1. Hypertension: Revisited by Prof. Mohammad Ishaq Professor of Cardiology Karachi Institute of Heart Diseases President Pakistan Hypertension League

2. Symposium Theme: Prevent Heart Diseases – Save Lives World Hypertension Day 2010 Theme : Healthy Weight – Healthy Blood Pressure

3. PAKISTAN HYPERTENSION LEAGUE(PHL) Found June 1997, Karachi

4. Chronic diseases and injuries Infectious, maternal, perinatal and nutritional conditions Changing patterns of death Global Burden of Disease Project, 1996

5. *Residual lifetime risk of developing hypertension among adults at 65 years of age with a blood pressure <140/90 mm Hg. Lifetime Risk of Developing Hypertension Among Adults at 65 Years of Age * Vasan RS, et al. JAMA. 2002;287:1003-1010. Risk of Hypertension (%) Years MenWomen

6. Global Burden: Prevalence Over 20% of adult population. I Billion world wide 55 million in USA. 12 million in Pakistan. 120 million in SAARC region. 70% the hypertension fall into stage 1

7. Complications of Hypertension: End-Organ Damage Chobanian AV, et al. JAMA. 2003;289:2560-2572. Peripheral Vascular Disease Renal Failure, Proteinuria LVH, CHD, CHF Hemorrhage, Stroke Retinopathy CHD = coronary heart disease CHF = congestive heart failure LVH = left ventricular hypertrophy Hypertension

8. *Defined as death due to cardiovascular disease or as having recognized myocardial infarction, stroke, or congestive heart failure. Cumulative Incidence of Major Cardiovascular Events (%) 16 12 10 8 6 4 2 0 14 0246810 12 Time (Years) Optimal <120/80 mm Hg Normal 120–129/80–84 mm Hg High-Normal 130–139/85 – 89 mm Hg Impact of High-Normal Blood Pressure on Risk of Major Cardiovascular Events * in Men Vasan RS. N Engl J Med. 2001;345:1291-1297. Blood Pressure:

9. Age-adjusted annual incidence of CHD per 1000 Based on 30 year follow-up of Framingham Heart Study subjects free of coronary heart disease (CHD) at baseline Systolic blood pressure (mmHg) Blood Pressure and Risk for Coronary Heart Disease in Men Diastolic blood pressure (mmHg) Age 65-94 Age 35-64 Age 65-94 Age 35-64 Framingham Heart Study, 30-year Follow-up. NHLBI, 1987.

10. Relative Risk of Stroke Death <112 <71 Risk of Stroke Death According to Blood Pressure (mm Hg): MRFIT 123456789 10 Decile 112  71  118  76  121  79  125  81  129  84  132  86  137  89  142  92  ≥151 ≥98 (Lowest 10%) (Highest 10%) SBP DBP Systolic Blood Pressure (SBP) Diastolic Blood Pressure (DBP) Stamler J, et al. Arch Intern Med. 1993;153:598-615; He J, Whelton PK. Am Heart J. 1999;138(Pt 2):211-219. MRFIT = Multiple Risk Factor Intervention Trial; *P < 0.01; †P < 0.001. *** * * † † † † †

11. CV mortality rate per 10,000 person-years Systolic BP and CV Death in MRFIT Nondiabetic (n=342,815) Diabetic (n=5,163) <120120-139 Systolic BP (mmHg) 140-159160-179180-199  200 Stamler J, et al. Diabetes Care. 1993;16:434-444. BP= blood pressure CV=cardiovascular MRFIT=Multiple Risk Factor Intervention Trial

12. Relative risk of CHD mortality He J, et at. Am Heart J. 1999;138:211-219. Copyright 1999, Mosby Inc. <112 <71 Risk of CHD Death According to SBP and DBP in MRFIT 123456789 10 Decile 112- 71- 118- 76- 121- 79- 125- 81- 129- 84- 132- 86- 137- 89- 142- 92- >151 >98 (lowest 10%)(highest 10%) SBP (mmHg) DBP (mmHg) Systolic blood pressure (SBP) Diastolic blood pressure (DBP) CHD=coronary heart disease

13. <117 Systolic Blood Pressure (mm Hg) Incidence of ESRD by Systolic Blood Pressure: Multiple Risk Factor Intervention Trial * Klag MJ, et al. JAMA. 1997;277:1293-1298. Incidence of ESRD per 100,000 Person-Years (%) * The original cohort of 332,544 men included 11,677 men in other ethnic groups whose data are excluded from this comparison. ESRD = end-stage renal disease White Men (n = 300,645) Black Men (n = 20,222) 117-123124-130131-140>140 5.4 15.8 5.4 9.1 14.2 32.4 27.3 26.2 37.2 83.1

14. Diabetes Increases Hypertension-Related Cardiovascular Risk: MRFIT Stamler J, et al. Diabetes Care. 1993;16:434-444. MRFIT = Multiple Risk Factor Intervention Trial Cardiovascular Mortality Rate per 10,000 Person-Years Systolic Blood Pressure (mm Hg) <120 120  139140  159160  179180  199 ≤200 Nondiabetic Men (n = 342,815) Diabetic Men (n = 5,163)

15. Hypertension Increases the Risk of Symptomatic Peripheral Artery Disease Norgren L, et al. J Vasc Surg. 2007;45(Suppl 1):S5A-S67A. Male Gender Age/10 Years Diabetes Smoking Hypertension Dyslipidemia Hyperhomocysteinemia Race (Asian/Hispanic/Black vs. White) C-Reactive Protein Renal Insufficiency 1 2 3 4 Odds Ratio (95% CI) CI = confidence interval

16. Factors in the development & Evolution of Hypertension A. NON MODIFIABLE B. MODIFIABLE  Age  Salt & K Intake  Sex  Alcohol Excess  Ethnicity  Contraceptives  Heredity  NSAIDS  Sedentary Living  Sedentary Living  Obesity  Obesity  Socio economic factors

17. Management of Hypertension Individual Hypertensive: Treatment Community control: Life style modification Management of Hypertension Individual Hypertensive: Treatment Community control: Life style modification

18. Effects of Lifestyle Modifications on Blood Pressure

19. Recommended Lifestyle Modifications and Their Individual Effects on Blood Pressure Chobanian AV, et al. JAMA. 2003;289:2560-2572; Blumenthal JA, et al. Arch Intern Med. 2000;160:1947-1958. Modifications*Recommendation Approximate SBP Reduction Reduce weight Maintain normal body weight (BMI of 18.524.9 kg/m 2 ) 320 mm Hg Adopt DASH diet Rich in fruit, vegetables, and low- fat dairy; reduced saturated and total fat content 814 mm Hg Reduce dietary sodium<100 mmol (2.4 g)/day 28 mm Hg Increase physical activity Aerobic activity >30 min/day most days of the week 49 mm Hg Moderate alcohol consumption Men: ≤ 2 drinks/day Women: ≤ 1 drink/day 24 mm Hg *Combining 2 or more of these modifications may or may not have an additive effect on blood pressure reduction. SBP = systolic blood pressure; BMI = body mass index; DASH = Dietary Approaches to Stop Hypertension

20. Effects of Lifestyle Modifications on Blood Pressure Reduce systolic and diastolic blood pressuresReduce systolic and diastolic blood pressures Correct obesity or overweightCorrect obesity or overweight Decrease insulin resistanceDecrease insulin resistance Prevent or delay the onset of hypertensionPrevent or delay the onset of hypertension Enhance antihypertensive drug efficacyEnhance antihypertensive drug efficacy Decrease cardiovascular riskDecrease cardiovascular risk Augment antihypertensive effect when two or more lifestyle modifications are used concurrently*Augment antihypertensive effect when two or more lifestyle modifications are used concurrently* Chobanian AV, et al. JAMA. 2003;289:2560-2572; Hyman DJ, et al. Arch Intern Med. 2007;167:1152-1158. *Data from a randomized trial conducted by Hyman et al. (2007) provide some evidence favoring the simultaneous adoption of multiple lifestyle modifications.

21. Blood Pressure Reductions Resulting from Various Lifestyle Modifications Trials of Hypertension Prevention  Phase I Trials of Hypertension Prevention Collaborative Research Group. JAMA. 1992;267:1213-1220. Copyright © 1992, American Medical Association. All rights reserved. Net Mean Change in Blood Pressure (mm Hg) Weight Loss Reduced Sodium Added Calcium Added Potassium Measures* 44.4 mmol/24 h 1.22 mmol/24 h –58.45 mmol/24 h –5.67 kg Systolic Blood Pressure *All values are averages and are statistically significant at P < 0.01. Diastolic Blood Pressure

22. Combining Lifestyle Modifications Can Have Additive Effects to Reduce Blood Pressure Study Group* Change in Systolic BP† Change in Diastolic BP† Control (n=22) –0.9 mm Hg–1.4 mm Hg Exercise Only (n=44) –4.4 mm Hg–4.3 mm Hg Weight Loss and Exercise (n=46) –7.4 mm Hg–5.6 mm Hg *The differences in mean blood pressure (BP) values between the study groups at 6 months were statistically significant (multivariate F 4,258 = 6.76, P < 0.001). †All values are expressed as averages of the blood pressure reductions achieved by all participants within a single study group. Blumenthal JA, et al. Arch Intern Med. 2000;160:1947-1958.

23. Effects of Diet on Blood Pressure Dietary Approaches to Stop Hypertension Sodium Trial Appel LJ, et al. N Engl J Med. 1997;336:1117-1124. Copyright © 1997, Massachusetts Medical Society. All rights reserved. Fruits-and- Vegetables Diet Combination Diet* Systolic Blood Pressure (mm Hg) Control Diet Diastolic Blood Pressure (mm Hg) Week of Intervention 0 1234567 8 80 82 84 86 88 0 12 3 4 5 6 7 8 Week of Intervention *Rich in fruits and vegetables, and rich in low-fat dairy products and low in saturated and total fat. 0 = baseline.

24. Greater Restriction of Sodium Intake Lowers Diet-Reduced Blood Pressure Dietary Approaches to Stop Hypertension Sodium Trial Sacks FM, et al. N Engl J Med. 2001;344:3-10. Copyright © 2001, Massachusetts Medical Society. All rights reserved. *P < 0.05; †P < 0.011; ‡P < 0.01; ( ) denote 95% confidence interval. DASH = Dietary Approaches to Stop Hypertension 50 mmol/day Systolic Blood Pressure (mm Hg) 150 mmol/day100 mmol/day Daily Dietary Sodium Content Control Diet DASH Diet –5.9 (–8.0 to –3.7)† –5.0 (–7.6 to –2.5)† –1.3 (–2.6 to –0.0)† –2.1 (–3.4 to –0.8)* –2.2 (–4.4 to –0.1)† –1.7 (–3.0 to –0.4)‡ –4.6 (–5.9 to –3.2)† 120 125 130 135

25. Regular Aerobic Exercise Lowers Blood Pressure in Adults with Mild to Moderate Hypertension* Tsai JC, et al. Clin Exp Hypertens. 2004;26:255-265. *Values are expressed as the mean ± standard deviation. †P < 0.05 vs. baseline; ‡P < 0.001 vs. baseline. Control Group Exercise Group 141.2 144.4 BaselineWeek 6 Week 10 Systolic Blood Pressure mm Hg † ‡ 136.2 137.9137.6 131.3 mm Hg BaselineWeek 6Week 10 Diastolic Blood Pressure † ‡ 94.9 95.2 96.2 92.0 98.9 88.9

26. Even Modest Amounts of Aerobic Exercise Can Lower Systolic Blood Pressure Reprinted from Ishikawa-Takata K, et al. Am J Hypertens. 2003;16:629-633, with permission from Elsevier. 149±15149±11149±10149±9 Changes in Systolic Blood Pressure (mm Hg) None 30–40 min/wk 61–90 min/wk 91–120 min/wk >120 min/wk * *† *P < 0.01 vs. sedentary control group. †P < 0.01 vs. 30–60 min/wk exercise group. SD = standard deviation Baseline Value (mm Hg ± SD) Exercise Duration

27. Decreasing Dietary Salt Intake Reduces Systolic Blood Pressure Dietary Approaches to Stop Hypertension Trial *Error bars represent standard deviation; †140 mmol/day; ‡62 mmol/day. Reprinted from Obarzanek E, et al. Hypertension. 2003;42: 459-467, with permission from Lippincott Williams & Wilkins. High-Salt Diet † Systolic Blood Pressure (mm Hg) 1234 Weeks on Low-Salt Diet Weeks on Low-Salt Diet ‡ * * * * *

28. 28 Central obesity: a driving force for cardiovascular disease & diabetes “Balzac” by Rodin Front Back

29. 29 A continuing epidemic: 2 of 3 adults are overweight or obese National Health and Nutrition Examination Surveys 1999-2004 US adults ≥20 years of age Ogden CL et al. JAMA. 2006;295:1549-55. Year of survey Overweight = BMI 25-29.9 kg/m 2 Obesity = BMI ≥30 kg/m 2

30. 30 13 year old boy weighing 11.2kg more than normal runs 33% increased probability of a cardiovascular event before the age of 60

31. OBESITY – ASIA PASIFIC REGION WHO, International Task Force BMI >23Over Weight BMI >25Obesity

32. 32 Associations of adiposity with CVD Matsuzawa Y. Nat Clin Pract Cardiovasc Med. 2006;3:35-42. Insulin resistanceDysglycemia Left ventricular dysfunction HypertensionCAD Sleep apnea syndrome Dyslipidemia White = visceral fat area (VFA) Black = subcutaneous (sc) fat

33. 33 Central adiposity: Better marker of CVD than BMI BMI, WHR, WC tertiles Dagenais GR et al. Am Heart J. 2005;149:54-60. N = 8802 HOPE Study participants P = 0.14P = 0.003P = 0.0127 0 0.5 1 1.5 BMI (kg/m 2 ) WHRWC (cm) Adjusted RR of CVD death First Second Third WC = waist circumference WHR = waist/hip ratio

34. 34

35. 35 Insulin Resistance: Associated Conditions

36. 36 A new vital sign: Waist circumference Adapted from Després J-P et al. BMJ. 2001;322:716-20. RISK Abdominal adiposity Coronary heart disease DyslipidemiaHypertension Dysglycemia

37. 37 Intra-abdominal adiposity is a major contributor to increased cardiometabolic risk Kershaw EE et al, 2004; Lee YH et al, 2005; Boden G et al, 2002 Associated with inflammatory markers (C-reactive protein)  Free fatty acids  Inflammation Insulin resistance Dyslipidaemia Increased cardiometabolic risk IAA = high risk fat Secretion of adipokines ( ↓ adiponectin)  IAA: intra-abdominal adiposity

38. Prevalence of Obesity in Pakistan BMI >25 25-44 Years

39. Effect of Weight Loss on Blood Pressure in Overweight or Obese Subjects by Gender Trials of Hypertension Prevention  Phase I Stevens VJ, et al. Arch Intern Med. 1993;153:849-858. Diastolic Blood Pressure Systolic Blood Pressure Mean Change (mm Hg) -2.8 -1.1 Men Women -2.0 -3.1

40. Summary  The risk of fatal and nonfatal CV and renal events (stroke, CAD, ESRD is closely linked to both systolic and diastolic blood pressure  Central obesity is a major & rising C.V risk factor  CV and renal risks are exaggerated in patients with diabetes mellitus Life style modifications are crucial in BP prevention & control at community level Life style modifications are crucial in BP prevention & control at community level

41. Summary  Among hypertensive patients, the extent to which cardiovascular and renal events are reduced is closely linked to the extent to which blood pressure is reduced  Evidence from clinical trials supports the current recommendations to reduce blood pressure to 130/80 mm Hg in patients who have diabetes, chronic kidney disease, and coronary artery disease

42. Summary Modification of unhealthy lifestyle practices can lower B P among hypertensive patients, regardless of age, ethnicity, or gender. These practices include: –Restriction of dietary sodium intake –Reduction of weight if overweight or obese –Initiation or maintenance of a regular aerobic exercise program. Lifestyle modifications can augment B P reduction caused by antihypertensive drugs.

43. THANK YOU