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HYPERTENSION When, what, co-morbid conditions ?

HYPERTENSION When, what, co-morbid conditions ?. George Mangos DEPARTMENT OF MEDICINE ST GEORGE HOSPITAL www.med.unsw.edu.au/stgrenal UNSW. When to start treatment?. 40 yo male, confirmed Blood Pressure 144/92 mmHg (St 1)? 160/84 mmHg (St 2)? 136/84 mmHg (high(n))?.

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HYPERTENSION When, what, co-morbid conditions ?

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  1. HYPERTENSIONWhen, what, co-morbid conditions ? George Mangos DEPARTMENT OF MEDICINEST GEORGE HOSPITAL www.med.unsw.edu.au/stgrenal UNSW

  2. When to start treatment? • 40 yo male, confirmed Blood Pressure • 144/92 mmHg (St 1)? • 160/84 mmHg (St 2)? • 136/84 mmHg (high(n))?

  3. 61 prospective observational studies of BP (Oxford University) • N > 1 000 000 ! • 12.7 million person-years • 56000 vascular deaths • Cardiovascular outcomes using original raw data Prospective Studies Collaboration Lancet 2002

  4. 256 Age at risk: 20 mmHg  SBP 128 80-89 33%  risk 64 70-79 50%  risk 32 60-69 57%  risk 16 Stroke mortality (floating absolute risks & 95% CI) 50-59 62%  risk 8 (40-49 64%  risk) 4 2 1 120 140 160 180 Usual systolic blood pressure (mmHg) Stroke mortality rate in each decade of age versus usual SBP at the start of that decade 11 274 deaths at ages 50 - 89

  5. Age at risk: 10 mmHg  DBP 256 80-89 37%  risk 128 70-79 52%  risk 64 60-69 60%  risk 32 Stroke mortality (floating absolute risks & 95% CI) 50-59 66%  risk 16 (40-49 65%  risk) 8 4 2 1 70 80 90 100 110 Stroke mortality rate in each decade of age versus usual DBP at the start of that decade 11 274 deaths at ages 50 - 89 Usual diastolic blood pressure (mmHg)

  6. Age at risk 20 mmHg  SBP 256 80-89 31%  risk 128 70-79 40%  risk 64 60-69 46%  risk 32 50-59 50%  risk IHD mortality (floating absolute risks & 95% CI) 16 40-49 51%  risk 8 4 2 1 120 140 160 180 Usual systolic blood pressure (mmHg) IHD mortality rate in each decade of age versus usual SBP at the start of that decade 33 867 deaths at ages 40 - 89

  7. 256 Age at risk 10 mmHg  DBP 80-89 30%  risk 128 70-79 38%  risk 64 60-69 44%  risk 32 50-59 48%  risk IHD mortality (floating absolute risks & 95% CI) 16 40-49 53%  risk 8 4 2 1 70 80 90 100 110 Usual diastolic blood pressure (mmHg) IHD mortality rate in each decade of age versus usual DBP at the start of that decade 33 867 deaths at ages 40 - 89

  8. Prospective Studies Collaboration tells us that the risk of hypertension; • Continues through normal BP range • Risk is stronger than originally thought • Reduction in BP 10 / 5 mmHg • 40% reduced risk of stroke death • 30 % reduced risk of IHD or other vascular death • Benefit of lower BP extends to 115/75 mmHg

  9. PSC Meta-analysis – Summary “incremental increases of 20/10 systolic/diastolic blood pressure beginning with values of 115/75 result in a doubling of cardiovascular risk mortality.”

  10. Evidence that rising BP and risk is overwhelming • Predictive • Reproducible • Independent • Continuous • All populations

  11. When to Start Therapy ? High Normal Blood Pressure 136/84 mmHg • “Prehypertension” – benefit from treatment with candesartan for 2 years in healthy young males • Lower rates of subsequent hypertension N Engl J Med 2006; 355:1551-1562, Oct 12, 2006;

  12. HOPE Study • The Heart Outcomes Prevention Evaluation (HOPE) Study was a multicenter, randomized trial enrolling 9,297 patients 55 years old with a history of cardiovascular disease, or diabetes plus at least one other cardiovascular risk factor • Patients were treated with ramipril or placebo and vitamin E or placebo for an average of 4.5 years • Combined primary endpoint was the development of myocardial infarction, stroke, or cardiovascular death • Secondary endpoints were total mortality, admission to hospital for congestive heart failure or unstable angina, complications related to diabetes, and cardiovascular revascularization Yusuf S, et al. N Engl J Med. 2000;342:145-153.

  13. HOPE Study Outcomes: Events Per Patient Group RR=22% P<0.001 RR=20% P<0.001 RR=16% P=0.005 RR=26% P<0.001 Events per patient group (%) RR=32% P<0.001 RR=0% P=NS Combined Primary Outcome* Cardio- vascular Death Myocardial Infarction Stroke Non-Cardiovascular Death Total Mortality *The occurrence of myocardial infarction, stroke or cardiovascular death RR=Relative risk reduction Yusuf S, et al. N Engl J Med. 2000;342:145-153.

  14. When to Start Therapy ? HOPE Study • In presence of TOD it is probably beneficial to start ACEI in high risk patients, regardless of blood pressure.

  15. High – Normal BP(130-139/85-89 mmHg) • No TOD • Lifestyle modifications • TOD • Consider ACEI or ARB

  16. Lifestyle modifications to manage hypertension JNC VII Report 2003. JAMA 289 2560-2572

  17. Stage 1 hypertension (140-159/90-99 mmHg) • Lifestyle Modification for 6 months BUT • Microalbuminuria • Hypertensive retinopathy • eGFR < 60 • PVD • LVH or IHD • Cerebrovascular disease • Treatment SHOULD be initiated • Target Organ Damage

  18. Stage 2 hypertension • 160/84 mmHg • Once confirmed, treatment SHOULD be initiated • Lifestyle modification recommended • Isolated Systolic Hypertension

  19. 1 2 3 4 5 6 7 8 9 10 CHD Death according to SBP and DBP in MRFIT (n=350,000) Systolic blood pressure Diastolic blood pressure Relative risk of CHD mortality Decile <112<71 112-71- 118-76- 121-79- 125-81- 129-84- 132-86- 137-89- 142-92- >151>98 SBP DBP He J, et at. Am Heart J. 1999;138:211-219.

  20. 1 2 3 4 5 6 7 8 9 10 Stroke Death According to SBP and DBP in MRFIT (n=350,000) Systolic blood pressure Diastolic blood pressure Relative risk of stroke death <112<71 112-71- 118-76- 121-79- 125-81- 129-84- 132-86- 137-89- 142-92- >151>98 SBP DBP He J, et at. Am Heart J. 1999;138:211-219.

  21. Isolated Systolic Hypertension and Cardiovascular Disease Risk in Framingham 2.5 ISH BP 160/<95 mmHg BP <140/95 mmHg 82 2.4 Age-adjusted annual CVD event rate per 1000 43 33 18 Men Women P<0.001 for difference between both men and women with ISH and blood pressure (BP) <140/95 mmHg Wilking SV et al. JAMA. 1988;260:3451-3455.

  22. CLINICAL PEARL • Systolic hypertension is a more important risk factor than diastolic blood pressure.

  23. How low to treat ?

  24. Is there a J-Curve ? CV Disease  risk 0 mmHg Blood Pressure 200 mmHg

  25. Is there a J-Curve ? CV Disease  risk 0 mmHg Blood Pressure 200 mmHg

  26. Evidence for J-curve BP = 0 mmHg –> patient is dead “Overwhelming evidence now that our BP targets should be much lower.”

  27. TREATING TO TARGETHow low should our BP targets be ?Do we achieve BP targets in treatment of hypertension ?

  28. HOT - Target blood pressure is an achievable goal (% patients reaching target) DBP mm Hg 105 target £80 mm Hg 100 target £85 mm Hg target £90 mm Hg 95 90 74% 60% 86% 85 73% 43% 55% 80 0 0 3 6 Months 12 24 36 Finalfollow-up Hansson et al 1998

  29. Risk of a major cardiovascular event reduced by 30% in the HOT Study Achieved DBPmm Hg 105 100 95 90 85 80 0 5 Optimal DBPreduction in theHOT Study 10 15 20 25 30 % risk reduction Hansson et al 1998

  30. Significant benefits from intensive blood pressure reduction in diabetics Major CV events/1000 patient years 25 20 15 p=0.005 for trend 10 5 0 £90 £85 £80 mm HgTarget DBP Hansson et al 1998

  31. HOT - Combination therapy needed to achieve target blood pressure Enrolment Final 59% 32% Monotherapy Combinationtherapy SBP/DBPmm Hg 161/98 142/83 £90 mm Hg £85 mm Hg £80 mm Hg 37% 32% 26% SBP/DBPmm Hg 144/85 142/83 140/81 Hansson et al 1998

  32. HOT Study results (1998) • No difference in achieved BP between the 3 groups • (85.2 mmHg, 83.2 mmHg, and 81.1 mmHg) • No difference in CV outcomes between groups • BEST OUTCOMES AT 139/83 mmHg • No J-curve demonstrated • 70 % of patients required 2 or more drugs • BP targets achieved in > 50-80 % subjects HOT Study Group. Lancet. 1998;351(9118):1755-1762.

  33. Heart Foundation Guidelines 2004 Targets • Adults > 65 < 140/90 mmHg • All others <130/85 mmHg • Proteinuria > 1g < 125/75 mmHg “MOST of your patients will require combined therapy”

  34. ALLHAT Randomized Design of ALLHAT BP Trial 42,418 High-risk hypertensive patients Consent / Randomize Amlodipine Chlorthalidone Doxazosin Lisinopril Follow until death or end of study (4-8 years, mean 4.9 years)

  35. ALLHAT Inclusion Criteria • Men and women aged > 55 years • Seated blood pressure (2 categories): 1) Treated for @ least 2 months. 2) Not on drugs or on drugs < 2 months. • Additional risk factor or target organ damage.

  36. ALLHAT Blood Pressure Control Cushman, et al. J Clinical Hypertens 2002; 4:393-404

  37. CLINICAL PEARL #2 • It is often more difficult to control systolic blood pressure than diastolic blood pressure.

  38. ALLHAT Treatment and Blood Pressure Control 1 Drug 2 Drugs 3 Drugs 2.0 1.7 1.4 1.3 Patients (%) Average # of drugs 6 mos 1 yr 3 yr 5 yr Cushman WC, et al. J Clin Hypertens. 2002;4:393-405.

  39. Proportion of Uncontrolled ALLHAT Participants Not Stepped Up at Annual Visits Cushman, et al. J Clinical Hypertens 2002; 4:393-404

  40. CLINICAL PEARLS #3-5 • Monotherapy only effective in only 30-40% patients • Treating down to targets IS possible in most patients • Doctors do not always follow guidelines, even in studies.

  41. Hypertension – Target BP !(<160/95, *<140/90) 20 % 18 % 16 %* 6 %* 34 % 9 % 2.5 % 19 % JNC VI. Arch Int Med 1997;157:2413Colhourn et al. J Hypertens 1998;16:747Marques-Vidal et al. J Hum Hypertens 1997;11:213

  42. Heart Foundation Guidelines 2004 Targets • Adults > 65 < 140/90 mmHg • All others <130/85 mmHg • Proteinuria > 1g < 125/75 mmHg “MOST of your patients will require combined therapy”

  43. How do we get blood pressure under control ?

  44. Non-pharmacological Measures • Pharmacotherapy

  45. Lifestyle modifications to manage hypertension JNC VII Report 2003. JAMA 289 2560-2572

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