CARDIOMETABOLIC SYNDROME

1. Cardio-metabolic Syndrome HOSSAM ATEF ASSOCIATE PROFESSOR OF ANESTHESIA & ICU

2. Clustering of Components: • Hypertension: BP. > 140/90 • Dyslipidemia: TG > 150 mg/ dL ( 1.7 mmol/L ) HDL- C < 35 mg/ dL (0.9 mmol/L) • Obesity (central): BMI > 30 kg/M2 Waist girth > 94 cm (37 inch) Waist/Hip ratio > 0.9 • Impaired Glucose Handling: IR , IGT or DM FPG > 110 mg/dL (6.1mmol/L) 2hr.PG >200 mg/dL(11.1mmol/L) • Microalbuninuria (WHO)

3. Global cardiometabolic risk*

4. International Diabetes Federation (IDF) Consensus Definition 2005 The new IDF definition focusses on abdominal obesity rather than insulin resistance

5. Why a New Definition of the MeS: IDF Objectives Needs: • To identify individuals at high risk of developing cardiovascular disease (and diabetes) • To be useful for clinicians • To be useful for international comparisons

6. Fat Topography In Type 2 Diabetic Subjects FFA* TNF-alpha* Leptin* IL-6 (CRP)* Tissue Factor* PAI-1* Angiotensinogen* Intramuscular Subcutaneous Intrahepatic Intra- abdominal

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. Abdominal obesity and increased risk of cardiovascular events The HOPE study Men Women Tertile 1 <95 <87 Waistcircumference (cm): Tertile 2 95–103 87–98 Tertile 3 >103 >98 1.4 1.35 1.29 1.27 1.17 1.2 1.16 1.14 Adjusted relative risk 1 1 1 1 0.8 CVD death MI All-cause deaths

9. Abdominal obesity increases the risk of developing type 2 diabetes 24 20 16 12 Relative risk 8 4 0 <71 71–75.9 76–81 81.1–86 86.1–91 91.1–96.3 >96.3 Waist circumference (cm)

10. 3.0 2.44 p for trend = 0.007 2.31 2.5 2.06 2.0 Relative risk 1.5 1.27 1.0 0.5 0.0 <69.8 69.8<74.2 74.2<79.2 79.2<86.3 86.3<139.7 Quintiles of waist circumference (cm) Abdominal obesity is linked to an increased risk of coronary heart disease Waist circumference has been shown to be independently associated with increased age-adjusted risk of CHD, even after adjusting for BMI and other cardiovascular risk factors

11. Diabetes in the new millenniumInterdisciplinary problem Diabetes

12. Diabetes in the new millenniumInterdisciplinary problem OBESITY

13. Diabetes in the new millenniumInterdisciplinary problem DIAB ESITY

14. Look at your patient’s shape

15. Targeting Cardiometabolic Risk

16. Insulin Resistance: Associated Conditions

17. Linked Metabolic Abnormalities: • Impaired glucose handling/ insulin resistance • Atherogenic dyslipidemia • Endothelial dysfunction • Prothrombotic state • Hemodynamic changes • Proinflammatory state • Excess ovarian testosterone production • Sleep-disordered breathing

18. Resulting Clinical Conditions: • Type 2 diabetes • Essential hypertension • Polycystic ovary syndrome (PCOS) • Nonalcoholic fatty liver disease • Sleep apnea • Cardiovascular Disease (MI, PVD, Stroke) • Cancer (Breast, Prostate, Colorectal, Liver)

19. Multiple Risk Factor Management • Obesity • Glucose Intolerance • Insulin Resistance • Lipid Disorders • Hypertension • Goals: Minimize Risk of Type 2 Diabetes and Cardiovascular Disease

20. Glucose Abnormalities: • IDF: • FPG >100 mg/dL (5.6 mmol. L) or previously diagnosed type 2 diabetes • (ADA: FBS >100 mg/dL [ 5.6 mmol/L ])

21. Hypertension: • IDF: • BP >130/85 or on Rx for previously diagnosed hypertension

22. Dyslipidemia: • IDF: • Triglycerides - >150mg/dL (1.7 mmol /L) • HDL - <40 mg/dL (men), <50 mg/dL (women)

23. EBM Recommendations • Any person at 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

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

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

26. Screening/Public Health Approach • Public Education • Screening for at risk individuals: • Blood Sugar/ HbA1c • Lipids • Blood pressure • Tobacco use • Body habitus • Family history

27. Life-Style Modification: Is it Important? • Exercise • Improves CV fitness, weight control, sensitivity to insulin, reduces incidence of diabetes • Weight loss • Improves lipids, insulin sensitivity, BP levels, reduces incidence of diabetes • Goals: Brisk walking - 30 min./day 10% reduction in body wt.

28. Smoking Cessation / Avoidance: • A risk factor for development in children and adults • Both passive and active exposure harmful • A majorrisk factorfor: • insulin resistance and metabolic syndrome • macrovascular disease (PVD, MI, Stroke) • microvascular complications of diabetes • pulmonary disease, etc.

29. Diabetes Control - How Important? Goals: • FBS - premeal <110, • postmeal<180. • HbA1c <7% • For every 1% rise in Hb A1c there is an 18% rise in risk of cardiovascular events & a 28% increase in peripheral arterial disease • Evidence is accumulating to show that tight blood sugar control in both Type 1 and Type 2 diabetes reduces risk of CVD

30. Lifestyle modification Diet Exercise Weight loss Smoking cessation If a 1% reduction in HbA1c is achieved, you could expect a reduction in risk of: 21% for any diabetes-related endpoint 37% for microvascular complications 14% for myocardial infarction However, compliance is poor and most patients will require oral pharmacotherapy within a few years of diagnosis

31. BP Control - How Important? • Goal:BP.<130/80 • Conclusively proved the increased risk of CVD with long-term sustained hypertension • Demonstrated a 10 year risk of cardiovascular disease in treated patients vs non-treated patients to be 0.40. • 40% reduction in stroke with control of HTN • Precedes literature on Metabolic Syndrome

32. Lipid Control - How Important? • Goals:HDL >40 mg% (>1.1 mmol /l) LDL <100 mg/dL (<3.0 mmol /l) TG <150 mg% (<1.7 mmol /l) • Multiple major studies show 24 - 37% reductions in cardiovascular disease risk with use of statins and fibrates in the control of hyperlipidemia.

33. Medications: • Hypertension: • ACE inhibitors, ARBs • Others - thiazides, calcium channel blockers, beta blockers, alpha blockers • Dylipidemia: • Statins, Fibrates • Platelet inhibitors:ASA, clopidogrel

34. A Critical Look at the Metabolic Syndrome Is it a Syndrome?* • “…too much clinically important information is missing to warrant its designations as a syndrome.” • Unclear pathogenesis, Insulin resistance is not a consistent finding in some definitions. • CVD risks has not shown to be greater than the sum of it’s individual components. *ADA

35. A Critical Look at the Metabolic Syndrome Research • “Until much needed research is completed, clinicians should evaluate and treat all CVD risk factors without regard to whether a patient meets the criteria for diagnosis of the ‘metabolicsyndrome’.”

36. A Critical Look at the Metabolic Syndrome Lifestyle • The advice remains to treat individual risk factors when present & to prescribe therapeutic lifestyle changes & weight management for obese patients with multiple risk factors.

37. Central obesity: a driving force for cardiovascular disease & diabetes “Balzac” by Rodin Front Back

39. International Diabetes Federation (IDF) Consensus Definition 2005

40. Stop smoking Oral hypoglycaemics ACEI &/or A2 receptor blockers Diet, Exercise, Lifestyle change Aspirin Insulin CB1 Receptor Blocker Statins & Fibrates Antihypertensives Treatment of Metabolic Syndrome: 2005

41. Recommendations for treatment Primary management for the Metabolic Syndrome is healthy lifestyle promotion. This includes: • moderate calorie restriction (to achieve a 5-10% loss of body weight in the first year) • moderate increases in physical activity • change dietary composition to reduce saturated fat and total intake, increase fibre and, if appropriate, reduce salt intake.

42. Management of the Metabolic Syndrome • Appropriate & aggressive therapy is essentialfor reducing patient risk of cardiovascular disease • Lifestyle measures should be the first action • Pharmacotherapy should have beneficial effects on • Glucose intolerance/diabetes • Obesity • Hypertension • Dyslipidaemia • Ideally, treatment should address all of the components of the syndrome and not the individual components

44. Thank You