Intestinal Microbiota and Cardiovascular Diseases

Abstract Recently, gut microbiota has emerged as an important mediator of several diseases such as diabetes, atherosclerosis, arterial hypertension, obesity, cancers and neuropsychiatric diseases including Alzheimer, autism and depression. Intestinal microbiota is formed by bacteria, fungi and viruses and its main function is to facilitate the absorption and metabolism of foods (protein, fat and carbohydrate). One example of the multiple actions of the gut microbiota is the bidirectional relationship between the intestine and the brain, the so-called "gut/brain axis". Furthermore, metabolites produced by gut microbiota can induce effects locally or at distance, which suggests that the intestine is an endocrine organ. Given the participation of the gut microbiota in several diseases, there is great interest in strategies that may positively affect the gut flora and prevent or even treat diseases. Among these strategies, lifestyle change, but specially diet modulation has gained importance. In this article, we review the mechanisms through which intestinal microbiota participates in cardiovascular diseases and possible therapeutic interventions.

[Lack of knowledge of Guidelines for Prevention of Atherosclerosis in Childhood and Adolescence by pediatricians in the city of São Paulo]. / Desconhecimento da diretriz de prevenção da aterosclerose na infância e adolescência por pediatras em São Paulo.

OBJECTIVE: To report the extent of knowledge of pediatricians in São Paulo concerning the Guidelines. METHODS: At pediatric events or hospitals, pediatricians were given a questionnaire about the time of training, work, dedication in the area of pediatrics, and academic performance for reply to multiple choice questions with information drawn from the Guidelines. The Chi -square and the Chi -square of linear trend tests were chosen for statistical calculations. RESULTS: Among 370 pediatricians surveyed, 65.7% had no previous knowledge of the Guidelines. The cut-off for the hits was > or = 70% (> or = 5 correct replies). Only 136 pediatricians (36.7%) reached the cut-off and no gender differences were found in knowledge (p = 0.25). Among 187 professionals involved in academic activities, 45 (24%) hit the cut-off and about 183 participants from non-academic activities, 23 (12.7%) reached > or = 5 hit points (p <0.001). Pediatricians in the public sector had better knowledge about preventive measures for atherosclerosis risk factors (46.1%, p = 0.01). Awareness of the Guidelines was independent from training time. CONCLUSION: The majority of pediatricians in the city of São Paulo were not familiar with the Guidelines for Prevention of Atherosclerosis in Childhood and Adolescence and individual strategies were rarely found. Medical education and adequate disclosure of the Guidelines are necessary for active control of populational risk factors.

Desconhecimento da diretriz de prevenção da aterosclerose na infância e adolescência por pediatras em São Paulo / Lack of knowledge of guidelines for prevention of atherosclerosis in childhood and adolescence by pediatricians in the city of São Paulo

OBJETIVO: Relatar a extensão do conhecimento de pediatras de São Paulo sobre a diretriz. MÉTODOS: Durante eventos de pediatria ou nos locais de trabalho, pediatras responderam um questionário contendo informações sobre o tempo de formação, local de trabalho, dedicação dentro da área de pediatria, atuação em área acadêmica e questões de múltipla escolha com informações retiradas da diretriz. As diferenças de expressão e associações foram consideradas significantes estatisticamente quando p<0,05. Todas as análises foram realizadas usando teste de Quiquadrado e teste de Quiquadrado de tendência linear por meio dos Softwares Primer of Biostatistics ou SPSS for Windows. RESULTADOS: Dos 370 pediatras entrevistados, 65,7 por cento afirmaram não ter tido conhecimento prévio da diretriz. O valor de corte para os acertos foi maior ou igual a 70 por cento (maior ou igual a cinco questões corretas). Apenas 136 pediatras (36,7 por cento) alcançaram tal valor e dentre esses não havia relação no conhecimento da diretriz quanto aos sexos (p=0,25). Dos 187 profissionais envolvidos em atividades acadêmicas, 45 (24 por cento) acertaram o valor de corte e dos 183 não participantes de atividades acadêmicas, 23 (12,7 por cento) acertaram maior ou igual a cinco questões (p<0,001). Pediatras do setor público apresentaram melhor conhecimento da prática preventiva da aterosclerose (46,1 por cento; p=0,01). O desconhecimento da diretriz foi independente do tempo de formação. CONCLUSÃO: A meta da diretriz de servir como referência para o estabelecimento de estratégias individuais e populacionais no controle dos fatores de risco para a aterosclerose desde a infância não foi alcançada na cidade de São Paulo. A divulgação mais adequada e cursos de educação médica continuada em que o conhecimento da diretriz se torne mais efetivo são sugeridos para corrigir tais achados.

OBJECTIVE: To report the extent of knowledge of pediatricians in São Paulo concerning the Guidelines. METHODS: At pediatric events or hospitals, pediatricians were given a questionnaire about the time of training, work, dedication in the area of pediatrics, and academic performance for reply to multiple choice questions with information drawn from the Guidelines. The Chi -square and the Chi -square of linear trend tests were chosen for statistical calculations. RESULTS: Among 370 pediatricians surveyed, 65.7 percent had no previous knowledge of the Guidelines. The cut-off for the hits was > or = 70 percent (> or = 5 correct replies). Only 136 pediatricians (36.7 percent) reached the cut-off and no gender differences were found in knowledge (p = 0.25). Among 187 professionals involved in academic activities, 45 (24 percent) hit the cut-off and about 183 participants from non-academic activities, 23 (12.7 percent) reached > or = 5 hit points (p <0.001). Pediatricians in the public sector had better knowledge about preventive measures for atherosclerosis risk factors (46.1 percent, p = 0.01). Awareness of the Guidelines was independent from training time. CONCLUSION: The majority of pediatricians in the city of São Paulo were not familiar with the Guidelines for Prevention of Atherosclerosis in Childhood and Adolescence and individual strategies were rarely found. Medical education and adequade disclosure of the Guidelines are necessary for active control of populational risk factors.

Vascular and metabolic response to statin in the mildly hypertensive hypercholesterolemic elderly.

INTRODUCTION: Much evidence indicates the importance of the endothelium and hypercholesterolemia in atherosclerosis, as well as the decline in endothelial function with aging. However, it is unclear if treating dyslipidemia in elderly patients improves endothelial function and reduces C-reactive protein levels. OBJECTIVES: To evaluate vasomotor function, lipids and C-reactive protein in mildly hypertensive and hypercholesterolemic elderly patients treated with atorvastatin. METHODS: Forty-seven elderly Brazilian subjects (> or = 65 years old) with LDL cholesterol (LDL-c) > or = 130 mg/dL were randomly assigned, in a double-blinded manner, to receive either placebo (n = 23) or 20 mg/day of atorvastatin (n = 24) for 4 weeks. Exclusion criteria included diabetes, serious hypertension, obesity, steroid use, hormone replacement, and statin use within the previous six months. All patients underwent clinical examinations, laboratory tests (glucose, lipids, liver enzymes, creatine phosphokinase and high sensitivity C-reactive protein) and assessment of vasomotor function by high-resolution ultrasound examination of the brachial artery (flow-mediated dilation and sublingual nitrate), both before and after treatment. RESULTS: The patients were 65 to 91 years old; there was no significant difference between basal flow-mediated dilation of placebo (7.3 +/- 6.1%) and atorvastatin (4.5 +/- 5.1%; p = 0.20). The same was observed after treatment (6.6 +/- 6.2 vs. 5.0 +/- 5.6; p = 0.55). The initial nitrate dilatation (8.1 +/- 5.4% vs. 10.8 +/- 7.5%; p = 0.24) and that after 4 week treatment (7.1 +/- 4.7% vs. 8.6 +/- 5.0%; p = 0.37) were similar. Atorvastatin produced a reduction of 20% of the C-reactive protein and 42% in the LDL-c; however, there were no changes in the flow-mediated dilation. CONCLUSIONS: Atorvastatin produced a significant change of lipids and C-reactive protein; however, there were no changes in vasomotor function, suggesting the existence of intrinsic age-related vessel alterations.

Vascular and metabolic response to statin in the mildly hypertensive hypercholesterolemic elderly

INTRODUCTION: Much evidence indicates the importance of the endothelium and hypercholesterolemia in atherosclerosis, as well as the decline in endothelial function with aging. However, it is unclear if treating dyslipidemia in elderly patients improves endothelial function and reduces C-reactive protein levels. OBJECTIVES: To evaluate vasomotor function, lipids and C-reactive protein in mildly hypertensive and hypercholesterolemic elderly patients treated with atorvastatin. METHODS: Forty-seven elderly Brazilian subjects (> 65 years old) with LDL cholesterol (LDL-c) > 130 mg/dL were randomly assigned, in a double-blinded manner, to receive either placebo (n = 23) or 20 mg/day of atorvastatin (n = 24) for 4 weeks. Exclusion criteria included diabetes, serious hypertension, obesity, steroid use, hormone replacement, and statin use within the previous six months. All patients underwent clinical examinations, laboratory tests (glucose, lipids, liver enzymes, creatine phosphokinase and high sensitivity C-reactive protein) and assessment of vasomotor function by high-resolution ultrasound examination of the brachial artery (flow-mediated dilation and sublingual nitrate), both before and after treatment. RESULTS: The patients were 65 to 91 years old; there was no significant difference between basal flow-mediated dilation of placebo (7.3 ± 6.1 percent) and atorvastatin (4.5 ± 5.1 percent; p = 0.20). The same was observed after treatment (6.6 ± 6.2 vs. 5.0 ± 5.6; p = 0.55). The initial nitrate dilatation (8.1 ± 5.4 percent vs. 10.8 ± 7.5 percent; p = 0.24) and that after 4 week treatment (7.1 ± 4.7 percent vs. 8.6 ± 5.0 percent; p = 0.37) were similar. Atorvastatin produced a reduction of 20 percent of the C-reactive protein and 42 percent in the LDL-c; however, there were no changes in the flow-mediated dilation. CONCLUSIONS: Atorvastatin produced a significant change of lipids and C-reactive protein; however, there were no changes in vasomotor ...

Terapia hipolipemiante em situações especiais: hipotireoidismo e hepatopatias / Hypolipidemic therapy in special situations: hypothyroidism and liver disease

O hipotireoidismo é comum entre pessoas idosas, especialmente entre as mulheres. A suspeita diagnóstica deve se basear na presença de sinais e sintomas clássicos e a detecção pode ser feita pela elevação dos níveis do hormônio tireo-estimulante (TSH). Anormalidades lipídicas na presença de hipotireoidismo sub-clínico são de menor impacto. Entretanto, a reposição específica de hormônio tireoideano é tão mais importante quanto a magnitude do distúrbio glandular. Na vigência de doença hepática, alguns agentes hipolipemiantes podem levar a um agravamento do quadro, entretanto, estudos recentes têm mostrado que as estatinas podem ser utilizadas na presença de esteatose hepática. Terapia hipolipemiante combinada pode induzir aumentos de enzimas hepáticas e o monitoramento cuidadoso é recomendado nestes pacientes.

[Hypolipidemic therapy in special situations: hypothyroidism and liver disease]. / Terapia hipolipemiante em situações especiais--hipotireoidismo e hepatopatias.

Hypothyroidism is common in the elderly, especially among women. It should be suspected in the presence of classic signals and symptoms, and can be detected by an elevation of serum thyroid stimulating hormone (TSH). Lipid abnormalities in the presence of subclinical hypothyroidism are of minor importance. However, the importance of specific treatment (hormone replacement) increases with the magnitude of thyroid disturbance. Some hypolipidemic agents can aggravate prior liver disease, however, recent studies have shown that statins might be useful in the presence of steatohepatitis. Some associations of hypolipidemic drugs can increase liver enzymes, and careful monitoring is recommended.

Ativação endotelial na disfunção ventricular / Endothelial activation in ventricular dysfunction

As alterações hemodinâmicas e hormonais que ocorrem nos quadros de disfunção ventricular e que são responsáveis pelo remodelamento são relativamente bem conhecidas, porém a importância das alterações locais, ou seja, o papel do endotélio no remodelamento ainda é motivo de controvérsias, pelo desconhecido papel dessas células na regulação do estado contrátil do coração. As célulasendocárdicas e as células endoteliais da vasculatura coronária secretam substâncias que modificam acontratilidade dos cardiomiócitos. As células endoteliais podem produzir pelo menos duas substâncias, as quais parecem ter grande relevância no processo de remodelamento: o óxido nítrico e a endotelina.Em portadores de insuficiência cardíaca, evidências recentes sugerem que a disfunção vascular endotelial pode também contribuir para o aumento do tônus vasomotor e para a perpetuação do círculo vicioso na insuficiência cardíaca. O aumento da endotelina circulante e o aumento dos receptores da endotelina no tecido cardíaco, bem como da expressão gênica desse polipeptídeo nos pacientescom insuficiência cardíaca, associados às alterações da expressão e da atividade das isoenzimasresponsáveis pela produção de óxido nítrico (sintase do óxido nítrico endotelial ou constitutiva e sintase de óxido nítrico induzível) no tecido cardíaco, dão significativa importância à regulação que o endotélio promove nos quadros em que haja disfunção ventricular. Acresça-se a isso o fato de a enzima precursora do óxido nítrico estar presente no endotélio vascular e também nos cardiomiócitos. Embora os estudos que testaram drogas que bloqueavam os receptores da endotelina não tenham resultado em melhora da mortalidade, a correção da disfunção endotelial poderá oferecer novo meio terapêuticopara melhorar o desempenho cardíaco nos casos de importante disfunção ventricular...

O gemfibrozil reduz níveis elevados de lipoproteína (a) em pacientes hipercolesterolêmicos / Gemfibrozil reduces elevated lipoprotein (a) levels in hypercholesterolemic patients

PURPOSE: To compare the effects of gemfibrozil and lovastatin in patients with hypercholesterolemia and increased lipoprotein(a) [Lp(a)] levels. METHODS: Twenty-seven subjects with total cholesterol (TC) > 240 mg/dL, LDL-C > 160 mg/dL and Lp(a) > 25 mg/dL were studied. Patients were randomized to receive gemfibrozil 1200 mg/day, (n = 14, 54 +/- 7 years) or lovastatin 40-80 mg at night (n = 13, 55 +/- 9 years) for 12 weeks. Lipid profile and Lp(a) were determined at 4 and 12 weeks of treatment. RESULTS: Gemfibrozil reduced TC (-21), LDL-C (-26), triglycerides (TG)(-48) and Lp(a) (-25), increased HDL-C (+48)(p < 0.001). Lovastatin reduced TC (-29), LDL-C (-37) and TG (-25) (p < 0.001) however, it did not affect Lp(a). CONCLUSION: Besides reducing plasma LDL-C, TG and increasing HDL-C, gemfibrozil effectively lowers Lp(a) levels. Lovastatin did not affect Lp(a) levels.

Active oxygen species as signaling mediators in the vascular system

There is increasing evidence that active oxygen species (AOS) can act as autocrine or paracrine regulatory mediators, perhaps as part of a more general cellular redox messenger system. This signaling role of AOS has been particularly studied in the vascular system, considering that: 1) Nitric oxide, a gaseous free radical, or a related compound, is a major endothelium-derived vasodilator which is scavenged by superoxide. This interaction not only promotes vasoconstriction, but can generate peroxynitrite, which may be toxic to cells; 2) AOS modulate cytoplasmic calcium and hydrogen concentration and are related to other messenger systems such as membrane G-proteins and protein kinase C; 3) through EPR techniques we showed recently that in vitro and in vivo release of vascular free radicals (probably superoxide) can be triggered by physiological stimuli such as shear stress increases. Flow-induced spin adduct signals were abolished by endothelium removal; 4) we showed previously that superoxide dismutase completely prevents vasoconstriction soon after vascular injury induced by angioplasty, thus implicating the superoxide radical in this acute phenomenon. In addition, we showed that allopurinol or N-acetylcysteine markedly increases vascular diameter up to 7 days after vascular injury, suggesting that redox phenomena may be involved in sustained vessel recoil; 5) endothelial free radical production is increased in atherosclerosis; likewise, lipoprotein oxidation within the vascular wall appears to be a critical in vivo step for atherogenesis. In addition, oxidative stress contributes to dysfunction of endothelium-dependent relaxation in hypertension and diabetes; 6) AOS were shown to mediate growth-related responses in vascular cells. Recently, we showed that in vivo administration of oxidized glutathione markedly enhances vascular proliferation after injury. Therefore , it is suggested that AOS may work as vascular mediators that may exert useful physiological roles; derangements of redox signaling mechanisms are likely involved in endothelial dysfunction and pathological vascular responses.