Obesity: Després JP

Després JP. · No affiliation provided · BMJ. · Pubmed #11397730 links to  free full text

This publication has no abstract.

Sharma AM, Després JP. · No affiliation provided · J Mol Med. · Pubmed #11327105 No free full text.

This publication has no abstract.

Mathieu P, Poirier P, Pibarot P, Lemieux I, Després JP. · Laval Hospital, 2725 Chemin Ste-Foy, Quebec, Canada. · Hypertension. · Pubmed #19237685 No free full text.

This publication has no abstract.

Després JP. · Québec Heart Institute, Hôpital Laval Research Centre, Pavilion Marguerite-D'Youville, Québec City, QC, Canada. · Curr Pharm Des. · Pubmed #19199981 No free full text.

Abstract: Abdominal obesity (high waist circumference) is more strongly associated with cardiovascular disease and type 2 diabetes than generalized adiposity (high body mass index). Recent research has highlighted the role of chronic overactivation of the endogenous endocannabinoid system, acting through its CB(1) receptor, as a key factor involved in the development of abdominal obesity and related cardiometabolic risk abnormalities such as insulin resistance, low HDL-cholesterol, hypertriglyceridemia, inflammation and low adiponectin. Evidence suggests that these cardiometabolic risk factors/markers are not optimally managed by current treatments. Improving the nutrition and physical activity/exercise habits of patients remains the cornerstone of management of elevated global cardiometabolic risk. Antagonism of the endocannabinoid system provides a novel strategy to target several unaddressed cardiometabolic risk markers/factors. Randomized trials of rimonabant in patients with overweight or obesity and/or type 2 diabetes have demonstrated marked and significant improvements in body weight, waist circumference, glycemic control (in patients with type 2 diabetes), features of atherogenic dyslipidemia, insulin resistance, adipose tissue-derived cytokines (leptin and adiponectin) and C-reactive protein (a marker of systemic inflammation). Further analyses suggested that about half of the improvements of several cardiometabolic risk markers were independent from concomitant weight loss. Blood pressure also improved with rimonabant treatment, this effect being consistent with the blood pressure lowering effect of weight loss. The tolerability and safety of rimonabant have been extensively studied and most transient side effects include some gastrointestinal side effects, anxiety, mood changes and incidence of depressive disorders, particularly in patients with previous history of depression. Rimonabant is a useful option for patients with abdominal obesity and with related cardiometabolic risk abnormalities such as an atherogenic dyslipidemia and/or type 2 diabetes.

Arsenault BJ, Pibarot P, Després JP. · Department of Anatomy and Physiology, Université Laval, Québec, Qué., Canada. · Cardiology. · Pubmed #18971578 No free full text.

Abstract: Global risk calculators such as the Framingham risk score generally take into account traditional risk factors such as age, sex, blood pressure, smoking status, total cholesterol and high-density lipoprotein cholesterol levels, and the presence of diabetes which are recommended to be used in clinical practice to estimate patients' cardiovascular disease (CVD) risk. Over the last decades, the prevalence of obesity has dramatically increased all over the world. The deleterious form of obesity, visceral obesity, is the most prevalent form of the so-called metabolic syndrome, a constellation of risk factors associated with perturbations of the lipoprotein-lipid profile and of the plasma glucose-insulin homeostasis also likely to be associated with increased blood pressure and a proinflammatory and prothrombotic state. To this date, metabolic syndrome is still in need of a place in global CVD risk prediction. As the metabolic syndrome is not likely to replace currently used global risk scoring algorithms, both traditional risk factors and emerging metabolic markers associated with the metabolic syndrome should be incorporated in future risk scoring systems to be developed in order to adapt CVD risk prediction tools to the epidemic of obesity which has direct consequences on the daily life of health professionals.

Després JP, Arsenault BJ, Côté M, Cartier A, Lemieux I. · Québec Heart Institute, Quebec City, Quebec. · Can J Cardiol. · Pubmed #18787730 No free full text.

Abstract: Cardiovascular disease (CVD) is a leading cause of morbidity and death in many countries worldwide. With the help of epidemiological, metabolic and clinical studies conducted over the past decades, the key factors contributing to the development of CVD have been identified. In this regard, several modifiable (hypertension, smoking, elevated cholesterol or low-density lipoprotein-cholesterol concentrations, reduced levels of high-density lipoprotein-cholesterol, type 2 diabetes) and nonmodifiable (age, sex, genetic predisposition) CVD risk factors have been recognized. Although better acute care and chronic pharmacological management have contributed to reduce CVD mortality, CVD morbidity remains very high. It has been proposed that this situation could be the consequence of the evolving landscape of CVD risk factors, which include, among others, poor nutritional habits and a reduction in physical activity contributing to the epidemic of obesity sweeping the world. However, obesity is heterogeneous both in terms of its etiology and its metabolic complications. Body fat distribution, especially visceral adipose tissue accumulation, has been found to be a major correlate of a cluster of diabetogenic and atherogenic abnormalities that has been described as the metabolic syndrome. The importance of abdominal obesity in association with the development of CVD and type 2 diabetes has been recognized in several studies, beyond the contribution of overall obesity. Additional evidence also suggests that the CVD risk related to the hyperglycemic state observed in subjects with the metabolic syndrome or type 2 diabetes is largely explained by the high prevalence of the metabolic complications of abdominal obesity. Although the presence of the metabolic syndrome clearly increases CVD risk, its clinical diagnosis is not sufficient to classify a patient at high risk for a cardiovascular event because attention must also be paid to the presence of traditional risk factors in the calculation of global CVD risk. The additional information provided by the metabolic syndrome to the risk attributed to traditional risk factors in the calculation of global CVD risk has been defined as global cardiometabolic risk. The fight against abdominal obesity as a major cause of CVD morbidity and mortality will require major societal changes and the involvement of dieticians, kinesiologists and behaviour modification specialists in clinical practice to reshape our physical activity and dietary habits. Finally, the early prevention of overweight/obesity/abdominal obesity in children, starting as early as conception, and the identification of key drivers of unhealthy nutritional and sedentary behaviours are the cornerstone of a successful comprehensive plan to fight CVD morbidity.

Després JP, Cartier A, Côté M, Arsenault BJ. · Hôpital Laval Research Centre, Québec, Canada. · Ann Med. · Pubmed #18608131 No free full text.

Abstract: The lack of physical activity and the adoption of poor nutritional habits is the major cause of the obesity epidemic that is currently sweeping the world. The expansion of adipose tissue mass, especially of the visceral adipose tissue depot, is observed in the vast majority of individuals carrying the clinical features of the metabolic syndrome, an important (and reversible) risk factor of type 2 diabetes and cardiovascular disease. As waist circumference can be used as a crude estimate of visceral fat accumulation, its measurement provides further information on cardiovascular and type 2 diabetes risk, at any given body mass index value. However, an elevated waist circumference might also be the result of an increased 'cardioprotective' subcutaneous adipose tissue mass. We have proposed that the measurement of plasma triglycerides along with waist circumference, the so-called 'hypertriglyceridemic waist' might better quantify visceral obesity and its health hazards than waist circumference alone. "Hypertriglyceridemic waist" is thought to represent an altered, dysfunctional, and highly lipolytic adipose tissue that is a major culprit abnormality behind the metabolic syndrome and associated cardiometabolic risk, independently from classical cardiovascular disease risk factors such as age, sex, and plasma low density lipoprotein (LDL) cholesterol levels.

Després JP, Lemieux I, Bergeron J, Pibarot P, Mathieu P, Larose E, Rodés-Cabau J, Bertrand OF, Poirier P. · Hôpital Laval Research Centre, 2725 Chemin Ste-Foy, Pavilion Marguerite-D'Youville, 4th Floor, Québec City, QC G1V4G5, Canada. · Arterioscler Thromb Vasc Biol. · Pubmed #18356555 links to  free full text

Abstract: There is currently substantial confusion between the conceptual definition of the metabolic syndrome and the clinical screening parameters and cut-off values proposed by various organizations (NCEP-ATP III, IDF, WHO, etc) to identify individuals with the metabolic syndrome. Although it is clear that in vivo insulin resistance is a key abnormality associated with an atherogenic, prothrombotic, and inflammatory profile which has been named by some the "metabolic syndrome" or by others "syndrome X" or "insulin resistance syndrome", it is more and more recognized that the most prevalent form of this constellation of metabolic abnormalities linked to insulin resistance is found in patients with abdominal obesity, especially with an excess of intra-abdominal or visceral adipose tissue. We have previously proposed that visceral obesity may represent a clinical intermediate phenotype reflecting the relative inability of subcutaneous adipose tissue to act as a protective metabolic sink for the clearance and storage of the extra energy derived from dietary triglycerides, leading to ectopic fat deposition in visceral adipose depots, skeletal muscle, liver, heart, etc. Thus, visceral obesity may partly be a marker of a dysmetabolic state and partly a cause of the metabolic syndrome. Although waist circumference is a better marker of abdominal fat accumulation than the body mass index, an elevated waistline alone is not sufficient to diagnose visceral obesity and we have proposed that an elevated fasting triglyceride concentration could represent, when waist circumference is increased, a simple clinical marker of excess visceral/ectopic fat. Finally, a clinical diagnosis of visceral obesity, insulin resistance, or of the metabolic syndrome is not sufficient to assess global risk of cardiovascular disease. To achieve this goal, physicians should first pay attention to the classical risk factors while also considering the additional risk resulting from the presence of abdominal obesity and the metabolic syndrome, such global risk being defined as cardiometabolic risk.

Mathieu P, Pibarot P, Larose E, Poirier P, Marette A, Després JP. · Laval Hospital Research Center/Quebec Heart Institute, Department of Surgery, Laval University, 2725 Chemin Ste-Foy, Quebec, Canada, G1V-4G5. · Int J Biochem Cell Biol. · Pubmed #18201922 No free full text.

Abstract: Obesity and particularly its deleterious form, visceral adiposity, has reached a high prevalence in the industrialized world owing to the lack of exercise and the widely available energy-dense diet. As a consequence, cardiovascular diseases and metabolic disorders are afflicting an unprecedented number of individuals at a world-wide scale. Over the last decades, investigations have established firm links between visceral obesity and the development of cardiovascular diseases. Moreover, studies in the field of lipid partitioning have demonstrated that inadequacy of homeostatic mechanism ensuring adequate handling of energy surplus is associated with accumulation of visceral fat and lipid overload of internal organs, which are participating to the development of heart diseases. Visceral obesity and its metabolic consequences often referred to as the metabolic syndrome is associated with the production of an atherosclerosis prone milieu. In this review, clinical implications of visceral obesity on the development of cardiovascular disorders are reviewed along with important mechanisms participating to the development of these disorders. Implications and failure of lipid partitioning and some of the potential pathways mediating development of heart diseases are also covered in view of recent development of therapeutic options.

Ross R, Berentzen T, Bradshaw AJ, Janssen I, Kahn HS, Katzmarzyk PT, Kuk JL, Seidell JC, Snijder MB, Sørensen TI, Després JP. · School of Kinesiology and Health Studies, Queen's University, Kingston, ON, Canada. · Obes Rev. · Pubmed #17956544 No free full text.

Abstract: There is currently no consensus regarding the optimal protocol for measurement of waist circumference (WC), and no scientific rationale is provided for any of the WC protocols recommended by leading health authorities. A panel of experts conducted a systematic review of 120 studies (236 samples) to determine whether measurement protocol influenced the relationship of WC with morbidity of cardiovascular disease (CVD) and diabetes and with mortality from all causes and from CVD. Statistically significant associations with WC were reported for 65% (152) of the samples across all outcomes combined. Common WC protocols performed measurement at the minimal waist (33%), midpoint (26%) and umbilicus (27%). Non-significant associations were reported for 27% (64) of the samples. Most of these protocols measured WC at the midpoint (36%), umbilicus (28%) or minimal waist (25%). Significant associations were observed for 17 of the remaining 20 samples, but these were not significant when adjustment was made for covariates. For these samples, the most common WC protocols were the midpoint (35%) and umbilicus (30%). Similar patterns of association between the outcomes and all WC protocols were observed across sample size, sex, age, race and ethnicity. Our findings suggest that WC measurement protocol has no substantial influence on the association between WC, all-cause and CVD mortality, CVD and diabetes.

Mathieu P, Després JP, Pibarot P. · Laboratoire d'Etudes Moléculaires des Valvulopathies, Groupe de Recherche en Valvulopathies, Laval Hospital Research Center/Quebec Heart Institute, Department of Surgery, Québec, Quebec. · Can J Cardiol. · Pubmed #17932585 No free full text.

Abstract: Calcific aortic stenosis (AS) has been considered a degenerative and unmodifiable process resulting from aging and 'wear and tear' of the aortic valve. Over the past decade, studies in the field of epidemiology, molecular biology and lipid metabolism have highlighted similarities between vascular atherosclerosis and calcific AS. In particular, work from the Quebec Heart Institute and from that of others has documented evidence of valvular infiltration by oxidized low-density lipoproteins and the presence of inflammatory cells, along with important tissue remodelling in valves explanted from patients with AS. Recent studies have also emphasized the role of visceral obesity in the development and progression of AS. In addition, visceral obesity, with its attendant metabolic complications, commonly referred to as the metabolic syndrome, has been associated with degenerative changes in bioprosthetic heart valves. The purpose of the present review is to introduce the concept of 'valvulo-metabolic risk' and to provide an update on the recent and important discoveries regarding the pathogenesis of heart valve diseases in relation to obesity, and to discuss how these novel mechanisms might translate into clinical practice.

Lemieux I, Poirier P, Bergeron J, Alméras N, Lamarche B, Cantin B, Dagenais GR, Després JP. · Hôpital Laval Research Centre, Quebec. · Can J Cardiol. · Pubmed #17932584 No free full text.

Abstract: The worldwide increase in the prevalence and incidence of type 2 diabetes represents a tremendous challenge for the Canadian health care system, especially if we consider that this phenomenon may largely be explained by the epidemic of obesity. However, despite the well-recognized increased morbidity and mortality associated with an elevated body weight, there is now more and more evidence highlighting the importance of intra-abdominal adipose tissue (visceral adipose tissue) as the fat depot conveying the greatest risk of metabolic complications. In this regard, body fat distribution, especially visceral adipose tissue accumulation, has been found to be a key correlate of a cluster of diabetogenic, atherogenic, prothrombotic and inflammatory metabolic abnormalities now often referred to as the metabolic syndrome. This dysmetabolic profile is predictive of a substantially increased risk of coronary artery disease (CAD) even in the absence of hyperglycemia, elevated low-density lipoprotein cholesterol or hypertension. For instance, some features of the metabolic syndrome (hyperinsulinemia, elevated apolipoprotein B and small low-density lipoprotein particles--the so-called atherogenic metabolic triad) have been associated with a more than 20-fold increase in the risk of ischemic heart disease in middle-aged men enrolled in the Quebec Cardiovascular Study. This cluster of metabolic complications has also been found to be predictive of a substantially increased risk of CAD beyond the presence of traditional risk factors. These results emphasize the importance of taking into account in daily clinical practice the presence of metabolic complications associated with abdominal obesity together with traditional risk factors to properly evaluate the cardiovascular risk profile of patients. From a risk assessment standpoint, on the basis of additional work conducted by several groups, there is now evidence that the simultaneous presence of an elevated waist circumference and fasting triglyceride levels (a condition that has been described as hypertriglyceridemic waist) may represent a relevant first-step approach to identify a subgroup of individuals at higher risk of being carriers of the features of the metabolic syndrome. Moreover, a moderate weight loss in initially abdominally obese patients is associated with a selective mobilization of visceral adipose tissue, leading to improvements in the metabolic risk profile predictive of a reduced risk of CAD and type 2 diabetes. In conclusion, hypertriglyceridemic waist as a marker of visceral obesity and related metabolic abnormalities is a useful and practical clinical phenotype to screen persons at risk for CAD and type 2 diabetes.

Després JP. · Québec Heart Institute, Québec, QC, Canada. · Crit Pathw Cardiol. · Pubmed #17667865 No free full text.

Abstract: Diabetes and cardiovascular disease have emerged as major threats to human health, and the risk of developing these chronic conditions is increased in individuals with abdominal obesity and the metabolic syndrome. Excess visceral abdominal tissue (VAT) accumulation appears to be a key feature of abdominal obesity contributing to the development of the metabolic syndrome. For instance, excess VAT is accompanied by elevated triglycerides, reduced high-density lipoprotein (HDL) cholesterol, elevated blood pressure, and/or elevated fasting plasma glucose. In addition, the rather normal or only marginally elevated low-density lipoprotein (LDL) cholesterol concentrations in patients with excess VAT could provide misleading information as viscerally obese patients have an increased plasma concentration of small, dense LDL particles. Prospective studies have suggested that even among patients with LDL cholesterol concentrations within normal limits, an increased concentration of small LDL particles is associated with higher risk of cardiovascular disease. With the treatment of abdominal obesity and excess VAT, an increase in patients' LDL particle size and improvements in other cardiovascular risk factors (eg, insulin levels, glucose tolerance, HDL, C-reactive protein [CRP], and adiponectin levels) can be achieved. Waist circumference can be used in clinical practice as a first approach and as a crude index to identify patients who have excess VAT, particularly when the elevated waistline is accompanied by the clinical features of the metabolic syndrome, among which an elevated fasting triglyceride concentration appears to be predictive of a reduced LDL particle size and of further metabolic abnormalities frequently referred to as the metabolic syndrome. Lifestyle changes, including more physical activity and healthier nutritional habits, are the cornerstone of therapy for high-risk abdominally obese patients with an excess of VAT. In addition, results from the RIO-Lipids study, which was conducted in high-risk obese, dyslipidemic patients, have provided evidence that CB1 receptor blockade with rimonabant can induce significant weight loss, and, more importantly, improve the cardiometabolic risk profile beyond what could be explained by the weight loss effects of the drug.

Després JP. · Québec Heart Institute, Québec QC, Canada. · Crit Pathw Cardiol. · Pubmed #17667864 No free full text.

Abstract: Recent studies have provided evidence that the endocannabinoid (EC) system has very significant effects on energy balance and metabolism through the central control of appetite and by affecting peripheral metabolism. Endocannabinoids are endogenous phospholipid derivatives which bind and activate cannabinoid receptors type 1 and type 2 (CB1 and CB2 receptors). The CB1 receptor, a G-protein coupled receptor, is believed to be responsible for the majority of the central effects of endocannaboids on appetite. Chronic positive energy balance and obesity have been associated with an overactivation of the endocannaboid system which has been suggested to contribute to the development of abdominal obesity and to associated metabolic abnormalities which increase the risk of cardiovascular disease and type 2 diabetes. Animal studies had shown that stimulation of the cannabinoid CB1 receptor with endocannaboids such as anandamide could induce first an increase in food intake leading to body weight gain. Furthermore, an exciting development in this field has been the discovery of CB1 receptors in many peripheral tissues, including key organs involved in carbohydrate and lipid metabolism such as the adipose tissue and liver. Thus, blocking CB1 receptors located in the liver and adipose tissue could have an additional impact on the metabolic risk profile beyond what could be explained by the reduction in food intake and the related body weight loss. Preclinical studies have shown that rimonabant, the first CB1-receptor blocker to be available in clinical practice, could not only induce a reduction in food intake, but could also produce body weight loss beyond what could be explained by its effect on food intake. Thus, the evidence from preclinical studies have suggested that CB1 blockade could represent a relevant approach to reduce food intake, to induce body weight loss, and, most importantly, to "fix" the dysmetabolic state of viscerally obese patients at increased cardiometabolic risk.

Després JP, Lemieux I. · Québec Heart Institute, Hôpital Laval Research Centre, 2725 chemin Sainte-Foy, Pavilion Marguerite-D'Youville, 4th Floor, Quebec City, QC G1V 4G5, Canada. · Nature. · Pubmed #17167477 No free full text.

Abstract: 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.

Scheen AJ, Van Gaal LG, Després JP, Pi-Sunyer X, Golay A, Hanotin C. · Université de Liège, Service de diabétologie, nutrition et maladies métaboliques, CHU Sart Tilman, Liège, Belgique. · Rev Med Suisse. · Pubmed #16972542 No free full text.

Abstract: RIO (Rimonabant In Obesity and related disorders) is a large phase 3 programme (>6600 patients) evaluating the efficacy and safety of rimonabant (5 or 20 mg/day), a CBI receptor antagonist of endocannabinoid system, in obese or overweight patients with or without comorbidities (RIO-Europe and RIO-North America), with untreated dyslipidaemia (RIO-Lipids) or with type 2 diabetes treated with metformin or sulfonylurea (RIO-Diabetes). Compared to placebo, rimonabant 20 mg/day consistently increases weight loss, reduces waist circumference, increases HDL cholesterol, lowers triglyceride levels, diminishes insulin resistance, and reduces the prevalence of metabolic syndrome. Almost half of the metabolic effects, including adiponectin increase, occur beyond weight loss, suggesting a direct peripheral effect of rimonabant.

Després JP. · Québec Heart Institute, Laval Hospital Research Center, Ste-Foy (Québec), Canada. · J Endocrinol Invest. · Pubmed #16751711 No free full text.

Abstract: The prevalence of Type 2 diabetes is showing a rapid progression worldwide, a phenomenon largely resulting from the epidemic proportions reached by obesity in various populations of the world. However, physicians have been puzzled by the heterogeneity of obesity as not every obese patient is characterized by chronic complications. In this regard, body fat distribution, especially intra-abdominal adipose tissue accumulation, has been found to be a key correlate of a cluster of diabetogenic, atherogenic, prothrombotic and inflammatory metabolic abnormalities increasing the risk of Type 2 diabetes and cardiovascular disease. In this regard, it has been recently demonstrated that abdominal obesity was independently associated with an increased risk of coronary heart disease and Type 2 diabetes independently of overall adiposity. Lifestyle modification programs have shown the benefits on cardiometabolic risk variables of a moderate weight loss as it has been found to be associated with a substantial loss of intra-abdominal fat in viscerally obese patients. However, to be successful, such programs require the support of a multidisciplinary team not available to most clinicians. In this context, it is proposed that pharmacotherapy of obesity should target abdominally obese patients at high risk of Type 2 diabetes and cardiovascular disease, such risk being encompassed by the notion of "cardiometabolic risk". The recent discovery of the endocannabinoid-cannabinoid receptor type 1 (CB1 receptor) system and of its impact on the regulation of energy metabolism represents a significant advance which could help physicians to target abdominal obesity and its related metabolic complications. In this regard, studies have shown that rimonabant (the first CB1 blocker developed) therapy could be useful for the management of clustering cardiovascular disease risk factors in high-risk abdominally obese patients through its marked effects on both abdominal adiposity and related metabolic risk factors.

Poirier P, Després JP. · Institut universitaire de cardiologie et de pneumologie, Centre de recherche de I'Hôpital Laval, 2725, chemin Sainte-Foy, Sainte-Foy;-Québec, G1V 4G5, Canada. · Med Sci (Paris). · Pubmed #16598898 No free full text.

Abstract: Available evidence clearly indicates a rapid progression in the prevalence of obesity worldwide. As a consequence, there has also been a marked increase in the prevalence of type 2 diabetes all over the world and this chronic metabolic disease is now considered as a coronary heart disease risk equivalent. However, even in the absence of the hyperglycaemic state which characterizes type 2 diabetic patients, non diabetic individuals with a specific form of obesity, named abdominal obesity, often show clustering metabolic abnormalities which include high triglyceride levels, increased apolipoprotein B, small dense low dendity lipoproteins and decreased high density lipoproteins-cholesterol levels, a hyperinsulinemic-insulin resistant state, alterations in coagulation factors as well as an inflammatory profile. This agglomeration of abnormalities has been referred to as the metabolic syndrome which can be identified by the presence of three of the five following variables: abdominal obesity, elevated triglyceride concentrations, low HDL-cholesterol levels, increased blood pressure and elevated fasting glucose. Post-mortem analyses of coronary arteries have indicated that obesity (associated with a high accumulation of abdominal fat measured at autopsy) was predictive of earlier and greater extent of large vessels atherosclerosis as well as increase of coronary fatty streaks. Metabolic syndrome linked to abdominal obesity is also predictive of recurrent coronary events both in post-myocardial infarction patients and among coronary artery disease men who underwent a revascularization procedures. It is suggested that until the epidemic progression of obesity is stopped and obesity prevented or at least properly managed, cardiologists will be confronted to an evolving contribution of risk factors where smoking, hypercholesterolemia and hypertension may be relatively less prevalent but at the expense of a much greater contribution of abdominal obesity and related features of the metabolic syndrome.

Després JP, Lemieux I, Alméras N. · Québec Heart Institute, Hôpital Laval Research Center, Québec, Québec, Canada. · Int J Obes (Lond). · Pubmed #16570106 No free full text.

Abstract: The worldwide increase in the prevalence of type 2 diabetes represents a tremendous challenge for our healthcare system, especially if we consider that this phenomenon is largely explained by the epidemic of obesity. However, despite the well-recognized increased morbidity and mortality associated with an elevated body weight, there is now more and more evidence highlighting that abdominal adipose tissue is the fat depot that conveys the greatest risk of metabolic complications. This cluster of metabolic abnormalities has been referred to as the metabolic syndrome and this condition is largely the consequence of abdominal obesity, especially when accompanied by a high accumulation of visceral adipose tissue. This cluster of metabolic complications has also been found to be predictive of a substantially increased risk of coronary heart disease beyond the presence of traditional risk factors. Moreover, a moderate weight loss in initially abdominally obese patients is associated with a selective mobilization of visceral adipose tissue, leading to improvements in the metabolic risk profile predictive of a reduced risk of coronary heart disease and of type 2 diabetes. The recent discovery of the endocannabinoid-CB1 receptor system and of its impact on the regulation of energy metabolism represents a significant advance, which will help physicians target abdominal obesity and its related metabolic complications. In this regard, studies have shown that rimonabant therapy (the first developed CB1 blocker) could be useful for the management of clustering cardiovascular disease risk factors in high-risk abdominally obese patients through its effects not only on energy balance but also on adipose tissue metabolism. For instance, the presence of CB1 receptors in adipose tissue and the recently reported effect of rimonabant on adiponectin production by adipose cells may represent a key factor responsible for the weight loss-independent effect of this CB1 blocker on cardiometabolic risk variables.

Després JP. · Québec Heart Institute, Laval Hospital Research Center, Ste-Foy, Québec, Canada. · Ann Med. · Pubmed #16448989 No free full text.

Abstract: 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.

St-Pierre J, Vohl MC, Després JP, Gaudet D, Poirier P. · Dyslipidemia, Diabetes and Atherosclerosis Research Group, Chicoutimi Hospital, Chicoutimi, Quebec. · Can J Cardiol. · Pubmed #15729423 links to  free full text

Abstract: Diabetes mellitus is a source of great concern in contemporary cardiology. It is a heterogeneous disease and patients are often characterized by features of the insulin resistance syndrome, also referred to as the metabolic syndrome. The objectives of the present review were to discuss some genes that potentially modulate the risk of coronary artery disease in diabetes mellitus; to address how the genes' respective contributions could possibly influence the global risk assessment of coronary artery disease among diabetic patients; and to present simple clinical markers, such as plasma glycerol concentration and the 'hypertriglyceridemic waist' phenotype, that could help to identify high-risk individuals.

Després JP, Lemieux I, Robins SJ. · Québec Heart Institute, Laval Hospital Research Center, Québec, Canada. · Drugs. · Pubmed #15456334 No free full text.

Abstract: Although elevated low-density lipoprotein (LDL)-cholesterol is a well established coronary heart disease (CHD) risk factor, the ability to adequately discriminate high-risk individuals by this risk factor alone is limited and other metabolic risk variables are known to modulate CHD risk. For instance, it has been reported that the cluster of metabolic disturbances observed among individuals with abdominal obesity, the so-called metabolic syndrome, is associated with a substantially increased risk of CHD. Among the features of the dyslipidaemic profile observed in these individuals, the high triglyceride-low high-density lipoprotein (HDL)-cholesterol dyslipidaemia is predictive of an elevated risk of CHD. Fibric acid derivatives (fibrates) have been used in clinical practice for more than 2 decades as a class of agents known to decrease triglyceride levels while substantially increasing HDL-cholesterol levels, with a limited but significant additional lowering effect on LDL-cholesterol levels. Although the clinical benefits of HMG-CoA reductase inhibitors (statins) have been well documented by primary and secondary prevention trials that justify their widespread use, it was not until the publication of the VA-HIT (Veterans Affairs High-Density Lipoprotein Intervention Trial) that the relevance of identifying HDL-cholesterol as a therapeutic target to reduce the risk of recurrent CHD events was finally confirmed. The clinical benefits of fibrate therapy are especially important in the subpopulation of patients with low HDL-cholesterol levels with the metabolic syndrome, particularly in patients with type 2 diabetes mellitus or in abdominally obese, hyperinsulinaemic patients. Evidence also suggests that there is a 'fibrate effect' that mediates the reduction in CHD risk beyond the favourable impact of these agents on HDL-cholesterol levels. This last notion is consistent with the pleiotropic effects of fibrates which are known to be related to their mechanisms of action. Through peroxisome proliferator-activated alpha-receptors, fibrates have a significant impact on the synthesis of several apolipoproteins (apo) and enzymes of lipoprotein metabolism as well as on the expression of several genes involved in fibrinolysis and inflammation. Fibrate therapy has been reported to decrease apo CIII levels (a powerful inhibitor of lipoprotein lipase) and increase apo AI levels, as well as to increase lipoprotein lipase activity. Such changes contribute to improve the catabolism of triglyceride-rich lipoproteins, leading to a substantial increase in HDL-cholesterol levels accompanied by a shift in the size and density of LDL particles (from small, dense LDL particles to larger, more buoyant cholesteryl ester-rich LDL). It is proposed that some of these pleiotropic effects could explain some of the clinical benefits of fibrate therapy beyond its HDL-raising properties, particularly among patients with abdominal obesity, hyperinsulinaemia or type 2 diabetes with both low HDL- and low/normal LDL-cholesterol levels.

Després JP. · Québec Heart Institute, Laval Hospital Research Center, and Department of Food Sciences and Nutrition, Laval University, Ste-Foy, Québec, Canada. · Int J Obes Relat Metab Disord. · Pubmed #14704739 No free full text.

This publication has no abstract.

Poirier P, Després JP. · Institut universitaire de cardiologie et de pneumologie, Centre de recherche de l'Hôpital Laval, 2725, chemin Sainte-Foy, Sainte-Foy, Québec, G1V 4G5, Canada. · Med Sci (Paris). · Pubmed #14613004 links to  free full text

Abstract: Available evidence clearly indicates a rapid progression in the prevalence of obesity worldwide. As a consequence, there has also been a marked increase in the prevalence of type 2 diabetes all over the world and this chronic metabolic disease is now considered as a coronary heart disease risk equivalent. However, even in the absence of the hyperglycaemic state which characterizes type 2 diabetic patients, non diabetic individuals with a specific form of obesity, named abdominal obesity, often show clustering metabolic abnormalities which include high triglyceride levels, increased apolipoprotein B, small dense low density lipoproteins and decreased high density lipoproteins-cholesterol levels, a hyperinsulinemic-insulin resistant state, alterations in coagulation factors as well as an inflammatory profile. This agglomeration of abnormalities has been referred to as the metabolic syndrome which can be identified by the presence of three of the five following variables: abdominal obesity, elevated triglyceride concentrations, low HDL-cholesterol levels, increased blood pressure and elevated fasting glucose. Post-mortem analyses of coronary arteries have indicated that obesity (associated with a high accumulation of abdominal fat measured at autopsy) was predictive of earlier and greater extent of large vessels atherosclerosis as well as increase of coronary fatty streaks. Metabolic syndrome linked to abdominal obesity is also predictive of recurrent coronary events both in post-myocardial infarction patients and among coronary artery disease men who underwent a revascularization procedures. It is suggested that until the epidemic progression of obesity is stopped and obesity prevented or at least properly managed, cardiologists will be confronted to an evolving contribution of risk factors where smoking, hypercholesterolemia and hypertension may be relatively less prevalent but at the expense of a much greater contribution of abdominal obesity and related features of the metabolic syndrome.

Després JP. · Québec Heart Institute, Laval Hospital Research Center, Québec Lipid Research Center, CHUL Research Center (CHUQ), and Department of Food Sciences and Nutrition, Laval University, Ste-Foy, Québec, Canada. · Diabetes Metab. · Pubmed #14502101 links to  free full text

Abstract: With an evolving landscape of a growing number of obese and/or type 2 diabetic patients in our affluent population, the metabolic syndrome has become a major issue because of its impact on cardiovascular disease risk. In this regard, although it is appropriate to aim at a better glycaemic control in type 2 diabetic patients, hyperglycaemia does not appear to be the main culprit responsible for the markedly increased cardiovascular disease risk in this population. Rather, studies have suggested that a cluster of metabolic abnormalities, which includes an atherogenic dyslipidaemic state, an impaired glucose/insulin homeostasis, and a pro-thrombotic and inflammatory profile, substantially increases the risk of coronary heart disease in type 2 diabetic patients in a manner which is partly independent of glycaemic control. These results imply that in order to reduce the risk of atherosclerotic macrovascular disease in type 2 diabetic patients, physicians need not only to focus on a better glycaemic control but also to improve the features of the metabolic syndrome. As a consequence, in order to evaluate the clinical benefits of pharmacotherapy in type 2 diabetic patients, we need to quantify the impact of any pharmacological intervention beyond glucose control. In this context, metformin has been shown to not only contribute to a better glycaemic control but also to induce some weight loss (especially in the visceral depot) which may contribute to the improvement of the features of the metabolic syndrome. Thus, metformin treatment may represent a relevant element of an integrated lifestyle modification-pharmacotherapy to prevent not only type 2 diabetes but also cardiovascular disease.