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BACKGROUND: Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagon-like peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, injected subcutaneously. METHODS: We conducted a 56-week, double-blind trial involving 3731 patients who did not have type 2 diabetes and who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension. We randomly assigned patients in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. The coprimary end points were the change in body weight and the proportions of patients losing at least 5% and more than 10% of their initial body weight. RESULTS: At baseline, the mean (±SD) age of the patients was 45.1±12.0 years, the mean weight was 106.2±21.4 kg, and the mean BMI was 38.3±6.4; a total of 78.5% of the patients were women and 61.2% had prediabetes. At week 56, patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg (a difference of -5.6 kg; 95% confidence interval, -6.0 to -5.1; P

Background The long-term effects of sibutramine treatment on the rates of cardiovascular events and cardiovascular death among subjects at high cardiovascular risk have not been established. Methods We enrolled in our study 10,744 overweight or obese subjects, 55 years of age or older, with preexisting cardiovascular disease, type 2 diabetes mellitus, or both to assess the cardiovascular consequences of weight management with and without sibutramine in subjects at high risk for cardiovascular events. All the subjects received sibutramine in addition to participating in a weight-management program during a 6-week, single-blind, lead-in period, after which 9804 subjects underwent random assignment in a double-blind fashion to sibutramine (4906 subjects) or placebo (4898 subjects). The primary end point was the time from randomization to the first occurrence of a primary outcome event (nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death). Results The mean duration of treatment was 3.4 years. The mean weight loss during the lead-in period was 2.6 kg; after randomization, the subjects in the sibutramine group achieved and maintained further weight reduction (mean, 1.7 kg). The mean blood pressure decreased in both groups, with greater reductions in the placebo group than in the sibutramine group (mean difference, 1.2/1.4 mm Hg). The risk of a primary outcome event was 11.4% in the sibutramine group as compared with 10.0% in the placebo group (hazard ratio, 1.16; 95% confidence interval [CI], 1.03 to 1.31; P=0.02). The rates of nonfatal myocardial infarction and nonfatal stroke were 4.1% and 2.6% in the sibutramine group and 3.2% and 1.9% in the placebo group, respectively (hazard ratio for nonfatal myocardial infarction, 1.28; 95% CI, 1.04 to 1.57; P=0.02; hazard ratio for nonfatal stroke, 1.36; 95% CI, 1.04 to 1.77; P=0.03). The rates of cardiovascular death and death from any cause were not increased. Conclusions Subjects with preexisting cardiovascular conditions who were receiving long-term sibutramine treatment had an increased risk of nonfatal myocardial infarction and nonfatal stroke but not of cardiovascular death or death from any cause. (Funded by Abbott; ClinicalTrials.gov number, NCT00234832.)

Obesity is known to be a risk factor of cardiac death, that is associated first of all with cardiac arrhythmias. Increased QT dispersion (QTd) and ventricular late potentials (LP) are measurable indices of ventricular arrhythmias risk. The aim of this study is to asses QTd and LP in women with obesity. 62 obese women (mean BMI 36.7 kg/m2) and 15 apparently healthy subjects (mean BMI 24.5 kg/m2) were included in our study. QTd and correlated QT interval dispersion (QTdc) were calculated from 12-lead ECG. LVM were assessed from echocardiograms. LP were obtained by signal averaging of surface electrocardiograms.QTd, QTdc, LVM were significantly higher in patients. We found LP in six cases and higher QTdc in this subgroup. According to our research, increased QTd in obese women seems to be associated with left ventricular hypertrophy and increased QTd is significantly higher in subjects with LP.

The aim of the study is the assessment whether weight loss treatment with adrenergic modulation drugs modifies neuropeptide Y (NPY) plasma concentration in obese women.13 obese women (BMI 38.3 +/- 4.4) were tested before and subsequently 10 and 20 days after weight loss treatment. The treatment consisted of a very low caloric diet of 400 kcal (1670 kJ) daily combined with ephedrine with caffeine (E + C) or ephedrine with caffeine and yohimbine (E + C + Y) administered for 10 days using the cross-over method. The patients underwent physical examination, including heart rate and blood pressure measurements, spectral heart rate variability (HRV) at rest and after 3 minute handgrip and a 15 minute cycloergometer exercise at 75 W. All the above mentioned tests were carried out thrice in each patient. In 13 obese patients and in 6 control women plasma NPY concentrations were determined by a specific radioimmunoassay using rabbit anti-NPY antiserum and a standard synthetic porcine NPY (Peninsula Lab.).Plasma NPY concentrations were significantly lower in the obese persons compared with the control group. During weight loss treatment with adrenergic modulation drugs no changes in plasma NPY were found at rest and after physical exercise. Also no differences in HRV indices were observed.1. Low plasma NPY concentration observed in obesity may be a contraregulatory factor that could prevent further weight increase. 2. Weight reduction treatment did not affect plasma NPY concentration and cardiovascular response to physical exercise. 3. The doses of adrenergic modulation drugs used in our study did not induce any serious side effects, and were so low that no change of plasma NPY concentration and cardiovascular responses were observed at rest.

Evidence for the role of chronic inflammation in atherogenesis has been well documented. Selectins mediate the first step in leukocyte adhesion and may contribute to the pathogenesis of stable and unstable angina.The study group consisted of 59 patients (pts) with coronary artery disease (CAD) documented coronarographically: 27 pts with stable exertional angina (group A), 32 pts with unstable angina (group B). 20 healthy persons were the control group (group C). Serum levels of E-selectin and P-selectin were measured by ELISA method both before and after the treadmill ECG stress test (ST) in groups A and C. In group B the measurements were carried out at 6, 24, and 48 hours following an episode of chest pain.There were no differences between the baseline serum levels of selectins as determined in groups A and C. In patients with stable angina, the post-ST concentrations of E-selectin were significantly higher (68.8 +/- 29 ng/ml) in comparison to both baseline (38.7 +/- 15 ng/ml), and group C-values (pre-ST: 35.1 +/- 16; post-ST: 49.9 +/- 15 ng/ml). In unstable patients, serum P-selectin levels were higher when compared to those found in groups A and C (group A: 142.3 +/- 24; group B: 190.1 +/- 99; group K: 136.4 +/- 33 ng/ml). No differences between selectins concentrations were observed at fixed times after an episode of chest pain.Soluble selectins levels in pts with stable angina are comparable to those of healthy persons. Significant increase of E-selectin concentration as induced by ST may reflect endothelial response to exercise. Patients with unstable angina had elevated levels of P-selectin, which seems to be associated with enhanced platelet and leukocyte activation. The serum levels of selectins may indirectly reflect clinical condition of pts with CAD.

It is suggested that gut microbiota play a role in the pathogenesis of obesity enhancing energy utilization from digested food. The influence of gut microbiota on resting energy expenditure (REE) has not been evaluated yet.The aim of the study is to assess the composition on gut microbiota and its association with REE in obese and normal weight subjects.REE measurement and semi-quantitative analysis of gut microbiota composition in aerobic and anaerobic conditions were performed in 50 obese and 30 normal weight subjects without concomitant diseases.A count of bacterial colony was greater in obese than in normal weight subjects. However, the proportion of Bacteroides spp. and Firmicutes was similar in both study groups. A positive correlation between REE (kcal/d) and total bacterial count (r = 0.26, p0.05), as well as between REE and the percentage of Firmicutes (r = -0.24, p0.05) was found. The multiple regression analysis did not prove an independent impact of total bacterial as well as Bacteroides spp. and Firmicutes counts on REE.The composition of gut microbiota is not associated with the level of resting energy expenditure. The proportion of Bacteroides and Firmicutes in gut microbiota is not related to body mass.

The risk of sudden cardiac death is higher in patients with obesity, particularly in the upper body obesity. The most common cause of cardiac events are serious ventricular arrhythmias. Delayed cardiac repolarization leading to the prolongation of the QT interval is a well characterised precursor of arrhythmias. The QT interval dispersion reflects inhomogeneity of repolarization. The aim of this study was to assess QT interval dispersion (QTd) in obese women and to establish the relationship between obesity and QTd. 62 patients with obesity (group 1) and 15 apparently healthy women (group 2) were included in our study. Obese subjects were distinguished in accordance to the waist to hip ratio (WHR) into three subgroups: 1a--obese women with upper body obesity; 1b--obese women with WHR: 0.75-0.85; 1c--obese women with lower body obesity. A standard 12-lead ECG was performed in each subjects and QTd, QTdc (QT correlated interval dispersion), QTdR (QTd ratio) were calculated. The left ventricular mass (LVM) and left ventricular mass index (LVMI) were obtained from echocardiograms. We found QTd, QTdc, QTdR and LVM, LVMI to be significantly higher in obese women as well as positive correlation between BMI and both LVM, LVMI. QTdR was significantly higher in subgroup 1a compared with subgroup 1c.1) QT interval dispersion was increased in obese women compared with healthy subjects, 2) supposedly increased QTd was associated with the type of obesity.

Background and Objectives: Alexithymia is a personality trait that may affect the development and course of obesity and effectiveness of treatment. The aim of the study is to assess the prevalence of alexithymia in obese women beginning a weight reduction program and determine the relationships between alexithymia and anxiety, depression, and binge eating. Methods: Obese women (n = 100; age 45 ± 13 yr) completed the following self-report inventories: Toronto Alexithymia Scale (TAS 26), Hospital Anxiety and Depression Scale (HADS), and Binge Eating Scale (BES). Results: Alexithymia was found in 46 patients and was more frequent among women who had attained only primary and vocational education than in those with a higher education level (39.1% vs. 10.9%; p = 0.002) and in those >45 years old than in younger women (30.4% vs. 69.6%; p = 0.03). The frequency of severe depression symptoms was higher in alexithymic women than in non-alexithymic women (19.6% vs. 5.6%; p = 0.03); however, the anxiety state was equally prevalent in both subgroups. The prevalence of alexithymia (52.6% vs. 44.4%) and its level (73.2 ± 8.9 vs. 71.2 ± 11.3 points) were similar in women with and without binge eating disorder. Multivariate mixed linear regression analysis revealed that higher body mass index was associated with primary and vocational education (odds ratio [OR] = 16.69) and severe depression symptoms (OR = 52.45), but not alexithymia. Conclusions: In addition to severe depression and low education level, obesity may predispose for the development of alexithymia. However, alexithymia does not affect the severity of obesity in women.

TNF-alpha as a pleiotropic, proinflammatory cytokine seems to play a role in the pathogenesis of atherosclerosis and coronary artery disease (CAD). TNF-alpha is binding to two cell surface receptors and its serum activity is modified by soluble forms of these receptors: sTNF-R I and sTNF-R II. The aim of this study was to assess serum concentrations of TNF-alpha, sTNF-R I and sTNF-R II in patients (pts) with CAD. We examined serum concentrations of TNF-alpha, sTNF-R I and sTNF-R II by ELISA in: 45 pts with stable exertional angina (group I); 32 pts with unstable angina (group II) within 6, 24, and 48 h after the chest pain; and 23 pts before and 6, 24, and 48 h after PTCA (group III). The control group (group C) consisted of 20 healthy subjects. We evaluated: clinical state of patients and results of some diagnostic examinations (lipids, ECG, echocardiography, coronary angiography). Mean serum concentrations of TNF-alpha were significantly higher in pts ith CAD (group I: 18.25 +/- 5.5 pg/ml; group II: 17.24 +/- 4.0 pg/ml; group III: 18.70 +/- 0.6 pg/ml; p0.001) than in healthy pts (8.31 +/- 1.4 pg/ml). In turn mean serum concentrations of sTNF-R I were significantly higher both in group I (1399.6 +/- 536.3 pg/ml; p0.05) and III (1544.0 +/- 391.4 pg/ml; p0.01) than in control group (1093.9 +/- 456.9 pg/ml). There were not differences in mean serum concentrations of sTNF-R II. We found no differences between mean serum concentrations of TNF-alpha, sTNF-R I and sTNF-R II either after the chest pain (group II); or before and after PTCA (group III). In group I mean TNF-alpha correlated with serum triglycerides and HDL-cholesterol (r = 0.412 and r = -0.424; p0.01); sTNF-R I correlated with LDL-cholesterol (r = -0.309; p0.05); and sTNF-R II correlated with total cholesterol and LDL-cholesterol (r = 0.311 and r = 0.316; p0.05). The serum concentrations of TNF-alpha are increased in patients with CAD, but this does not reflect the clinical state of patients. In pts with stable angina these increased levels of TNF-alpha may be accompanied with higher concentrations of sTNF-R I--it seems to be the compensatory mechanism in long-term atherosclerosis. Lipid disturbances may influence the cytokines metabolism in pts with CAD.

Obesity is associated with decreased physical activity. The aim of the study was to assess the anaerobic threshold in obese and normal weight women and to analyse the effect of weight-reduction therapy on the determined thresholds.42 obese women without concomitant disease (age 30.5 ± 6.9y; BMI 33.6 ± 3.7 kg·m(-2)) and 19 healthy normal weight women (age 27.6 ± 7.0y; BMI 21.2 ± 1.9 kg·m(-2)) performed cycle ergometer incremental ramp exercise test up to exhaustion. The test was repeated in 19 obese women after 12.3 ± 4.2% weight loss. The lactate threshold (LT) and the ventilatory threshold (VT) were determined. Obese women had higher lactate (expressed as oxygen consumption) and ventilator threshold than normal weight women. The lactate threshold was higher than ventilatory one both in obese and normal weight women (1.11 ± 0.21 vs 0.88 ± 0.18 L·min(-1), p0.001; 0.94 ± 0.15 vs 0.79 ± 0.23 L·min(- 1), p0.01, respectively). After weight reduction therapy neither the lactate nor the ventilatory threshold changed significantly. The results concluded that; 1. The higher lactate threshold noted in obese women may be related to the increased fat acid usage in metabolism. 2. Both in obese and normal weight women lactate threshold appears at higher oxygen consumption than ventilatory threshold. 3. The obtained weight reduction, without weight normalisation was insufficient to cause significant changes of lactate and ventilatory thresholds in obese women. Key pointsResults showed that adolescent young female gymnasts have an altered serum inflammatory markers and endothelial activation, compared to their less physically active peers.Physical activities improved immune system.Differences in these biochemical data kept significant after adjustment for body weight and height.

Current cardiovascular risk scores do not include obesity or fat distribution as independent factors, and may underestimate risk in obese individuals. Assessment of early vascular ageing (EVA) biomarkers including arterial stiffness, central blood pressure, carotid intima-media thickness and flow-mediated vasodilation may help to refine risk assessment in obese individuals in whom traditional cardiovascular risk scores and factors suggest no need for specific medical attention. A number of issues need to be addressed before this approach is ready for translation into routine clinical practice. Methodologies for measurements of vascular markers need to be further standardized and less operator-dependent. The utility of these nontraditional risk factors will also need to be proven in sufficiently large and properly designed interventional studies. Indeed, published studies on vascular markers in obesity and weight loss vary in quality and study design, are sometimes conducted in small populations, use a variety of differing methodologies and study differing vascular beds. Finally, current vascular measurements are still crude and may not be sufficient to cover the different aspects of EVA in obesity.

Obese patients are prone to arterial hypertension, require more antihypertensive medications, and have an increased risk of treatment-resistant arterial hypertension. Obesity-induced neurohumoral activation appears to be involved. The association between obesity and hypertension shows large inter-individual variability, likely through genetic mechanisms. Obesity affects overall cardiovascular and metabolic risk; yet, the relationship between obesity and cardiovascular risk is complex and not sufficiently addressed in clinical guidelines. The epidemiological observation that obesity may be protective in patients with established cardiovascular disease is difficult to translate into clinical experience and practice. Weight loss is often recommended as a means to lower blood pressure. However, current hypertension guidelines do not provide evidence-based guidance on how to institute weight loss. In fact, weight loss influences on blood pressure may be overestimated. Nevertheless, weight loss through bariatric surgery appears to decrease cardiovascular risk in severely obese patients. Eventually, most obese hypertensive patients will require antihypertensive medications. Data from large-scale studies with hard clinical endpoints on antihypertensive medications specifically addressing obese patients are lacking and the morbidity from the growing population of severely obese patients is poorly recognized or addressed. Because of their broad spectrum of beneficial effects, renin-angiotensin system inhibitors are considered to be the most appropriate drugs for antihypertensive treatment of obese patients. Most obese hypertensive patients require two or more antihypertensive drugs. Finally, how to combine weight loss strategies and antihypertensive treatment to achieve an optimal clinical outcome is unresolved.