1. Managing Cardiometabolic Risk Lifestyle modification and weight reduction strategies

2. NHLBI guidelines: Adiposity assessment Use BMI to assess body fat –Body weight alone can be used to track weight loss, and to determine efficacy of therapy (Evidence Category C) Use BMI to classify overweight/obesity –Estimate relative risk of disease compared to normal weight (Evidence Category C) Use waist circumference to assess abdominal fat content (Evidence Category C) NHLBI. www.nhlbi.nih.gov.

3. BMI classifications BMI (kg/m 2 ) Underweight<18.5 Normal weight18.5-24.9 Overweight25-29.9 Class 1 obesity30-34.9 Class 2 obesity35-39.9 Class 3 (extreme) obesity≥40 NHLBI. www.nhlbi.nih.gov.

4. Measuring waist circumference Locate upper hip bone and top of right iliac crest Place measuring tape horizontally around abdomen at level of iliac crest Tape should be snug without causing compression NHLBI. www.nhlbi.nih.gov. Iliac crest

5. Hypertension Dyslipidemia BP ≥130/85 mm Hg HDL-C <40 mg/dL (men) HDL-C <50 mg/dL (women) TG ≥150 mg/dL Diagnostic criteria for metabolic syndrome Grundy SM. J Am Coll Cardiol. 2006;47:1093-100. Adiposity Dysglycemia WC (men) ≥35 (Asian) ≥40 (other ethnicities) WC (women) ≥31 (Asian) ≥35 (other ethnicities) FG ≥100 mg/dL WC = waist circumference (inches) Any 3 criteria

6. NHLBI guidelines: Weight loss goals Goal is ~10% reduction from baseline weight (Evidence Category A) If successful, assess continued weight loss (Evidence Category A) Aim for weight loss ~1–2 lb/week for 6 months –Base subsequent strategies on the amount of weight lost (Evidence Category B) NHLBI. www.nhlbi.nih.gov.

7. Guide to adiposity management BMI category (kg/m 2 ) Strategy25.0-26.927.0-29.930.0-34.935.0-39.9≥40 Diet Physical activity Behavior therapy  With comorbidities  Pharmacotherapy  With comorbidities  Surgery  With comorbidities  NHLBI. www.nhlbi.nih.gov. Lee M, Aronne LJ. Am J Cardiol. 2007;99(suppl):68B-79B.

8. NHLBI guidelines: Lifestyle modification Combined intervention of a calorie-deficit diet,  physical activity, and behavioral treatment is most successful for weight loss and maintenance (Evidence Category A) –500-1000 kcal/day deficit –Moderate physical activity 30-45 min, 3-5 days/week, with eventual goal of ≥30 min on most (and preferably all) days of the week Maintain for ≥6 months before considering pharmacotherapy NHLBI. www.nhlbi.nih.gov.

9. Some moderate-intensity physical activities Daily lifeSports Washing car, 45–60 minWalking 3 mph, 35 minLess vigorous Washing windows or floors, 45–60 min Bicycling 10 mph, 30 min Gardening, 30–45 minDancing, 30 min Raking leaves, 30 minWater aerobics, 30 min Swimming, 20 min Jogging 1 mile, 15 min More vigorous Moderate activity  150 calories of energy per day NHLBI. www.nhlbi.nih.gov.

10. 3-Week diet + exercise regimen yields favorable metabolic changes *P < 0.01 † P < 0.05 Roberts CK et al. J Appl Physiol. 2006;100:1657-65. μU/mL N = 31 overweight/obese men; weight  8.4 lbs Baseline Follow-up

11. Physical activity may reduce CV and all-cause mortality Fang J et al. Am J Hypertens. 2005;18:751-8. N = 9791; moderate physical activity vs little or no physical activity 0.75 (0.53–1.05) 0.76 (0.39–1.49) 0.79 (0.65–0.97) All-cause death CV death All-cause death Prehypertension CV death Hypertension Hazard ratio 1.51.00.5 Normal BP 0 2.0 All-cause death CV death 0.79 (0.58–1.09) 0.88 (0.80–0.98) 0.84 (0.73–0.97) Adjusted HR (95% CI) Favors exercise Favors no exercise NHANES 1 Epidemiological Follow-up Survey (1971–1992)

12. Lifestyle modification associated with diabetes prevention Yamaoka K, Tango T. Diabetes Care. 2005;28:2780-6. Meta-analysis of 5 randomized, controlled trials Pan et al, 1997 Wein et al, 1999 Tuomilehto et al, 2001 DPPRG, 2002 Watanabe et al, 2003 Combined: Fixed Combined: Random Combined: Bayesian Relative risk (95% CI) 0.10.51.05.010.0

13. *vs placebo (unadjusted) † Achieve/maintain ≥7% reduction of initial body weight via diet + moderate-intensity physical activity ≥150 minutes/week DPP: Benefit of diet + exercise or metformin on diabetes prevention in at-risk patients DPP Research Group. N Engl J Med. 2002;346:393-403. Year N = 3234 with IFG and IGT without diabetes 0 0 10 20 30 40 1234 Placebo Metformin Lifestyle † Cumulative incidence of diabetes (%)  31%  58% P* <0.001

14. Popular dietary programs: Effective yet difficult to maintain N = 160 overweight or obese with ≥1 CV risk factor Dansinger ML et al. JAMA. 2005;293:43-53.

15. Look AHEAD: Study design Usual medical care + lifestyle intervention* for 4 years, with maintenance counseling thereafter *≥7% mean weight loss with hypocaloric diet ± pharmacologic therapy + ≥175 min/week moderate physical activity Diet = 1200-1500 kcal/day (<250 lbs) or 1500-1800 kcal/day (≥250 lbs) Primary endpoint: CV death, nonfatal MI, nonfatal stroke Look AHEAD Research Group. Control Clin Trials. 2003;24:610-28; Obesity. 2006;14:737-52. Look Action for Health in Diabetes N = 5145 45-74 years with T2DM, BMI ≥25 kg/m 2 (≥27 kg/m 2 if taking insulin) Usual medical care + diabetes support and education for 4 years Total follow-up 11.5 years

16. NHLBI guidelines: Pharmacologic therapy FDA-approved drugs may be used as part of a comprehensive weight-loss program, including dietary therapy and physical activity (Evidence Category B) in these individuals: –BMI ≥30 kg/m 2 with no concomitant risk factors or diseases –BMI ≥27 kg/m 2 with concomitant risk factors or diseases (hypertension, dyslipidemia, CHD, T2DM, sleep apnea) Herbal preparations are not recommended. These preparations have unpredictable amounts of active ingredients and unpredictable, and potentially harmful, effects. NHLBI. www.nhlbi.nih.gov.

17. Pharmacologic weight management options Orlistat*Sibutramine Mechanism of actionInhibits fat absorption Inhibits NE and serotonin reuptake Mean weight loss 1 yr † 6.4 lbs9.9 lbs Pooled data22 trials5 trials Adverse eventsGI discomfort  BP  Heart rate *Available Rx and OTC (1/2 dose) † Placebo-corrected NE = norepinephrine Arterburn DE et al. Arch Intern Med. 2004;164:994-1003. Li Z et al. Ann Intern Med. 2005;142:532-46.

18. Efficacy of orlistat as adjunct to lifestyle modification N = 3305, mean BMI 37 kg/m 2 All subjects prescribed a reduced-calorie diet (~800 kcal/day deficit) and encouraged to  physical activity Torgerson JS et al. Diabetes Care. 2004;27:155-61. P < 0.001 Δ Body weight (kg) Weeks 052156208 -12 -9 -6 -3 0 Placebo + lifestyleOrlistat + lifestyle 104 -3.0 kg -5.8 kg

19. Efficacy of sibutramine as adjunct to lifestyle modification Wadden TA et al. N Engl J Med. 2005;353:2111-20. All subjects prescribed balanced 1200-1500 kcal/day diet and encouraged to walk 30 min/day N = 224 with obesity, mean BMI 38 kg/m 2 Weight loss (kg) Sibutramine alone Lifestyle modification alone Sibutramine + brief therapy Combined therapy Weeks 03610184052 16 14 12 10 8 6 4 2 0

20. Effects of sibutramine and lifestyle modification on cardiometabolic risk factors Sibutramine alone Lifestyle modification aloneCombined Total-C (mg/dL)  3.4  2.7  7.9 LDL-C (mg/dL)  2.2  1.0  4.6 HDL-C (mg/dL)  0.9  0.8  2.7 TG (mg/dL)  12.0  31.6  33.9 Glucose (mg/dL)  0.6  4.2  3.0 Insulin (  U/mL)  0.5  4.3  6.2 HOMA-IR  0.3  1.1  1.5 Wadden TA et al. N Engl J Med. 2005;353:2111-20. Change from baseline at 1 year

21. SCOUT: Study design 6-week single-blind lead-in Sibutramine 10 mg + lifestyle intervention* Sibutramine 10–15 mg + lifestyle intervention* *Hypocaloric diet (-600 kcal/day) + ≥150 min/week moderate physical activity Primary endpoint: MI, stroke, resuscitated cardiac arrest, CV death James WPT. Eur Heart J Suppl. 2005;7(suppl L):L44-8. Sibutramine Cardiovascular OUtcome Trial N  9000 ≥55 years with BMI 27–45 kg/m 2 (or 25 to <27 kg/m 2 + waist ≥40" men, ≥35" women) + History of CV event (or T2DM + 1 other CV risk factor) Placebo + lifestyle intervention* 3-year randomized, double-blind phase

22. NHLBI guidelines: Weight loss surgery An option for carefully selected patients when less- invasive methods have failed and the patient is at high risk for obesity-associated morbidity or mortality (Evidence Category B) –BMI ≥40 kg/m 2 –BMI ≥35 kg/m 2 with comorbid conditions NHLBI. www.nhlbi.nih.gov.

23. SOS: Bariatric surgery-associated improvements in cardiometabolic risk Sjöström L et al. N Engl J Med. 2004;351:2683-93. Conventional treatment (n = 1660) Gastric surgery (n = 1845) *At 2 years Swedish Obese Subjects (SOS) Study, N = 4047, mean BMI 41 kg/m 2

24. Improved Framingham risk score following bariatric surgery Vogel JA et al. Am J Cardiol. 2007;99:222-6. N = 109, mean BMI 49 kg/m 2 (preoperative), 36 kg/m 2 (13-month follow-up) 10-year CHD risk (%) 2 4 6 8 10 12 MenWomen P < 0.0001 P = 0.002 Before surgeryAfter surgery