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.

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.

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.

Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial.

BACKGROUND: Evidence suggests a role for excessive inflammation in COVID-19 complications. Colchicine is an oral anti-inflammatory medication beneficial in gout, pericarditis, and coronary disease. We aimed to investigate the effect of colchicine on the composite of COVID-19-related death or hospital admission. METHODS: The present study is a phase 3, randomised, double-blind, adaptive, placebo-controlled, multicentre trial. The study was done in Brazil, Canada, Greece, South Africa, Spain, and the USA, and was led by the Montreal Heart Institute. Patients with COVID-19 diagnosed by PCR testing or clinical criteria who were not being treated in hospital were eligible if they were at least 40 years old and had at least one high-risk characteristic. The randomisation list was computer-generated by an unmasked biostatistician, and masked randomisation was centralised and done electronically through an automated interactive web-response system. The allocation sequence was unstratified and used a 1:1 ratio with a blocking schema and block sizes of six. Patients were randomly assigned to receive orally administered colchicine (0·5 mg twice per day for 3 days and then once per day for 27 days thereafter) or matching placebo. The primary efficacy endpoint was the composite of death or hospital admission for COVID-19. Vital status at the end of the study was available for 97·9% of patients. The analyses were done according to the intention-to-treat principle. The COLCORONA trial is registered with ClinicalTrials.gov (NCT04322682) and is now closed to new participants. FINDINGS: Trial enrolment began in March 23, 2020, and was completed in Dec 22, 2020. A total of 4488 patients (53·9% women; median age 54·0 years, IQR 47·0-61·0) were enrolled and 2235 patients were randomly assigned to colchicine and 2253 to placebo. The primary endpoint occurred in 104 (4·7%) of 2235 patients in the colchicine group and 131 (5·8%) of 2253 patients in the placebo group (odds ratio [OR] 0·79, 95·1% CI 0·61-1·03; p=0·081). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 96 (4·6%) of 2075 patients in the colchicine group and 126 (6·0%) of 2084 patients in the placebo group (OR 0·75, 0·57-0·99; p=0·042). Serious adverse events were reported in 108 (4·9%) of 2195 patients in the colchicine group and 139 (6·3%) of 2217 patients in the placebo group (p=0·051); pneumonia occurred in 63 (2·9%) of 2195 patients in the colchicine group and 92 (4·1%) of 2217 patients in the placebo group (p=0·021). Diarrhoea was reported in 300 (13·7%) of 2195 patients in the colchicine group and 161 (7·3%) of 2217 patients in the placebo group (p<0·0001). INTERPRETATION: In community-treated patients including those without a mandatory diagnostic test, the effect of colchicine on COVID-19-related clinical events was not statistically significant. Among patients with PCR-confirmed COVID-19, colchicine led to a lower rate of the composite of death or hospital admission than placebo. Given the absence of orally administered therapies to prevent COVID-19 complications in community-treated patients and the benefit of colchicine in patients with PCR-proven COVID-19, this safe and inexpensive anti-inflammatory agent could be considered for use in those at risk of complications. Notwithstanding these considerations, replication in other studies of PCR-positive community-treated patients is recommended. FUNDING: The Government of Quebec, the Bill & Melinda Gates Foundation, the National Heart, Lung, and Blood Institute of the US National Institutes of Health, the Montreal Heart Institute Foundation, the NYU Grossman School of Medicine, the Rudin Family Foundation, and philanthropist Sophie Desmarais.

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.

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.

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.

Effect of exercise training on plasma levels and functional properties of high-density lipoprotein cholesterol in the metabolic syndrome.

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.

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.

Prognostic value of left atrial volume in patients who underwent dobutamine stress echocardiography for known or suspected coronary artery disease.

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.

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.

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.

Accumulation of chylomicron remnants and impaired vascular reactivity occur in subjects with isolated low HDL cholesterol: effects of niacin treatment.

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.

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.