Dr Asso AminGeneral Internal Medicine and Elderly Physician

Definition BHS/ ISH/ WHO/ ESH

Category of Blood Pressure

Optimal < 120 < 80

Normal < 130 < 85

High normal BP 130-139 85-89

Grade 1 Mild 140-159 90-99

Grade 2 Moderate 160-169 100-109

Grade 3 Severe >= 180 >= 110

Isolated systolic Hypertension grade 1

140-159 < 90

Isolated systolic Hypertension grade

>=160 < 90

Survey in England adult above 16 years, 42% men and 33% women were hypertensive *

>50% of those above 65 Systolic BP increase while diastolic falls and therefore

ISH ( better prediction of CVD risk) North England Socio-economic class Ethnic minorities. Migration

* Primatesta et al , Hypertension 2001 , 38: 827-832

Primary 90-95% and secondary 5-10%

Causes of secondary:- Renal:- 75% intrinsic and 25% renovascular. Endocrine Coarctation of aorta Pregnancy medication

Primary-Essential ( precipitating factors)• Excess sodium intake• Lack of physical activity• Overweight• Insufficient dietary fibre • Excess saturated fat• Stress• Alcohol excess• Low dietary potassium• Magnesium deficiency• Low calcium intake• Low vitamin C• Coffee• Lead exposure

Cardiac which include CHD and MI Heart failure LVH ( concentric, concentric remoldelling, and eccentric)

Central nervous system Stroke Cerebral haemorrhage Hypertensive encephalopathy

Concentric:- typical LV wall thickness and dilated LV causing increase in LV mass Concentric remodelling hypertrophyEccentric hypertrophy

Chronic renal failure Pre-clampsia and eclampsia Blindness PVD Cognitive function*

*Hanon and Leys 2002, Cognistive decline and dementia in the elderly hypertensive JRAAS

Blood pressure measurement. Large variation in normal person and therefore should

follow BHS guidelines to measure BP Larger variation associated higher risk of CHD* Bp in both arms with lying and standing BP in diabetic and

elderly Cuff size

* BHS The lancet 375, March 2010

• Use a properly maintained, calibrated and validated device• Measure sitting blood pressure routinely: standing blood

pressure should be recorded at the initial estimation in elderly and diabetic patients

• Remove tight clothing, support arm at heart level, ensure hand relaxed and avoid talking during the measurement procedure

• Use cuff of appropriate size • Lower mercury column slowly (2 mm/s)• Read blood pressure to the nearest 2mmHg• Measure diastolic as disappearance of sounds (phase V)• Take the mean of at least two readings, more recordings are

needed if marked differences between initial measurements are found.

• Do not treat on the basis of an isolated reading

Home self BP monitoring Advantage vs disadvantage Levels are lower than clinic one** How frequent and what level. Ambulatory BP monitoring More use of AMBP with guidelines from BHS/ESH* Indications ( student to search for indication)

* O’Brien at al .European Society of hypertension recommendation for conventional, ambulatory and home blood pressure measurement. J hypertension 2003

** ( Yarows et al Home blood pressure monitoring. Arch Inter Medicine 2000

Document the following Possible secondary causes Contributory factors Complication of hypertension CVD risk Contraindication of specific medication

History taking Examination Signs of secondary causes Signs of end organ damage

Investigation (routine)* urine strip test for protein and blood; _ serum creatinine and electrolytes; _ blood glucose—ideally fasted; _ lipid profile—ideally fasted; _ electrocardiogram (ECG). *BHS –Guidlines 2004

Many tools are available • Framingham risk score for CHD• Cardiovascular Risk Predictor Charts for primary

prevention ( modified Framingham) *• Adult Treatment Panel III (ATP III)• SCORE (Systematic Coronary Risk Evaluation)

project• Reynolds Risk score• ASSIGN( Assessing cardiovascular Risk to Scottish

Intercollegiate Guidelines Network • QRISK ( QRESEARCH Cardiovascular Risk

Algorithm)* Heart 2005

Comparing the tools Cardiovascular Risk Prediction Chart1. Absolute risk- age issue2. More CHD>CVD risk assessment 3. No Consideration to FHx, Weight, Ethnicity

NICE-2008- guidelines 65 lipid modification-cardiovascular risk assessment (Modified version) .

Increase by 1.5 Fhx of premature CHD ( male 1st degree < 55 + female <65) Increase by 1.5-2.0 if more than one member Increase by 1.4 for South Asian men ( ?Kurdish men) BMI > 40 LVH and above 75

Q RISK include the following:- age, sex, ethnicity, smoking status, systolic BP, ratio

TSC/HDL, BMI, family hx of CHD in first degree relative under 60, deprivation score, treated hypertension-DM-renal disease- AF-RA.

QRISK Vs modified CVD predictor chart suggested by NICE*

* 2.3 million patients 35-74, from different areas , and different ethnic background (BMJ 2008)

More accurate High PPV ( false positive in CVD predictor 41.1% ( risk was 16%) Vs 15% but

risk was still 23% above 20% target)

Diabetic considered as coronary equivalent

ATP III report and Finnish study *

* Evaluation and treatment of high blood pressure and cholesterol in adult . Adult Treatment Panel III , circulation 2003

*Haffner et al Ne Eng.J Med 1998 ( Finnish)

Who to treat? Malignant hypertension Admission for emergency

treatmento BP >= 220/120 Treat immediately. BP>= 180-219/ 110-119 Confirm over 1-2 weeks then treat BP 160-179/ 100-109 Yes confirm 3-4 weeks

BP 140-159/90-99 CVD complication/TOD/CV risk>20%

Yes confirm in 12 weeks and treat

X measure monthly < 140/90 Reassess annually <130/85 Reassess every 5 years

Life style measures Weight reduction Reduced salt intake Limitation of alcohol consumption Increased physical activity Increased fruit and vegetable consumption Reduced total fat and saturated fat intake

2. Measures to reduce cardiovascular disease risk Cessation of smoking Reduced total fat and saturated fat intake Replacement of saturated fats with mono-unsaturated fats Increased oily fish consumption

*Bianchi et al (2008), Internal and emergency medicine

* Ahmed N et al (2008) Journal of Ayub Medical College

ACE and ARB thiazide type diuretic calcium channel blockers B-blocker alpha blockers K-sparing diuretic like spironolactone and amiloride

How far should we treat?? Systolic Hypertension in the Elderly Program (SHEP) trial* HOT in diabetic / UKPDS/ ABCD* Heart Outcome Prevention Evaluation (HOPE)* European trial On Reduction of cardiac events with peindropril in stable

coronary artery disease (EUROPA)* ALLHAT* HOT trial in non diabetic*

* SHEP in JAMA 1991

* HOT lancet 1998

* UKPDS 38 Br Med J 1998

* HOPE N Engl J Med 2000

* EUROPA Lancet 2003

*ALLHAT JAMA 2002

Target to achieve

ESH-ESC WHO-ISH BHS

< 140/90 mmHg SBP < 140 < 140/85

DM

<130/80

DMRenalCVD

<130/80

DM

< 130/80

Up to 80 years old

After 80 years old HYVET Hypertension in the Very Elderly Trial 3845 patient 80 years or above from Europe, China, Australia and Tunisia BP > 160 received indapamide m/r Vs placebo and perindripril Vs

placebo Well matched 1933 on treatment Vs 1912 mean age 83 and bp 170/90 30% reduction of fatal/non fatal stroke, 39% reduction in rate of death

from stroke, 21% reduction in rate of death any cause, 23% reduction death from CVD, 64% in rate of HF

Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Blood Pressure Lowering Treatment Trialsits’ Collaboration ( BPLTTC).

CAPPP ( captopril and B-blocker) SYST-EURO STOP-2 ( Swedish Trial in Older Patient with Hypertension-2)

compared ACE/CCB/diuretic/B-blocker INSIGHT.

Studies for each group of medication.

a) Amlodpine b) Thiazide-diuretic c) ACE inhibitord) ARBe) Alpha blocker f) Diltiazemg) B-blocker1. 75 years old man with history of gout has persistent BP > 170/802. 50 Afro-Carribean with persistent BP > 175/893. 70 years old with history of prostatic hypertrophy had BP of 168/904. 53 years old female diabetic , with history of CCF has BP of 155/85 5. 60 years old women on amlodipine and ramipril complaining of

persistence cough 6. 65 years old patient with history of angina has BP of 166/90 for 4

weeks

65 years old from Kirkuk, presented with headache for 3 weeks , associated with feeling unwell and tired.

O/E looking well, BP 165/ 105. QUESION ???1. What do you do like to ask now?2. What do you like to examine? Or to measure next?3. Investigation ?4. Do you start treatment now?5. What do you advise him to do ? 6. What drug do you start on?

Past medical history :- Nil Family history:- mother had a MI at the age of 60 Social history:- Lives with wife and a daughter,

smokes 5 cigarette a day , no alcohol, retired. Drug history :- nil

O/E :- height 178 weight 93, HS normal, JVP not elevated, Apex beat in 5th ICS mid-clavicular line, no retinopathy

Investigation:- U&E normal, TSC 6.1, HDL 1.1, glucose 5.0 , urine nad

46 years old man from Rania, presented with weakness, Blood pressure was checked by a HCA on 3 occasion, 2 weeks a part and was consistently high at 155/94.

What do you like to do next?

Past medical history:- appendicectomy , and chronic back pain

Family history:- father had Angioplasty at age of 55 Social history:- smokes 10 a day, no alcohol,

shopkeeper , lives with family Drug history:- Nil O/E BMI 29, BP 154/93 , HS normal, no eye signs Ix:- Cholesterol 5.9, HDL 1.2, glucose 4.0, ECG no

LVH, urine normal.

Bendrofluazide and indapamide Mechanism of action Benefits in ALLHAT study similar decrease of CVD risk compared to ACE and

CCB , with no change in renal function can be used with GFR of 30

Side Effect Hypo Na, K, Ca, Mg Activate renin-angiotensin system limiting their antipertensive action* Metabolic:- glucose , uric acid cholesterol Hyperglycaemia risk is double and more with severe hypokalaemia. **Kjeldesen SE et al Am J Cardiovascular drugs 2005

*Zillich AJ Hypertension 2006

Mechanism of action ramipril, lisinopril, captopril, enalapril, fosinopril, perindripril, cilzapril,

imidapril,quinapril

Benefits reduce CVD mortality and morbidity specially in diabetic

HOPE The Captopril Prevention Project Trial CAPPP The Fosinopril versus Amlodipine Cardiovascular Events rndomized trial

(FACET) The Appropriate BP Control Diabetes (ABCD)

Side effects

Mechanism of action Candesartan, irbesartan, telmisartan, olmesartan, eprosartan, valsartan Advantages* • As effective as ACE in reducing BP but even more sustained in PRISMA (

Protective, Randomized, Investigation of Safety and efficacy of Micardis vs ramipril using AMBP. Also MICCAT-2 ( Micardis Community Ambulatory Monitoring Trial 2).

• Work for all ethnicity, age, sex, diabetic and non diabetic ( INCLUSIVE) • Reduce CVD , fatal and non fatal stroke, CVS death ( ON TARGET,

LIFE, VALUE, MOSES) • Reduce hospital admission in HF ( VALUE and CHARM)• Reduce AF by 30% compared to b-blocker (LIFE)• Diabetes by 23% compared to CCB in (VALUE) • Tolerability (INCLUSIVE and ON TARGET) * Michael weber , Acheiving blood pressure goals :should angiotensin II receptor blockers

become first line treatment in hypertension ? J ournal of Hypertension 2009.

A novel direct renin inhibitor Licensed to use in hypertension either alone or in conjunction

with ACE/ARB/thizide Reduce SBP by 12-16mmHg and DBP by 2-12mmHg Better tolerated No studies available for CVD risk reduction 150-300mg od

* Aliskiren : an oral renin inhibitor for the treatment of hypertension , Cardiology in Review 2007

Mechanism of action • Interfere with the inward displacement of calcium ions through the active

cell membrane. Influence myocardial cells , cells of within the specialised conducting system of the heart and cells of vascular smooth muscle .

Types • Dihydropyridine like amlodipine, nimodipine, lacidipine, felodipine ..etc• Verapamil and diltiazem.

Advantages • In hypertension, angina, arrhythmia, • 25 % reduction of non-fatal stroke in all studies (STOP-2, ABCD, INDT,

FACET)• May increase risk of MI by adrenergic stimulation (FACET) • Compared to ACE less affect on albuminuria but renoprotection through

afferent and efferent renal arteriole dilitation.

More than 50% of hypertensive will require combined therapy and more 75% of diabetic will need more than one agent.*

Combined therapy had additive affect on lowering BP and less than additive for SE*

Better tolerability

* UKPD 38 in BMJ 1998

* Law et al , value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomized trials BMJ 2003

Advantages Compliance Cost reduction

Disadvantages Does not always allow dose adjustment More postural hypotension Sometimes size of tablet

With diuretic 1983 two multicentre trials compared captopril alone or in combination of

diuretic HCTZ. The combination had less hypokalaemia, hyperuricaemia or hyperglycaemia.

RCT (ADVANCE)* no deterioration in glycaemia control in type 2 diabetes randomised to perindropril and indapamide . The combination had less CV events, death and synergic affect on albuminuria

Preterax in Albuminuria Regression trial (PREMIER)* 457 DM+BP+Albuminuria on perindropril/indapamide Vs Enalapril alone. The combination showed more reduction of SBP+DBP and also 2.5% Vs 6.3% CV events .

* The ADVANCE trial in Lancet 2007,370, 829-840

* PREMIER in Hypertension 2003, 41(5) , 1063-1071.

With CCB• Improved BP control• Favourable metabolic effects obvious in ASCOT-BPLA• Counterbalance the reflex increase in sympathetic nervous system induced by

CCB which induce renin excretion.• Less vasodilatation oedema induced by CCB• Synergistic reduction of proteinuria and better GFR *( but ACEI+thiazide had

more reduction of proteinuria) • Reduce cytokine production .• Less CV events in ACCOMPLISH study• Conclusion :- better combination in diabetic without

Protienuria

* Bakris GL et al Effect of different ACE inhibitor combination on albuminuria: result of GUARD study. Kidney Int. 2008, 73 , 203-1309

With ARB ONTARGET- No evidence for reducing CV events, MI, or stroke.

VALIANT – Valsartan compared to captopril in post MI patient the combination provided no further secondary prevention.

ValHeFT and CHARM-ADDED combined ACE with valsartan or candesartan has reduced mortality and morbidity in patients with heart failure and also more reduction of proteinuria in diabetic nephropathy.

Conclusion:- good combination in HF and Diabetic nephropathy.

Aspirin

Statin

Vitamins

Poor compliance Ignore the importance of life style modification. Drug side effect Ineffective drugs Physician inertia- despite of evidence 60% in England still on

single therapy Drugs cost Guidelines confusion Resistance hypertension

* Exercise and carotid atherosclerosis, European Journal of Vascular& Endovascular surgery 2008* Optimizing management of metabolic syndrome to reduce risk: focus on life

style, Internal& Emergency Medicine 2008* Compliance to antihypertensive drugs, salt restriction, exercise, and control of

systematic hypertensive patient at Abbotabad , Journal of Ayub Medical College, Abbotabad, JAMC, 2008.

50% of stroke patients will have history of hypertension and 40% on antihypertensive.

BP increases after stroke, more than 80% will have BP>=160/95 with first 48 hours

The International stroke trial (IST)* in 2002 for every 10mmHg drop below 150mmhg, death risk increase by 18% , for every 10mmHg above 150 death increase by 4%

ACCESS- candesartan for persistent high SBP>= 220 CHIPPS –RCT double blinded ( labetolol/lisinopril) slightly

lower mortality (P=0.05) at 3month with active treatment.

Post ischemic administration of candesartan reduces cerebral infarction size in rats*

Omura-Matsuoka et al, Hypertension Research 2009

Contraception and BP HRT Pregnancy Chronic hypertension Pre-eclampsia Pre-eclampsia superimposed on chronic hypertension Gestational hypertension

Antihypertensive reduce risk of pre-eclampsia and hospitalisation

Starting treatment 150-160/100-110 ? Why not before Aims for treatment What is pre-eclampsia o Increase of SBP >30 or DBP > 15 from base line in early pregnancy or

DBP > 90 on 2 occasional 4 hours a part or >110 on one occasion. WITHo Proteinuria + or >300mg/24 h Risk of pre-eclampsia Treatment of choice

Hypertension and stroke are major CV risk of fracture* This study included 124,655 fracture cases

* Vestergaard P et al Calcified tissue international, 2009