Core Curriculum

• Contemporary Management of Cardiometabolic Risk

VBWG_07_CMCR.pdf (2.6MB)VBWG_07_CMCR.pdf (2.6MB)

Contemporary Management of Cardiometabolic Risk

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Contemporary Management of Cardiometabolic Risk A continuing epidemic: 2 of 3 US adults are overweight or obese Parallel epidemics of diabetes and obesity Defining cardiometabolic risk Associations of adiposity with CVD Adiposity predicts mortality Adiposity associated with premature MI Majority of patients undergoing PCI are overweight or obese Adverse consequences of chronic adiposity and ectopic fat Epicardial adipose tissue may be increased in visceral obesity Adiposity in the development of NASH Visceral vs subcutaneous adiposity Neutral effect of liposuction on cardiometabolic risk factors Central adiposity: Better marker of CVD than BMI A new vital sign: Waist circumference Continued burden of disease

Adiposity in CVD

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Adiposity in CVD Role of adipose tissue in atherogenesis Elevated FFA contribute to hypertension, dyslipidemia, and insulin resistance Energy homeostasis is linked to immune balance Weight gain induces inflammatory changes in adipose tissue Adipose tissue: An endocrine organ Adiponectin associated with decreased risk of MI Beneficial associations of adiponectin Low adiponectin in visceral adiposity Even moderate weight loss may improve cardiometabolic risk Summary

The Endocannabinoid System

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The EndocannabinoidSystem Cannabinoid classification with selected examples ECS: Widely distributed with multiple cardiometabolic effects Potential therapeutic implications of CB1 receptor blockade Circulating 2-AG elevated in persons with visceral vs sc adiposity CB1 receptor blockade blunts overeating in rats CB1 receptor blockade: Weight reduction independent of food intake in obese mice CB1 receptor blockade modulates adipocyte function in mice CB1 receptors modulate liver lipogenesis in mice CB1 receptor blockade increases skeletal muscle glucose uptake in obese mice CB1 receptor blockade and mood: Range of effects observed in animal models Endocannabinoid system overview

Managing Cardiometabolic Risk

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Managing Cardiometabolic Risk NHLBI guidelines: Adiposity assessment BMI classifications Measuring waist circumference Diagnostic criteria for metabolic syndrome NHLBI guidelines: Weight loss goals Guide to adiposity management NHLBI guidelines: Lifestyle modification Some moderate-intensity physical activities 3-Week diet + exercise regimen yields favorable metabolic changes Physical activity may reduce CV and all-cause mortality Lifestyle modification associated with diabetes prevention DPP: Benefit of diet + exercise or metformin on diabetes prevention in at-risk patients Popular dietary programs: Effective yet difficult to maintain Look AHEAD: Study design NHLBI guidelines: Pharmacologic therapy Pharmacologic weight management options Efficacy of orlistat as adjunct to lifestyle modification Efficacy of sibutramine as adjunct to lifestyle modification Effects of sibutramine and lifestyle modification on cardiometabolic risk factors SCOUT: Study design NHLBI guidelines: Weight loss surgery SOS: Bariatric surgery-associated improvements in cardiometabolic risk Improved Framingham risk score following bariatric surgery

Clinical evaluation of CB1 receptor blockade

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Clinical evaluation of CB1 receptor blockade Rimonabant In Obesity (RIO) program RIO program: Improved cardiometabolic risk factors at 1 year RIO program: Decreased metabolic syndrome incidence RIO program: Safety and tolerability RIO program: No significant effect on mood RIO program: Mood at 1 year RIO clinical trial program efficacy summary SERENADE: Study design SERENADE: Change in A1C at 6 months Summary Ongoing trials with rimonabant in abdominal adiposity Current and emerging pharmacologic combinations for treating cardiometabolic risk Managing cardiometabolic risk

Data Supplement

Download VBWG_07_CMCR_Sec6.ppt (28 slides - 1.0MB)

Data Supplement RIO-Europe: Study design RIO-Europe: Treatment effect on weight and waist circumference RIO-Europe: Treatment effect on lipids RIO-Europe: Adverse events RIO-Lipids: Study design RIO-Lipids: Treatment effect on weight and WC RIO-Lipids: Treatment effect on lipids RIO-Lipids: Rimonabant weight-independent effect on adiponectin RIO-Lipids: Adverse events RIO-Diabetes: Study design RIO-Diabetes: Treatment effect on weight and waist circumference RIO-Diabetes: Treatment effect on lipids RIO-Diabetes: Treatment effect on glucose metabolism RIO-Diabetes: Adverse events RIO-North America: Study design RIO-North America: Weight change by treatment assignment RIO-North America: Waist circumference by treatment assignment RIO-North America: Treatment effect on lipids at 1 year RIO-North America: Weight-independent and weight-dependent effects on lipids RIO-North America: Weight-independent and weight-dependent effects on insulin and IR RIO-North America: Adverse events RIO-North America: Adverse events, cont’d Obesity program* depression-related events: Overall incidences Completed phase 2 and 3 studies* as of March 2007: All suicidality-related events Rimonabant clinical safety: Summary ACOMPLIA: European product information ACOMPLIA: European product information, cont’d
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