A red wine intervention does not modify plasma trimethylamine N-oxide but is associated with broad shifts in the plasma metabolome and gut microbiota composition.

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.

Red wine and equivalent oral pharmacological doses of resveratrol delay vascular aging but do not extend life span in rats.

OBJECTIVE: To investigate, in male Wistar rats, the effects of long-term moderate red wine (RW) consumption (equivalent to ∼0.15 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 ∼50% ∼with RW and LRS (p < 0.05 vs. C), p16 by ∼29% 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.

Characterization of high density lipoprotein particles in familial apolipoprotein A-I deficiency.

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.

Enhanced inflammatory response to coronary stenting marks the development of clinically relevant restenosis.

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.

Relative cost comparison of treatments for coronary artery disease: the First Year Follow-Up of MASS II Study.

BACKGROUND: Prior comparisons of costs following CABG and PTCA have demonstrated higher initial costs after CABG but following PTCA, recurrent symptoms and repeat revascularization result in increased late costs and over time their costs equilibrate. The MASS II trial provides an opportunity to compare the costs of CABG and PTCA in addition to a strategy of medical therapy. METHODS: We studied the 611 patients of MASS II [Medical (203), Angioplasty (205), or Surgery (203) Study], a randomized study to compare treatments for multivessel CAD and preserved left ventricle function. The costs were: CABG 10,650.00 US dollars; PTCA 6400.00 US dollars; new AMI hospitalization AMI 2550 US dollars; angiography not followed-up of PTCA 1900.00 US dollars; and medication 1200.00 US dollars for medical, and 1000.00 US dollars for the other groups. We did adjustment for average event-free time, and angina-free proportion. The statistical analysis carried out was chi-square, t test, and analysis of variance. RESULTS: After 1 year, 49% Medical, 79% PTCA, and 88% CABG became angina-free; P<0.0001. There were 26 coronary angiograms (5 medical, 17 PTCA, and 4 CABG), 23 AMI (8 medical, 17 PTCA, and 6 CABG; P=0.03); PTCA was performed in 7 Medical, 17 PTCA, and 1 CABG, (P=0.0003), CABG was performed in 15 Medical, 8 PTCA, and zero CABG; P=0.002. The event-free and event and angina-free-costs in the first year were 2453.50 US dollars and 5006.32 US dollars for Medical; 10348,43 US dollars; and 13,099.31 US dollars for PTCA; and 12,404.21 US dollars and 14,095.09 US dollars for CABG group. An increase from expected costs of 317%, 77%, and 21%, respectively. CONCLUSIONS: PTCA effective costs were similar to CAGB costs, Medical treatment presented the lowest cost, and however, the greatest increment, and CABG presented the most stable costs.

Ten-year clinical laboratory follow-up after application of a symptom-based therapeutic strategy to patients with severe chronic aortic regurgitation of predominant rheumatic etiology.

OBJECTIVES: This study was designed to assess the feasibility and the long-term results of a symptom-based strategy of aortic valve replacement in a Brazilian population with predominant rheumatic etiology. BACKGROUND: Optimal criteria for valve replacement in aortic regurgitation (AR) are still not entirely clear. The appearance of symptoms is an indication for surgery, but may be associated with myocardial damage. Although cardiac imaging data have provided a safer guide for such decisions, the use of symptom-based surgical indication has not been validated and might conceivably be better in populations with predominant rheumatic etiology and younger age. METHODS: Echocardiography and rest-exercise radionuclide ventriculography were performed in 75 patients with severe AR, age 28 +/- 9 years, over a period of 10 +/- 0.69 years. Thirty-seven patients developed symptoms and underwent aortic valve replacement surgery within six months. Thirty-eight patients remained asymptomatic and were managed medically. RESULTS: Survival was 100% in asymptomatic patients and 82% in symptomatic. Surgical treatment caused marked ventricular remodeling, with ventricular diameter involution and an improvement of rest-exercise ejection fraction percent variation. Multivariate analysis showed that the probability of developing symptoms within 10 years was 58% for a patient with a left ventricular end-diastolic diameter > or =70 mm and 76% for a patient with left ventricular end-systolic (LVESD) > or =50 mm. Logistic regression identified LVESD and age as the most predictive and specific, but not sensitive, indicators of symptom development. CONCLUSIONS: Application of a standardized therapeutic strategy to patients with severe AR and predominant rheumatic etiology resulted in 90.6% survival after 10 years of follow-up.

Alcohol and atherosclerosis

Atherosclerosis is manifested as coronary artery disease (CAD), ischemic stroke and peripheral vascular disease. Moderate alcohol consumption has been associated with reduction of CAD complications. Apparently, red wine offers more benefits than any other kind of drinks, probably due to flavonoids. Alcohol alters lipoproteins and the coagulation system. The flavonoids induce vascular relaxation by mechanisms that are both dependent and independent of nitric oxide, inhibits many of the cellular reactions associated with atherosclerosis and inflammation, such as endothelial expression of vascular adhesion molecules and release of cytokines from polymorphonuclear leukocytes. Hypertension is also influenced by the alcohol intake. Thus, heavy alcohol intake is almost always associated with systemic hypertension, and hence shall be avoided. In individuals that ingest excess alcohol, there is higher risk of coronary occlusion, arrhythmias, hepatic cirrhosis, upper gastrointestinal cancers, fetal alcohol syndrome, murders, sex crimes, traffic and industrial accidents, robberies, and psychosis. Alcohol is no treatment for atherosclerosis; but it doesn't need to be prohibited for everyone. Thus moderate amounts of alcohol (1-2 drinks/day), especially red wine, may be allowed for those at risk for atherosclerosis complications