Long term effects of red wine consumption in brain: an MRI, fMRI and neuropsychological evaluation study.

Red wine (RW) consumption has been proposed to have a potential health benefit. However, the effect of RW consumption on the brain is not entirely known, mainly when associated with aging. Regular red wine consumers (n = 30) and abstainers (ABST; n = 27) without cognitive impairment were evaluated for brain structural characteristics (Fazekas score and voxel-based morphometry) and for functional adaptations assessed by fMRI (using the Word Tasks Color Stroop (WCST) and Two-Back (TBT)), as well as by neuropsychological tests in different domains. There were no significant differences regarding brain morphological features. RW consumers showed greater activation in the thalamus during WCST and in paracingulate/anterior cingulate cortices, left superior frontal gyrus and frontal pole during TBT. ABST required higher activation of different cortical areas in the left parietal lobe during WCST. Age and intelligence quotient influenced those activations. In Stroop and trail-making neuropsychological tests, RW consumers performed slightly better than ABST. This study should be viewed as hypothesis-generating rather than conclusive.HighlightsWhite matter hyperintensities and gray matter volume did not differ between the RW and ABST groups.RW consumers could depend more on right thalamus during WSCT due to its role in visual integration.ABST could depend more on left parietal lobe during WSCT due to its role in sensory and phonological encoding.RW consumers with inferior cognitive abilities could depend more on letter recognition to solve a TBT correctly.Younger abstainers could depend more on different areas involved in integrating cognitive processes and attention regulation to solve a TBT correctly.

The effects of macronutrients composition on hormones and substrates during a meal tolerance test in drugnaive and sitagliptin-treated individuals with type 2 diabetes: a randomized crossover study.

Objective: To evaluate the effect of sitagliptin treatment in early type 2 diabetes mellitus (T2DM) and the impact of different macronutrient compositions on hormones and substrates during meal tolerance tests (MTT). Methods: Half of the drug-naive patients with T2DM were randomly assigned for treatment with 100 mg of sitagliptin, q.d., or placebo for 4 weeks and then submitted to 3 consecutive MTT intercalated every 48 h. The MTTs differed in terms of macronutrient composition, with 70% of total energy from carbohydrates, proteins, or lipids. After 4 weeks of washout, a crossover treatment design was repeated. Both patients and researchers were blinded, and a repeated-measures ANOVA was employed for statistical analysis. Results: Sitagliptin treatment reduced but did not normalize fasting and post-meal glucose values in the three MTTs, with lowered area-under-glucose-curve values varying from 7% to 15%. The sitagliptin treatment also improved the insulinogenic index (+86%) and the insulin/glucose (+25%), glucagon-like peptide-1/glucose (+46%) incremental area under the curves. Patients with early T2DM maintained the lowest glucose excursion after a protein- or lipid-rich meal without any major change in insulin, C-peptide, glucagon, or NEFA levels. Conclusion: We conclude that sitagliptin treatment is tolerable and contributes to better control of glucose homeostasis in early T2DM, irrespective of macronutrient composition. The blood glucose excursion during meal ingestion is minimal in protein- or fat-rich meals, which can be a positive ally for the management of T2DM. Clinical trial no: NCT00881543.

Association between hypertriglyceridemia and protein oxidation and proinflammatory markers in normocholesterolemic and hypercholesterolemic individuals.

BACKGROUND: Although hypercholesterolemia is a well-established risk factor for coronary heart disease, evidence suggests that increased triglyceride (TG) concentrations are also an independent risk factor. TG concentrations >150mg/dl are observed nearly twice as often in subjects with atherosclerosis. We assessed the association between hypertriglyceridemia and protein oxidation and proinflammatory markers in normocholesterolemic and hypercholesterolemic individuals. METHODS: We included 127 volunteers enrolled in Cruz Alta, RS, Brazil. The patients were stratified based on total cholesterol and TG concentrations for analysis of associations with inflammation (high-sensitivity C-reactive protein - hs-CRP), endothelial dysfunction (nitric oxide - NOx) and oxidative stress (advanced oxidation protein products - AOPPs; ischemia-modified albumin - IMA). Correlations between variables were determined and multiple regression analysis was employed to investigate whether some variables correlate with TG concentrations. RESULTS: Hypertriglyceridemia was related to oxidative stress and proinflammatory markers in individuals independent of total cholesterol concentrations. Moreover, the results indicate a stronger association of tested biomarkers with TG concentrations than with total cholesterol. The results indicate a positive correlation between oxidative stress and TG concentrations in the sera of hypercholesterolemia subjects. AOPPs and IMA concentrations were associated with the presence of hypertriglyceridemia in a manner that was independent of age, gender, hypertension and diabetes mellitus disease, smoking habits, sedentary lifestyle, BMI, waist circumference, LDL, HDL and total cholesterol concentrations. CONCLUSIONS: We speculate that TG concentrations can reflect the enhancement of protein oxidation and proinflammation.

Synergistic anti-inflammatory effect: simvastatin and pioglitazone reduce inflammatory markers of plasma and epicardial adipose tissue of coronary patients with metabolic syndrome.

BACKGROUND: The inappropriate secretion of adipocytokines plays a critical role in chronic inflammatory states associated with obesity-linked type 2 diabetes and atherosclerosis. The pleiotropic actions of simvastatin and pioglitazone on epicardial adipose tissue (EAT) are unknown. This study assessed the anti-inflammatory actions of simvastatin and pioglitazone on EAT in patients with coronary artery disease (CAD) and metabolic syndrome (MS). METHODS: A total of 73 patients with multivessel CAD who underwent elective bypass grafting were non-randomly allocated to one of four subgroups: Control (n = 17), simvastatin (20 mg/day, n = 20), pioglitazone (15 mg or 30 mg/day, n = 18), or simvastatin + pioglitazone (20 mg/day + 30 mg/day, respectively, n = 18); 20 valvar patients were also included. EAT samples were obtained during surgery. The infiltration of macrophages and lymphocytes and cytokines secretion were investigated using immunohistochemical staining and compared to plasma inflammatory biomarkers. RESULTS: Simvastatin significantly reduced plasma interleukin-6, leptin, resistin and monocyte chemoattractant protein-1 (p < 0.001 for all); pioglitazone reduced interleukin-6, tumoral necrose factor-alpha, resistin and matrix metalloproteinase-9 (p < 0.001 for all). Simvastatin + pioglitazone treatment further reduced plasmatic variables, including interleukin-6, tumoral necrose factor-alpha, resistin, asymmetric dimethylarginine and metalloproteinase-9 vs. the control group (p < 0.001). Higher plasma adiponectin and lower high sensitivity C-reactive protein concentrations were found simultaneously in the combined treatment group. A positive correlation between the mean percentage systemic and tissue cytokines was observed after treatments. T- and B-lymphocytes and macrophages clusters were observed in the fat fragments of patients treated with simvastatin for the first time. CONCLUSIONS: Pioglitazone, simvastatin or combination treatment substantially reduced EAT and plasma inflammatory markers in CAD and MS patients. These tissue effects may contribute to the control of coronary atherosclerosis progression.

The relationship between body mass index and the variation in plasma levels of triglycerides after short-term red wine consumption.

BACKGROUND: Alcoholic beverages may have protective cardiovascular effects but are known to increase the plasma levels of triglycerides (TG). Both TG and the ratio of TG to high-density lipoprotein cholesterol (TG/HDL-cholesterol) are associated with increased cardiovascular risk. OBJECTIVES: To determine the predictive factors for variations in plasma levels of TG and the TG/HDL-cholesterol ratio in patients after they had consumed red wine for 14 days. METHODS: Forty-two subjects (64% men, 46 ± 9 years, baseline body mass index [BMI] 25.13 ± 2.76 kg/m(2)) were given red wine (12% or 12.2% alc/vol, 250 mL/day with meals). Plasma concentration of lipids and glucose were measured before and after red wine consumption. Blood was collected after 12 hours of fast and alcohol abstention. RESULTS: Red wine increased plasma levels of TG from 105 ± 42 mg/dL to 120 ± 56 mg/dL (P = .001) and the TG/HDL-cholesterol ratio from 2.16 ± 1.10 to 2.50 ± 1.66 (P = .014). In a multivariate linear regression model that included age, baseline BMI, blood pressure, lipids, and glucose, only BMI was independently predictive of the variation in plasma TG after red wine (beta coefficient 0.592, P < .001). BMI also predicted the variation in TG/HDL-cholesterol ratio (beta coefficient 0.505, P = .001, adjusted model). When individuals were divided into three categories, according to their BMI, the average percentage variation in TG after red wine was -4%, 17%, and 33% in the lower (19.60-24.45 kg/m(2)), intermediate, and greater (26.30-30.44 kg/m(2)) tertiles, respectively (P = .001). CONCLUSIONS: Individuals with higher BMI, although nonobese, might be at greater risk for elevation in plasma TG levels and the TG/HDL-cholesterol ratio after short-term red wine consumption.

Comparison of non-invasive methods for the detection of coronary atherosclerosis.

BACKGROUND: Non-invasive detection of atherosclerosis is critical for its prevention. OBJECTIVE: To correlate non-invasively detectable indicators of coronary atherosclerosis, or Coronary Artery Disease (i.e., classical risk factors, hs-CRP test results, carotid intima-media thickness, endothelial function, ankle-brachial index and calcium score by computed tomography) with the extent of coronary disease assessed by the Friesinger index from conventional coronary angiography. METHODS: We conducted a prospective study of 100 consecutive patients, mean age 55.1 +/- 10.7 years, 55% men and 45% women. Patients with acute coronary syndrome, renal dialytic insufficiency, collagen disease and cancer were not included. All patients were subjected to clinical evaluation and laboratory tests. Endothelial function of the brachial artery and carotid artery were evaluated by high-resolution ultrasound; ankle-brachial index and computed tomography for coronary determination of calcium score were also performed, and non-HDL cholesterol and TG/HDL-c ratio were calculated. All patients were subjected to coronary angiography at the request of the assistant physician. We considered patients without an obstructive lesion (< 29% stenosis) demonstrated by coronary angiography to be normal. RESULTS: Univariate analysis showed that calcium score, HDL-c, TG/HDL ratio and IMT were significantly correlated with the Friesinger index. However, multivariate analysis indicated that only calcium score and low HDL-c levels correlated significantly with the extension of CAD. On the other hand, hs-CRP, LDL-c, flow-mediated dilation, and Framingham score did not correlate with the Friesinger index. ROC analysis showed that calcium score, HDL-c and TG-HDL ratio accurately predicted extensive CAD in a statistically significant manner. CONCLUSION: It is possible to approximately determine the presence and extent of CAD by non-invasive methods, especially by calcium score, HDL-c and TG/HDL-c ratio assays.

Evidence that the degree of obstructive sleep apnea may not increase myocardial ischemia and arrhythmias in patients with stable coronary artery disease.

UNLABELLED: There is controversy regarding whether obstructive sleep apnea is responsible for triggering myocardial ischemia, arrhythmias and heart rate variability in patients with coronary artery disease. OBJECTIVE: The objective of this study was to identify relationships between sleep apnea, myocardial ischemia and cardiac arrhythmia in patients with coronary artery disease. METHODS: Fifty-three patients with stable coronary disease underwent simultaneous polysomnography and electrocardiographic Holter recording. The apnea-hypopnea index (AHI) was defined as the number of apneas/hypopneas per hour of sleep. Patients were divided into a Control group (AHI15, n=23 pts) and an Apnea group (AHI>15, n=30 pts). A subgroup of 13 patients with an AHI>30 (Severe Apnea group) was also studied. We analyzed ischemic episodes (ST-segment depressions >1 mm, > 1 min), heart rate variability and the occurrence of arrhythmias during wakefulness and sleep. RESULTS: Baseline clinical characteristics among the groups were similar except for higher blood pressure in the Apnea groups (p<0.05). Myocardial ischemia was recorded in 39 (73.6%) patients. The number and duration of ischemic episodes significantly decreased during sleep in all groups; during wakefulness, patients with severe apnea exhibited fewer and shorter episodes in comparison with the controls. There were no significant differences in heart rate variability or in the occurrence of arrhythmias among the groups. Malignant ventricular arrhythmias, atrial fibrillation/flutter, bradycardia and high-degree atrioventricular blocks were not detected. CONCLUSION: Obstructive sleep apnea was not related to myocardial ischemia, heart rate variability or arrhythmias in patients with stable coronary artery disease and did not alter the circadian pattern of myocardial ischemia.

High ratio of triglycerides to HDL-cholesterol predicts extensive coronary disease.

UNLABELLED: An abnormal ratio of triglycerides to HDL-cholesterol (TG/HDL-c) indicates an atherogenic lipid profile and a risk for the development of coronary disease. OBJECTIVE: To investigate the association between lipid levels, specifically TG/HDL-c, and the extent of coronary disease. METHODS: High-risk patients (n=374) submitted for coronary angiography had their lipid variables measured and coronary disease extent scored by the Friesinger index. RESULTS: The subjects consisted of 220 males and 154 females, age 57.2+/-11.1 years, with total cholesterol of 210+/-50.3 mg/dL, triglycerides of 173.8+/-169.8 mg/dL, HDL-cholesterol (HDL-c) of 40.1+/-12.8 mg/dL, LDL-cholesterol (LDL-c) of 137.3+/-46.2 mg/dL, TG/HDL-c of 5.1+/-5.3, and a Friesinger index of 6.6+/-4.7. The relationship between the extent of coronary disease (dichotomized by a Friesenger index of 5 and lipid levels (normal vs. abnormal) was statistically significant for the following: triglycerides, odds ratio of 2.02 (1.31-3.1; p=0.0018); HDL-c, odds ratio of 2.21 (1.42-3.43; p=0.0005); and TG/HDL-c, odds ratio of 2.01(1.30-3.09; p=0.0018). However, the relationship was not significant between extent of coronary disease and total cholesterol [1.25 (0.82-1.91; p=0.33)] or LDL-c [1.47 (0.96-2.25; p=0.0842)]. The chi-square for linear trends for Friesinger >4 and lipid quartiles was statistically significant for triglycerides (p=0.0017), HDL-c (p=0.0001), and TG/HDL-c (p=0.0018), but not for total cholesterol (p=0.393) or LDL-c (p=0.0568). The multivariate analysis by logistic regression OR gave 1.3+/-0.79 (p= .0001) for TG/HDL-c, 0.779+/-0.074 (p= .0001) for HDL-c, and 1.234+/-0.097 (p=0.03) for LDL. Analysis of receiver operating characteristic curves showed that only TG/HDL-c and HDL-c were useful for detecting extensive coronary disease, with the former more strongly associated with disease. CONCLUSIONS: Although some lipid variables were associated with the extent of coronary disease, the ratio of triglycerides to HDL-cholesterol showed the strongest association with extent.

Ontario score and cardiac risk during waiting for elective coronary bypass grafting.

BACKGROUND: Waiting lists for coronary bypass grafting are of major concern in several countries and prioritisation systems to the surgery have been proposed. The aim of this study was to verify the adequacy of Ontario score in predicting cardiac events during the waiting for elective coronary bypass grafting. METHODS: A composite end-point (sudden or cardiac death, myocardial infarction, unstable angina or hospital admission) and sudden, cardiac death were analysed in 460 patients referred to the surgery. The relation between Ontario score and events was verified. RESULTS: Median waiting time was 126 days. The composite end-point and sudden, cardiac death occurred in 21.7% and 2.7% of the cases, respectively. In relation to Ontario score > or = 6.00, considered the lower-risk subset, only patients in score <4.00 (7.2% of whole study population) presented a higher chance of the composite end-point during the waiting. ROC curve did not show adequate accuracy of Ontario score in predicting the composite end-point (area under the curve 0.53, p = 0.36). Ontario score could not predict the risk of death. Total complications and death occurred within acceptable waiting times by Ontario recommendation in 47.8% and 36.4% of the cases, respectively. Waiting longer than maximum wait defined by Ontario was not associated with an excess of complications. CONCLUSIONS: Ontario score showed a limited value in predicting cardiac events during the waiting for elective coronary bypass grafting. The results emphasise the need for shortening the wait in order to reduce complications in the period.

Noninvasive detection of coronary artery disease -- challenges for prevention of disease and clinical events.

Atherosclerosis is a chronic inflammatory disease that affects essentially all arterial beds including the aorta, coronaries, carotids, and peripheral arteries. It is the main cause of death in the western hemisphere, due to cardiovascular syndromes such as myocardial infarction, heart failure, and cerebrovascular accidents. Very substantial economic and human resources have been used on treatments of its complications, including imaging studies, coronary bypass surgery, catheter interventions, pacemakers, and medical treatments. Treating complications, however, are remedial actions. A better alternative is to prevent the development of atherosclerosis, or at least to identify patients who are at risk of acute events and intervene before they occur. The aims of this review are to discuss the predictive value of traditional and emerging risk factors, as well as the role of noninvasive diagnostic methods for coronary atherosclerosis, including exercise stress test, echo stress test, duplex ultrasound, computed tomography, and magnetic resonance. A combination of serum biomarkers and noninvasive approaches is of practical utility for identifying early disease. It is to be expected that future developments will soon perfect our ability to identify the vulnerable patient and allow a more individualized approach.

Cardiac complications during waiting for elective coronary artery bypass graft surgery: incidence, temporal distribution and predictive factors.

OBJECTIVES: Since waiting lists for coronary artery bypass graft surgery are common and carry a risk of severe events, the purposes of this study were: (1) to analyse the incidence and temporal distribution of cardiac complications during waiting for elective coronary artery bypass grafting; (2) to identify predictive factors of such complications. METHODS: Data were collected from 574 patients referred to surgery from 1 January 1998 to 12 July 2001. Two types of complications were defined: (1) a composite end-point, which included cardiac death, myocardial infarction, unstable angina or hospital admission due to cardiac cause; (2) sudden or any cardiac death. Previous cardiac events, risk factors, clinical features, laboratory exams, non-invasive tests for myocardial ischemia, left ventricular function and coronary anatomy were analysed. Kaplan-Meier method, multivariate Cox regression and Student's t-test were used for statistical analyses. RESULTS: Median time to surgery was 126 days (5-1022). Among 516 patients consecutively referred to the surgery from 1 January 1998 to 31 December 2000, sudden or cardiac death occurred in 2.5% and the composite end-point in 22.9%. Most complications (72.1%) were observed within 120 days. The main factors predictive of sudden or cardiac death were severe left ventricular dysfunction and heart failure (univariate analysis). Independent predictive factors of the composite end-point were angina, heart failure functional classes and high triglyceride levels. CONCLUSIONS: During long delay for coronary artery bypass surgery, cardiac events are frequent and tend to occur early. Severe left ventricular dysfunction, advanced angina, heart failure functional classes and high triglyceride level must be considered when selection is necessary, in order to diminish morbidity and mortality during the waiting period.

Pregnancy in patients with heart disease: experience with 1,000 cases.

BACKGROUND: Previously, the high maternal mortality in cardiac patients who became pregnant prompted the assertion: Women with an abnormal heart should not become pregnant. This long-standing notion needs to be revised today. HYPOTHESIS: The study was undertaken to ascertain the experience with a large series of pregnant women with cardiac disease cared for in the same referral center. METHODS: From 1989 to 1999, 1,000 pregnant women with heart disease were followed by the same clinical and obstetric team. The cardiac diseases included rheumatic heart disease (55.7%), congenital heart disease (19.1%), Chagas' disease (8.5%), cardiac arrhythmias (5.1%), cardiomyopathies (4.3%), and others (7.3%). RESULTS: Of the pregnant women studied, 765 (76.5%) experienced no cardiovascular events during the study; 235 (23.5%) patients had the following cardiovascular complications: congestive heart failure (12.3%), cardiac arrhythmias (6%), thromboembolism (1.9%), angina (1.4%), hypoxemia (0.7%), infective endocarditis (0.5%), and other complications (0.7%). Clinical treatment allowed adequate management in 161 (68.8%) patients; however, 46 (19.6%) patients underwent interventional procedures because of refractory complications. The general maternal mortality rate was 2.7%. Of the 915 (91.5%) infants who were discharged, 119 (13%) were premature. CONCLUSION: Pregnancy in women with heart disease is still associated with considerable morbidity and mortality rates, which strongly correlate to maternal underlying disease. Strict prenatal care and early risk stratification during gestation are fundamental measures to improve the prognosis of pregnancy in women with heart disease.

Comparison between young males and females with acute myocardial infarction.

OBJECTIVE: To assess the differences between young males and females after acute myocardial infarction. METHODS: We retrospectively studied 236 patients (54 females and 182 males) after acute myocardial infarction and during hospital stay assessed the following parameters: risk factors; the treatment used; the pattern of coronary artery obstruction; left ventricular ejection fraction; complications; and, using a logistic regression model, the factors related to the occurrence of reinfarction and death. RESULTS: No significant difference was observed between the sexes in risk factors, pattern of coronary artery obstruction, and left ventricular function. The time interval between symptom onset and treatment was longer in females (p=0.03), who underwent thrombolysis (p=0.01) and angioplasty (p=0.03) less frequently than males did, but not myocardial revascularization. Female sex (OR = 5.98) and diabetes (OR = 14.52) were independent factors related to the occurrence of reinfarction and death. CONCLUSION: Young males and females after acute myocardial infarction did not differ in coronary risk factors, and clinical and hemodynamic characteristics. Females had their treatment started later, and they underwent chemical thrombolysis and angioplasty less frequently than males did. Female sex and diabetes were related to the occurrence of reinfarction and death.