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7th Annual International Diovan Symposium

7th Annual International Diovan Symposium. Lisbon, 3–5 February 2006.  ↓ CVrisk = (BP ↓Power + CV Protection)↑Compliance. Addressing the Variables: Solving the Formula to Reduce CV Risk. Host’s Welcome. Cassiano Abreu-Lima University of Porto School of Medicine Portugal. 69.4 %. 7.2%.

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7th Annual International Diovan Symposium

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  1. 7th Annual International Diovan Symposium Lisbon, 3–5 February 2006

  2. ↓CVrisk = (BP↓Power +CV Protection)↑Compliance Addressing the Variables: Solving the Formula to Reduce CV Risk

  3. Host’s Welcome Cassiano Abreu-Lima University of Porto School of MedicinePortugal

  4. 69.4 % 7.2% Prevalence of HF Stages in Porto Age  45 years Azevedo et al. Heart, 2006

  5. Heart Failure Risk Factors in Porto Age  45 years Azevedo et al. Heart, 2006

  6. Hypertension in Portugal N=2115 N=5023 18–90 years 46.1 42.1 39.0 11.2 Macedo et al. J Hypertension, 2005

  7. 55% Cerebrovascular Disease Portugal Proportional Cardiovascular Disease Mortality Total CV mortality 38% Other 25% 20% Coronary Artery Disease

  8. Chairs’ Welcome and Objectives: Setting the Challenge Victor Dzau Duke University, Durham, USA & Marc Pfeffer Harvard Medical School, USA

  9. Introduction • Welcome to the 7th Annual International Diovan Symposium • 700 hypertension, cardiology and lipidology experts from 44 countries as far apart as Nigeria, Saudi Arabia, Croatia and Japan • This year’s theme ‘Addressing the Variables: Solving the Formula to Reduce CV Risk’

  10. The formula ↓CV risk= (BP↓Power + CV Protection)↑Compliance Adapted from Feldman et al. Can Med Assoc J 1999;1611 (12 Suppl):S1–S17

  11. ↓CV risk = (BP↓Power + CV Protection)↑Compliance • Global risk reduction: the goal of HTN management? • Can you stratify CV risk factors to develop treatment algorithms? • Metabolic syndrome: how relevant and useful is it as an entity? • How important is IGT and how prevalent is it?

  12. ↓CV risk= (BP↓Power + CV Protection)↑Compliance • How should HTN be defined and what is abnormal BP? • How important are BP guideline targets in clinical practice? • How low is low enough for BP? • Does it matter by what route BP is lowered (e.g. via the RAAS or via fluid balance)?

  13. ↓CV risk= (BP↓Power + CV Protection)↑Compliance • Protective benefits beyond BP lowering: what’s the evidence? • What is the relationship between BP and renopathology? • What are the mechanisms behind the reduction in new-onset diabetes seen with RAAS blockade? • Does the cause of heart failure impact clinical management?

  14. ↓CV risk= (BP↓Power + CV Protection)↑Compliance • Why are compliance and persistence rates so low in patients with HTN? • Is tolerability an important issue when selecting a RAAS blocker? • What can physicians do to improve patient compliance in hypertensive patients • What effect does improved compliance have on clinical outcomes?

  15. From the Expert’s Files: Case Presentation Marc Pfeffer Harvard Medical School, USA

  16. Presentation • 56-year-old British female • Presents to primary care physician for medical examination (new job) • Mother alive and well, father died from MI aged 70 • No current meds • Smokes 20 cigarettes/day (30 pack-years)

  17. Examination • Height: 1.65 m • Weight: 79 kg • BMI = 29 • BP = 156/86 mmHg (confirmed on subsequent occasions) • Heart sounds normal, chest clear

  18. Investigations • ECG = Normal • Electrolytes = Normal • Glucose = 5.8 mmol/L (104 mg/dL) • Dipstick protein + • Total cholesterol = 6.2 mmol/L (240 mg/dL) • LDL = 3.7 mmol/L (142 mg/dL) • HDL = 0.9 mmol/L (35 mg/dL)

  19. 7th Annual International Diovan Symposium Lisbon, 3–5 February 2006 VARIABLE 1: Hypertension

  20. What is Normal and What is Abnormal Blood Pressure? Toshiro Fujita University of Tokyo

  21. Conceptual Definition of Hypertension Sir George Pickering decried the search for an arbitrary dividing line between normal and high blood pressure. In 1972 he restated his argument: “There is no dividing line between normal and high blood pressure. The relationship between arterial blood pressure and mortality is quantitative; the higher the pressure, the worse the prognosis.

  22. However, medical practice requires that some criteria be used to determine the need for workup and therapy. The criteria should be established on some rational basis that includes the risks of disability and death associated with various levels of blood pressure as well as the ability to decrease those risks by lowering the blood pressure.

  23. Operational Definition of Hypertension Evans JG and Rose G: Br Med Bull 1971:27:37-42 ‘Hypertension should be defined in terms of a BP level above which investigation and treatment do more good than harm’ Any numerical definition must be determined resulting from evidence of risk and availability of effective and well-tolerated drugs.

  24. Correlation of Stroke Incidencewith Blood Pressure Levels No Drug Intervention 18 years follow-up in Hisayama, Japan Male Female 1000 patient years 1000 patient years *p<0.01 (vs <120/80) *p<0.01 (vs <120/80) 30 30 Stroke Incidence Stroke Incidence * 24 24 18 18 * 12 12 * * * 6 6 * 0 0 Systolic BP <120 120 – 130 – 140 – 160 – 180 – mmHg <120 120 – 130 – 140 – 160 – 180 – mmHg Diastolic BP <80 80 – 85 – 90 – 100 – 110 – mmHg <80 80 – 85 – 90 – 100 – 110 – mmHg

  25. Classification of BP in Adult JSH2004 (Japanese Guidelines) Classification Optimal BP Normal BP High Normal BP Mild Hypertension Moderate Hypertension Severe Hypertension Systolic Hypertension Systolic BP (mmHg) <120 <130 130～139 140～159 160～179 >180 >140 and and or or or or and Diastolic BP (mmHg) <80 <85 85～89 90～99 100～109 >120 <90

  26. Classification of BP in Adult JSH2004 (Japanese Guidelines) Classification Optimal BP Normal BP High Normal BP Mild Hypertension Moderate Hypertension Severe Hypertension Systolic Hypertension Systolic BP (mmHg) <120 <130 130～139 140～159 160～179 >180 >140 and and or or or or and Diastolic BP (mmHg) <80 <85 85～89 90～99 100～109 >120 <90

  27. What is Normal and What is Abnormal Blood Pressure? • High Normal Blood Pressure • Total Individual Risk and Blood Pressure • Home and Ambulatory Blood Pressure

  28. IHD Mortality Rate in each Decade of Age versus Usual BP at the Start of that Decade Lewington S, et al: Lancet 2002; 360: 1903-13 7 80-89 years 80-89 years 128 128 70-79 years 70-79 years 32 32 IHD Mortality (floating absolute risk) 60-69 years 60-69 years 8 8 50-59 years 50-59 years 2 2 40-49 years 40-49 years 0 0 120 140 160 180 70 80 90 100 110 SBP (mmHg) DBP (mmHg) Death from both IHD (and stroke) increases progressively and linearly from BP levels as low as 115 mmHg SBP and 75 mmHg DBP.

  29. Impact of High-Normal Blood Pressure on the Risk of Cardiovascular Disease CUMULATIVE INCIDENCE OF CV EVENTS IN MEN WITHOUT HYPERTENSION ACCORDING TO BASELINE BLOOD PRESSURE mmHg mmHg High normal (130-139) (130-139) Normal (121-129) (121-129) Optimal (< 120) (< 120) Last JM, et al: N Engl J Med 2001;345:1291-7

  30. CHD Deaths in Men Screened for the MRFIT Study Julius S: AJH 2000; 13: 11S-17S Death Excess Death % Excess Death 1500 20 1000 % Deaths 10 500 0 0 <110 110- 119 120- 129 130- 139 140- 139 150- 159 160- 169 170- 179 >180 Systolic BP (mmHg)

  31. BP to Initiate Antihypertensive Drug Therapy (Julius S: AJH 2000; 13: 11S-17S) Very conservative recommendations about starting treatment in stage 1 hypertension have been made in New Zealand and Norway. In both countries the health care system is government funded and within such a modus operandi, cost containment is at a premium. However, early intervention may be more beneficial than late treatment and treating mild hypertension may have a major positive impact on public health.

  32. Strategies Aimed at Diets and Physical Activity of the Population Shifts the BP Distribution of the Whole Population to the Left 2003 WHO/ISH Statement:Journal of Hypertension 2003, 21:1983–1992 Present distribution Optimal distribution ％ of population High risk strategy focuses on about 25% of the population 60 80 100 120 140 160 180 200 220 240 SBP (mmHg) Distribution of systolic blood pressure in adults Present and optimal systolic blood pressure distribution of the population. These smoothed curves portray the present distribution (blue line) and the optimal distribution (yellow line) of systolic blood pressure in adults. A combination of population and high-risk strategies of blood pressure control is necessary to achieve the optimal blood pressure distribution.

  33. Classification of BP for Adults (mmHg) ESH/ESC and JSH Optimal BP Normal BP High normal BP Grade 1 hypertension (mild) Grade 2 hypertension (moderate) Grade 3 hypertension (severe) JNC 7 Normal Prehypertension Stage 1 hypertension Stage 2 Hypertension SBP and DBP <120 and <80 120-9 or 80-4 130-9 or 85-9 140-59 or 90-9 160-79 or 100-9 >180 or >110

  34. Classification of BP in ESH/ESC Although it would be appropriate to use a classification of BP without term ‘hypertension’, this could be confusing. Thus, the classification has been retained with the reservation that the real threshold for hypertension must be considered as flexible, being higher or lower based on the total cardiovascular risk profile of each individuals.

  35. What is Normal and What is Abnormal Blood Pressure? • High normal blood pressure had better be controlled for risk reduction: a major positive impact on public health. • Total Individual Risk and Blood Pressure • Home and Ambulatory Blood Pressure

  36. Estimated Effect of a 12 mm Hg Reduction in SBP Over 10 Years on the Number-Needed-to-Treat to Prevent a Cardiovascular Death NHANES I Epidemiologic Follow-Up Study(Ogden LG, et al: Hypertension. 2000;35:539) Baseline SBP/DBP (mmHg) High Normal (130-139/85-89) Mild Hyperternsion (140-159/90-99) Moderate to Severe Hypertension (>160/>100) Risk Group A 486 273 34 Risk Group B 36 27 12 Risk Group C 21 18 11 Corrected for regression dilution bias using a reliability coefficient of 0.53 to correct for imprecision in the measurement of SBP. Risk group A includes participants with no evidence of target organ damage, clinical cardiovascular disease, or additional major risk factors for cardiovascular disease. Risk group B includes participants who were men or postmenopausal women 60 years of age, current smokers, or had a serum total cholesterol 240 mg/dL. Risk group C includes participants who had a self-reported history of diabetes, heart attack, heart failure, stroke, or renal disease at baseline or had used medication for these conditions during the preceding 6 months.

  37. BP and relative Hazards of Cardiovascular Death in Subjects with Impaired Glucose Tolerance (Igaku-no-ayumi 2004;210:717-8) Systolic BP (mmHg) * 16 Normal GT IGT * * * * P<0.05 vs <120/Normal GT 12 Relative Hazard * 8 4 0 <120 120- 129 130- 139 140- 159 >160 <120 120- 129 130- 139 140- 159 >160 Diastolic BP (mmHg) * 10 Normal GT IGT * * * 8 * P<0.05 vs <80/Normal GT * * 6 Relative Hazard 4 2 0 <80 80- 84 85- 89 90- 99 >100 <80 80- 84 85- 89 90- 99 >100

  38. Stratification of Risk to Quantify Prognosis BP Other risk factors and disease history Normal SBP 120-129 or DBP 80-84 High Normal SBP 130-139 or DBP 85-89 Grade III SBP>180 or DBP>110 Grade I SBP 140-159 or DBP 90-99 Grade II SBP 160-179 or DBP 100-109 Low added risk Moderate added risk High added risk Average risk Average risk No other risk factors Low added risk Low added risk Moderate added risk Very high added risk Moderate added risk 1-2 risk factors 3 or more risk factors or TOD or diabetes High added risk High added risk Moderate added risk High added risk Very high added risk High added risk Very high added risk Very high added risk Very high added risk Very high added risk ACC Drug Treatment ACC: Associated clinical conditions; TOD: Target organ damage; SZBP systolic blood pressure DBP: Diastolic blood pressure Journal of Hypertension 2003,Vol 21 No6：1011-1053

  39. What is Normal and What is Abnormal Blood Pressure? • High normal blood pressure had better be controlled for risk reduction: a major positive impact on public health. • Total individual risk should determine the real threshold for high blood pressure. • Home and Ambulatory Blood Pressure

  40. Home and Ambulatory BP Monitoring Measuring blood pressure at home is becoming increasingly popular for both doctors and patients. Usual office blood pressure is significantly higher than daytime home blood pressure, and usual office blood pressure measurement often leads to significant overestimation of BP and thereby overdiagnosis of hypertension: white-coat hypertension. Ambulatory BP monitoring and home BP monitoring are useful for the evaluation of white-coat hypertension. Moreover, this method gives a more comprehensive representation of the vascular burden of hypertension than a small number of BP readings in the office of a clinician.

  41. Criteria for Hypertension (Units: mmHg) JNC 7 ESH-ESC JSH 2004 Office BP  140/90  135/85 Home (self-measured) BP 24-hour ambulatory BP Awake  135/85  125/80  135/80 Asleep  120/75

  42. Relative Hazards and 95% CI of Home Systolic/Diastolic BP for Overall Mortality Ohasama Study (AJH 1997;10:409) Systolic BP <113 mmHg (n=380, 13 death) 113-120 mmHg (n=363, 22 death) 120-128 mmHg (n=375, 17 death) 128-138 mmHg (n=406, 27 death) * >138 mmHg (n=389, 62 death) Diastolic BP <67 mmHg (n=360, 32 death) * 67-72 mmHg (n=362, 20 death) 72-77 mmHg (n=390, 21 death) 77-83 mmHg (n=381, 25 death) * >83 mmHg (n=420, 43 death) 0 1 2 3 4 5 Relative Hazard Home BP: >135/>85 mmHg Hypertension

  43. Relative Hazards and 95% CIs of 24-hour Systolic and Diastolic BP Values for Overall Mortality Ohasama Study (Hypertension 1998;32:255) The curves fitted to the second-degree equation determined by the Cox proportional hazards model adjusted for age, gender, smoking status, use of antihypertensive medication at baseline, and history of cardiovascular disease, diabetes, and hypercholesterolemia. 24 hr BP: >135/>80 mmHg Hypertension

  44. Cardiovascular Risk in Office and 24-Hour Ambulatory Blood pressure in Elderly Systolic Hypertension (Syst-Eur) 0.20 Nighttime BP 0.16 24-hour BP 0.12 2 Year Incidence Rate of Cardiovascular Events Daytime BP 0.08 Office BP 0.04 0 130 210 90 110 150 170 190 230 Systolic BP （mmHg） Staessen JA, et al.：JAMA.282；:539-546 (1999)

  45. Prediction of Stroke by Self-Measurement BP at Home vs. Casual Screening BP: The Ohasama Study (Stroke 2004;35:2356) Risk of First Stroke Home BP Office BP 4 Relative Hazard and 95%CI* 2 Trend p<0.0001 1 Trend p<0.0009 2 3 4 2 3 4 Group *Adjusted for age, sex, diabetes, hypercholesterolemia, smoking, history of cardiovascular disease; Group 1: normotensive (relative hazard=1), Group 2: prehypertensive; Group 3: stage 1 hypertensive; Group 4: stage 2 hypertensive

  46. Diagnosis of Masked Hypertension Masked Hypertension Hypertension ABP 135/80 mmHg Homed BP 135/85 mmHg White-coat HT Normal BP Clinic BP 140/90 mmHg

  47. Jichii Morning-Hypertension Research-J-MORE study Morning Systolic Pressure (mmHg) 200 180 160 150 135 120 100 90 23% -MMH 38% -PCH r=0.25 n=969 21% -WCH 18% -WCHT 100 120 140 160 180 200 220 Clinic systolic pressure (mmHg) (Kario Circulation 2003,108:72e-73e)

  48. Patients with Masked Hypertension have High Cardiovascular Risk (/1,000 person x year) 40 30 20 10 0 CV Events 30.6 25.6 12.1 11.1 Normal BP n=685 White-coat HT n=656 Masked HT n=462 Sustained HT n=3,125 (Bobrie G et al. JAMA 291:1342-1349,2004)

  49. Canadian Hypertension Education Program Algorithm for Diagnosis of Hypertension Am J Hypertens 2005;18:1369-1374 Elevated Out of Office BP Elevated Random Office BP Hypertensive Urgency/ Emergency Hypertension Visit 1 BP Measurement, History, Physical Diagnostic tests at visit 1 or 2 Hypertension Visit 2 Within 1 month BP>140/90+target organ damage or diabetes or renal disease BP>180/110 Yes Diagnosis of Hypertension No BP:140-179/90-109 Office BPM Hypertension Visit 3 Diagnosis of Hypertension >160 SBP or >100 DBP <160/100 ABPM (if available) SBPM (if available) ABPM or SBPM if available Awake <135/85 or 24-hour <130/80 Awake >135 SBP or >85 DBP or 24-hour >130 SBP or >80 DBP <135/85 >135 SBP or >85 DBP or or Hypertension Visit 4-5 Diagnosis of Hypertension >140 SBP or >90 DBP <140/90 continue to follow-up continue to follow-up Diagnosis of Hypertension continue to follow-up Diagnosis of Hypertension Office BPM: Office BP monitoring; ABPM: Ambulatory BP monitoring; SBPM: Self BP monitoring

  50. Home Blood Pressure and Antihypertensive Therapy ~Japanese HT Guideline~ The normotensive value of the home blood pressure differs from the target level of the home blood pressure during antihypertensive therapy. The intervention studies using home BP measurement are needed for the determination of the target BP level .

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