Management of Hypertension

1. Management of Hypertension Dr Asso Amin General Internal Medicine and Elderly Physician

2. What is hypertension • Definition • BHS/ ISH/ WHO/ ESH

3. Prevalence • 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

4. Age and hypertension

5. Aetiology and precipitating factors • Primary 90-95% and secondary 5-10% • Causes of secondary:- • Renal:- 75% intrinsic and 25% renovascular. • Endocrine • Coarctation of aorta • Pregnancy • medication

6. Aetiology and precipitating factors • 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

7. Precipitating factors

8. Disease attributed to hypertension • Cardiac which include • CHD and MI • Heart failure • LVH ( concentric, concentric remoldelling, and eccentric) • Central nervous system • Stroke • Cerebral haemorrhage • Hypertensive encephalopathy

9. Left Ventricular Hypertrophy • Concentric:- typical LV wall thickness and dilated LV causing increase in LV mass • Concentric remodelling hypertrophy • Eccentric hypertrophy

10. Disease attributed to hypertension • Chronic renal failure • Pre-clampsia and eclampsia • Blindness • PVD • Cognitive function* *Hanon and Leys 2002, Cognistive decline and dementia in the elderly hypertensive JRAAS

11. Affects of high blood pressure

12. Assessment of hypertensive patients • 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

13. Blood pressure measurement. • 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

15. 5 MINUTES BREAK

16. Blood pressure measurement • 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

17. 24- hours BP measurement

18. Hypertensive patient initial evaluation • Document the following • Possible secondary causes • Contributory factors • Complication of hypertension • CVD risk • Contraindication of specific medication

19. Hypertensive patient initial evaluation • 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

20. CVD risk assessment • 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

21. CVD risk assessment • Comparing the tools • 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 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

23. CVD risk assessment • 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)

24. CVD risk assessment • 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)

25. Blood Pressure Treatment Threshold • Who to treat? • 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

26. Blood Pressure Treatment Threshold

27. Treatment of hypertension • 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

29. Treatment of hypertension • ACE and ARB • thiazide type diuretic • calcium channel blockers • B-blocker • alpha blockers • K-sparing diuretic like spironolactone and amiloride

30. Treatment of hypertension

31. Blood Pressure Target • 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

32. Blood Pressure Target • Target to achieve

33. Upper Age to treat • Up to 80 years old • After 80 years old • HYVETHypertension 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

34. Lowering BP or a specific drug • 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.

35. Evidence-based management of hypertension (QUIZ) • 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

36. Case Studies 1 • 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 ??? • What do you do like to ask now? • What do you like to examine? Or to measure next? • Investigation ? • Do you start treatment now? • What do you advise him to do ? • What drug do you start on?

37. Case Studies 1 • 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

38. Case study 2 • 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?

39. Case study 2 • 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.

40. Thiazide like diuretic • 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

41. ACE Inhibitor • 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

42. ARB • 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 Micardisvsramipril 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.

43. Aliskiren • 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

44. Calcium Channel Blockers • 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.

45. Mono or Combined therapy • 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

46. Separate or Fixed combined • Advantages • Compliance • Cost reduction • Disadvantages • Does not always allow dose adjustment • More postural hypotension • Sometimes size of tablet

47. ACE combination • 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.

48. ACE combination • 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

49. ACE combination • 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.

50. Added therapy • Aspirin • Statin • Vitamins