高血压-并发症和（人群）社会影响.2006.E

1 Hypertension Hypertension -- Complications Complications and Social Impactand Social Impact Dr. Ho Hung Kwong, Duncan 何鴻光何鴻光何鴻光何鴻光 MBBS(HK), MRCP(UK), FHKAM(Med), FHKCP, FRCP(Edin) FAHA, FSCAI Specialist in Cardiology Definition and classification of Definition and classification of hypertension: JNC VIIhypertension: JNC VII Hypertension is defined as blood pressure ≥140/90 mmHg or ≥100≥160Stage 2 hypertension or 90-99140-159Stage 1 hypertension or 80-89120-139Prehypertension and <80<120Normal Diastolic (mmHg) Systolic (mmHg) Category JNC VII. JAMA 2003;289:2560-2572 2 Prevalence of HypertensionPrevalence of Hypertension Prevalence of hypertension*: Prevalence of hypertension*: North America and EuropeNorth America and Europe 0 10 20 30 40 50 60 70 80 Un ite d S tat es Ca na da Eu ro pe Ita ly Sw ed en En gla nd Sp ain Fin lan d Ge rm an y Pr ev al en ce (% ) Men Women Total Wolf-Maier K, et al. JAMA 2003;289:2363-2369* BP ≥140/90 mmHg or treatment with antihypertensive medication 3 Prevalence of hypertension: AsiaPrevalence of hypertension: Asia 0 10 20 30 40 50 60 70 80 Ch ina (20 00 /20 01 ) Ta iwa n (19 94 ) Ho ng Ko ng (19 97 ) Sin ga po re (19 98 ) Ma lay sia (19 96 ) Th aila nd (19 91 ) Ph ilip pin es (19 99 ) Ind on es ia (19 94 ) Ind ia (Mu m ba i, 1 99 9) Ja pa n (19 92 - 95 ) Pr ev al en ce (% ) Men Women Total Gu DF, et al. Hypertension 2002;40:920-927; Singh RB, et al. J Hum Hypertens 2000;14:749-763; Janus ED. Clin Exp Pharmacol Physiol 1997;24:987-988; 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;27:405-409; Muhilal H. Asia Pacific J Clin Nutr 1996;5:132-134; Gupta R. J Hum Hypertens 2004;18:73-78; Asai Y, et al. Nippon Koshu Eisei Zasshi 2001;48:827-836 [in Japanese] Hypertension control rates around the worldHypertension 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;157:2413-2446; Joffres MR, et al. Am J Hypertens 1997;10:1097-1102; Colhoun HM, et al. J Hypertens 1998;16:747-752; Chamotin B, et al. Am J Hypertens 1998;11:759-762; Marques-Vidal P, et al. J Hum Hypertens 1997;11:213-220 4 National Health and Nutrition National Health and Nutrition Examination Survey (NHANES) Examination Survey (NHANES) 34%27%29%10%Control† 59%54%55%31%Treatment 70%68%73%51%Awareness 1999-2000 III (Phase 2 1991-94) III (Phase 1 1988-91) II (1976-80) Trends in awareness, treatment and control of high blood pressure in adults aged 18-74* * High blood pressure * High blood pressure defined asdefined as SBP ≥140 mmHg or SBP ≥140 mmHg or DBP ≥90 mmHg or takingDBP ≥90 mmHg or taking antihypertensiveantihypertensive medicationmedication † SBP <140 mmHg and DBP <90 mmHg† SBP <140 mmHg and DBP <90 mmHg Unpublished data for 1999Unpublished data for 1999––2000 compiled by M. 2000 compiled by M. WolzWolz, , National Heart, Lung and Blood Institute: JNC VINational 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 5 Impact of HypertensionImpact of Hypertension Millimetres matter …Millimetres matter … “A 2“A 2--mmHg reduction in DBP would mmHg reduction in DBP would result in … a 6% reduction in the risk of result in … a 6% reduction in the risk of CHD and a 15% reduction in the risk of CHD and a 15% reduction in the risk of stroke and stroke and TIAsTIAs”” Cook NR, et al. Arch Intern Med 1995;155:701-709DBP, diastolic blood pressure; CHD, coronary heart disease; DBP, diastolic blood pressure; CHD, coronary heart disease; TIA, transient TIA, transient ischaemicischaemic attackattack 6 Millimetres matter …Millimetres matter … “For individuals 40“For individuals 40--70 years of age, each 70 years of age, each increment of 20 mmHg in systolic BP or increment of 20 mmHg in systolic BP or 10 mmHg in diastolic BP doubles the risk 10 mmHg in diastolic BP doubles the risk of CVD across the entire BP range from of CVD across the entire BP range from 115/75 to 185/115 mmHg”115/75 to 185/115 mmHg” JNC VII. JAMA 2003;289:2560-2572BP, blood pressure; CVD, cardiovascular diseaseBP, blood pressure; CVD, cardiovascular disease Hypertension: A risk factor for Hypertension: A risk factor for cardiovascular diseasecardiovascular disease 9.5 3.3 2.4 5.0 2.0 3.5 2.1 45.5 21.3 12.4 6.2 9.9 7.3 13.9 6.3 22.7 0 5 10 15 20 25 30 35 40 45 50 Men Women Men Women Men Women Men Women Bi e n n ia l a ge - ad jus te d ra te pe r 1, 00 0 s u bje c ts Normotensive Hypertensive Coronary disease Stroke Peripheral artery disease Cardiac failure Kannel WB. JAMA 1996;275:1571-1576 Risk ratio: 2.0 2.2 3.8 2.6 2.0 3.7 4.0 3.0 7 EndEnd--Stage Renal Disease (ERSD)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 2003. • Diabetes continues to be the most common reported cause of ESRD. AtherosclerosisAtherosclerosis 8 Other Related DiseaseOther Related Disease Relative importance of SBP and DBP as Relative importance of SBP and DBP as predictors of CHD risk as a function of agepredictors of CHD risk as a function of age * 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 25 6545 5535 75 β(SBP) - β(DBP) * Age (years) Favours DBP Favours SBP -1.0 -0.5 0.0 0.5 1.0 -1.5 p=0.008 Franklin SS, et al. Circulation 2001;103:1245-1249 9 Impact of highImpact of high--normal BP on CV risknormal BP on CV risk Optimal BP: <120/80 mmHg; normal BP: 120-129/80-84 mmHg; high-normal BP: 130-139/85-89 mmHg BP, blood pressure; CV, cardiovascular Cumulative incidence of CV events (%) 16 12 10 8 6 4 2 0 14 Optimal BP Normal BP 12 10 8 6 4 2 0 0 2 4 6 8 10 12 Years Optimal BP Normal BP High-normal BP Women Men Cumulative incidence of CV events (%) High-normal BP Vasan RS, et al. N Engl J Med 2001;345:1291-1297 Implications of small reductions in DBPImplications of small reductions in DBP for primary preventionfor primary prevention DBP, diastolic blood pressure; CHD, coronary heart disease -21 -16 -6 -46 -38 -15 -50 -40 -30 -20 -10 0 7.5 mmHg 5-6 mmHg 2 mmHg CHD Stroke R is k re du ct io n (% ) DBP reduction Cook NR, et al. Arch Intern Med 1995;155:701-709 10 Hypertension Treatment GuidelinesHypertension Treatment Guidelines Treatment initiation: JNC VIITreatment initiation: JNC VII Drug(s) for compelling indications; other antihypertensive drugs (diuretics, ACE-I, ARB, BB, CCB) as needed Thiazide-type diuretics for most; may consider ACE-I, ARB, BB, CCB, or combination Yes Stage 1 hypertension Drug(s) for compelling indications No antihypertensive drug indicated Encourage Normal Yes Pre- hypertension YesLifestyle modification With compelling indications Two-drug combination for most (usually thiazide-type diuretic and ACE-I or ARB or BB or CCB) Without compelling indication Initial drug therapy Stage 2 hypertension ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BB, beta-blocker; CCB, calcium-channel blocker JNC VII. JAMA 2003;289:2560-2572 11 Goals of treatment: JNC VIIGoals 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 JNC VII. JAMA 2003;289:2560-2572 SBP, systolic blood pressure; DBP, diastolic blood pressure; BP, blood pressure Treatment initiation: ESH/ESC 2003Treatment initiation: ESH/ESC 2003 Blood pressure Immediate drug treatment and lifestyle changes Immediate drug treatment and lifestyle changes Immediate drug treatment and lifestyle changes Immediate drug treatment and lifestyle changes Drug treatment and lifestyle changes Associated clinical conditions Immediate drug treatment and lifestyle changes Drug treatment and lifestyle changes Drug treatment and lifestyle changes Drug treatment and lifestyle changes Lifestyle changes 3 or more risk factors, target organ damage, or diabetes Immediate drug treatment and lifestyle changes Lifestyle changes for several months, then drug treatment Lifestyle changes for several months, then drug treatment Lifestyle changes Lifestyle changes 1-2 risk factors Immediate drug treatment and lifestyle changes Lifestyle changes for several months, then drug treatment Lifestyle changes for several months, then drug treatment if preferred by the patient and resources available No BP intervention No BP intervention No other risk factors Grade 3Grade 2Grade 1High normalNormalOther risk factors and disease history ESH/ESC Guidelines 2003. J Hypertens 2003;21:1011-1053 12 Goals of treatment: ESH/ESC 2003Goals 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 2003. J Hypertens 2003;21:1011-1053 Hypertension treatment strategy: Hypertension treatment strategy: ESH/ESC 2003ESH/ESC 2003 Consider: Untreated BP level Presence or absence of TOD and risk factors Choose between: Single agent at low dose Two-drug combination at low dose If goal BP not achieved Previous agent at full dose Switch to different agent at low dose Previous combination at full dose Add a third drug at low dose Three-drug combination at effective doses Two- to three-drug combination Full-dose monotherapy If goal BP not achieved BP, blood pressure; TOD, target organ damage ESH/ESC Guidelines 2003. J Hypertens 2003;21:1011-1053 13 Choice of Choice of antihypertensiveantihypertensive therapy:therapy: ESH/ESC 2003ESH/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 ESH/ESC Guidelines 2003. J Hypertens 2003;21:1011-1053BP, blood pressure Younger (eg <55 years) and non-black Older (eg ≥≥≥≥55 years) or black Step 1 Step 2 Step 3 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) A (or B) A A or B C or D C or D+ +C D Brown MJ, et al. J Hum Hypertens 2003;17:81-86 The BHS recommendations for combining The BHS recommendations for combining blood pressureblood pressure--lowering drugslowering drugs + BHS, British Hypertension Society; ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker 14 Putting Hypertension Guidelines into Putting Hypertension Guidelines into Clinical PracticeClinical Practice 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 A randomised controlled trial of the prevention of CHD and other vascular events by BP and cholesterol lowering in a factorial study design ASCOT-BPLA, LANCET, vol 366 September 10, 2005 15 AngloAnglo--Scandinavian Cardiac Scandinavian Cardiac Outcome Trial (ASCOT)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 designStudy design atenolol ± bendroflumethiazide amlodipine ± perindopril 19,257 hypertensive patients PROBE design ASCOT-BPLA Investigator-led, multinational randomised controlled trial placeboatorvastatin 10 mg Double-blind ASCOT-LLA 10,305 patients TC ≤ 6.5 mmol/L (250 mg/dL) ASCOT-BPLA, LANCET, vol 366 September 10, 2005 16 Treatment algorithm to BP targets < 140/90 mm Hg or < 130/80 mm Hg in patients with diabetes amlodipine 5-10 mg atenolol 50-100 mg perindopril 4-8 mg bendroflumethiazide-K1.25-2.5 mg doxazosin GITS 4-8 mg add add add additional drugs, eg, moxonidine/spironolactone add ASCOT-BPLA, LANCET, vol 366 September 10, 2005 Mean proportion of time on Mean proportion of time on antihypertensiveantihypertensive medication by treatment groupmedication by treatment group Randomised to Atenolol Randomised to Amlodipine All Study 54.9Atenolol + bendroflumethiazide (+/- others) 65.7Bendroflumethiazide (+/- others) 79.4Atenolol (+/- others) 49.5Amlodipine + perindopril (+/- others) 58.5Perindopril (+/- others) 82.5Amlodipine (+/- others) ASCOT-BPLA, LANCET, vol 366 September 10, 2005 17 Systolic and diastolic blood pressureSystolic and diastolic blood pressure m m Hg 60 80 100 120 140 160 180 Time (years) Baseline 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 atenolol ± thiazide amlodipine ± perindopril 137.7 136.1 79.2 77.4 Mean difference 1.9mmHg Last visit Mean difference 2.7mmHg SBP DBP 163.9 164.1 94.8 94.5 ASCOT-BPLA, LANCET, vol 366 September 10, 2005 Data safety monitoring board Data safety monitoring board (DSMB)(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 2005. 18 CV mortalityCV mortality Number at risk Amlodipine ± perindopril 9639 9544 9441 9322 9167 8078 Atenolol ± thiazide 9618 9532 9415 9261 9085 7975 0.0 1.0 2.0 3.0 4.0 5.0 Years 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 Amlodipine ±±±± perindopril (No. of events 263) Atenolol ±±±± thiazide (No. of events 342) HR = 0.76 (0.65-0.90) p = 0.0010 % AllAll--cause mortality cause mortality Number at risk Amlodipine ± perindopril 9639 9544 9441 9332 9167 8078 Atenolol ± thiazide 9618 9532 9415 9261 9085 7975 % 0.0 1.0 2.0 3.0 4.0 5.0 Years 0.0 2.0 4.0 6.0 8.0 10.0 HR = 0.89 (0.81-0.99) p = 0.0247 Amlodipine ±±±± perindopril (No. of events 738) Atenolol ±±±± thiazide (No. of events 820) 19 NewNew--onset diabetes mellitus onset diabetes mellitus Number at risk Amlodipine ± perindopril 9639 9383 9165 8966 8726 7618 Atenolol ± thiazide 9618 9295 9014 8735 8455 7319 0.0 1.0 2.0 3.0 4.0 5.0 Years 0.0 2.0 4.0 6.0 8.0 10.0 Amlodipine ±±±± perindopril (No. of events = 567) Atenolol ±±±± thiazide (No. of events = 799) HR = 0.70 (0.63-0.78) p < 0.0001 % Primary end point + coronary revascularisation procedures Number at risk Amlodipine ± perindopril 9639 9458 9288 9086 8857 7732 Atenolol ± thiazide 9618 9447 9236 8986 8719 7590 % 0.0 1.0 2.0 3.0 4.0 5.0 Years 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 HR = 0.86 (0.77-0.96) p = 0.0058 Atenolol ±±±± thiazide (No. of events 688) Amlodipine ±±±± perindopril (No. of events 596) 8.0 20 Number at risk Amlodipine ± perindopril 9639 9400 9204 8984 8744 7614 Atenolol ± thiazide 9618 9373 9136 8864 8591 7470 Total coronary end point Total coronary end point Years0.0 1.0 2.0 3.0 4.0 5.0 0.0 2.0 4.0 6.0 8.0 10.0 Amlodipine ±±±± perindopril (No. of events 753) Atenolol ±±±± thiazide (No. of events 852) HR = 0.87 (0.79-0.96) p = 0.0070 % Fatal and nonFatal and non--fatal stroke fatal stroke Number at risk Amlodipine ± perindopril 9639 9483 9331 9156 8972 7863 Atenolol ± thiazide 9618 9461 9274 9059 8843 7720 0.0 1.0 2.0 3.0 4.0 5.0 Years 0.0 1.0 2.0 3.0 4.0 5.0 Amlodipine ±±±± perindopril (No. of events 327) Atenolol ±±±± thiazide (No. of events 422) HR = 0.77 (0.66-0.89) p = 0.0003 % 21 Total CV events and proceduresTotal CV events and procedures Number at risk Amlodipine ± perindopril 9639 9277 8957 8646 8353 7207 Atenolol ± thiazide 9618 9210 8848 8465 8121 6977 0.0 1.0 2.0 3.0 4.0 5.0 Years 0.0 2.0 4.0 6.0 8.0 10.0 12.0 14.0 16.0 18.0 Amlodipine ±±±± perindopril (No. of events 1362) Atenolol ±±±± thiazide (No. of events 1602) HR = 0.84 (0.78-0.90) p < 0.0001 % NewNew--onset renal impairmentonset renal impairment Number at risk Amlodipine ± perindopril 9639 9426 9277 9093 8877 7775 Atenolol ± thiazide 9618 9431 9247 9021 8782 7640 HR = 0.85 (0.75-0.97) p = 0.0187 0.0 1.0 2.0 3.0 4.0 5.0 Years 0.0 1.0 3.0 4.0 5.0% 2.0 Amlodipine ±±±± perindopril (No. of events = 403) Atenolol ±±±± thiazide (No. of events = 469) 22 Summary of all end pointsSummary of all end points The area of the blue square is proportional to the amount of statistical information Amlodipine ±±±± perindopril better Atenolol ±±±± thiazide better 0.50 0.70 1.00 1.45 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 Post hoc Primary end point + coronary revasc procs CV death + MI + stroke 2.00 Unadjusted Hazard ratio (95% CI) 0.90 (0.79-1.02) 0.87 (0.76-1.00) 0.87 (0.79-0.96) 0.84 (0.78-0.90) 0.89 (0.81-0.99) 0.76 (0.65-0.90) 0.77 (0.66-0.89) 0.84 (0.66-1.05) 1.27 (0.80-2.00) 0.68 (0.51-0.92) 0.98 (0.81-1.19) 0.65 (0.52-0.81) 1.07 (0.62-1.85) 0.70 (0.63-.078) 0.85 (0.75-0.97) 0.86 (0.77-0.96) 0.84 (0.76-0.92) ASCOT-BPLA, LANCET, vol 366 September 10, 2005 ConclusionsConclusions • 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, 2005 23 ASCOTASCOT--BPLABPLA Implications on Hypertension Implications on Hypertension GuidelinesGuidelines NICE Guideline 2006NICE Guideline 2006 24 Pharmacological interventionsPharmacological interventions • Drug therapy reduces the risk of cardiovascu