hypertension -complications and social impact hypertension -complications and social impact dr. ho...

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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

United

Sta

tes

Canad

a

Europ

eIta

ly

Sweden

Englan

dSpa

in

Finlan

d

Germ

any

Pre

vale

nce

(%)

MenWomenTotal

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

01020304050607080

China

(200

0/20

01)

Taiwan

(199

4)

Hong K

ong

(199

7)

Singap

ore

(199

8)

Mala

ysia

(199

6)

Thaila

nd (1

991)

Philipp

ines

(199

9)

Indo

nesia

(199

4)

India

(Mum

bai, 1

999)

Japa

n (19

92-9

5)

Pre

vale

nce

(%)

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 Physiol1997;24:987-988; National Health Survey 1998, Singap ore. 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 27France 24Canada 22Italy 9Egypt 8England 6Korea 5China 3Poland 2

<160/95 mmHg (%)Germany 23Finland 21Spain 20Australia 19Scotland 18India 9Zaire 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 TablesMales 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 2.45.0

2.03.5 2.1

45.5

21.3

12.4

6.2

9.97.3

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

Bie

nnia

l age

-adj

uste

d ra

te

per

1,00

0 su

bjec

ts NormotensiveHypertensive

Coronarydisease

Stroke Peripheral arterydisease

Cardiacfailure

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

121086420

14

Optimal BP

Normal BP

121086420

0 2 4 6 8 10 12Years

Optimal BP

Normal BP

High-normal BPWomen

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 DBPfor primary preventionfor primary prevention

DBP, diastolic blood pressure; CHD, coronary heart disease

-21

-16

-6

-46

-38

-15

-50

-40

-30

-20

-10

07.5 mmHg 5-6 mmHg 2 mmHg

CHDStroke

Ris

k re

duct

ion

(%)

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;289:2560-2572SBP, systolic blood pressure; DBP, diastolic blood pressure; BP, blood pressure

Treatment initiation: ESH/ESC 2003Treatment initiation: ESH/ESC 2003Blood pressure

Immediate drug treatment and lifestyle changes




Drug treatment and lifestyle changes

Associated clinical conditions





Lifestyle changes

3 or more risk factors, target organ damage, or diabetes


Lifestyle changes for several months, then drug treatment


Lifestyle changes

Lifestyle changes

1-2 risk factors



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

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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 agentat low dose

Two-drug combinationat low dose

If goal BP not achieved

Previous agent at full dose

Switch to differentagent 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-dosemonotherapy

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 4Resistant hypertension

Add: either alpha-blocker or spironolactone or other diuretic

A: ACE inhibitor or ARB B: Beta-blockerC: 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 (Secr etary) H. Wedel (Statistician), G. Beevers, M. Caulfield, R. Co llins

S. Kjeldsen, A. Kristinsson, J. Mehlsen, G. McInnes, M. Nieminen E. O’Brien, J. Östergren, on behalf of the ASCOT Inv estigators

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.


Study designStudy design

atenolol ±bendroflumethiazide

amlodipine ±perindopril

19,257hypertensive

patients

PROBE design

ASCOT-BPLA

Investigator-led, multinational randomised controlled trial

placeboatorvastatin 10 mg Double-blind

ASCOT-LLA10,305 patients

TC ≤ 6.5 mmol/L (250 mg/dL)


16

Treatment algorithm to BP targets < 140/90 mm Hgor < 130/80 mm Hg in patients with diabetes

amlodipine 5-10 mg atenolol 50-100 mg

perindopril 4-8 mgbendroflumethiazide-K

1.25-2.5 mg

doxazosin GITS 4-8 mg

add

add add

additional drugs, eg, moxonidine/spironolactone

add


Mean proportion of time on Mean proportion of time on antihypertensiveantihypertensivemedication 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)


17

Systolic and diastolic blood pressureSystolic and diastolic blood pressurem

m H

g

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 ± thiazideamlodipine ± 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


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.

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CV mortalityCV mortality

Number at riskAmlodipine ± perindopril 9639 9544 9441 9322 9167 8078Atenolol ± thiazide 9618 9532 9415 9261 9085 7975

0.0 1.0 2.0 3.0 4.0 5.0 Years0.0

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


%

0.0 1.0 2.0 3.0 4.0 5.0 Years0.0

2.0

4.0

6.0

8.0

10.0

HR = 0.89 (0.81-0.99)p = 0.0247



19

NewNew--onset diabetes mellitus onset diabetes mellitus


0.0 1.0 2.0 3.0 4.0 5.0 Years0.0

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 + coronaryrevascularisation procedures


%

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



8.0

20


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



HR = 0.87 (0.79-0.96)p = 0.0070

%

Fatal and nonFatal and non --fatal stroke fatal stroke


0.0 1.0 2.0 3.0 4.0 5.0 Years0.0

1.0

2.0

3.0

4.0

5.0



HR = 0.77 (0.66-0.89)p = 0.0003

%

21

Total CV events and proceduresTotal CV events and procedures


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



HR = 0.84 (0.78-0.90)p < 0.0001

%

NewNew--onset renal impairmentonset renal impairment


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 better0.50 0.70 1.00 1.45

PrimaryNon-fatal MI (incl silent) + fatal CHD

SecondaryNon-fatal MI (exc. Silent) +fatal CHDTotal coronary end pointTotal CV event and proceduresAll-cause mortalityCardiovascular mortalityFatal and non-fatal strokeFatal and non-fatal heart failure

TertiarySilent MIUnstable anginaChronic stable anginaPeripheral arterial diseaseLife-threatening arrhythmiasNew-onset diabetes mellitusNew-onset renal impairment

Post hocPrimary end point + coronary revasc procsCV 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)


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 statintherapy, the amlodipine ± perindopril regimen plus atorvastatinreduced coronary and stroke events by almost 50%


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 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 interventionsPharmacological 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.

25

Pharmacological interventionsPharmacological 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 recept or 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 co-morbidity and other drugs they are taking.

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 treatmentDrug 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 thiazide-type 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.

27

Drug treatmentDrug treatmentKey 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 thiazide-type 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.

28

BetaBeta --blockerblocker• 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 calcium-channel blocker rather than a thiazide-type diuretic, to reduce the patient’s risk of developing diabetes.

BetaBeta --blockerblocker• 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 toreplace 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.

29

PharmcoPharmco --economic Analysis 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 The cost of cardiovascular diseases and strokeand stroke


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