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Hypertension

Management Seminar–

executive summary

Dr C P Ho20060204

Definition and classification

of hypertension: 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 hypertension*:

North 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:

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, Singapo re. 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]

Goals of treatment: JNC VII

The SBP and DBP targets are <140/90 mmHg The primary focus should be on achieving the SBP goalIn 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

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<90 (DBP)

<90 (DBP)

<160/90

(SBP/DBP)

<90 (DBP)

<95 (DBP)

<160 (SBP)

Treatment failures

Study Blood pressure goal (mm Hg)

Patients not achieving goal on

active treatment (%)

HDFP

Australian Trial

EWPHE

IPPSH

HAPPHY

SHEP

23–37

36.1

22–32

34.6

23

28–35

Reference

HDFP, 1979

ANBP, 1980

Amery et al, 1991

IPPSH, 1985

Wilhelmsen et al, 1987

SHEP, 1991

24-h average blood pressure is correlated with:

Hypertension and

cardiovascular disease

Overall target organ damage score

Left ventricular mass

Impaired left ventricular function

(Micro) albuminuria

Brain damage

Retinopathy

Opsahl et al, 1988; Giaconi et al, 1989; Shimida et al , 1990; Hansen et al, 1992; White et al, 1993; Mancia et al, 1997

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Hypertensive kidney

Kidney damage asymptomatic till late stageViscous cycle to augment renal damage through the renin-angiotensin systemRate of damage predictableTreatment can reduce rate of progression

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Hypertensive kidney

Kidney damage asymptomatic till late stageViscous cycle to augment renal damage through the renin-angiotensin systemRate of damage predictableTreatment can reduce rate of progression

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The cost of cardiovascular

diseases and stroke

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

Millimetres matter …

“A 2-mmHg 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”

Cook NR, et al. Arch Intern Med 1995;155:701-709DBP, diastolic blood pressure; CHD, coronary heart disease; TIA, transient ischaemic attack

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Millimetres matter …

“For individuals 40-70 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 ”

JNC VII. JAMA 2003;289:2560-2572BP, blood pressure; CVD, cardiovascular disease

24-h blood pressure profile

in (dipper and non-dipper)Blood pressure (mm Hg)

7:00 11:00 15:00 19:00 23:00 3:00 7:00

Sleep

Dipper

Non-dipper

Time of day

175

135

115

95

75

55

155

Redman et al, 1976; Mancia et al, 1983; Kobrin et al, 1984; Baumgart et al, 1989; Imai et al, 1990; Portaluppi et al, 1991

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Current evidence suggests that:

� Measures of 24-h blood pressure more closely predict target organ damage than do clinic or casual measurements� There is a higher incidence of cardiovascular compl ications when

night-time blood pressure remains elevated

� Blood pressure variability is an additional and in dependent

determinant of target organ damage

� The highest incidence of cardiovascular events occu rs in the

morning at (approximately) 24 h post dose

Blood pressure and

target organ damage

Sokolow et al, 1966; Devereux et al, 1983; Devereux et al, 1987; Parati et al,1987; Mancia , 1990

Current evidence suggests that:

� Measures of 24-h blood pressure more closely predic t target organ

damage than do clinic or casual measurements

� There is a higher incidence of cardiovascular compl ications when

night-time blood pressure remains elevated

� Blood pressure variability is an additional

and independent determinant of target organ

damage

� The highest incidence of cardiovascular events occu rs in the morning

at (approximately) 24 h post dose

Blood pressure and

target organ damage

Sokolow et al, 1966; Pessina et al, 1985; Stanton et al, 1993; Veermanet al, 1993

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“The optimal formulation should provide 24-hourefficacy with a once- daily dose with at least 50% ofthe peak effect remaining at the end of the 24 hour s”

“Agents with a duration of action beyond 24 hoursare attractive because many patients inadvertentlymiss at least 1 dose of medication each week”

JNC-VI, 1997

JNC-VI Hypertension

Management Guidelines

Dippers *

(n=20)

BP: Night vs Day: *>10%; †<10%

*†Matched for age, sex, BMI, office BP, creatinin, li pids, antihypertensive R x

Fall in Cr Cl (ml/min.month)

Level of proteinuria (mg/24 h)

Night-time BP vs Cr Cl

Night-time BP vsproteinuria

Timio et al, 1993

-0.19

390

<0.001

<0.01

The importance of night-

time blood pressure

Non-dippers †

(n=28)

-0.33

659

r2=0.45

r2=0.22

<0.01

<0.01

Pvalue

11

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2 Important Directions

1. Life-Style Management2. Medical Therapy

General issues when

prescribingPrescribe 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.

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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 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.

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).

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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.

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

Beta-blockerIf 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.

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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 profileacross the range of other cardiovascular disease risks.

Target for blood

pressure control in CKD

With ACEI or ARB, reduce blood pressure to 130/80 mm HgIf urine protein >1 g/day, 120/75 mm HgIn type 2 diabetics, renal protection more clearly proven with ARB

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Angiotensin converting

enzymes inhibitor

For the same degree of BP reduction, also reduce proteinuriaPreservation of renal function (small study)� Lisinopril (Zestril) slows renal deterioration� Can be combined with verapamil or

diltiazem

Angiotensin Receptor

Blocker

Irbesartan Diabetic nephropathy TrialRENAAL Trial (Reduction of end-points in NIDDM with AA Losartan)

Clear renoprotection in diabetic nephropathy in type 2 diabeticsNo head to head comparison with ACEI

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Combination of ACEI and ARB Combination of ACEI and ARB Combination of ACEI and ARB Combination of ACEI and ARB

therapytherapytherapytherapy

Candesartan 16 mg and Lisinopril 20 mg Microalbuminuria Study (CALM)Combination therapy afforded greater reductions in blood pressure and albuminuria than either treatment alone. More complete blockage of the renin angiotensin system

K/DOQI Clinical practice

guidelines

Target� Reduction of proteinuria <1 g/day� blood pressure <130/80 mm Hg

Start with ACEI/ARBAdd DiureticsAdd non-dihydropyridine (verapamil or diltiazem)Add ARB/ACEI

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Dialysis outcome

Blood pressure controlCa and phosphate controlHb around 11 – 12 g/dlNutrition of the patient, serum albumin >30 g/lDialysis dose

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How to improve dialysis

outcome

The most important determinant is the FREQUENCY of dialysisProvide quality dialysis Affordable DialysisThree times per week

Daily dialysis in home HD case

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