impacting aging and cardiometabolic health. This study investigated the influence of different blended coffees on serum sirtuin-1, blood lipids, and plasma homocysteine. Methods: An eight-week randomized clinical trial that included 53 healthy adults of both sexes analyzed the effects of daily intake of 450 to 600 mL of pure Arabica or blended (Arabica + Robusta) coffee intake of filtered coffee on blood sirtuin-1, lipids, and homocysteine. Results: Both Arabica and blended coffees similarly increased serum sirtuin-1 concentration, from 0.51 to 0.58 ng/mL (p = 0.004) and from 0.40 to 0.49 ng/mL (p = 0.003), respectively, without changing plasma homocysteine, folic acid, glucose, and CRP. However, the blended coffee intake increased total cholesterol from 4.70 to 5.17 mmol/L (p < 0.001) and LDL-cholesterol from 2.98 to 3.32 mmol/L (p < 0.001), as well as HDL-c from 1.26 to 1.36 mmol/L (p < 0.001). Conclusion: Both coffee powders increased sirtuin-1 expression, but our results suggest that blended coffee had hypercholesterolemic effects which could increase cardiovascular risk. Therefore, preference should be given to Arabica coffee for the best cardiometabolic benefits of coffee.

Omega-3 Fatty Acids in Erythrocyte Membranes as Predictors of Lower Cardiovascular Risk in Adults without Previous Cardiovascular Events.

Background: This study investigated the association of omega-3 polyunsaturated fatty acids (n-3 PUFA) within erythrocyte membranes and cardiovascular risk assessed by three different estimates. Methods: Inclusion criteria were individuals of both sexes, 30 to 74 years, with at least one cardiovascular risk factor, and no previous cardiovascular events (n = 356). Exclusion criteria were individuals with acute or chronic severe diseases, infectious diseases, pregnant, and/or lactating women. Plasma biomarkers (lipids, glucose, and C-reactive protein) were analyzed, and nineteen erythrocyte membrane fatty acids (FA) were identified. The cardiovascular risk was estimated by Framingham (FRS), Reynolds (RRS), and ACC/AHA-2013 Risk Scores. Three patterns of FA were identified (Factor 1, poor in n-3 PUFA), (Factor 2, poor in PUFA), and (Factor 3, rich in n-3 PUFA). Results: Total cholesterol was inversely correlated with erythrocyte membranes C18:3 n-3 (r = -0.155; p = 0.004), C22:6 n-3 (r = -0.112; p = 0.041), and total n-3 (r = -0.211; p < 0.001). Total n-3 PUFA was associated with lower cardiovascular risk by FRS (OR = 0.811; 95% CI= 0.675-0.976). Regarding RRS, Factor 3 was associated with 25.3% lower odds to have moderate and high cardiovascular risk (OR = 0.747; 95% CI = 0.589-0.948). The ACC/AHA-2013 risk score was not associated with isolated and pooled FA. Conclusions:n-3 PUFA in erythrocyte membranes are independent predictors of low-risk classification estimated by FRS and RRS, which could be explained by cholesterol-lowering effects of n-3 PUFA.

Comparison of Resveratrol Supplementation and Energy Restriction Effects on Sympathetic Nervous System Activity and Vascular Reactivity: A Randomized Clinical Trial.

Background: Chronic sympathetic nervous system activation is associated with endothelial dysfunction and cardiometabolic disease, which may be modulated by resveratrol (RSV) and energy restriction (ER). This study aimed to examine the effects of RSV and ER on plasma noradrenaline (NA), flow-mediated vasodilation (ed-FMD), and endothelium-independent nitrate-mediated vasodilation (ei-NMD). Methods: The study included 48 healthy adults randomized to 30-days intervention of RSV or ER. Results: Waist circumference, total cholesterol, HDL-c, LDL-c, apoA-I, and plasma NA decreased in the ER group, whilst RSV increased apoB and total cholesterol, without changing plasma NA. No effects on vascular reactivity were observed in both groups. Plasma NA change was positively correlated with total cholesterol (r = 0.443; p = 0.002), triglycerides (r = 0.438; p = 0.002), apoA-I (r = 0.467; p = 0.001), apoB (r = 0.318; p = 0.032) changes, and ei-NMD (OR = 1.294; 95%CI: 1.021-1.640). Conclusions: RSV does not improve cardiometabolic risk factors, sympathetic activity, and endothelial function. ER decreases plasma NA and waist circumference as well as improves blood lipids, but does not modify endothelial function. Finally, plasma NA was associated with ei-NMD, which could be attributed to a higher response to nitrate in patients with greater resting sympathetic vasoconstriction.

A possible link between polyunsaturated fatty acids and uremic toxins from the gut microbiota in hemodialysis patients: A hypothesis.

INTRODUCTION: Indoxyl sulfate (IS) and p-cresyl sulfate (p-CS) are albumin-bound uremic toxins that are difficult to remove by hemodialysis (HD). Human serum albumin (HSA) carries several compounds, including fatty acids that can bind to site II of HSA and represent competing ligands for uremic toxins. The aim of this study was to investigate the association between fatty acids and uremic toxin plasma levels in patients undergoing HD. METHODS: Thirty-three HD patients (51.5% male, 54.9 ± 10.2 years old, 44.63 ± 28.4 months on HD, albumin level of 3.8 ± 0.3 g/dL) were evaluated. The erythrocyte fatty acid content (saturated fatty acid [SFA], monounsaturated fatty acid [MUFA], and polyunsaturated fatty acid [PUFA]) was measured by gas chromatography, and total IS and p-CS plasma levels were measured by reversed-phase high-performance liquid chromatography. FINDINGS: The mean percentages of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) + DHA and gamma-linolenic (GLA) acid in the erythrocyte membrane were 1.35% ± 0.74%, 1.85% ± 0.79%, and 0.33% ± 0.26%, respectively. The mean levels of IS and p-CS were 19.4 ± 11.9 mg/dL and 101.5 ± 57.2 mg/dL, respectively. There was no significant association between SFA and MUFA and IS and p-CS; however, a negative correlation was found between p-CS and specific PUFAs, and the association between GLA and p-CS levels was retained after adjusting for potential confounding variables (ß = -0.49, P = 0.007). DISCUSSION: Polyunsaturated fatty acids may contribute to the decrease in p-CS uremic toxin plasma levels in patients with chronic kidney disease undergoing HD.

Perfil de ácidos graxos ômega-3 nas membranas eritrocitárias e sua associação com equações preditivas aplicadas à estimativa do risco cardiovascular / Erythrocyte membranes' omega-3 fatty acids profile and its association with predictive equations applied in the estimation of cardiovascular risk

Introdução: Embora diversos mecanismos indiquem o papel cardioprotetor dos ácidos graxos ômega-3 (AG n-3), há controvérsias quanto seu impacto nos desfechos cardiovasculares. Nós hipotetizamos que os AG n-3 das membranas eritrocitárias refletem melhor o consumo e metabolização desses AG, permitindo identificar seus reais benefícios cardiovasculares. Objetivo: Associar os AG n-3 com biomarcadores cardiometabólicos e com o risco cardiovascular (RC) global. Métodos: Estudo transversal baseado no ensaio clínico CARDIONUTRI (n=356), com indivíduos de ambos os sexos (30-74 anos) e com pelo menos um dos seguintes fatores de risco: tabagismo, hipertensão, dislipidemia, diabetes mellitus ou obesidade. Foram analisados o lipidograma, subfrações de lipoproteínas, LDL(-), glicemia, HbA1c, insulina, HOMA-IR e biomarcadores de inflamação. Os AG dos eritrócitos foram analisados por meio de cromatografia gasosa. O RC global foi estimado pelos escores de Framingham (ERF), Reynolds (ERR) e da ACC/AHA 2013. Os resultados obtidos foram analisados no programa estatístico SPSS v.20.0 e Stata v.14.0. Resultados: Indivíduos com AG n-3 >6,24% e com razão n-6/n-3<=1,27 apresentaram menos colesterol não-HDL, Apo B, TG, LDL(-) e maior tamanho de LDL. O total de AG n-3 foi associado a menor RC estimado pelo ERF (OR=0,811; IC95%=0,675-0,976) e o padrão de membranas que contém mais n-6 e menos n-3 foi associado a maior risco (OR=1,469; IC95%=1,056-2,043). Perfil semelhante foi associado a maior RC estimado pelo ERR (OR: 1,276; IC95%=1,010-1,612), enquanto o padrão oposto, com mais n-3 e menos n-6, foi associado a menor RC (OR=0,747; IC95%=0,589-0,948). Não houve associações significativas com o RC estimado segundo o ACC/AHA 2013. Conclusão: Membranas eritrocitárias com mais AG n-3 e menos n-6 foram associadas a um perfil lipídico com menos lipoproteínas aterogênicas, menos TG e menor modificação da LDL. Esse perfil reduziu a chance de os indivíduos apresentarem RC moderado ou alto estimado pelos Escores de Risco de Reynolds e de Framingham.

Introduction: Although several mechanisms confirm the cardioprotective role of omega-3 fatty acids (n-3 PUFA), there is still controversy regarding the impact on cardiovascular outcomes. We hypothesized that the erythrocytes membranes' n-3 PUFA reflect better intake and metabolization of these fatty acids, allowing to identify their cardiovascular benefits. Objective: To evaluate the association of the n-3 PUFA with cardiometabolic biomarkers and absolute cardiovascular risk. Methods: A crosssectional study based on the CARDIONUTRI clinical trial (n = 356) with individuals of both sexes (30-74 years) with at least one of the following risk factors: smoking, hypertension, dyslipidemias, diabetes mellitus or obesity. We analyzed the lipid profile, lipoprotein subfractions, LDL(-), glycemia, HbA1c, insulin, HOMA-IR and inflammation biomarkers. Fatty acids were analyzed by gas chromatography. The 10- years projection of absolute cardiovascular risk was estimated by the Framingham (FRS), Reynolds (RRS) and ACC/AHA 2013 risk scores. The obtained results were analyzed by the statistical softwares SPSS v.20.0 and Stata v.14.0. Results: Individuals with n-3 PUFA > 6,24% and n-6/n-3 <= 1,27 had less plasma non-HDL cholesterol, Apo B, TG, LDL(-) and had bigger LDL size. Regarding FRS, the total n- 3 PUFA had association with lower cardiovascular risk (OR=0,811; IC95%=0,675- 0,976) and the membrane pattern containing more n-6 and less n-3 PUFA was associated with higher risk (OR=1,469; IC95%=1,056-2,043). Regarding RRS, the same pattern had association with higher risk (OR: 1,276; IC95%=1,010-1,612) whilst the opposite pattern, containing more n-3 and less n-6 PUFA, had association with lower risk (OR=0,747; IC95%=0,589-0,948). Associations with ACC/AHA 2013 were not significant. Conclusion: Erythrocyte membranes containing more n-3 and less n-6 PUFA were associated with a lipid profile characterized by less plasma atherogenic lipoproteins, less TG and fewer LDL modification. This membrane profile was associated with reduced chance to be classified as moderate or higher cardiovascular risk by the Reynolds and Framingham risk scores.