1. The Era of Hips & Waists

2. Hypertension in Metabolic syndrome

3. Common risk factors for chronic diseases Deaths from 4 chronic diseases Deaths from all other causes 50% of all deaths 3 risk factors Tobacco Poor diet Lack of exercice 4 chronic diseases Cancer Type 2 diabetes Chronic respiratory disease Cardiovascular Oxford Health Alliance 2003

4. Obesity, Type 2 Diabetes, Hypertension or Dyslipidemia Relative risk Waist circumference (cm) Adapted from Lee ZSK et al. Obes Rev 2002; 3: 173-82 and Ko GT et al. Int J Obes Relat Metab Disord 1997; 21: 995-1001 0

5. History of MS History of MS 1923 - Kylin first to describe the clustering of hypertension, hyperglycemia, hyperuricemia 1936 - Himsworth first reported Insulin insensitivity in diabetics 1965 - Yalow and Berson developed insulin assay and correlated insulin levels & glucose lowering effects in resistant and non-resistant individuals

6. 1988 - Reaven in his Banting lecture at the ADA meeting coined the term Syndrome X and brought into focus the clustering of features of Metabolic Syndrome Reaven now prefers the name, Insulin- Resistance Syndrome - feels insulin resistance is the common denominator for Metabolic Syndrome

7. Metabolic Syndrome Etiology – not fully elucidated Insulin Resistance Acquired causes Overweight and central (visceral) obesity Physical inactivity, aging, ethnicity High CHO diets (>60%) Proinflammatory state, hormones Poly Genic causes

8. INSULIN RESISTANCE - MECHANISMS  Pre receptor ( abnormal insulin or insulin antibodies)  Receptor ( decreased receptor number or affinity)  Postreceptor (abnormal signal transduction and phosphorylation)  Glucose transporter ( decreased GLUT 4 molecule)

9. INSULIN RESISTANCE & HYPERTENSION More than 50 % of hypertensives are found to be Insulin Resistant and Hyperinsulinemic. IR and Hyperinsulinemia have been documented to be present even in lean Hypertensives who are not Diabetic

11. MS 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)

12. Necessary Criteria to Make Diagnosis WHO: WHO: Impaired G handling + 2 other criteria. Impaired G handling + 2 other criteria. ◦ Also requires microalbuminuria - Albumen/ creatinine ratio >30 mg/gm creatinine NCEP/ATP III: NCEP/ATP III: ◦ Require three or more of the five criteria

13. IDF(2006) : Abdominal obesity plus two other components: elevated BP, low HDL, elevated TG, or impaired fasting glucose

14. Measurement of Waist

15. Normal Visceral Adiposity Courtesy of Wilfred Y. Fujimoto, MD. Visceral Fat Distribution

16. IDF Waist Circumference

17. MS MS 2 times increase risk of HT 3 times increase risk of CHD or stroke 5 times increase risk of DM Chronic liver disease Increase risk of more than 60 diseases

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. Hypertension in MS: IDF: ◦ BP >130/85 or on Rx for previously Dxed hypertension WHO: ◦ BP >140/90 NCEP ATP III: ◦ BP >130/80

20. Obesity Effects on Blood Pressure

21. Mean DBP (mmHg) Clock time (hours) Intra-abdominal (Visceral) Fat Area Tertiles and 24-hour Ambulatory Blood Pressure and Pulse Rate in Chinese Type 2 Diabetic Patients Clock time (hours) Mean HR (bpm) Clock time (hours) Mean SBP (mmHg) DBP:diastolic blood pressure HR:heart rate SBP:systolic blood pressure Copyright © 1997 American Diabetes Association Adapted from Diabetes Care ®, Vol. 20, 1997; 1854-8 Reprinted with permission from The American Diabetes Association

22. Metabolic variables in white coat (WC) and sustained (SUST) borderline hypertension Tecumseh study Julius et al., Hypertension 16, 1990. Tecumseh NORMAL WC SUST N=621 N=28 N=34 n.s. p<.001 26 22 18 14 Insulin Level 10 p<.001

23. Hypertension is a very prominent feature of the metabolic syndrome, present in up to 85% of patients.

24. Metabolic Syndrome & Hypertension Randomized prospective study in Italy with >1700 people with HTN (mean 155/95) & no CVD, followed for a mean of 4 years During follow up, 162 pts developed CV events, a total of 593 pts had metabolic syndrome using NCEP guidelines Those with MS had an almost double CV event rate 3.23 vs 1.76per 100pt years.

25. Insulin Resistance and Hypertension Mechanisms Hyperinsulinemia  Produces renal sodium retention.  Stimulates Sympathetic Nervous activity  Vascular smooth muscle hypertrophy ( mitogenic action of insulin)  cytokines and other lipokines  Augmentation of the pressor and aldosterone response to angiotensin II  Endothelial dysfunction and decreased production of NO

26. Results of current long term outcome studies support the hemodynamic concept of insulin resistance in hypertension

27. HYPOTHESIS If in addition to cardiovascular responses, the metabolic responses were also decreased in hypertension, the patient’s ability to dissipate calories would be diminished and they would gain more weight.

28. BP Control - How Important? 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

29. therapy a multi-target approach based on the assessment of the overall cardiovascular risk should be applied; A-non-pharmacological therapy; sodium restriction, alcohol and calorie restriction, smoking cessation, weight reduction, and increase physical activity.

30. Antihypertensive Medications: Angiotensin -converting Enzyme Inhibitors (ACEI) Angiotensin II Receptor (ARB) Blockers Combination with Thiazides, Calcium Channel Blockers, Cardioselective Beta Blockers <130/80 Target BP: <130/80

33. Fit vs. Fat: Can you be both? Overweight and obese people who are fit are less likely to die prematurely than unfit people who are lean (Lee, CD, et al., Am J Clin Nutr 1999; 69:373-380) Highly Fit men with 2 or 3 risk factors had about the same mortality risk as Low Fit men with no risk (Blair, SN, et al., JAMA 1996; 276: 205-210) Low Fitness is as significant a risk factor for premature death as smoking, high blood pressure, diabetes, and high blood cholesterol, regardless of weight ( Barlow et al., Int J Obes Metab Disord, 19(suppl 4):41, 1995 and Wei et al., JAMA, 282: 1547, 1999)

35. -For preventive purposes

36. THANK YOU