1. Hypertension & Cardiovascular Risk Factors Final Year Cardiology Teaching 2003-4

2. Outline Global burden of cardiovascular disease Epidemiology of cardiovascular disease Hypertension –Epidemiology –Clinical features –Investigation Cardiovascular risk assessment

3. The Global Burden of Disease The scope of the problem

4. Leading Causes of Death and Disability (DALY’s) RankCause%RankCause% 1Lower respiratory infections8.21Ischemic heart disease5.9 2Diarrhoeal diseases7.22Major depression5.7 3Perinatal conditions6.73Road traffic accidents5.1 4Major depression3.74Cerebrovascular disease4.4 5Ischemic heart disease3.45COPD4.2 6Cerebrovascular disease2.86Lower respiratory infections3.1 7Tuberculosis2.87Tuberculosis3.0 8Measles2.78War3.0 9Road traffic accidents2.59Diarrhoeal diseases2.7 10Congenital abnormalities2.410 HIV2.6 19902020 Global Burden of Disease Study, 1996

5. * * * * World Health Report 2002 Mortality due to leading global risk factors

6. Burden of disease due to leading global risk factors * * * * World Health Report 2002

7. Cardiovascular risk factors Blood pressure Lipids Diabetes Smoking

8. BP and relative risk of stroke and CHD Brit Med Bull 1994;50:272-98 Approximate mean usual BP 123 76 123 76 136 84 136 84 148 91 148 91 162 98 162 98 175 105 175 105 4.00 2.00 1.00 0.50 0.25 4.00 2.00 1.00 0.50 0.25 StrokeCHD

9. Blood Pressure and Risk of Congestive Heart Failure: the Framingham Study Average annual rate/ 10,000 Age at examination Normotensive BP <140/90 mmHg Hypertensive BP >160/95 mmHg Kannel et al. 1972

10. Systolic BP as a risk factor for renal failure Systolic BP, mmHg Incidence / 100,000 person years MRFIT ‘screenees’ Klag MJ, JAMA ‘97; 277: 1293

12. Association between cholesterol and ischemic stroke 4.04.56.05.55.0 Relative risk Approximate mean usual cholesterol concentration (mmol/L) Asia Pacific Cohort Studies Collaboration

13. Worldwide Prevalence of Diabetes 1997

14. CHD CHF Stroke All CVD Non-CVD All cause Other CVD Non-diabetics Diabetics Asia-Pacific Cohort Studies Collaboration Risks of death in diabetics and non-diabetics

15. Smoking

16. Premature Deaths From Tobacco Use Preventable if adults quit (halving global cigarette consumption by 2020) Preventable if young adults do not start (halving global uptake by 2020) Other premature deaths from tobacco-related causes 2000-20242025-2049 The World Health Report, 1999: Making a Difference

18. Blood Pressure or Hypertension?

26. Hypertension and alcohol C. Lian, French army physician, 1915 0 5 10 15 20 25 30 SobresMoyens BuveursGrands Buveurs % hypertensive Sobres<1 litre wine/ day Moyens buveurs:1-1.5 litres wine/ day Grands buveurs:2-2.5 litres wine/ day Tres grands buveurs:  3 litres wine/ day + 4-6 aperitifs Tres Grands Buveurs

30. Blood Pressure or Hypertension?

31. Blood pressure measurement

32. The ‘normal’ distribution of diastolic BP within a population 5060708090100110120130 Diastolic BP, mmHg % of screened population

33. Hypertension: a practical definition That level of blood pressure at which investigation and treatment do less harm than good Rose

34. Prevalence of ‘Hypertension’ by different cut points 5060708090100110120130 Diastolic BP, mmHg % of screened population  90 = 25.3%  95 = 14.5%  100 = 8.4%  105 = 4.7%  110 = 2.9%  115 = 1.4%

35. Most MIs & strokes occur in individuals with ‘normal’ levels of BP Most people have ‘normal’ BP levels. Cardiovascular risk – hypertension or blood pressure? Relationship between BP & CV risk is linear (i.e no ‘threshold’) +

36. ESH Guidelines 2003

37. Determinants of Blood Pressure

38. 75 100 125 150 20304050607080 systolic diastolic men women Age (years) Blood pressure (mmHg) Association of BP with age in ‘Western’ societies

39. Association of BP with age

40. Association between salt intake & BP Japanese (South) Japanese (North) Northern USA Marshall Islanders (Pacific) Eskimos (Alaska) The InterSalt Study, 1988

41. Ethnicity, blood pressure & diabetes Whitehall II: Whitty et al 1999 Relative risk

42. Assessment of the Hypertensive Patient

43. History + Examination Hypertension risk factors Weight Family history Salt, Alcohol,Stress Target organ damage Heart Brain Eyes Kidneys Clues to 2 o HT Symptoms Drugs Signs Other CV risk factors Lipids Smoking Diabetes Exercise Concurrent conditions Asthma Gout Pregnancy

44. Investigations Urine Blood ECG ?Specialised investigations Renal USS 24-hour ABPM Echocardiography Angiography Hormone assays CT / MRI scanning

45. Indications for further investigations Clinical features of an underlying cause Early onset (< 30 y) Rapid progression Proteinuria, haematuria, glycosuria Severe hypertension, difficult to control Vascular disease: peripheral, coronary, carotid Heart failure, ‘flash’ pulmonary oedema Lack of nocturnal dip on ABPM

46. Secondary causes of hypertension… …. comprise a small proportion of overall cases, probably < 5%

47. The Heinz guide to hypertension Renal artery stenosis Pyelonephritis Obstruct nephropathy Vesico-ureteric reflux Ask-Upmark kidney Renal dysplasia Renin JGA tumor Glomerulonephritis Polycystic disease Analgesic kidney Systemic sclerosis ITT purpura Haemolytic uremic 1 o Aldosteronism Cushing’s syndrome Phaeochromocytoma DOC excess Cong adrenal h’plasia Gluc remediable Diabetes Amyloidosis Carbenoxalone Obstruct sleep apnoea Alcohol MAO-I inhibitors Pre-eclampsia Liquorice Sympathomimetics Chronic renal failure Poliomyelitis 11-  OH-St dehyd def Porphyria Acromegaly Aortic coarctation  intracranial pressure Oral contraceptive Endothelinoma Lead poisoning Corticosteroids

48. Cushing’s Acromegaly Secondary causes of hypertension

49. Renal artery stenosis Secondary causes of hypertension

50. Polycystic kidney Secondary causes of hypertension Phaeochromocytoma

51. MIBG scan

52. Secondary causes of hypertension Neurofibromatosis

53. Target Organ Damage & Complications of Hypertension

54. Target organ damage: left ventricular hypertrophy

55. Target organ damage: hypertensive retinopathy

56. Grade 4 hypertensive retinopathy

57. Intra-cerebral haemorrhage Complications of hypertension Myocardial infarction in hypertrophied left ventricle

58. Management of Hypertension Non-pharmacological/ lifestyle Pharmacological

59. Measures that lower blood pressure: l  weight l  salt intake l  alcohol consumption l  physical exercise l  fruit & vegetable consumption Measures to reduce cardiovascular risk: l Stop smoking l  saturated fat,  poly- & mono-unsaturates l  oily fish consumption l  total fat intake Non-pharmacological interventions BHS Guidelines 1999

60. The Mediterranean Diet

61. BP lowering treatment and cardiovascular risk Brit Med Bull 1994;50:272-98 Total number of individuals affected StrokeCHDAll vascular deaths All other deaths 1200 1000 800 600 400 200 % reduction in odds 38% SD 4 16% SD 4 T C T C T C T C Fatal events Non-fatal events T=treatment C=control

62. The ideal antihypertensive ? l No contraindications l Inexpensive l Effective as monotherapy l Simple once daily dosage l Prevents / reverses target organ damage l Improves mortality / morbidity l No side-effects or adverse metabolic effects l Combinable with other drugs l Genetically targeted

63. Drug treatment of hypertension Diuretic Beta-blocker Calcium-channel blocker ACE-inhibitor (Alpha-blocker) Angiotensin receptor blocker l Most hypertensives will need  2 drugs to control BP l Drug combinations may be synergistic

64. How to choose anti-hypertensive therapy ACE inhibitor (AII antagonist)A or  -blockerB Calcium antagonistCDiureticD One drug:Younger, non-blackA or B Older, blackC or D Two drugs:(A or B) + (C or D) Three drugs:(A or B) + C + D

65. Target blood pressure < 140/90 mmHg …. except in those with diabetes or chronic renal disease < 130/80 mmHg

67. % of hypertensives with controlled BP USA 1 27% England 2 6% <140/90 mm Hg Canada 3 16% Australia 4 19% Zaire 4 2.5% India 4 9% Scotland 4 17.5% Spain 4 20% Finland 4 20.5% <160/95 mm Hg Adapted from Mancia, 1997

68. Cholesterol & cardiovascular disease

69. “Large randomised trials demonstrate lowering LDL- cholesterol by 1 mmol/l reduces non-fatal MI and fatal CHD by about 25% ( about half the the effect predicted from epidemiological studies for a similar reduction in long term cholesterol lowering in people without vascular disease ) “ Collins 2002 With greater reductions in cholesterol there are correspondingly larger reductions in CHD endpoints.

70. Landmark Statin Trials: LDL-C Levels vs Events at 5 Years Follow-up 5.4 (210) 2.3 (90) 2.8 (110) 3.4 (130) 3.9 (150) 4.4 (170) 4.9 (190) 0 5 10 15 20 25 AFCAPS-S WOSCOPS-S WOSCOPS-P CARE-S LIPID-P 4S-P LIPID-S CARE-P 4S-S AFCAPS-P Modified from Kastelein JJP. Atherosclerosis. 1999;143(suppl 1):S17-S21. Percentage with CHD event LDL-C, mmol/L (mg/dL) S=statin treated; P=placebo treated * Extrapolated to 5 Years Secondary prevention Primary prevention Simvastatin Pravastatin Lovastatin ASCOT-S* ASCOT-P* Atorvastatin HPSl-S HPSh-S HPSl-P HPSh-P

72. Xanthelasma & corneal arcus Tendon xanthomata

73. Heart Protection Study: Effect of simvastatin on major vascular events 0123456 0 5 10 15 20 25 30 Years of follow-up 5(3)20(4)35(5) SIMVASTATIN PLACEBO 46(5)54(7)60(18)Benefit/1000 (SE): People suffering events (%)

74. 36% reduction HR = 0.64 (0.50-0.83) Atorvastatin 10 mgNumber of events100 PlaceboNumber of events 154 p=0.0005 ASCOT study: Effect of atorvastatin on CHD

75. ASCOT study: Effect of atorvastatin on stroke 27% reduction HR = 0.73 (0.56-0.96)p=0.0236 Atorvastatin 10 mgNumber of events 89 PlaceboNumber of events121

76. Cardiovascular risk assessment

79. Cardiovascular risk stratification ESH Guidelines 2003

80. Hypertension management algorithm: ESH 2003