Hypertension - Complications and Social Impact

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1 Hypertension - Complications and Social Impact Dr. Ho Hung Kwong, Duncan MBBS(HK), MRCP(UK), FHKAM(Med), FHKCP, FRCP(Edin) FAHA, FSCAI Specialist in Cardiology 何鴻光 Definition and classification of hypertension: JNC VII Hypertension is defined as blood pressure 140/90 mmhg Category Normal Prehypertension Stage 1 hypertension Stage 2 hypertension Systolic (mmhg) < Diastolic (mmhg) and <80 or or or 100 JNC VII. JAMA 2003;289:

2 Prevalence of Hypertension Prevalence of hypertension*: North America and Europe Prevalence (%) Men Women Total United States Canada Europe Italy Sweden England Spain Finland Germany * BP 140/90 mmhg or treatment with antihypertensive medication Wolf-Maier K, et al. JAMA 2003;289:

3 Prevalence of hypertension: Asia Prevalence (%) China (2000/2001) Taiwan (1994) Men Women Total Hong Kong (1997) Singapore (1998) Malaysia (1996) Thailand (1991) Philippines (1999) Indonesia (1994) India (Mumbai, 1999) Japan ( ) Gu DF, et al. Hypertension 2002;40: ; Singh RB, et al. J Hum Hypertens 2000;14: ; Janus ED. Clin Exp Pharmacol Physiol 1997;24: ; National Health Survey 1998, Singapore. Epidemiology and Disease Department, Ministry of Health, Singapore.; Lim TO, et al. Singapore Med J 2004;45:20-27; Tatsanavivat P, et al. Int J Epidemiol 1998;27: ; Muhilal H. Asia Pacific J Clin Nutr 1996;5: ; Gupta R. J Hum Hypertens 2004;18:73-78; Asai Y, et al. Nippon Koshu Eisei Zasshi 2001;48: [in Japanese] Hypertension control rates around the world <140/90 mmhg (%) United States 27 France 24 Canada 22 Italy 9 Egypt 8 England 6 Korea 5 China 3 Poland 2 <160/95 mmhg (%) Germany 23 Finland 21 Spain 20 Australia 19 Scotland 18 India 9 Zaire 3 JNC VI. Arch Intern Med 1997;157: ; Joffres MR, et al. Am J Hypertens 1997;10: ; Colhoun HM, et al. J Hypertens 1998;16: ; Chamotin B, et al. Am J Hypertens 1998;11: ; Marques-Vidal P, et al. J Hum Hypertens 1997;11:

4 National Health and Nutrition Examination Survey (NHANES) Trends in awareness, treatment and control of high blood pressure in adults aged 18-74* II ( ) III (Phase ) III (Phase ) Awareness 51% 73% 68% 70% Treatment 31% 55% 54% 59% Control 10% 29% 27% 34% * High blood pressure defined as SBP 140 mmhg or DBP 90 mmhg or taking antihypertensive medication SBP <140 mmhg and DBP <90 mmhg Unpublished data for compiled by M. Wolz, National Heart, Lung and Blood Institute: JNC VI At-a-Glance Summary Tables Males and Cardiovascular Diseases Heart Disease and Stroke Statistics 2006 Update, American Heart Association 4

5 Impact of Hypertension Millimetres matter A 2-mmHg 2 reduction in DBP would result in a 6% reduction in the risk of CHD and a 15% reduction in the risk of stroke and TIAs DBP, diastolic blood pressure; CHD, coronary heart disease; TIA, transient ischaemic attack Cook NR, et al. Arch Intern Med 1995;155:

6 Millimetres matter For individuals years of age, each increment of 20 mmhg in systolic BP or 10 mmhg in diastolic BP doubles the risk of CVD across the entire BP range from 115/75 to 185/115 mmhg BP, blood pressure; CVD, cardiovascular disease JNC VII. JAMA 2003;289: Hypertension: A risk factor for cardiovascular disease Coronary disease Stroke Peripheral artery disease Cardiac failure Biennial age-adjusted rate per 1,000 subjects Risk Men Women Men Women Men Women Men Women ratio: Normotensive Hypertensive Kannel WB. JAMA 1996;275:

7 End-Stage Renal Disease (ERSD) ESRD (also called end-stage kidney disease) is a condition closely related to high blood pressure, and occurs when the kidneys can no longer function normally on their own. The incidence of reported ESRD has almost doubled in the past 10 years. (NHLBI, from usrds.org Web site) 82,588 patients died from ESRD in Diabetes continues to be the most common reported cause of ESRD. Atherosclerosis 7

8 Other Related Disease Relative importance of SBP and DBP as predictors of CHD risk as a function of age Favours SBP β(sbp) - β(dbp) * Favours DBP p= Age (years) * The difference between SBP and DBP proportional hazard regression coefficients, ie, β(sbp) - β(dbp), was estimated for each age group SBP, systolic blood pressure; DBP, diastolic blood pressure; CHD, coronary heart disease Franklin SS, et al. Circulation 2001;103:

9 Cumulative incidence of CV events (%) Cumulative incidence of CV events (%) Impact of high-normal BP on CV risk Optimal BP: <120/80 mmhg; normal BP: /80-84 mmhg; high-normal BP: /85-89 mmhg Men Women Normal BP Optimal BP Optimal BP Years High-normal BP High-normal BP Normal BP BP, blood pressure; CV, cardiovascular Vasan RS, et al. N Engl J Med 2001;345: Implications of small reductions in DBP for primary prevention DBP reduction mmhg 5-6 mmhg 2 mmhg Risk reduction (%) CHD Stroke DBP, diastolic blood pressure; CHD, coronary heart disease Cook NR, et al. Arch Intern Med 1995;155:

10 Hypertension Treatment Guidelines Treatment initiation: JNC VII Normal Prehypertension Stage 1 hypertension Stage 2 hypertension Lifestyle modification Encourage Yes Yes Yes Initial drug therapy Without compelling indication With compelling indications No antihypertensive drug indicated Drug(s) for compelling indications Thiazide-type diuretics for most; may consider ACE-I, ARB, BB, CCB, or combination Two-drug combination for most (usually thiazide-type diuretic and ACE-I or ARB or BB or CCB) Drug(s) for compelling indications; other antihypertensive drugs (diuretics, ACE-I, ARB, BB, CCB) as needed ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BB, beta-blocker; CCB, calcium-channel blocker JNC VII. JAMA 2003;289:

11 Goals of treatment: JNC VII The SBP and DBP targets are <140/90 mmhg The primary focus should be on achieving the SBP goal In patients with hypertension and diabetes or renal disease, the BP goal is <130/80 mmhg SBP, systolic blood pressure; DBP, diastolic blood pressure; BP, blood pressure JNC VII. JAMA 2003;289: Treatment initiation: ESH/ESC 2003 Blood pressure Other risk factors and disease history Normal High normal Grade 1 Grade 2 Grade 3 No other risk factors No BP intervention No BP intervention Lifestyle changes for several months, then drug treatment if preferred by the patient and resources available Lifestyle changes for several months, then drug treatment Immediate drug treatment and lifestyle changes 1-2 risk factors Lifestyle changes Lifestyle changes Lifestyle changes for several months, then drug treatment Lifestyle changes for several months, then drug treatment Immediate drug treatment and lifestyle changes 3 or more risk factors, target organ damage, or diabetes Lifestyle changes Drug treatment and lifestyle changes Drug treatment and lifestyle changes Drug treatment and lifestyle changes Immediate drug treatment and lifestyle changes Associated clinical conditions Drug treatment and lifestyle changes Immediate drug treatment and lifestyle changes Immediate drug treatment and lifestyle changes Immediate drug treatment and lifestyle changes Immediate drug treatment and lifestyle changes ESH/ESC Guidelines J Hypertens 2003;21:

12 Goals of treatment: ESH/ESC 2003 Achieve maximum reduction in long term total cardiovascular risk Treat all reversible risk factors and associated clinical conditions in addition to treating raised blood pressure Target blood pressure <140/90 mmhg and to lower values, if tolerated For diabetics, target blood pressure is <130/80 mmhg ESH/ESC Guidelines J Hypertens 2003;21: Hypertension treatment strategy: ESH/ESC 2003 Consider: Untreated BP level Presence or absence of TOD and risk factors Choose between: Single agent at low dose If goal BP not achieved Two-drug combination at low dose Previous agent at full dose Switch to different agent at low dose Previous combination at full dose Add a third drug at low dose Two- to three-drug combination If goal BP not achieved Full-dose monotherapy Three-drug combination at effective doses BP, blood pressure; TOD, target organ damage ESH/ESC Guidelines J Hypertens 2003;21:

13 Choice of antihypertensive therapy: ESH/ESC 2003 Main benefits are due to BP lowering Specific drug classes may differ in their effects Drugs are not equal in adverse-event profiles Major drug classes are suitable for initiation and maintenance of therapy Choice of drug will be influenced by patient experience and preference, and cost and risk profile Long-acting drugs that provide once-daily, 24-hour efficacy are preferable BP, blood pressure ESH/ESC Guidelines J Hypertens 2003;21: The BHS recommendations for combining blood pressure-lowering drugs Younger (eg <55 years) and non-black Older (eg 55 years) or black Step 1 A or B C or D Step 2 A (or B) + C or D Step 3 A + C + D Step 4 Resistant hypertension Add: either alpha-blocker or spironolactone or other diuretic A: ACE inhibitor or ARB B: Beta-blocker C: Calcium-channel blocker D: Diuretic (thiazide) BHS, British Hypertension Society; ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker Brown MJ, et al. J Hum Hypertens 2003;17:

14 Putting Hypertension Guidelines into Clinical Practice A randomised controlled trial of the prevention of CHD and other vascular events by BP and cholesterol lowering in a factorial study design B.Dahlof (Co-chair), P.Sever (Co-chair), N. Poulter (Secretary) H. Wedel (Statistician), G. Beevers, M. Caulfield, R. Collins S. Kjeldsen, A. Kristinsson, J. Mehlsen, G. McInnes, M. Nieminen E. O Brien, J. Östergren, on behalf of the ASCOT Investigators ASCOT-BPLA, LANCET, vol 366 September 10,

15 Anglo-Scandinavian Cardiac Outcome Trial (ASCOT) 1. This Trial had to be stopped earlier than expected due to significant reductions in cardiovascular death and all cause mortality in patients taking CCB based regimen (amlodipine besylate) versus a standard Beta blocker based regimen. 2. In addition, they were less likely to develop diabetes compared to patients taking the Beta blocker-based regimen. ASCOT-BPLA, LANCET, vol 366 September 10, 2005 Study design 19,257 hypertensive patients ASCOT-BPLA atenolol ± bendroflumethiazide PROBE design amlodipine ± perindopril 10,305 patients TC 6.5 mmol/l (250 mg/dl) ASCOT-LLA atorvastatin 10 mg Double-blind placebo Investigator-led, multinational randomised controlled trial ASCOT-BPLA, LANCET, vol 366 September 10,

16 Treatment algorithm to BP targets < 140/90 mm Hg or < 130/80 mm Hg in patients with diabetes amlodipine 5-10 mg add perindopril 4-8 mg atenolol mg add bendroflumethiazide-k mg add doxazosin GITS 4-8 mg add additional drugs, eg, moxonidine/spironolactone ASCOT-BPLA, LANCET, vol 366 September 10, 2005 Mean proportion of time on antihypertensive medication by treatment group Randomised to Amlodipine All Study Amlodipine Perindopril Amlodipine + perindopril Randomised to Atenolol Atenolol Bendroflumethiazide (+/- others) (+/- others) (+/- others) (+/- others) (+/- others) Atenolol + bendroflumethiazide (+/- others) ASCOT-BPLA, LANCET, vol 366 September 10,

17 Systolic and diastolic blood pressure SBP Mean difference 2.7mmHg atenolol ± thiazide amlodipine ± perindopril mm Hg DBP Mean difference 1.9mmHg Baseline ASCOT-BPLA, LANCET, vol 366 September 10, 2005 Time (years) Last visit Data safety monitoring board (DSMB) In October 2004 the DSMB recommended that the BP arm of ASCOT should be stopped on account of concerns that those patients receiving atenolol ± thiazide would continue to be disadvantaged compared with the comparator group The Steering Committee endorsed the recommendation of the DSMB, and trial closure began Dec, 2004 and ended June

18 % CV mortality Atenolol ± thiazide (No. of events 342) Amlodipine ± perindopril (No. of events 263) HR = 0.76 ( ) p = Years Number at risk Amlodipine ± perindopril Atenolol ± thiazide % 10.0 All-cause mortality 8.0 Atenolol ± thiazide (No. of events 820) Amlodipine ± perindopril (No. of events 738) 2.0 HR = 0.89 ( ) p = Years Number at risk Amlodipine ± perindopril Atenolol ± thiazide

19 New-onset diabetes mellitus % Atenolol ± thiazide (No. of events = 799) Amlodipine ± perindopril (No. of events = 567) 2.0 HR = 0.70 ( ) p < Years Number at risk Amlodipine ± perindopril Atenolol ± thiazide Primary end point + coronary revascularisation procedures % Atenolol ± thiazide (No. of events 688) Amlodipine ± perindopril (No. of events 596) HR = 0.86 ( ) p = Years Number at risk Amlodipine ± perindopril Atenolol ± thiazide

20 Total coronary end point % Atenolol ± thiazide (No. of events 852) 6.0 Amlodipine ± perindopril (No. of events 753) HR = 0.87 ( ) p = Number at risk Amlodipine ± perindopril Atenolol ± thiazide Years % Fatal and non-fatal stroke Atenolol ± thiazide (No. of events 422) Amlodipine ± perindopril (No. of events 327) 1.0 HR = 0.77 ( ) p = Years Number at risk Amlodipine ± perindopril Atenolol ± thiazide

21 % Total CV events and procedures Atenolol ± thiazide (No. of events 1602) Amlodipine ± perindopril (No. of events 1362) HR = 0.84 ( ) p < Years Number at risk Amlodipine ± perindopril Atenolol ± thiazide % New-onset renal impairment Atenolol ± thiazide (No. of events = 469) 3.0 Amlodipine ± perindopril (No. of events = 403) HR = 0.85 ( ) p = Years Number at risk Amlodipine ± perindopril Atenolol ± thiazide

22 Primary Non-fatal MI (incl silent) + fatal CHD Secondary Non-fatal MI (exc. Silent) +fatal CHD Total coronary end point Total CV event and procedures All-cause mortality Cardiovascular mortality Fatal and non-fatal stroke Fatal and non-fatal heart failure Tertiary Silent MI Unstable angina Chronic stable angina Peripheral arterial disease Life-threatening arrhythmias New-onset diabetes mellitus New-onset renal impairment Summary of all end points Unadjusted Hazard ratio (95% CI) 0.90 ( ) 0.87 ( ) 0.87 ( ) 0.84 ( ) 0.89 ( ) 0.76 ( ) 0.77 ( ) 0.84 ( ) 1.27 ( ) 0.68 ( ) 0.98 ( ) 0.65 ( ) 1.07 ( ) 0.70 ( ) 0.85 ( ) Post hoc Primary end point + coronary revasc procs 0.86 ( ) CV death + MI + stroke 0.84 ( ) Amlodipine ± perindopril better Atenolol ± thiazide better The area of the blue square is proportional to the amount of statistical information ASCOT-BPLA, LANCET, vol 366 September 10, 2005 Conclusions Amlodipine ± perindopril based therapy confers an advantage over atenolol ± thiazide based therapy on all major CV end points, all-cause mortality and new-onset diabetes Irrespective of the reasons for benefit, the amlodipine ± perindopril regimen should be preferred to the standard regimen of atenolol ± thiazide for most patients with hypertension Compared with standard antihypertensive therapy without statin therapy, the amlodipine ± perindopril regimen plus atorvastatin reduced coronary and stroke events by almost 50% ASCOT-BPLA, LANCET, vol 366 September 10,

23 ASCOT-BPLA Implications on Hypertension Guidelines NICE Guideline

24 Pharmacological interventions Drug therapy reduces the risk of cardiovascular disease and death. Offer drug therapy to: patients with persistent high blood pressure of 160/100 mmhg or more patients at raised cardiovascular risk (10-year risk of CVD of 20% or more or existing CVD or target organ damage) with persistent blood pressure of more than 140/90 mmhg. Pharmacological interventions In hypertensive patients aged 55 or older or black patients of any age, the first choice for initial therapy should be either a calcium-channel blocker or a thiazide-type diuretic. For this recommendation, black patients are considered to be those of African or Caribbean descent, not mixed-race, Asian or Chinese. 24

25 Pharmacological interventions In hypertensive patients younger than 55, the first choice for initial therapy should be an angiotensin-converting enzyme (ACE) inhibitor (or an angiotensin-ii receptor antagonist if an ACE inhibitor is not tolerated). General issues when prescribing Offer patients with isolated systolic hypertension (systolic blood pressure more than 160 mmhg) the same treatment as patients with both raised systolic and diastolic blood pressure. Offer patients older than 80 years the same treatment as other patients aged 55 or older take account of any comorbidity and other drugs they are taking. 25

26 General issues when prescribing Prescribe drugs taken only once a day if possible. Prescribe non-proprietary drugs if these are appropriate and minimise cost. Give information about the benefits and side effects of drugs so that patients can make informed choices. Drug treatment Key issues in updating the recommendations Beta-blockers: In head-to-head trials, beta-blockers were usually less effective than a comparator drug at reducing major cardiovascular events, particularly stroke. Beta-blockers were also less effective than an ACE inhibitor or a calcium channel blocker at reducing the risk of diabetes, particularly in patients taking a beta-blocker and a thiazidetype diuretic. Calcium-channel blockers or thiazide-type diuretics: These are the most likely drugs to confer benefit as first-line treatment for most patients aged 55 or older. 26

27 Drug treatment Key issues in updating the recommendations People younger than 55 years: The evidence suggests that initial therapy with an ACE inhibitor may be better than initial therapy with a calcium-channel blocker or a thiazidetype diuretic. Using more than one drug: Adding an ACE inhibitor to a calcium-channel blocker or a diuretic (or vice versa) is a logical combination, and has been commonly done in trials. There is little evidence on using three drugs so the recommendation is based on the most straightforward option. 27

28 Beta-blocker Beta-blockers are no longer preferred as a routine initial therapy for hypertension But consider them for younger people, particularly: women of childbearing potential patients with evidence of increased sympathetic drive patients with intolerance of or contraindications to ACE inhibitors and angiotensin-ii receptor antagonists If a patient taking a beta-blocker needs a second drug, add a calciumchannel blocker rather than a thiazide-type diuretic, to reduce the patient s risk of developing diabetes. Beta-blocker If a patient s blood pressure is not controlled by a regimen that includes a beta-blocker (that is, it is still above 140/90 mmhg), change their treatment by following the flow chart above. If a patient s blood pressure is well controlled (that is,140/90 mmhg or less) by a regimen that includes a beta-blocker, consider long-term management at their routine review. There is no absolute need to replace the beta-blocker in this case. When withdrawing a beta-blocker, step down the dose gradually. Beta-blockers should not usually be withdrawn if a patient has a compelling indication for being treated with one, such as symptomatic angina or a previous myocardial infarction. 28

29 Pharmco-economic Analysis For 1st line treatment of essential hypertension (people at low risk of heart failure) Calcium Channel Blockers are the most cost effective option because they are associated with a low risk of diabetes and they also have a good effectiveness profile across the range of other cardiovascular disease risks. The cost of cardiovascular diseases and stroke Heart Disease and Stroke Statistics 2006 Update, American Heart Association 29

30 Heart Disease and Stroke Statistics 2006 Update, American Heart Association 30

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