1. Contemporary Management of Cardiometabolic Risk

2. A continuing epidemic: 2 of 3 US adults are overweight or obese National Health and Nutrition Examination Surveys 1999-2004 US adults ≥20 years of age Ogden CL et al. JAMA. 2006;295:1549-55. Year of survey Overweight = BMI 25-29.9 kg/m 2 Obesity = BMI ≥30 kg/m 2

3. CDC. www.cdc.gov. Parallel epidemics of diabetes and obesity Diabetes Obesity (BMI ≥30 kg/m 2 ) <4%4%-4.9%5%-5.9%≥6% 10%-14%15%-19%20%-24%≥25% 20041994

4. Defining cardiometabolic risk Eckel RH et al. Circulation. 2006;113:2943-6. AdiposityDysglycemia Hypertension Dyslipidemia Risk factors linked to cardiovascular disease (CVD) and diabetes Cardiometabolic risk factors

5. Associations of adiposity with CVD Matsuzawa Y. Nat Clin Pract Cardiovasc Med. 2006;3:35-42. Insulin resistanceDysglycemia Left ventricular dysfunction HypertensionCAD Sleep apnea syndrome Dyslipidemia White = visceral fat area (VFA) Black = subcutaneous (sc) fat

6. Adiposity predicts mortality Adams KF et al. New Engl J Med. 2006;355:763-78. Relative risk of death All men (n = 313,047; 42,173 deaths) All women (n = 214,218; 19,144 deaths) 2.0 1.5 1.0 0 0202530354045 Current BMI (kg/m 2 ) 3.0 2.5

7. Adiposity associated with premature MI Suwaidi JA et al. Clin Cardiol. 2001;24:542-7. N = 906 consecutive patients with AMI Age at presentation with AMI (years) <25 (n = 306) 25-30 (n = 362) >30 (n = 238) BMI (kg/m 2 ) 72.9 66.9 62.3 55 60 65 70 75 10.6 years earlier occurrence of MI

8. Majority of patients undergoing PCI are overweight or obese Gruberg L et al. J Am Coll Cardiol. 2002;39:578-84. N = 9633 BMI <25 kg/m 2 (n = 1923) BMI ≥25 kg/m 2 (n = 7710)

9. Adverse consequences of chronic adiposity and ectopic fat Altered FFA metabolism Altered release of adipokines Adapted from Després J-P, Lemieux I. Nature. 2006;444:881-7. Molavi B et al. Curr Opin Cardiol. 2006;21:479-85.  Cardiac function  Insulin sensitivity Dyslipidemia  β-cell function Atherosclerosis NASH  Muscle fat (  Intracellular lipid)  Epicardial fat  Liver fat and altered function Lipid overflow ectopic fat FFA = free fatty acids NASH = nonalcoholic steatohepatitis

10. Epicardial adipose tissue may be increased in visceral obesity Patient with visceral obesity Patient with peripheral obesity Hypertension Diabetes Dyslipidemia No metabolic complications Iacobellis G et al. Clin Cardiol. 2003;26:237.

11. Adiposity in the development of NASH Adapted from Ahima RS. Gastroenterology. 2007;132:444-6. Angulo P. N Engl J Med. 2002;346:1221-31. Adipose Insulin Leptin Adiponectin Fatty acids Liver NormalSteatosis (fatty liver) Steatohepatitis (steatosis and inflammation) Fibrosis (collagen deposition)

12. Visceral vs subcutaneous adiposity CT scans matched for BMI and total body fat Després J-P. Eur Heart J Suppl. 2006;8(suppl B):B4-12. Subcutaneous (sc) obesity Fat mass: 19.8 kg VFA: 96 cm 2 Visceral obesity Fat mass: 19.8 kg VFA: 155 cm 2 White = VFA Black = sc fat

13. Neutral effect of liposuction on cardiometabolic risk factors No significant change at 10-12 weeks BP Plasma glucose Plasma insulin Total-C, LDL-C, HDL-C, TG Adiponectin TNF-α IL-6 CRP Klein S et al. N Engl J Med. 2004;350:2549-57. Post- liposuction Pre- liposuction Magnetic resonance images sc fat

14. Central adiposity: Better marker of CVD than BMI BMI, WHR, WC tertiles Dagenais GR et al. Am Heart J. 2005;149:54-60. N = 8802 HOPE Study participants P = 0.14P = 0.003P = 0.0127 0 0.5 1 1.5 BMI (kg/m 2 ) WHRWC (cm) Adjusted RR of CVD death First Second Third WC = waist circumference WHR = waist/hip ratio

15. A new vital sign: Waist circumference Adapted from Després J-P et al. BMJ. 2001;322:716-20. RISK Abdominal adiposity Coronary heart disease DyslipidemiaHypertension Dysglycemia

16. Continued burden of disease Central adiposity, hypertension, dyslipidemia, and dysglycemia drive “cardiometabolic risk” Cardiometabolic risk is associated with substantial cardiovascular morbidity and mortality The ongoing epidemic of adiposity mandates evaluation of new approaches for managing cardiometabolic risk