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.

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.

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.