Cardiometabolic Syndrome Nabil Sulaiman Dr. Dhafir A. Mahmood

1. Cardiometabolic Syndrome Nabil Sulaiman Dr. Dhafir A. Mahmood

2. Cardiometabolic Syndrome Nabil Sulaiman HOD Family and Community Medicine, Sharjah University and University of Melbourne Dr. Dhafir A. Mahmood Consultant Endocrinologist Al- Qassimi & Al-Kuwait Hospital Sharjah

3. Cardiometabolic Syndrome II Aims • Abdominal obesity prevalence • Targeting Cardiometabolic Risk factors • Multiple Risk Factor management • A Critical Look at the Metabolic Syndrome

4. 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)

5. Global cardiometabolic risk* Gelfand EV et al, 2006; Vasudevan AR et al, 2005 * working definition

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

7. 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

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

9. 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 Adjusted for BMI, age, smoking, sex, CVD disease, DM, HDL-cholesterol, total-C; CVD: cardiovascular disease; MI: myocardial infarction; BMI: body mass index; DM: diabetes mellitus; HDL: high-density lipoprotein cholesterol Dagenais GR et al, 2005

10. 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) Carey VJ et al, 1997

11. 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 CHD: coronary heart disease; BMI: body mass index Rexrode KM et al, 1998

12. Diabetes in the new millenniumInterdisciplinary problem Diabetes

13. Diabetes in the new millenniumInterdisciplinary problem OBESITY

14. Diabetes in the new millenniumInterdisciplinary problem DIAB ESITY

15. Targeting Cardiometabolic Risk

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

17. Insulin Resistance: Associated Conditions

18. 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

19. 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)

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

21. 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 ])

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

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

24. Public Health Approach

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

26. 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.

27. 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.

28. 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

29. 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 Stratton IM et al. BMJ 2000; 321: 405–412.

30. Overcome Insulin Resistance/ Diabetes: • Insulin Sensitizers: • Biguanides – metformin • Glitazones, Gltazars • Can be used in combination • Insulin Secretagogues: • Sulfonylurea - glipizide, glyburide, glimeparide, glibenclamide • Meglitinides - repaglanide, netiglamide

31. BP Control - How Important? • Goal:BP.<130/80 • MRFIT and Framingham Heart Studies: • 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. Substantial residual cardiovascular risk in statin-treated patients The MRC/BHF Heart Protection Study 30 Placebo Statin 20 Risk reduction=24% (p<0.0001) 19.8% of statin-treatedpatients had a majorcardiovascular event by 5 years % patients 10 0 0 1 2 3 4 5 6 Year of follow-up Heart Protection Study Collaborative Group, 2002

34. Medications: • Hypertension: • ACE inhibitors, ARBs • Others - thiazides, calcium channel blockers, beta blockers, alpha blockers • Central acting Alfa agonist: Moxolidin • Dylipidemia: • Statins, Fibrates, Niacin • Platelet inhibitors: • ASA, clopidogrel

38. Individual metabolic abnormalities among Qatari population according to gender (Musallam et al 08) Men (n = 405) Women (n=412) Variable n(%) n(%) p-Value ATP III Abdominal obesity 227(56.0) 308(74.8) <0.001 Hypertension 143(35.3) 156(37.9) 0.448 Diabetes 77(19.0) 107(26.0) 0.017 Hypertriglyceridemia 113(27.9) 83(20.1) 0.009 Low HDL 95(23.5) 121(29.4) 0.055

39. Individual metabolic abnormalities among Qatari population according to gender Men (n = 405) Women (n = 412) Variable n(%) n(%) p-Value None 88(21.7) 74(18.0) – One 103(25.4) 100(24.3) 0.033 Two 125(30.9) 111(26.9) – Three or more 89(22.0) 127(30.8) – No of components of ATP III

40. Prevalence of MeS in different Countries * Crude rates Mussallam et al. Int J Food Safety and PH 2008

41. 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

42. 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 ‘metabolic syndrome’.”

43. 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.

44. Insulin Resistance: Associated Conditions

45. Thank You

47. Determinants and dynamics of the CVD Epidemic in the developing Countries Data from South Asian Immigrant studies • Excess, early, and extensive CHD in persons of South Asian origin • The excess mortality has not been fully explained by the major conventional risk factors. • Diabetes mellitus and impaired glucose tolerance highly prevalent. (Reddy KS, circ 1998). • Central obesity, ↑triglycerides, ↓HDL with or without glucose intolerance, characterize a phenotype. • Genetic factors predispose to ↑lipoprotein(a) levels, the central obesity/glucose intolerance/dyslipidemia complex collectively labeled as the “metabolic syndrome”

48. Determinants and dynamics of the CVD Epidemic in the developing Countries Other Possible factors • Relationship between early life characteristics and susceptibility to NCD in adult hood ( Barker’s hypothesis) (Baker DJP,BMJ,1993) • Low birth weight associated with increased CVD • Poor infant growth and CVD relation • Genetic–environment interactions (Enas EA, Clin. Cardiol. 1995; 18: 131–5) • Amplification of expression of risk to some environmental changes esp. South Asian population) • Thrifty gene (e.g. in South Asians)

49. CVD epidemic in developing &developed countries. Are they same? • Urban populations have higher levels of CVD risk factors related to diet and physical activity (overweight, hypertension, dyslipidaemia and diabetes) • Tobacco consumption is more widely prevalent in rural population • The social gradient will reverse as the epidemics mature. • The poor will become progressively vulnerable to the ravages of these diseases and will have little access to the expensive and technology-curative care. • The scarce societal resources to the treatment of these disorders dangerously depletes the resources available for the ‘unfinished agenda’ of infectious and nutritional disorders that almost exclusively afflict the poor

50. Burden of CVD in Pakistan • Coronary heart disease • Mortality statistics • Specific mortality data ideal for making comparisons with other countries are not available • Inadequate and inappropriate death certification, and multiple concurrent causes of death