RESUMO
BACKGROUND: Gut microbiota profiles are closely related to cardiovascular diseases through mechanisms that include the reported deleterious effects of metabolites, such as trimethylamine N-oxide (TMAO), which have been studied as diagnostic and therapeutic targets. Moderate red wine (RW) consumption is reportedly cardioprotective, possibly by affecting the gut microbiota. OBJECTIVES: To investigate the effects of RW consumption on the gut microbiota, plasma TMAO, and the plasma metabolome in men with documented coronary artery disease (CAD) using a multiomics assessment in a crossover trial. METHODS: We conducted a randomized, crossover, controlled trial involving 42 men (average age, 60 y) with documented CAD comparing 3-wk RW consumption (250 mL/d, 5 d/wk) with an equal period of alcohol abstention, both preceded by a 2-wk washout period. The gut microbiota was analyzed via 16S rRNA high-throughput sequencing. Plasma TMAO was evaluated by LC-MS/MS. The plasma metabolome of 20 randomly selected participants was evaluated by ultra-high-performance LC-MS/MS. The effect of RW consumption was assessed by individual comparisons using paired tests during the abstention and RW periods. RESULTS: Plasma TMAO did not differ between RW intervention and alcohol abstention, and TMAO concentrations showed low intraindividual concordance over time, with an intraclass correlation coefficient of 0.049 during the control period. After RW consumption, there was significant remodeling of the gut microbiota, with a difference in ß diversity and predominance of Parasutterella, Ruminococcaceae, several Bacteroides species, and Prevotella. Plasma metabolomic analysis revealed significant changes in metabolites after RW consumption, consistent with improved redox homeostasis. CONCLUSIONS: Modulation of the gut microbiota may contribute to the putative cardiovascular benefits of moderate RW consumption. The low intraindividual concordance of TMAO presents challenges regarding its role as a cardiovascular risk biomarker at the individual level. This study was registered at clinical trials.gov as NCT03232099.
Assuntos
Microbioma Gastrointestinal , Vinho , Masculino , Humanos , Pessoa de Meia-Idade , Cromatografia Líquida , RNA Ribossômico 16S , Espectrometria de Massas em Tandem , Metilaminas , MetabolomaRESUMO
OBJECTIVE: To investigate, in male Wistar rats, the effects of long-term moderate red wine (RW) consumption (equivalent to â¼0.15 mg% resveratrol RS), or RS in low (L, 0.15 mg%) or high (H, 400 mg%) doses in chow. BACKGROUND: Both RW and RS exhibit cardioprotection. RS extends lifespan in obese rats. It is unclear whether RW consumption or low-dose RS delay vascular aging and prolong life span in the absence of overt risk factors. METHODS: Endpoints were aerobic performance, exercise capacity, aging biomarkers (p53,p16,p21, telomere length and telomerase activity in aortic homogenates), vascular reactivity. Data were compared with controls (C) given regular chow. RESULTS: Expressions of p53 decreased â¼50% â¼with RW and LRS (p < 0.05 vs. C), p16 by â¼29% with RW (p < 0.05 vs. C) and p21 was unaltered. RW and LRS increased telomere length >6.5-fold vs. C, and telomerase activity increased with LRS and HRS. All treatments increased aerobic capacity (C 32.5 ± 1.2, RW 38.7 ± 1.7, LRS 38.5 ± 1.6, HRS 38.3 ± 1.8 mlO(2) min(-1) kg(-1)), and RW or LRS also improved time of exercise tolerance vs. C (p < 0.05). Endothelium-dependent relaxation improved with all treatments vs. C. Life span, however, was unaltered with each treatment vs. C = 673 ± 30 days, p = NS. CONCLUSIONS: RW and LRS can preserve vascular function indexes in normal rats, although not extending life span. These effects were translated into better aerobic performance and exercise capacity.
Assuntos
Envelhecimento/efeitos dos fármacos , Longevidade/efeitos dos fármacos , Estilbenos/administração & dosagem , Animais , Aorta/metabolismo , Vasos Sanguíneos/fisiologia , Fatores Relaxantes Dependentes do Endotélio/metabolismo , Teste de Esforço , Masculino , Ratos , Ratos Wistar , Resveratrol , Telômero/metabolismo , Proteína Supressora de Tumor p53/metabolismo , VinhoRESUMO
Intense lifestyle modifications can change the high-density lipoprotein (HDL) cholesterol concentration. The aim of the present study was to analyze the early effects of short-term exercise training, without any specific diet, on the HDL cholesterol plasma levels and HDL functional characteristics in patients with the metabolic syndrome (MS). We studied 30 sedentary subjects, 20 with and 10 without the MS. The patients with the MS underwent moderate intensity exercise training for 3 months on bicycle ergometers. Blood was sampled before and after training for biochemical analysis, paraoxonase-1 activity, and HDL subfraction composition and antioxidative capacity. Lipid transfer to HDL was assayed in vitro using a labeled nanoemulsion as the lipid donor. At baseline, the MS group had greater triglyceride levels and a lower HDL cholesterol concentration and lower paraoxonase-1 activity than did the controls. Training decreased the plasma triglycerides but did not change the low-density lipoprotein or HDL cholesterol levels. Nonetheless, exercise training increased the HDL subfractions' antioxidative capacity and paraoxonase-1 activity. After training, the MS group had compositional changes in the smallest HDL subfractions associated with increased free cholesterol and cholesterol ester transfers to HDL, reaching normal values. In conclusion, the present investigation has added relevant information about the dissociation between the quantitative and qualitative aspects of HDL after short-term exercise training without any specific diet in those with the MS, highlighting the importance of evaluating the functional aspects of the lipoproteins, in addition to their plasma levels.
Assuntos
Atividades Cotidianas , HDL-Colesterol/sangue , Terapia por Exercício/métodos , Exercício Físico/fisiologia , Estilo de Vida , Síndrome Metabólica/sangue , Adulto , Idoso , Feminino , Humanos , Masculino , Síndrome Metabólica/reabilitação , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Left atrial volume indexed (LAVI) has been reported as a predictor of cardiovascular events. We sought to determine the prognostic value of LAVI for predicting the outcome of patients who underwent dobutamine stress echocardiography (DSE) for known or suspected coronary artery disease (CAD). METHODS: From January 2000 to July 2005, we studied 981 patients who underwent DSE and off-line measurements of LAVI. The value of DSE over clinical and LAVI data was examined using a stepwise log-rank test. RESULTS: During a median follow-up of 24 months, 56 (6%) events occurred. By univariate analysis, predictors of events were male sex, diabetes mellitus, previous myocardial infarction, left ventricular ejection fraction (LVEF), left atrial diameter indexed, LAVI, and abnormal DSE. By multivariate analysis, independent predictors were LVEF (relative risk [RR] = 0.98, 95% CI 0.95-1.00), LAVI (RR = 1.04, 95% CI 1.02-1.05), and abnormal DSE (RR = 2.70, 95% CI 1.28-5.69). In an incremental multivariate model, LAVI was additional to clinical data for predicting events (chi(2) 36.8, P < .001). The addition of DSE to clinical and LAVI yielded incremental information (chi(2) 55.3, P < .001). The 3-year event-free survival in patients with normal DSE and LAVI < or =33 mL/m(2) was 96%; with abnormal DSE and LAVI < or =33 mL/m(2), 91%; with normal DSE and LAVI >34 mL/m(2), 83%; and with abnormal DSE and LAVI >34 mL/m(2), 51%. CONCLUSION: Left atrial volume indexed provides independent prognostic information in patients who underwent DSE for known or suspected CAD. Among patients with normal DSE, those with larger LAVI had worse outcome, and among patients with abnormal DSE, LAVI was still predictive.
Assuntos
Função do Átrio Esquerdo/fisiologia , Doença das Coronárias/diagnóstico por imagem , Ecocardiografia sob Estresse , Átrios do Coração/diagnóstico por imagem , Idoso , Volume Cardíaco/fisiologia , Doença das Coronárias/mortalidade , Doença das Coronárias/fisiopatologia , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Feminino , Seguimentos , Átrios do Coração/fisiopatologia , Hemodinâmica/fisiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Prognóstico , Fatores de RiscoRESUMO
Our aim was to characterize HDL subspecies and fat-soluble vitamin levels in a kindred with familial apolipoprotein A-I (apoA-I) deficiency. Sequencing of the APOA1 gene revealed a nonsense mutation at codon -2, Q[-2]X, with two documented homozygotes, eight heterozygotes, and two normal subjects in the kindred. Homozygotes presented markedly decreased HDL cholesterol levels, undetectable plasma apoA-1, tuboeruptive and planar xanthomas, mild corneal arcus and opacification, and severe premature coronary artery disease. In both homozygotes, analysis of HDL particles by two-dimensional gel electrophoresis revealed undetectable apoA-I, decreased amounts of small alpha-3 migrating apoA-II particles, and only modestly decreased normal amounts of slow alpha migrating apoA-IV- and apoE-containing HDL, while in the eight heterozygotes, there was loss of large alpha-1 HDL particles. There were no significant decreases in plasma fat-soluble vitamin levels noted in either homozygotes or heterozygotes compared with normal control subjects. Our data indicate that isolated apoA-I deficiency results in marked HDL deficiency with very low apoA-II alpha-3 HDL particles, modest reductions in the separate and distinct plasma apoA-IV and apoE HDL particles, tuboeruptive xanthomas, premature coronary atherosclerosis, and no evidence of fat malabsorption.
Assuntos
Apolipoproteína A-I/deficiência , Apolipoproteína A-I/genética , Hipolipoproteinemias/genética , Hipolipoproteinemias/metabolismo , Lipoproteínas HDL/química , Adulto , Idoso , Apolipoproteína A-I/sangue , Criança , Pré-Escolar , HDL-Colesterol/sangue , Feminino , Humanos , Hipolipoproteinemias/sangue , Lipoproteínas HDL/sangue , Masculino , Tamanho da Partícula , Linhagem , Xantomatose/metabolismoAssuntos
Hospitais de Ensino , Hospitais Universitários , Projetos de Pesquisa , Ensino , Brasil , HumanosRESUMO
OBJECTIVES: The aims of this study were to investigate the effect of coronary stenting on the release of cytokines and cell-mediated immunity factors and to evaluate the association between inflammation and clinical outcomes at 6 months. BACKGROUND: Circulating levels of inflammatory markers and cytokines are elevated in patients with acute coronary syndromes and are related to an unfavorable outcome. The aims of this study were to investigate the effect of coronary stenting on the release of cytokines and cell-mediated immunity factors and to evaluate the association between inflammation and clinical outcomes at 6 months. METHODS: Forty patients with single native coronary artery disease treated with stenting were enrolled. Peripheral venous blood samples were collected before and 6 h, 48 h, and 12 weeks after stenting. Serum concentrations of high-sensitivity C-reactive protein, interleukin-6, interleukin-8, tumor necrosis factor-alpha (markers of inflammation) and serum-soluble interleukin-2 receptor for T-lymphocyte activation (sIL2-R, marker of cell-mediated immunity) were measured. Patients also were evaluated clinically one, 3, and 6 months post-stenting or when they presented with cardiovascular symptoms to identify major adverse cardiac events (cardiac death, MI, revascularization). RESULTS: Concentrations of interleukins 6 and 8 and tumor necrosis factor-alpha peaked at 6 h (11.0, 12.6, and 5.3 pg/ml, respectively). The peak level of high-sensitivity C-reactive protein (2.77 mg/dL) occurred 48 h post stenting, while sIL2-R peaked (495 U/ml) at 12 weeks. Patients who experienced restenosis had higher levels of C-reactive protein at 48 h (4.94 vs. 1.84 mg/dl; P = 0.043) and of IL-8 at 6 h (26.75 vs. 13.55 pg/mL; P = 0.048) than those without restenosis. CONCLUSIONS: Proinflammatory cytokines and inflammatory markers are released into the peripheral circulation early after coronary stenting, and increased levels of some are associated with clinically relevant restenosis.
Assuntos
Reestenose Coronária/sangue , Reestenose Coronária/etiologia , Estenose Coronária/terapia , Citocinas/sangue , Mediadores da Inflamação/sangue , Stents , Idoso , Angina Pectoris/sangue , Angina Pectoris/diagnóstico por imagem , Angina Pectoris/terapia , Angioplastia Coronária com Balão , Biomarcadores/sangue , Implante de Prótese Vascular , Proteína C-Reativa/metabolismo , Ensaios Clínicos Controlados como Assunto , Angiografia Coronária , Reestenose Coronária/diagnóstico por imagem , Estenose Coronária/sangue , Estenose Coronária/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Interleucina-6/sangue , Interleucina-8/sangue , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina-2/sangue , Projetos de Pesquisa , Fatores de Tempo , Resultado do Tratamento , Troponina I/sangue , Fator de Necrose Tumoral alfa/sangueRESUMO
Fasting hypertriglyceridemia relates with high-density lipoprotein (HDL) cholesterol, but it is not known whether low HDL cholesterol is associated with disturbances of chylomicron metabolism. To clarify this issue this metabolism was studied in subjects with low HDL cholesterol together with vascular reactivity and evaluation of no-flush niacin treatment. Thirty men with HDL < 1.04 mmol/L and no other risk factors for coronary artery disease (CAD) and 11 normal controls with HDL > 1.04 mmol/L were studied. The plasma kinetics of a chylomicron-like emulsion labeled with 14C-cholesterol oleate (CO) and 3H-triolein (TG) was determined and the fractional clearance rate (FCR, min(-1)) was calculated. Vascular reactivity was evaluated using high-resolution ultrasonography. CO FCR was markedly reduced in the low HDL group compared to controls (3.6 x 10(-3) +/- 5.1 x 10(-3) min(-1) versus 12.2 x 10(-3) +/- 8.4 x 10(-3) min(-1), p < 0.001) but TG FCR was similar. Flow-mediated dilation (FMD) was diminished in low HDL (7.4 +/- 4.1 versus 12.8 +/- 4.6%, p < 0.001), whereas nitrate-mediated dilation was similar. Twenty-two low HDL subjects with reduced FMD were randomized into two groups, one given 1.5 g/day niacin and a placebo group. After 3-month treatment, plasma lipids and chylomicron kinetics were not changed by niacin treatment but FMD improved to normal values (5.44 +/- 1.89 to 11.13 +/- 3.4%, p < 0.01). In conclusion, isolated low HDL cholesterol subjects may also bear chylomicron remnant accumulation and endothelial dysfunction, which highlight the importance of their preventive treatment.
Assuntos
Artéria Braquial/efeitos dos fármacos , HDL-Colesterol/metabolismo , Quilomícrons/química , Hipolipemiantes/farmacologia , Lipoproteínas/química , Niacina/farmacologia , Adulto , Idoso , Quilomícrons/metabolismo , Emulsões , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Triglicerídeos/química , Triglicerídeos/metabolismoRESUMO
We evaluated the relation between lipids and precocity of coronary artery disease (CAD) in the real world as characterized by increasing statin use. The highest mean values of total cholesterol, low-density lipoprotein cholesterol, triglycerides, non-high-density lipoprotein (HDL) cholesterol, and ratio of triglycerides to HDL cholesterol were found when CAD was detected in patients who were <50 years of age (p <0.01 for all); the opposite occurred for HDL cholesterol (p <0.01). Triglycerides and ratio of triglycerides to HDL cholesterol were the most powerful, independent variables related to precocity of CAD.