Metabolic Syndrome

1. Metabolic Syndrome Metabolic Syndrome MAJ(P) J. Scott Earwood MAJ(P) J. Scott Earwood

2. Goals • Define Metabolic Syndrome • Emphasize that visceral obesity is an indicator of the syndrome and an independent marker for CVD • Review current and some potential future treatment options

3. An estimated 47 million people have metabolic syndrome in the U.S. NHANES III 1988-94, JAMA 2002

4. ATP III Clinical Identification of the Metabolic Syndrome • Waist circumference: • Men>102 cm (>40 in) • Women>88 cm (>35 in) • Triglycerides >150 mg/dL • HDL cholesterol:  • Men<40 mg/dL   • Women<50 mg/dL • Blood pressure 130/ 85 mm Hg • Fasting glucose >110 mg/dL* * New ADA guidelines suggest >100mg/dl increases risk for Metabolic Syndrome

5. International Diabetes Federation (IDF) Definition • Modified ATPIII definition • Fasting Glucose > 100mg/dl • Adjusted waist circumference based on ethnicity (i.e. asians with lower waist circumference threshold than pacific islanders)

6. Lahey Clinic Study--50-60% of Pt’s <45yo who suffered MI had Metabolic Syndrome, a mean BMI of approximately 32, and relatively normal LDL(The Framingham Risk scores of these patients is typically very low—because age is low)

7. Obesity is a Cardiovascular Risk Factor: • Linear Increase in Risk for Cardiovascular Disease with increase in BMI from 25 to 35 (unrelated to HDL, and LDL)

8. Specifically, Visceral Obesity • Elevated waist circumference • TG<150 probably normal metabolic risk (CVD) • TG≥150 excess visceral fat and increased risk (CVD) • Waist-to-Hip ratio (peripheral fat, protective) • No specific measurement (hip circumference>Waist circumference)

9. Look at your patient’s shape

10. Other Indicators of Metabolic Syndrome and CV Risk • CRP • Borderline LDL

11. EBM Recommendations • Any person at high risk or moderately high risk who has lifestyle-related risk factors (e.g., obesity, physical inactivity, elevated triglyceride, low HDL-C, or metabolic syndrome) is a candidate for therapeutic lifestyle changes to modify these risk factors regardless of LDL-C level.

12. EBM Recommendations (cont.) • There is some evidence that insulin sensitizing agents such as metformin are effective in treating features of metabolic syndrome.

13. Current Treatments • Weight reduction • TLC: Diet and Exercise • Lower BP goals • Lower LDL goals • Statins • Metformin • Aspirin therapy

14. Possible New Markers • Adiponectin (cytokine released from peripheral adipose tissue) low levels associated with increased risk for MI

15. Possible New Therapies • Endocannabinoid system • Phospholipid derivatives over-produced in obese patients • CB1 receptor

16. Possible New Therapies (Cont.) • CB1 receptors—animal studies • Hypothalamus—regulates energy metabolism • Liver—lipogenesis • Adipose tissues • Lipogenesis • Fat accumulation • Inhibition of adiponectin

17. Placebo group ↓ weight 2kg 4kg ↓ Abdominal circumference 2.5cm 4.5cm ↑ HDL-C 15% CB1 receptor blocker ↓ weight 8kg ↓ Abdominal circumference 9cm ↑ HDL-C 25% ↓ CRP 27% ↑ Adiponectin 46% Possible New Therapies (Cont.)RIO-LIPID trial (2005 NEJM)

18. Summary • The definition for metabolic syndrome is straight forward • We see these patients every day in our practices • Weight reduction is the key to preventing CVD • There are some new exciting treatments on the horizon

19. Question?

20. References • Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). (2)Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. • International Diabetes Federation • Insulin-sensitising drugs, The Cochrane Database of Systematic Reviews Date of last Substantial Update: December 31. 2002 • Effects of Rimonabant on Metabolic Risk Factors in Overweight Patients with Dyslipidemia, NEJM. Nov 2005