Alcohol and a high-fat diet: a combination favoring overfeeding.

We analyze a two-node tandem queue with Brownian input. We first derive an explicit expression for the joint distribution function of the workloads of the first and second queue, which also allows us to calculate their exact large-buffer asymptotics. The nature of these asymptotics depends on the model parameters, i.e., there are different regimes. By using sample-path large-deviations (Schilder's theorem) these regimes can be interpreted: we explicitly characterize the most likely way the buffers fil

The hypertriglyceridemic-waist phenotype and the risk of coronary artery disease: results from the EPIC-Norfolk Prospective Population Study

Background: Screening for increased waist circumference and hypertriglyceridemia (the hypertriglyceridemic-waist phenotype) has been proposed as an inexpensive approach to identify patients with excess intra-abdominal adiposity and associated metabolic abnormalities. We examined the relationship between the hypertriglyceridemic-waist phenotype to the risk of coronary artery disease in apparently healthy individuals. Methods: A total of 21 787 participants aged 45-79 years were followed for a mean of 9.8 (standard deviation 1.7) years. Coronary artery disease developed in 2109 of them during follow-up. The hypertriglyceridemic-waist phenotype was defined as a waist circumference of 90 cm or more and a triglyceride level of 2.0 mmol/L or more in men, and a waist circumference of 85 cm or more and a triglyceride level of 1.5 mmol/L or more in women. Results: Compared with participants who had a waist circumference and triglyceride level below the threshold, those with the hypertriglyceridemic-waist phenotype had higher blood pressure indices, higher levels of apolipoprotein B and C-reactive protein, lower levels of high-density lipoprotein cholesterol and apolipoprotein A-I, and smaller low-density lipoprotein particles. Among men, those with the hypertriglyceridemic- waist phenotype had an unadjusted hazard ratio for future coronary artery disease of 2.40 (95% confidence interval [CI] 2.02-2.87) compared with men who did not have the phenotype. Women with the phenotype had an unadjusted hazard ratio of 3.84 (95% CI 3.20-4.62) compared with women who did not have the phenotype. Interpretation: Among participants from a European cohort representative of a contemporary Western population, the hypertriglyceridemic-waist phenotype was associated with a deteriorated cardiometabolic risk profile and an increased risk for coronary artery diseas

Effect of rimonabant on carotid intima-media thickness (CIMT) progression in patients with abdominal obesity and metabolic syndrome: the AUDITOR Trial

OBJECTIVE: The aim of this trial was to determine whether obese patients benefit from treatment with rimonabant in terms of progression of carotid atherosclerosis. Rimonabant, a selective cannabinoid-1 receptor blocker, reduces body weight and improves cardiometabolic risk factors in patients who are obese. DESIGN, SETTING, PATIENTS, INTERVENTIONS AND RESULTS: A prospective, double-blind, placebo-controlled trial (Atherosclerosis Underlying Development assessed by Intima-media Thickness in patients On Rimonabant (AUDITOR)) randomised 661 patients with abdominal obesity and metabolic syndrome to rimonabant or placebo for 30 months of treatment. The absolute change in the average value for six segments of far wall carotid intima-media thickness from baseline to month 30 was 0.010 ± 0.095 mm in the rimonabant group and 0.012 ± 0.091 mm in the placebo group (p=0.67). The annualised change was an increase of 0.005 ± 0.042 mm for the rimonabant-treated group and 0.007 ± 0.043 mm for the placebo-treated group (p=0.45). CONCLUSIONS: There was no difference in atherosclerosis progression between patients receiving rimonabant for 30 months and those receiving placebo for the primary efficacy measure (absolute change in carotid intima-media thickness). These findings are consistent with a similar study using coronary intravascular ultrasound and another study evaluating the occurrence of cardiovascular events. Our findings suggest that a 5% loss of body weight over a 30-month period with rimonabant is insufficient to modify atherosclerosis progression in the carotid artery in obese patients with metabolic syndrome. Clinical trial registration information clinicaltrials.gov Identifier: NCT0022817

Metabolically obese normal-weight subjects. Part two: prognosis and management

Metabolically obese normal-weight (MONW) individuals are frequently not detected because of a falsely reassuring body weight. However, they have most of the metabolic syndrome markers known to be associated with a higher risk of type 2 diabetes, cardiovascular disease and mortality. The present review paper aims to describe the clinical consequences to which MONW people are exposed and the main principles of managing this syndromeLes personnes non obèses « métaboliquement anormales » (MONW) sont rarement dépistées en raison d’un poids corporel faussement rassurant. Elles présentent pourtant bon nombre de marqueurs du syndrome métabolique, connus pour être associés à un risque accru de diabète de type 2, de maladies cardiovasculaires et de mortalité. Cet article vise à évaluer les conséquences cliniques auxquelles sont exposées les personnes MONW et à décrire les grands principes de la prise en charge thérapeutique de ce syndrome

Low plasma adiponectin exacerbates the risk of premature coronary heart disease in familial hypercholesterolemia

Familial hypercholesterolemia (FH) is characterized by increased risk for premature coronary artery disease (CAD). This risk is exacerbated in the presence of abdominal obesity and insulin resistance. Low adiponectin is part of the clustering of metabolic abnormalities associated with abdominal obesity and insulin resistance. The present study, therefore, aims to examine the relationship between plasma adiponectin and age at CAD diagnosis in FH patients. Plasma adiponectin was measured by ELISA in 568 non-diabetic FH individuals of French-Canadian origin. CAD was defined according to strict clinical criteria. Prior to analyses, patients were grouped according to age and gender-specific tertiles of plasma adiponectin levels. Multivariate Cox proportional hazards regression was used to estimate the association between plasma adiponectin levels and age at diagnosis of CAD. Overall, FH patients in the lowest tertile of plasma adiponectin exhibited CAD at a significantly younger age (hazard ratio = 1.73, confidence interval 95%: [1.19–2.53]; p = 0.004). These results suggest that low plasma adiponectin is associated with an increased risk of premature CAD over and above the already exaggerated risk seen in FH patients

Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease - The STRADIVARIUS randomized controlled trial

Context Abdominal obesity is associated with metabolic abnormalities and increased risk of atherosclerotic cardiovascular disease. However, no obesity management strategy has demonstrated the ability to slow progression of coronary disease. Objective To determine whether weight loss and metabolic effects of the selective cannabinoid type 1 receptor antagonist rimonabant reduces progression of coronary disease in patients with abdominal obesity and the metabolic syndrome. Design, Setting, and Patients Randomized, double- blinded, placebo- controlled, 2- group, parallel- group trial ( enrollment December 2004- December 2005) comparing rimonabant with placebo in 839 patients at 112 centers in North America, Europe, and Australia. Interventions Patients received dietary counseling, were randomized to receive rimonabant ( 20 mg daily) or matching placebo, and underwent coronary intravascular ultrasonography at baseline ( n= 839) and study completion ( n= 676). Main Outcome Measures The primary efficacy parameter was change in percent atheroma volume ( PAV); the secondary efficacy parameter was change in normalized total atheroma volume ( TAV). Results In the rimonabant vs placebo groups, PAV ( 95% confidence interval [ CI]) increased 0.25% (- 0.04% to 0.54%) vs 0.51% ( 0.22% to 0.80%) ( P=. 22), respectively, and TAV decreased 2.2 mm(3) (- 4.09 to - 0.24) vs an increase of 0.88 mm(3) (- 1.03 to 2.79) ( P=. 03). In the rimonabant vs placebo groups, imputingresultsbasedonbaselinecharacteristics for patients not completing the trial, PAV increased 0.25% (- 0.04% to 0.55%) vs 0.57% ( 0.29% to 0.84%) ( P=. 13), and TAV decreased 1.95 mm(3) (- 3.8 to - 0.10) vs an increase of 1.19 mm(3) (- 0.73 to 3.12) ( P=. 02). Rimonabant- treated patients had a larger reduction in body weight ( 4.3 kg [- 5.1 to - 3.5] vs 0.5 kg [- 1.3 to 0.3]) and greater decrease in waist circumference ( 4.5 cm [- 5.4 to - 3.7] vs 1.0 cm [- 1.9 to - 0.2]) ( P <. 001 for both comparisons). In the rimonabant vs placebo groups, high- density lipoprotein cholesterol levels increased 5.8 mg/dL( 4.9 to 6.8) ( 22.4%) vs 1.8 mg/ dL( 0.9 to 2.7) ( 6.9%) ( P <. 001), and median triglyceride levels decreased 24.8mg/ dL(- 35.4 to - 17.3) ( 20.5%) vs 8.9 mg/ dL (- 14.2 to - 1.8) ( 6.2%) ( P <. 001). Rimonabant- treated patients had greater decreases in high- sensitivity C- reactive protein ( 1.3 mg/ dL[- 1.7 to - 1.2] [ 50.3%] vs 0.9 mg/ dL[- 1.4 to - 0.5][ 30.9%]) and less increase in glycated hemoglobin levels( 0.11%[ 0.02% to 0.20%] vs 0.40% [ 0.31% to 0.49%]) ( P <. 001 for both comparisons). Psychiatric adverse effects were more common in the rimonabant group ( 43.4% vs 28.4%, P <. 001). Conclusions After 18 months of treatment, the study failed to show an effect for rimonabant on disease progression for the primary end point ( PAV) but showed a favorable effect on the secondary end point ( TAV). Determining whether rimonabant is useful in management of coronary disease will require additional imaging and outcomes trials, which are currently under way. Trial Registration clinicaltrials. gov Identifier: NCT0012433