Dr Asso Amin General Internal Medicine and Elderly Physician

  Definition BHS/ ISH/ WHO/ ESH Category of Blood Pressure Optimal Normal High normal BP Grade 1 Mild Grade 2 Moderate Grade 3 Severe Isolated systolic Hypertension grade 1 Isolated systolic Hypertension grade < 120 < 130 130-139 140-159 160-169 >= 180 140-159 >=160 < 80 < 85 85-89 90-99 100-109 >= 110 < 90 < 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 hypertrophy  Eccentric 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 1.

2.

3.

 Cardiovascular Risk Prediction Chart Absolute risk- age issue More CHD>CVD risk assessment 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 1 st 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?

   o  Malignant hypertension Admission for emergency treatment 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 < 140/90 mmHg DM <130/80 SBP < 140 DM Renal CVD <130/80 BHS < 140/85 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) b) c) d) e) f) g) 1.

2.

3.

4.

5.

6.

Amlodpine Thiazide-diuretic ACE inhibitor ARB Alpha blocker Diltiazem B-blocker 75 years old man with history of gout has persistent BP > 170/80 50 Afro-Carribean with persistent BP > 175/89 70 years old with history of prostatic hypertrophy had BP of 168/90 53 years old female diabetic , with history of CCF has BP of 155/85 60 years old women on amlodipine and ramipril complaining of persistence cough 65 years old patient with history of angina has BP of 166/90 for 4 weeks

1.

 O/E looking well, BP 165/ 105.  QUESION ???

What do you do like to ask now?

2.

3.

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

What do you like to examine? Or to measure next?

Investigation ?

4.

5.

6.

Do you start treatment now?

What do you advise him to do ? 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 5 th 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 o o  What is pre-eclampsia 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. WITH 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