PubMed Health⌕ Search

Biomedical subjects

Jean-Pierre Després

Publications and source records attributed to Jean-Pierre Després.

At least 19 recordsLinked to original sources
PubMed2007

The effect of topiramate on energy balance in obese men: a 6-month double-blind randomized placebo-controlled study with a 6-month open-label extension.

OBJECTIVE: Topiramate (TPM) has been reported to reduce body weight beyond a placebo in the treatment of obese participants, but the effect of this agent on components of energy balance has not yet been established in humans. Thus, the aim of this study was to study the impact of TPM on food preferences, measures of satiety, food intake, resting metabolic rate (RMR), and 24-h energy expenditure. METHODS: The study design consisted of a 6-month, single-center, randomized, double-blind, parallel group, placebo-controlled trial with a 6-month open-label extension. The study included 68 sedentary men with abdominal obesity (waist circumference > or = 100 cm), of between 25 and 55 years of age, with a dyslipidemic profile and a body mass index (BMI) > or = 27 and < or = 40 kg/m(2). RESULTS: Treatment with TPM produced significant changes in anthropometric variables and body composition compared with placebo. However, at the end of the 1-year study, the placebo/TPM group showed similar weight loss and reduction in body fatness compared with the TPM/TPM group. For instance, at the end of the 12-month intervention, mean percentage of body weight loss from baseline was about -5% in both groups (-4 kg fat loss). Topiramate treatment reduced energy intake, be it in the context of an ad libitum buffet-type meal or under free living conditions. The 24-h daily energy expenditure (DEE) assessed by whole-body indirect calorimetry adjusted for body weight and age was not altered by TPM treatment. CONCLUSION: Topiramate treatment produced significantly greater weight loss than placebo and the majority of this loss was explained by a decrease in body fat stores. Most of the weight loss effect produced by TPM therapy was observed within a period of 6 months. Finally, TPM treatment had an impact on energy balance through a reduction in food intake that appears to have created an energy deficit of about 30,000-40,000 kcal compared with treatment with the placebo over 6 months.

Adipose Tissue↗
PubMed2007

Short sleep duration is associated with reduced leptin levels and increased adiposity: Results from the Quebec family study.

OBJECTIVE: To explore cross-sectional associations between short sleep duration and variations in body fat indices and leptin levels during adulthood in a sample of men and women involved in the Québec Family Study. RESEARCH METHODS AND PROCEDURES: Anthropometric measurements, plasma lipid-lipoprotein profile, plasma leptin concentrations, and total sleep duration were determined in a sample of 323 men and 417 women ages 21 to 64 years. RESULTS: When compared with adults reporting 7 to 8 hours of sleep per day, the adjusted odds ratio for overweight/obesity was 1.38 (95% confidence interval, 0.89 to 2.10) for those with 9 to 10 hours of sleep and 1.69 (95% confidence interval, 1.15 to 2.39) for those with 5 to 6 hours of sleep, after adjustment for age, sex, and physical activity level. In each sex, we observed lower adiposity indices in the 7- to 8-hour sleeping group than in the 5- to 6-hour sleeping group. However, all of these significant differences disappeared after statistical adjustment for plasma leptin levels. Finally, the well-documented regression of plasma leptin levels over body fat mass was used to predict leptin levels of short-duration sleepers (5 and 6 hours of sleep), which were then compared with their measured values. As expected, the measured leptin values were significantly lower than predicted values. DISCUSSION: There may be optimal sleeping hours at which body weight regulation is facilitated. Indeed, short sleep duration predicts an increased risk of being overweight/obese in adults and is related to a reduced circulating leptin level relative to what is predicted by fat mass. Because sleep duration is a potentially modifiable risk factor, these findings might have important clinical implications for the prevention and treatment of obesity.

Adipose Tissue↗
PubMed2006

Effects of cholesterol ester transfer protein (CETP) gene on adiposity in response to long-term overfeeding.

Cholesterol ester transfer protein (CETP) plays a key role in remodeling triglyceride-rich particles and high-density lipoproteins (HDL). We investigated CETP sequence variants in response to long-term overfeeding (100 days) in 12 pairs of male monozygotic twins (mean age+/-S.D.: 21+/-2 years). Body fat mass (FM), abdominal subcutaneous (ASF) and visceral fat (AVF), and plasma lipoproteins were determined. The CETP variants C>T/In9 (rs289714) and G>A/Ex14 (rs5882, or I405V) were investigated by RFLP-PCR methodologies. Before overfeeding, the CETP CC/In9 (n=18) genotype was associated with lower FM compared to the C>T/In9 heterozygotes. Overfeeding induced more FM and ASF accretion in C>T/In9 carriers (P<or=0.05). CETP V405V homozygotes (n=8) had lower BMI, FM, and ASF before overfeeding than those with the I405I (n=6) or I405V (n=10) genotypes. However, V405V subjects had the largest gain in AVF with overfeeding (P=0.02). Decreases from baseline were significantly different across the I405V genotypes for HDL-C, HDL-Apo AI, HDL(2), and HDL(3) (P<or=0.05). Our data suggests that CETP sequence variation contributes to the undesirable changes in adiposity and HDL-C levels when exposed to excessive calorie consumption and may be potentially helpful to identify individuals with the metabolic syndrome who are at higher risk of cardiovascular disease.

Adipose Tissue↗
PubMed2006

Abdominal obesity and metabolic syndrome.

Metabolic syndrome is associated with abdominal obesity, blood lipid disorders, inflammation, insulin resistance or full-blown diabetes, and increased risk of developing cardiovascular disease. Proposed criteria for identifying patients with metabolic syndrome have contributed greatly to preventive medicine, but the value of metabolic syndrome as a scientific concept remains controversial. The presence of metabolic syndrome alone cannot predict global cardiovascular disease risk. But abdominal obesity - the most prevalent manifestation of metabolic syndrome - is a marker of 'dysfunctional adipose tissue', and is of central importance in clinical diagnosis. Better risk assessment algorithms are needed to quantify diabetes and cardiovascular disease risk on a global scale.

Abdomen↗
PubMed2006

Low plasma adiponectin exacerbates the risk of premature coronary artery 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.

Adiponectin↗
PubMed2006

Metabolic syndrome is associated with faster degeneration of bioprosthetic valves.

BACKGROUND: Several studies have reported similarities between calcification of the native aortic valve and atherosclerosis. Recent studies also suggested that hypercholesterolemia may be a risk factor for calcific degeneration of bioprosthetic valves. The metabolic syndrome (MS) is associated with a higher risk of vascular atherosclerosis. We thus hypothesized that the atherogenic features of MS could accelerate bioprosthetic valve degeneration. METHODS AND RESULTS: We included 217 patients who underwent aortic valve replacement with a bioprosthetic valve in the study. Of these patients, 71 patients (33%) had MS defined according to the modified criteria proposed by the National Cholesterol Education Program Adult Treatment Panel III. The annualized increase in mean transprosthetic gradient and the worsening of transprosthetic regurgitation measured by Doppler echocardiography were used to assess the deterioration of valve hemodynamic function. Patients with MS had higher progression of gradient (+4+/-5 mm Hg/year versus +2+/-2 mm Hg/year, P<0.001), higher proportion of > or = 1/3 degree worsening of regurgitation (25% versus 12%, P=0.02), and higher proportion of valve function deterioration defined as regurgitation worsening and/or > or = 3 mm Hg/year increase in gradient (41% versus 25%, P=0.02) when compared with patients without MS. On multivariate analysis, MS was an independent predictor of gradient progression (P=0.01), regurgitation worsening (P=0.02), and valve function deterioration (P=0.02). The other independent predictors were diabetes, renal insufficiency, and higher mean gradient at baseline. CONCLUSIONS: This is the first study to report that the MS is independently associated with faster bioprosthetic valve degeneration. This study could pave the way for the development of a new medical therapy able to significantly reduce the structural valve deterioration of bioprostheses.

Aged↗
PubMed2006

Metabolic syndrome negatively influences disease progression and prognosis in aortic stenosis.

OBJECTIVES: This study sought to examine the association between the metabolic syndrome (MS) and the progression of aortic stenosis (AS). BACKGROUND: It has been suggested that aortic valve sclerosis and its progression to AS are caused by an atherosclerotic process. Metabolic syndrome is associated with a higher risk of vascular atherosclerosis. Thus, we hypothesized that the atherogenic features of MS could negatively influence disease progression and prognosis in patients with AS. METHODS: We retrospectively analyzed the data of 105 consecutive patients (age 69 +/- 12 years, 64 men) with at least moderate AS. Of these patients, 40 (38%) had MS identified according to the modified clinical criteria proposed by the National Cholesterol Education Program-Adult Treatment Panel III. The hemodynamic progression of AS was assessed by the measurement of the annualized decrease in valve area during the follow-up period of the study, which averaged 28 +/- 13 months. Event-free survival was defined as the absence of death or aortic valve replacement during follow-up. RESULTS: The hemodynamic progression of the stenosis was twice as fast (-0.14 +/- 0.13 cm2/year vs. -0.08 +/- 0.08 cm2/year, p = 0.008) and the three-year event-free survival was markedly lower (44 +/- 8% vs. 69 +/- 6%, p = 0.002) among patients with MS. In multivariate analysis, MS was found to be a strong independent predictor of both stenosis progression (p = 0.006) and event-free survival (odds ratio 3.85, 95% CI 1.96 to 7.58, p < 0.001). CONCLUSIONS: The present study is the first to report that MS is associated with a faster disease progression and worse outcome in patients with AS. Such findings open new avenues of research and provide a strong impetus for the elaboration of additional prospective studies focusing on this association.

Aged↗
PubMed2006

Association of heterozygous familial hypercholesterolemia with smaller HDL particle size.

Small, dense HDL particles have been associated with factors known to increase the risk of cardiovascular disease, such as obesity, hypertriglyceridemia, small dense LDL particles, decreased HDL-cholesterol levels and increased apoA-I fractional catabolic rate from plasma. In order to assess the potential contribution of HDL particle size to atherosclerosis in heterozygous familial hypercholesterolemia (FH), we examined the electrophoretic characteristics of HDL particles in a large cohort of well defined FH heterozygotes and controls. A total of 259 FH heterozygotes and 208 controls participated in the study. FH subjects were carriers of one of the nine French Canadian mutations in the LDL receptor gene. All subjects were apoE3 homozygotes. HDL particles were characterized by non-denaturing polyacrylamide gradient gel electrophoresis following a 6-week lipid-lowering drug-free baseline period. The integrated HDL size was significantly smaller in the FH group compared to controls (FH=87.3+/-5.2 Angstroms versus controls=91.6+/-4.9 Angstroms, P<0.0001). In each groups, men had smaller HDL particles than women. Multiple regression linear analyses showed that the FH/Control status accounted for 20.3% of the variance in the integrated HDL size. These results suggest that the FH/control status was independently associated with variations in HDL particle size and that these variations could contribute to the development of premature atherosclerosis in these patients.

Adult↗
PubMed2006

Apolipoprotein-B, low-density lipoprotein cholesterol, and the long-term risk of coronary heart disease in men.

We examined whether plasma apolipoprotein-B (apo-B) levels add further information on the risk of coronary heart disease (CHD) after taking into account low-density lipoprotein (LDL) cholesterol concentrations and other traditional risk factors. Among 2,072 CHD-free men from the Québec Cardiovascular Study at entry and followed for 13 years, 230 had a first CHD event (CHD death or nonfatal myocardial infarction). Increased apo-B (tertile 1 vs 3) levels were associated with a significant increased risk of CHD after adjustment for nonlipid and lipid risk factors other than LDL cholesterol levels (relative risk 1.89, 95% confidence interval 1.31 to 2.73). High plasma LDL cholesterol concentrations (tertile 1 vs 3) were also associated with an increased risk of CHD independently of nonlipid and lipid risk factors (relative risk 2.02, 95% confidence interval 1.44 to 2.84). However, apo-B levels modulated to a significant extent the risk of CHD associated with increased concentrations of LDL cholesterol (>/=4.3 mmol/L). For instance, among men with high LDL cholesterol levels, those with an apo-B level <128 mg/dl were not at increased risk for CHD (relative risk 1.53, 95% confidence interval 0.89 to 2.62). In contrast, high levels of apo-B and LDL cholesterol were associated with a significant twofold increased risk of CHD (p <0.001). Receiver-operating curve analysis also indicated that plasma apo-B levels improved the ability to discriminate incident CHD cases among patients with high LDL cholesterol levels compared with a model based on LDL cholesterol levels (p = 0.04). In conclusion, plasma apo-B levels modulated the risk of CHD associated with LDL cholesterol over a 13-year follow-up.

Adult↗
PubMed2006

Genotype of the mutant LDL receptor allele is associated with LDL particle size heterogeneity in familial hypercholesterolemia.

Small, dense LDL particles have been associated with an increased risk of coronary artery disease. In order to assess the potential contribution of the genotype of the LDL receptor to LDL particle size heterogeneity in familial hypercholesterolemia (FH), we examined the electrophoretic characteristics of LDL particles in a large cohort of FH heterozygotes and controls. A total of 259 FH heterozygotes and 208 controls participated in the study. FH subjects were carriers of one of the nine French Canadian mutations in the LDL receptor gene. LDL particles were characterized by polyacrylamide gradient gel electrophoresis following a 6-week lipid-lowering drug-free baseline period. LDL-peak particle diameter (LDL-PPD), representing the most abundant LDL particle subpopulation, was significantly smaller in FH heterozygotes carrying a negative-receptor mutation than in subjects carrying a defective-receptor mutation (negative-receptor = 257.3 +/- 4.1 A versus defective-receptor = 259.0 +/- 4.3 A, p = 0.0006). No significant difference in plasma CETP concentrations was found between these two genotypic groups. Moreover, compared with controls having low triglyceride levels, negative-receptor subjects with high triglyceride levels had a relative risk of 19.6 (p < 0.0001) of having small, dense LDL particles while this risk was not significantly increased among defective-receptor subjects. Multivariate analysis showed that the LDL receptor status accounted for 5.7% of the variance in the LDL-PPD after adjustment for covariates. These results suggest that the genotype of the mutant LDL receptor allele was independently associated with variations in LDL-PPD and could partly explain why negative-receptor FH heterozygotes may be at greater risk of cardiovascular disease than defective-receptor FH subjects.

Adult↗
PubMed2006

Identifying which patients with diabetes should be tested for the presence of coronary artery disease--the importance of baseline electrocardiogram and exercise testing.

Numerous studies have reported that diabetic patients should not always be considered to be coronary artery disease (CAD)-equivalent as was previously suggested. Exercise testing is widely available at a relatively low cost, and even among patients in whom the diagnosis of CAD is highly probable on the basis of age, sex, description of chest pain and history of prior myocardial infarction, exercise testing is often a clinical requirement for risk or prognosis assessment to determine the need for possible coronary angiography or revascularization. Nevertheless, because of either the presence of atypical symptoms or the absence of symptoms often encountered, the screening approach may differ in patients with diabetes mellitus. Because CAD is the major cause of mortality in patients with diabetes, its early detection is important to improve medical interventions and outcomes. This is critical because the available evidence suggests that occult CAD is common among asymptomatic patients with diabetes. Therefore, noninvasive testing for asymptomatic CAD may be helpful for the identification of diabetic patients with severe coronary obstruction in whom revascularization therapy may be considered the first manifestation of silent CAD in patients with diabetes is a fatal cardiac event in approximately one-half of the patients. The present paper reviews some clinical markers that may be helpful to the clinician to increase the yield of finding significant occult CAD while screening patients with diabetes.

Coronary Artery Disease↗
PubMed2006

Ethnic differences in body composition and other markers of cardiovascular disease risk: study in matched Haitian and White subjects from Quebec.

OBJECTIVES: People of African descent may be at greater risk of metabolic syndrome (MS) compared with whites. We examined the associations among MS markers, body composition, and resting metabolic rate (RMR) in black Haitians and in white subjects living in Quebec, Canada. RESEARCH METHODS AND PROCEDURES: Forty randomly selected Haitians were matched with 40 white subjects for age, sex, and BMI. Glycemic status and insulin resistance were assessed based on a 3-hour glucose tolerance test. Blood lipids, blood pressure, abdominal fat (computed tomography), and waist circumference (WC) were measured. RMR was estimated by indirect calorimetry. RESULTS: Triglycerides were significantly correlated with blood pressure only in Haitians and with the area under the curve for insulin only in whites. Haitians had significantly (p < 0.05) lower triglycerides and higher high-density lipoprotein-cholesterol concentrations but higher blood pressure than whites at any given WC value. General linear models showed that Haitians had less visceral adipose tissue than whites for the same WC. RMR was lower among Haitians for any given value of BMI or WC than in whites. Also, WC was more strongly associated with glucose area under the curve and to log-homeostasis model assessment in white than in Haitian subjects. DISCUSSION: The MS may be ethnospecific in its features and etiology. The standard anthropometric indices of obesity may not be as effective in populations of African descent compared with whites, unless appropriate cut-off values are defined.

Adult↗
PubMed2006

Postprandial variations of plasma inflammatory markers in abdominally obese men.

OBJECTIVE: Abdominal obesity is associated with a fasting proinflammatory condition. However, not much is known of the potential variations in circulating inflammatory markers after food intake. The purpose of the present study was to examine postprandial changes in plasma tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and C-reactive protein (CRP) concentrations in men and their potential associations with fat distribution and metabolic profile variables. RESEARCH METHODS AND PROCEDURES: Thirty-eight men were given a high-fat meal in the morning after an overnight fast, and TNF-alpha, IL-6, and CRP levels were measured in plasma at 0, 4, and 8 hours after the meal. Physical and metabolic profiles were also assessed for each participant. RESULTS: We observed a substantial increase in circulating IL-6 levels (p < 0.0001) after the meal. Although postprandial variations in circulating TNF-alpha levels across time failed to reach statistical significance (p = 0.02), we noted a significant decrease in plasma TNF-alpha concentrations 4 hours (-10%, p < 0.001 vs. 0 hours) after food intake. Plasma CRP levels were not affected by the fat load. We also noted that insulin-sensitive individuals displayed a less pronounced inflammatory response after food intake than insulin-resistant subjects. DISCUSSION: Results of the present study show that consumption of a high-fat meal leads to an increase in plasma IL-6 concentrations and transient decrease in circulating TNF-alpha levels in overweight men. Our results suggest a possible role of insulin resistance in the modulation of the postprandial inflammatory response, which could, in turn, contribute to worsen the state of insulin resistance.

Abdominal Fat↗
PubMed2006

Is visceral obesity the cause of the metabolic syndrome?

Despite the fact that controversy remains around the underlying pathophysiological processes leading to the development of the metabolic syndrome (insulin resistance and/or hyperinsulinemia versus abdominal obesity), there is increased recognition that abdominal obesity is the most prevalent form of the metabolic syndrome. Although it has been well established that there is a greater prevalence of chronic metabolic diseases such as diabetes and cardiovascular diseases in obese patients than among normal weight individuals, obesity is a remarkably heterogeneous condition and not every obese patient is characterized by co-morbidities. In this regard, body fat distribution, especially visceral adipose tissue accumulation, has been found to be a major correlate of a cluster of diabetogenic, atherogenic, prothrombotic and proinflammatory metabolic abnormalities referred to as the metabolic syndrome. Due to its anatomic location and peculiar metabolic, hyperlipolytic activity, the expanded visceral adipose depot is a key correlate of the altered cardiometabolic risk profile observed among individuals with a high-risk abdominal obesity phenotype. Evidence suggests that this dysmetabolic profile is predictive of a substantially increased risk of coronary heart disease even in the absence of classical risk factors. Finally, a moderate weight loss in initially abdominally obese patients is associated with a preferential mobilization of visceral adipose tissue, which in turn leads to substantial improvements in the metabolic risk profile predictive of a reduced risk of coronary heart disease and of type 2 diabetes.

Humans↗
PubMed2006

Moderate alcohol consumption is more cardioprotective in men with the metabolic syndrome.

The aim of the present study was to evaluate the relation among alcohol consumption, the metabolic syndrome, and the risk of ischemic heart disease (IHD). The study was conducted in a cohort of 1966 men from the Quebec Cardiovascular Study. All men were initially free of IHD and, during the follow-up period of 13 y, 219 first cases of IHD were diagnosed. Alcohol consumption was determined by calculating the g/d intake based on standard portions of beer, wine, and spirits. Metabolic syndrome was diagnosed according to a modification of the National Cholesterol Education Program Adult Treatment Panel III definition. Men who consumed >or=15.2 g of alcohol/d (4th quartile of the distribution) were younger (P < 0.001), had elevated plasma HDL-C concentrations (P < 0.001), and lower plasma concentrations of insulin (P = 0.01), CRP (P = 0.01), and fibrinogen (P < 0.001) than men in the 1st quartile (<1.3 g of alcohol/d). After adjustment for a series of coronary risk factors, alcohol consumption >or=15.2 g/d was associated with a 39% reduction in the 13-y risk of IHD [relative risk (RR) of IHD = 0.61, P = 0.02]. Finally, an alcohol consumption <15.2 g/d was associated with an increase of the risk of IHD in men with the metabolic syndrome (RR = 2.24, P < 0.001) but not in men without the metabolic syndrome (RR = 1.31, P = 0.22). These results confirm that moderate daily alcohol consumption has cardioprotective properties and suggest that the effects may be more important in subjects with a deteriorated risk profile, such as those with the metabolic syndrome.

Adult↗
PubMed2006

Pleiotropic QTL on chromosome 12q23-q24 influences triglyceride and high-density lipoprotein cholesterol levels: the HERITAGE family study.

To determine whether a common quantitative trait locus (QTL) influences the variation of fasting triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels, we used a bivariate multipoint linkage analysis with 654 polymorphic markers in 99 white and 101 black families. The phenotypes were investigated under two conditions: at baseline and after a 20-week exercise training intervention. A maximum genome-wide bivariate LOD score of 3.0 (p = 0.00010) was found on chromosome 12q23-q24, located within the IGF1 gene (insulin-like growth factor 1, at 107 cM) for TG and HDL-C at baseline in whites. This bivariate linkage peak is considerably higher than the univariate linkage results at the same chromosome location for either trait (for TG, LOD = 2.07, p = 0.00108; for HDL-C, LOD = 2.04, p = 0.00101). The genetic correlations between baseline TG and HDL-C levels were -0.14 for the residual and -0.33 for the QTL components. Moreover, association analysis showed that TG, HDL-C, and IGF1 are significantly associated (p = 0.04). In conclusion, these results suggest that a QTL on chromosome 12q23-q24 influences the variation of plasma TG and HDL-C levels. Further investigation should confirm whether IGF1 or another nearby gene is responsible for the concomitant variation in TG and HDL-C levels.

Adolescent↗
PubMed2005

Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia.

BACKGROUND: Rimonabant, a selective cannabinoid-1 receptor (CB1) blocker, has been shown to reduce body weight and improve cardiovascular risk factors in obese patients. The Rimonabant in Obesity-Lipids (RIO-Lipids) study examined the effects of rimonabant on metabolic risk factors, including adiponectin levels, in high-risk patients who are overweight or obese and have dyslipidemia. METHODS: We randomly assigned 1036 overweight or obese patients (body-mass index [the weight in kilograms divided by the square of the height in meters], 27 to 40) with untreated dyslipidemia (triglyceride levels >1.69 to 7.90 mmol per liter, or a ratio of cholesterol to high-density lipoprotein [HDL] cholesterol of >4.5 among women and >5 among men) to double-blinded therapy with either placebo or rimonabant at a dose of 5 mg or 20 mg daily for 12 months in addition to a hypocaloric diet. RESULTS: The rates of completion of the study were 62.6 percent, 60.3 percent, and 63.9 percent in the placebo group, the group receiving 5 mg of rimonabant, and the group receiving 20 mg of rimonabant, respectively. The most frequent adverse events resulting in discontinuation of the drug were depression, anxiety, and nausea. As compared with placebo, rimonabant at a dose of 20 mg was associated with a significant (P<0.001) mean weight loss (repeated-measures method, -6.7+/-0.5 kg, and last-observation-carried-forward analyses, -5.4+/-0.4 kg), reduction in waist circumference (repeated-measures method, -5.8+/-0.5 cm, and last-observation-carried-forward analyses, -4.7+/-0.5 cm), increase in HDL cholesterol (repeated-measures method, +10.0+/-1.6 percent, and last-observation-carried-forward analyses, +8.1+/-1.5 percent), and reduction in triglycerides (repeated-measures method, -13.0+/-3.5 percent, and last-observation-carried-forward analyses, -12.4+/-3.2 percent). Rimonabant at a dose of 20 mg also resulted in an increase in plasma adiponectin levels (repeated-measures method, 57.7 percent, and last-observation-carried-forward analyses, 46.2 percent; P<0.001), for a change that was partly independent of weight loss alone. CONCLUSIONS: Selective CB1-receptor blockade with rimonabant significantly reduces body weight and waist circumference and improves the profile of several metabolic risk factors in high-risk patients who are overweight or obese and have an atherogenic dyslipidemia.

Adiponectin↗