Hypertension & Cardiovascular Risk Factors Final Year Cardiology Teaching

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

The Global Burden of Disease The scope of the problem

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 HIV Global Burden of Disease Study, 1996

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

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

Cardiovascular risk factors Blood pressure Lipids Diabetes Smoking

BP and relative risk of stroke and CHD Brit Med Bull 1994;50: Approximate mean usual BP StrokeCHD

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

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

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

Worldwide Prevalence of Diabetes 1997

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

Smoking

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 The World Health Report, 1999: Making a Difference

Blood Pressure or Hypertension?

Hypertension and alcohol C. Lian, French army physician, 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 aperitifs Tres Grands Buveurs

Blood Pressure or Hypertension?

Blood pressure measurement

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

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

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

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’) +

ESH Guidelines 2003

Determinants of Blood Pressure

systolic diastolic men women Age (years) Blood pressure (mmHg) Association of BP with age in ‘Western’ societies

Association of BP with age

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

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

Assessment of the Hypertensive Patient

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

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

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

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

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

Cushing’s Acromegaly Secondary causes of hypertension

Renal artery stenosis Secondary causes of hypertension

Polycystic kidney Secondary causes of hypertension Phaeochromocytoma

MIBG scan

Secondary causes of hypertension Neurofibromatosis

Target Organ Damage & Complications of Hypertension

Target organ damage: left ventricular hypertrophy

Target organ damage: hypertensive retinopathy

Grade 4 hypertensive retinopathy

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

Management of Hypertension Non-pharmacological/ lifestyle Pharmacological

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

The Mediterranean Diet

BP lowering treatment and cardiovascular risk Brit Med Bull 1994;50: Total number of individuals affected StrokeCHDAll vascular deaths All other deaths % 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

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

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

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

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

% 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 % Spain 4 20% Finland % <160/95 mm Hg Adapted from Mancia, 1997

Cholesterol & cardiovascular disease

“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.

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) 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

Xanthelasma & corneal arcus Tendon xanthomata

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

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

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

Cardiovascular risk assessment

Cardiovascular risk stratification ESH Guidelines 2003

Hypertension management algorithm: ESH 2003