British Hypertension Society guidelines for hypertension management 2004 (BHS-IV): summary

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British Hypertension Society guidelines for
hypertension management 2004 (BHS-IV):
summary
Bryan Williams, Neil R Poulter, Morris J Brown, Mark Davis, Gordon T
McInnes, John F Potter, Peter S Sever and Simon McG Thom
BMJ 2004;328;634-640
doi:10.1136/bmj.328.7440.634
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Education and debate
British Hypertension Society guidelines for hypertension
management 2004 (BHS-IV): summary
Bryan Williams, Neil R Poulter, Morris J Brown, Mark Davis, Gordon T McInnes, John F Potter,
Peter S Sever, Simon McG Thom; the BHS guidelines working party, for the
British Hypertension Society
Department of
Cardiovascular
Sciences, University
of Leicester, Clinical
Sciences Building,
Leicester Royal
Infirmary, Leicester
Bryan Williams
professor of medicine
International
Centre for
Circulatory Health,
Imperial College
London and St
Mary’s Hospital,
London
Neil R Poulter
professor of preventive
cardiovascular
medicine
Peter S Sever
professor of clinical
pharmacology
Simon McG Thom
reader in medicine
Clinical
Pharmacology Unit,
Addenbrooke’s
Hospital, University
of Cambridge,
Cambridge
Morris J Brown
professor of clinical
pharmacology
Moorfield House
Surgery, Garforth,
Leeds
Mark Davis
general practitioner
Section of Clinical
Pharmacology and
Stroke Medicine,
Division of
Cardiovascular and
Medical Sciences,
Gardiner Institute,
Western Infirmary,
University of
Glasgow, Glasgow
Gordon T McInnes
professor of clinical
pharmacology
continued over
BMJ 2004;328:634–40
634
Introduction
Objectives of the guidelines
Much new evidence has emerged on the importance of
blood pressure as a risk factor for cardiovascular
disease; the importance of lifestyle measures for the
prevention and treatment of hypertension; the efficacy
and safety of different drug classes; management of
hypertension in groups at higher risk, including people
with diabetes; the importance of assessing the total risk
of cardiovascular disease; and additional benefits associated with the use of statins.
Concern remains that national surveys continue to
show substantial underdiagnosis, undertreatment, and
poor rates of blood pressure control in the United
Kingdom.1 A key reason for this is the predominant use
of monotherapy by most doctors.1 To improve this suboptimal treatment, the British Hypertension Society
recommends a treatment algorithm based on the
AB/CD rule.2
Treatment of blood pressure alone will leave many
hypertensive patients at unacceptably high risk of
cardiovascular complications and death. This guideline
reinforces the view that doctors should not focus solely
on blood pressure but must also formally assess total
risk of cardiovascular disease and use multifactorial
interventions, including statins and aspirin, to reduce it.
Most management of blood pressure and risk of
cardiovascular disease will take place in primary care,
and these guidelines are intended for general
practitioners, practice nurses, and generalists in hospital practice. Detailed advice on implementation and
the implications of the national service frameworks
and the general medical services contract are
contained in the full document (www.bhsoc.org).3
These guidelines have been prepared by the guidelines working party of the British Hypertension Society
on behalf of the society. The working party reviewed
new data that have become available since the previous
guidelines were published4 and amended the recommendations accordingly. Drafts of the full document
were improved by consultation with national stakeholder organisations (appendix 1). The evidence
supporting the recommendations contained in
BHS-IV is graded by using the criteria of the North of
England group (see box on bmj.com).5
The objectives highlighted and prioritised in the
previous guidelines4 remain relevant and are reiterated.
x To promote the primary prevention of hypertension and cardiovascular disease by changes in the
diet and lifestyle of the whole population
x To increase the detection and treatment of
undiagnosed hypertension by routine screening and
increase awareness of hypertension among the public
x To ensure that patients taking antihypertensive
drugs are controlled to optimal blood pressure levels
x To reduce the risk of cardiovascular disease of
treated hypertensive patients by non-pharmacological
measures, and by appropriate use of statin and aspirin
treatment
x To increase the identification and treatment of
patients with mild hypertension who are at high risk of
cardiovascular disease—for example, elderly patients,
patients with ischaemic heart disease, people with
diabetes, people with target organ damage, or people
with multiple risk factors
Table 1 Classification of blood pressure levels of the British
Hypertension Society
Systolic blood pressure
(mm Hg)
Diastolic blood pressure
(mm Hg)
Optimal
<120
<80
Normal
<130
<85
130-139
85-89
Category
Blood pressure
High normal
Hypertension
Grade 1 (mild)
140-159
90-99
Grade 2 (moderate)
160-179
100-109
≥180
≥110
Grade 1
140-159
<90
Grade 2
≥160
<90
Grade 3 (severe)
Isolated systolic hypertension
This classification equates with those of the European Society of Hypertension6
and the World Health Organization-International Society of Hypertension7 and is
based on clinic blood pressure and not values for ambulatory blood pressure
measurement. Threshold blood pressure levels for the diagnosis of
hypertension using self/home monitoring are greater than 135/85 mm Hg. For
ambulatory monitoring 24 hour values are greater than 125/80 mm Hg. If
systolic blood pressure and diastolic blood pressure fall into different categories
the higher value should be taken for classification.
Categories of strength used in statements are on bmj.com
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Education and debate
x To promote continued adherence to drug treatment, by optimising the choice and use of drugs, minimising side effects, and increasing information and
choice for patients.
Blood pressure measurement
The British Hypertension Society’s classifications of
blood pressure levels have changed in line with recent
European guidelines (table 1).6
All adults should have blood pressure measured
routinely at least every five years until the age of 80
years. People with “high normal” systolic blood
pressure (130-139 mm Hg) or diastolic blood pressure
(85-89 mm Hg) and people who have had high blood
pressure readings at any time previously should have
their blood pressure measured annually. The European recommendations for measuring blood pressure
should be followed (box 1).8 Seated blood pressure
recordings are generally sufficient, but standing blood
pressure should be measured in elderly or diabetic
patients to exclude notable orthostatic hypotension.
The average of two readings at each of a number of
visits (depending on severity) should be used to guide
the decision to treat. Automated or semiautomated
devices are increasingly used for home or ambulatory
blood pressure measurement. Box 2 shows possible
indications for the use of ambulatory blood pressure
measurement, and detailed guidance on blood
pressure measurement and validated monitors is available at www.bhsoc.org.
Box 1: Blood pressure measurement by
standard mercury sphygmomanometer or
semiautomated device
• Use a properly maintained, calibrated, and validated
device
• Measure sitting blood pressure routinely: standing
blood pressure should be recorded at least at the initial
estimation in elderly or diabetic patients
• Remove tight clothing, support arm at heart level,
ensure arm relaxed and avoid talking during the
measurement procedure
• Use cuff of appropriate size (see box 3 in the full
guidelines,3 www.bhsoc.org)
• Lower mercury column slowly (2 mm per second)
• Read blood pressure to the nearest 2 mm Hg
• Measure diastolic blood pressure 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
For full details of methods see www.bhsoc.org and
reference 8
Absolute risk of cardiovascular disease
estimation
The treatment of hypertension and the primary
prevention of cardiovascular disease should be
informed by assessment of total risk of cardiovascular
disease. In collaboration with the Joint British Societies’
initiative for preventing cardiovascular disease, a new
cardiovascular disease chart and risk calculator
program have been produced (www.bhsoc.org).3 The
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Box 2: Potential indications for the use of
ambulatory blood pressure monitoring
• Unusual variability of blood pressure
• Possible white coat hypertension
• Informing equivocal treatment decisions
• Evaluation of nocturnal hypertension
• Evaluation of drug resistant hypertension
• Determining the efficacy of drug treatment over
24 hours
• Diagnosis and treatment of hypertension in
pregnancy
• Evaluation of symptomatic hypotension
Ageing and Stroke
Medicine Section,
Department of
Cardiovascular
Sciences, Glenfield
Hospital, University
of Leicester,
Leicester
John F Potter
professor of ageing
and stroke medicine
Correspondence to:
B Williams bw17@
le.ac.uk
chart and the program assess 10 year risk of cardiovascular disease rather than risk of coronary heart disease,
reflecting the treatment objective of reducing all
cardiovascular events, including stroke. The new chart
has been simplified since 1999 by including only three
age strata, to improve the balance of emphasis between
relative risk and short term absolute risk. No chart is
provided for patients with type 2 diabetes because for
the vast majority (people aged > 50 years or whose
condition has been diagnosed for ≥ 10 years) their risk
of cardiovascular disease is equivalent to people who
have had a myocardial infarction and therefore should
be considered for secondary prevention.9 The use of
this chart or computer program is recommended to
aid decisions on treatment for people with grade 1
(mild) hypertension and to help guide the appropriate
use of statins and aspirin for primary prevention.
Evaluation of hypertensive patients
All hypertensive patients should have a thorough
history and physical examination but need only a
limited number of routine investigations (box 3). The
purpose of the evaluation is to assess the cause(s) of the
hypertension, associated cardiovascular risk factors,
evidence of target organ damage and comorbid
diseases, all of which may influence treatment decisions
(box 4). More complex investigations may require
specialist referral—box 5 shows indications for this.
Thresholds for intervention with drug treatment
Figure 1 shows recommended blood pressure thresholds for intervention with drug treatment. Drug
treatment is recommended in patients with sustained
grade 2 hypertension ( ≥ 160/100 mm Hg). All patients
with grade I hypertension (systolic blood pressure 140159 or diastolic blood pressure 90-99 mm Hg, or both)
should be offered treatment with antihypertensive
drugs if there is any complication of hypertension or
target organ damage (defined in box 4), or diabetes, or
Box 3: Routine investigations
• Urine strip test for protein and blood
• Serum creatinine and electrolytes
• Blood glucose—ideally fasted
• Blood lipid profile (at least total and high density
lipoprotein (HDL) cholesterol)—ideally fasted for
consideration of triglycerides
• Electrocardiogram
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Box 4: Evaluation of hypertensive patients
Causes of hypertension
• Drugs (non-steroidal anti-inflammatory drugs, oral
contraceptives, steroids, liquorice, sympathomimetics,
some cold cures)
• Renal disease (present, past, or family history,
proteinuria or haematuria: palpable
kidney(s)—polycystic, hydronephrosis, or neoplasm)
• Renovascular disease (abdominal or loin bruit)
• Phaeochromocytoma (paroxysmal symptoms)
• Conn’s syndrome (tetany, muscle weakness, polyuria,
hypokalaemia)
• Coarctation (radio-femoral delay or weak femoral
pulses).
• Cushing’s (general appearance)
Contributory factors
• Overweight
• Excess alcohol ( > 3 units/day for men; > 2
units/day for women)
• Excess salt intake
• Lack of exercise
• Environmental stress
Complications of hypertension or target organ
damage
• Stroke, transient ischaemic attack, dementia, carotid
bruits
• Left ventricular hypertrophy or left ventricular strain
on electrocardiogram
• Heart failure
• Myocardial infarct, angina, coronary artery bypass
graft, or angioplasty
• Peripheral vascular disease
• Fundal haemorrhages or exudates, papillodoema
• Proteinuria
• Renal impairment (raised serum creatinine)
Risk factors for cardiovascular disease
• Smoking
• Diabetes
• Ratio of total cholesterol: HDL cholesterol
• Family history
• Age
• Sex
Drug contraindications
See table 2.
if there is an estimated 10 year risk of cardiovascular
disease of ≥ 20% despite lifestyle advice.
When it is decided not to treat grade I (mild)
hypertension with drugs, lifestyle measures should be
encouraged and blood pressure and risk of cardiovascular disease should be reassessed annually. The
reason for this is that blood pressure will rise within
five years to levels requiring treatment in about
10-15% of patients, and risk of cardiovascular disease
will rise with age.
Treatment goals or “targets”
Definitive evidence on optimal targets for blood
pressure lowering is lacking. The hypertension optimal
treatment (HOT) trial was underpowered but to date,
still provides the best evidence on optimal targets.10 It
reported, albeit on the basis of an on-treatment analy636
sis, that the optimal blood pressure for reduction of
major cardiovascular events was 139/83 mm Hg and
that reduction of blood pressure below this value
caused no harm. However, patients whose blood pressure was between 139/83 mm Hg and 150/90 mm Hg
were also not disadvantaged. In light of these observations we previously recommended a blood pressure
target of < 150/90 mm Hg as an “audit standard”—the
minimal target that all treated patients should attain.4
This recommendation remains unchanged. Box 6
shows recommendations for “optimal” blood pressure
targets during treatment. Evidence from intervention
trials in hypertensive people with diabetes, people at
high risk of cardiovascular disease, and people who
have had a stroke supports a “lower the better” policy
for optimal blood pressure.10–12 Hence, lower targets are
recommended for these “higher risk” populations.
Treatment
Lifestyle measures
Recent trial evidence has reinforced recommendations
that certain lifestyle measures can lower blood
pressure.13–15 Hence advice on lifestyle modifications
should be provided to all people with high blood pressure and people with borderline or high normal blood
pressure. This approach can reduce the age associated
rise in blood pressure and therefore reduce the large
proportion of people with high normal blood pressure
who would otherwise eventually require drug therapy.
For those with grade 1 (mild) hypertension and no
complications of cardiovascular disease or damage to
the target organ, lifestyle measures should be evaluated
for up to six months. For people who need antihypertensive therapy, lifestyle measures should still be
Box 5: Suggested indications for specialist
referral
Urgent treatment needed
• Accelerated hypertension (severe hypertension and
grade III-IV retinopathy)
• Particularly severe hypertension ( > 220/120 mm Hg)
• Impending complications (for example, transient
ischaemic attack, left ventricular failure)
Possible underlying cause
• Any clue in history or examination of a secondary
cause, such as hypokalaemia with increased or high
normal plasma sodium (Conn’s syndrome)
• Elevated serum creatinine
• Proteinuria or haematuria
• Sudden onset or worsening of hypertension
• Resistant to multidrug regimen ( ≥ 3 drugs)
• Young age (any hypertension < 20 years; needing
treatment < 30 years)
Therapeutic problems
• Multiple drug intolerance
• Multiple drug contraindications
• Persistent non-adherence or non-compliance
Special situations
• Unusual blood pressure variability
• Possible white coat hypertension
• Hypertension in pregnancy
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Thresholds for intervention
Initial blood pressure (mm Hg)
Box 6: Thresholds and treatment targets for
antihypertensive drug treatment
• Drug treatment should be started in all patients with
sustained systolic blood pressures ≥ 160 mm Hg or
sustained diastolic blood pressures ≥ 100 mmHg
despite non-pharmacological measures (A)
• Drug treatment is also indicated in patients with
sustained systolic blood pressures 140-159 mm Hg or
diastolic blood pressures 90-99 mm Hg if target organ
damage is present, or there is evidence of established
cardiovascular disease or diabetes, or if there is a 10
year cardiovascular disease risk of ≥ 20% (B)
• For most patients a target of ≤ 140 mm Hg systolic
blood pressure and ≤ 85 mm Hg diastolic blood
pressure is recommended (B). For patients with
diabetes, renal impairment or established cardiovascular
disease a lower target of ≤ 130/80 mm Hg is
recommended
• When using ambulatory blood pressure readings,
mean daytime pressures are preferred and this value
would be expected to be approximately 10/5 mm Hg
lower than the office blood pressure equivalent for
both thresholds and targets. Similar adjustments are
recommended for averages of home blood pressure
readings
recommended as they may complement the blood
pressure lowering effects of drugs and thus reduce the
dose or number of drugs required to control blood
pressure. Box 7 shows lifestyle measures that lower
blood pressure and pre-empt the rise of blood
pressure with age.
Lifestyle measures that reduce risk of cardiovascular disease include smoking cessation, reducing
intake of total and saturated fats, replacement of saturated with monounsaturated fats (such as olive oil,
rapeseed oil), and increasing consumption of fish.
Effective implementation of these lifestyle measures requires knowledge, enthusiasm, patience, considerable time spent with patients and other family
members, and reinforcement. It is best undertaken by
well trained health professionals such as practice or
clinic nurses and should be supported by clear written
information (www.bpassoc.org.uk).
Choice of antihypertensive drug therapy
For each major class of antihypertensive drug
compelling indications exist for use in specific groups
of patients and also compelling contraindications.
There are also indications, contraindications, and
• Maintain normal weight for adults (body mass index
20-25 kg/m2)
• Reduce salt intake to < 100 mmol/day ( < 6g NaCl
or < 2.4 g Na+/day)
• Limit alcohol consumption to ≤ 3 units/day for men
and ≤ 2 units/day for women
• Engage in regular aerobic physical exercise (brisk
walking rather than weightlifting) for ≥ 30 minutes per
day, ideally on most of days of the week but at least on
three days of the week
• Consume at least five portions/day of fresh fruit and
vegetables
• Reduce the intake of total and saturated fat
13 MARCH 2004
*
160-179
140-159
130-139
100-109
90-99
85-89
†
†
≥160/100
140-159
<130/85
<140/90
90-99
Target organ damage or
cardiovascular complications or
diabetes or 10 year risk of
cardiovascular disease§ ≥ 20%
Treat
Treat
Treat
No target organ damage and
no cardiovascular complications
and no diabetes and 10 year risk
of cardiovascular disease§ < 20%
Observe, reassess risk of
cardiovascular disease yearly
Reassess
yearly
Reassess
in 5 years
* Unless malignant phase of hypertensive emergency confirm over 1-2 weeks then treat
† If cardiovascular complications, target organ damage, or diabetes is present, confirm over 3-4 weeks
then treat; If absent remeasure weekly and treat if blood pressure persists at these levels over 4-12
weeks
† If cardiovascular complications, target organ damage, or diabetes is present, confirm over 12 weeks
then treat; If absent remeasure monthly and treat if these levels are maintained and if estimated 10
year cardiovascular disease risk is ≥20%
§ Assessed with risk chart for cardiovascular disease
Fig 1 Blood pressure thresholds for intervention
cautions that are less clear cut and that are given
different weight by different doctors (table 2). When
none of the special considerations apply, initial drug
selection should follow step 1 of the AB/CD
algorithm (fig 2).2
Step 1
Younger (<55 years)
and non-black
Older (≥55 years)
or black
A (or B*)
C or D
Step 2
A (or B*) + C or D
Step 3
A (or B*) + C + D
Step 4
Resistant hypertension
Add either α blocker
or spironolactone or other diuretic
A: ACE inhibitor or angiotensin receptor blocker
C: Calcium channel blocker
B: β blocker
D: Diuretic (thiazide
and thiazide-like)
* Combination therapy involving B and D may induce more new onset diabetes compared with
other combination therapies
Box 7: Lifestyle measures
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Fig 2 Recommendations for combining blood pressure lowering
drugs (AB/CD rule) (adapted from reference 2, Brown et al)
Meta-analyses of blood pressure lowering trials
Since 1999 4 many large scale morbidity and mortality
trials have compared different classes of antihypertensive drugs. The Blood Pressure Lowering Trialists’ Collaboration has conducted two major meta-analyses of
blood pressure lowering drugs.16 17 The first compared
the effectiveness of “newer therapies,” such as
treatments based on angiotensin converting enzyme
inhibitors or calcium channel blockers, with conventional therapies (based on diuretics or blockers) and
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Education and debate
Table 2 Compelling and possible indications, contraindications, and cautions for the major classes of antihypertensive drugs
Class of drug
Compelling indications
Possible indications
Caution
Compelling contraindications
blockers
Benign prostatic hypertrophy
—
Postural hypotension, heart failure*
Urinary incontinence
Angiotensin converting
enzyme inhibitors
Heart failure
Left ventricular dysfunction post-myocardial
infarction or established coronary heart disease
Type 1 diabetic nephropathy
Secondary stroke prevention¶
Chronic renal disease†
Type 2 diabetic nephropathy
Proteinuric renal disease
Renal impairment†
Peripheral vascular disease‡
Pregnancy
Renovascular disease§
Angiotensin II receptor
blockers
Angiotensin converting enzyme inhibitor
intolerance
Type 2 diabetic nephropathy
Hypertension with left ventricular hypertrophy
Heart failure in angiotensin converting enzyme
intolerant patients, after myocardial infarction
Left ventricular dysfunction after
myocardial infarction
Intolerance of other antihypertensive
drugs
Proteinuric renal disease, chronic renal
disease†
Heart failure
Renal impairment†
Peripheral vascular disease‡
Pregnancy
Renovascular disease§
blockers
Myocardial infarction, angina
Heart failure**
Heart failure**
Peripheral vascular disease,
Diabetes (except with coronary heart
disease)
Asthma or chronic obstructive
pulmonary disease,
Heart block
Calcium channel blockers
(dihydropyridine)
Elderly patient, isolated systolic hypertension
Angina
—
—
Calcium channel blockers
(rate limiting)
Angina
Elderly patient
Combination with blockade
Heart block, heart failure
Thiazides or thiazide-like
diuretics
Elderly patient, isolated systolic hypertension,
heart failure, secondary stroke prevention
—
—
Gout††
*In heart failure when used as monotherapy.
† Angiotensin converting enzyme inhibitors or angiotensin II receptor blockers may be beneficial in chronic renal failure but should only be used with caution, close supervision, and specialist
advice when there is established and significant renal impairment.
‡Caution with angiotensin converting enzyme inhibitors and angiotensin II receptor blockers in peripheral vascular disease because of association with renovascular disease.
§Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers are sometimes used in patients with renovascular disease under specialist supervision.
¶In combination with a thiazide or thiazide-like diuretic.
** blockers are used increasingly to treat stable heart failure but may worsen heart failure.
††Thiazides or thiazide-like diuretics may sometimes be necessary to control blood pressure in people with a history of gout, ideally used in combination with allopurinol.
concluded, while conceding that insufficient data
existed, that newer therapies were as effective as, but no
more effective than, conventional therapy at reducing
stroke, morbidity or mortality due to coronary heart
disease, or all cause mortality.16 The second metaanalysis included 29 major trials published as of 2003,
with over 700 000 years of patient follow up.17 The
findings of this second meta-analysis are largely
consistent with the first: the main driver of benefit from
blood pressure lowering therapy is blood pressure lowering per se, and little evidence exists of additional
benefits specific to a class of drug with regard to major
cardiovascular outcomes overall. The caveats to this
general conclusion are, firstly, that calcium channel
blockers may be less protective than other agents
against the development of heart failure. Secondly,
previous concerns regarding the safety and efficacy of
treatment with calcium channel blockers for prevention of cardiovascular disease are unfounded. Thirdly,
therapy based on calcium channel blockers may have
small benefits and treatment with angiotensin receptor
blockers may have possibly larger benefits with regard
to stroke prevention. Fourthly, specific drug classes
may have compelling indications (table 2).
The AB/CD algorithm
Most people require more than one drug to control
blood pressure. Clinical trials have clearly shown that
treatment algorithms deliver better blood pressure
control than current clinical practice.1 17 The British
Hypertension Society recommends the use of a
treatment algorithm based on the AB/CD rule to
inform the better use of logical combinations of drugs.2
Each letter refers to a blood pressure lowering drug
class (fig 2).
The theory underpinning the AB/CD algorithm is
that hypertension can be broadly classified as “high
renin” or “low renin” and is therefore best treated ini638
tially with one of two categories of antihypertensive
drug—those that inhibit the renin-angiotensin system
(angiotensin converting enzyme inhibitors or angiotensin receptor blockers (A) or blockers (B)), and
those that do not (calcium channel blockers (C) or
diuretics (D)). People who are younger than 55 and
white tend to have higher renin concentrations than
people aged 55 or older or the black population (of
African descent). A or B drugs are therefore generally
more effective as initial blood pressure lowering treatment in younger white patients than C or D drugs.
However, C or D drugs are more effective first line
agents for older white people or black people of any
age.18 19 When the first drug is well tolerated but the
response is small and insufficient, substitution of an
alternative drug is appropriate if hypertension is mild
and uncomplicated. In more severe or complicated
hypertension it is safer to add drugs stepwise until
blood pressure is controlled. Treatment can be
stepped down later if blood pressure falls substantially
below the optimal level.
If two drugs are required logical combinations are:
(A or B)+(C or D). Thereafter, if blood pressure is still
insufficiently controlled, the combination of (A or
B)+C+D is recommended. When fixed dose combinations replicate the desired treatment plan for a patient
and when there is no cost disadvantage to their use,
they represent a sensible way of reducing the number
of tablets required. When hypertension remains resistant, A+B+C+D or the addition of an blocker or low
dose spironolactone may be effective.
The AB/CD protocol is not restrictive and provides
a template that allows the use of all classes of
antihypertensive drugs. All things being equal and
when there are no compelling indications for
treatment with a specific class of drugs (table 2), the
least expensive drugs should be used.
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The AB/CD algorithm includes B in brackets. This
is to emphasise the fact that recent outcome trials have
reported an increased incidence of diabetes in patients
treated with B or D drugs compared with A or C drugs,
especially when B and D are combined.20 We advise
caution when using B+D in patients at especially high
risk of developing diabetes—for example, patients with
a strong family history of type 2 diabetes, obesity,
impaired glucose tolerance, features of the metabolic
syndrome, or of South Asian and African-Caribbean
descent.
Drug dosage
The drug or formulation used should ideally be effective for 24 hours when taken as a single daily dose. An
interval of at least four weeks should be allowed to
observe the full response, unless it is necessary to lower
blood pressure more urgently. The drug dose (except
for thiazides or thiazide-like diuretics, the ideal dose of
which is uncertain) should be titrated up according to
manufacturers’ instructions.
Recommendations for use of aspirin and statins
Aspirin—No new evidence to guide practice regarding the use of aspirin for patients with hypertension
has been produced since the 1999 guidelines of the
British Hypertension Society.4 Hence recommendations remain unchanged (box 8).
Statins—Recommendations relating to the use of
statins for patients with hypertension have been
updated in light of recent trial data21 22 and are in keeping with recent European guidance.6 Box 8 shows indications for using statins in the context of primary and
secondary prevention. Patients with type 2 diabetes are
considered as for secondary prevention in this context.
Target lipid concentrations are the same for primary
and secondary prevention and have been made more
stringent in light of the most recent trial evidence. New
ideal targets are to lower total cholesterol by 25% or
LDL cholesterol by 30% or to reach < 4.0 mmol/l or
< 2.0 mmol/l respectively, whichever is the greater.
Box 8: Other medications for hypertensive
patients
Primary prevention
(1) Aspirin: use 75 mg daily if patient is aged ≥ 50 years
with blood pressure controlled to < 150/90 mm Hg
and; target organ damage, diabetes mellitus, or 10 year
risk of cardiovascular disease of ≥ 20% (measured by
using the new Joint British Societies’ cardiovascular
disease risk chart)
(2) Statin: use sufficient doses to reach targets if patient
is aged up to at least 80 years, with a 10 year risk of
cardiovascular disease of ≥ 20% (measured by using
the new Joint British Societies’ cardiovascular disease
risk chart) and with total cholesterol concentration
≥ 3.5mmol/l
(3) Vitamins—no benefit shown, do not prescribe
Secondary prevention (including patients with
type 2 diabetes)
(1) Aspirin: use for all patients unless contraindicated
(2) Statin: use sufficient doses to reach targets if patient
is aged up to at least 80 years with a total cholesterol
concentration ≥ 3.5 mmol/l
(3) Vitamins—no benefit shown, do not prescribe
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Summary points
All people with high blood pressure, borderline
or high normal blood pressure should be advised
on lifestyle modifications
Initiate antihypertensive drug therapy if sustained
systolic blood pressure ≥ 160 mm Hg or
sustained diastolic blood pressure ≥ 100 mm Hg
If sustained systolic blood pressure is 140-159
mm Hg or sustained diastolic blood pressure
90-99 mm Hg, consider initiating treatment if
cardiovascular disease or other target organ
damage present, or if estimated 10 year risk of
cardiovascular disease is ≥ 20%
Non-diabetic people: optimal goals for blood
pressure treatment are: systolic blood pressure
< 140 mm Hg and diastolic blood pressure
< 85 mm Hg. The minimum acceptable level of
control (audit standard) recommended is
< 150/ < 90 mm Hg
In people with diabetes mellitus, initiate
antihypertensive drug treatment if systolic blood
pressure is sustained ≥ 140 mm Hg or diastolic
blood pressure is sustained ≥ 90 mm Hg
In hypertensive people with diabetes, chronic
renal disease, or established cardiovascular
disease optimal blood pressure goals are systolic
blood pressure < 130 mm Hg and diastolic blood
pressure < 80 mm Hg. Audit standard
< 140/ < 80 mm Hg
Most people with high blood pressure will require
at least two blood pressure lowering drugs to
achieve the recommended goals. When no
disadvantages of cost exist, fixed drug
combinations are recommended
Low dose aspirin (75 mg/day) is recommended
for secondary prevention of ischaemic
cardiovascular disease and for primary
prevention, in people over the age of 50 who have
a 10 year risk of cardiovascular disease of ≥ 20%
and in whom blood pressure is controlled to the
audit standard
Statins are recommended for all people with high
blood pressure complicated by cardiovascular
disease, irrespective of baseline concentrations
total cholesterol or low density lipoprotein (LDL)
cholesterol. Statins are also recommended for
primary prevention in people with high blood
pressure who have a 10 year risk of cardiovascular
disease of ≥ 20%
However a total cholesterol concentration < 5.0 mmol/l
or LDL cholesterol < 3.0 mmol/l or reductions of 25%
or 30%, respectively (whichever is the greater), provides
a minimal acceptable “audit” standard.
639
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Education and debate
Follow up
The frequency of follow up for treated patients with
adequate blood pressure control depends on factors
including severity and variability of blood pressure,
complexity of the treatment regimen, and compliance.
Six monthly review is probably sufficient when
treatment and blood pressure are stable. The routine
for follow up visits, at which trained nurse practitioners
have an important role, should be simple: measure
blood pressure and weight, inquire about general
health and side effects, reinforce lifestyle advice and
adherence to drug therapy, and test for proteinuria
annually.
Appendix 2: Contact details
British Hypertension Society Information Service
Blood Pressure Unit, St George’s Hospital Medical School,
Cranmer Terrace, London SW17 0RE (tel 020 8725 3412;
fax 020 8725 2959; [email protected]; www.bhsoc.org)
Blood Pressure Association
60 Cranmer Terrace, London SW17 0QS (tel 020 8772 4994;
fax 020 8772 4999; bpassoc.org.uk). To contact the
association by email, submit a query form through the website
1
2
3
Implementation
These guidelines come at an opportune time. The
reduction of cardiovascular events in the population
has been given a high priority by the Department of
Health, which has introduced several key initiatives
through the national service frameworks. The new
contract for general medical services has given
substantial prominence to the management of
hypertension as a key performance target, and primary
care trusts across the country participate in redesigning services. To implement this guideline effectively,
new systems of healthcare delivery will need to be
developed in primary care. Multidisciplinary teams will
need to work in a systematic and structured way to
advise, educate and support patients. A need exists for
an extended role for nurse practitioners, pharmacists,
and other healthcare professionals, to provide the
foundation for the more widespread and effective
detection, monitoring, and treatment of blood pressure
and risk of cardiovascular disease.
4
5
6
7
8
9
10
11
12
BW is chairman of the guideline working party; NRP, MJB, MD,
GTM, JFP, and PSS are members of the guideline working party;
SMcGT is a member of the British Hypertension Society. The
British Hypertension Society gratefully acknowledges the work
done by the representatives of the many stakeholder
organisations who reviewed the full guideline (appendix 1) and
whose comments greatly improved the final version. We also
acknowledge the outstanding administrative assistance provided
by Emma Fluck at the British Hypertension Society’s
information service.
Competing interests: All authors have received honorariums
from a number of pharmaceutical companies for lectures and
consultancy, and research grant support for clinical trials from
the pharmaceutical industry.
Appendix 1: Stakeholders who reviewed the
guidelines
Blood Pressure Association
Nurses’ Hypertension Association
Diabetes UK
British Cardiac Association
Renal Association
Heart UK
Primary Care Cardiovascular Society
London Hypertension Society
British Heart Foundation
Royal College of General Practitioners
Friends of the British Hypertension Society
Department of Health
640
13
14
15
16
17
18
19
20
21
22
Primatesta P, Brookes M, Poulter NR. Improved hypertension
management and control: results from the health survey for England
1998. Hypertension 2001;38:827-32.
Brown MJ, Cruickshank JK, Dominiczak AF, MacGregor GA, Poulter NR,
Russell GI, et al. Executive Committee, British Hypertension Society.
Better blood pressure control: how to combine drugs. J Hum Hypertens
2003;17:81-6.
Williams B, Poulter NR, Brown MJ, Davis M, McInnes GT, Potter JF, et al.
Guidelines for management of hypertension: report of the fourth working party of the British Hypertension Society, 2004—BHS IV. J Hum
Hypertens 2004;18:139-85.
Ramsay LE, Williams B, Johnston G, MacGregor G, Poston L, Potter J, et
al. Guidelines for management of hypertension: report of the third working party of the British Hypertension Society. J Human Hypertens
1999;13:569-92.
Eccles M, Freemantle N, Mason J. North of England evidence based
guidelines development project: methods of developing guidelines for
efficient drug use in primary care. BMJ 1998;316:1232-5.
Guidelines Committee. 2003 European Society of HypertensionEuropean Society of Cardiology guidelines for the management of
arterial hypertension. J Hypertens 2003;21:1011-53.
Guidelines Subcommittee. 1999 World Health Organization-International
Society of Hypertension guidelines for the management of hypertension.
J Hypertens 1999;17:151-83.
O’Brien E, Asmar R, Beilin L, Imai Y, Mallion JM, Mancia G, et al. European Society of Hypertension Working Group on Blood Pressure Monitoring. European Society of Hypertension recommendations for
conventional, ambulatory and home blood pressure measurement.
J Hypertens 2003;21:821-48.
Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). Executive summary of the
third report of the National Cholesterol Education Program (NCEP)
JAMA 2001;285:2486–2497
Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S, et
al. for the HOT Study Group. Effects of intensive blood pressure lowering
and low-dose aspirin in patients with hypertension: principal results of
the hypertension optimal treatment (HOT) randomised trial. Lancet
1998;351:1755-62.
The Heart Outcomes Prevention Evaluation Study Investigators. Effects
of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. New Eng J Med 2000;342:145-153
PROGRESS Collaborative Group. Randomised trial of a perindoprilbased blood-pressure-lowering regimen among 6105 individuals with
previous stroke or transient ischaemic attack. Lancet 2001;358:1033-41.
Whelton PK, He J, Appel LJ, Cutler JA, Havas S, Kotchen TA, et al.
National High Blood Pressure Education Program Coordinating
Committee. Primary prevention of hypertension. Clinical and public
health advisory from the National High Blood Pressure Education
Program. JAMA 2002;288:1882-8.
Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, et al.
DASH-Sodium Collaborative Research Group. Effects on blood pressure
of reduced dietary sodium and the dietary approaches to stop
hypertension (DASH) diet. N Engl J Med 2001;344:3-10
He J, Whelton PK. Long-term effects of weight loss and dietary sodium
restriction on incidence of hypertension. Hypertension 2000;35:544-9.
Blood Pressure Lowering Treatment Trialists’ Collaboration. Effects of
ACE inhibitors, calcium antagonists, and other blood-pressure-lowering
drugs: results of prospectively designed overviews of randomised trials.
Lancet 2000;356:1955-64.
Blood Pressure Lowering Treatment Trialists’ Collaboration. Effects of
different blood-pressure-lowering regimens on major cardiovascular
events: results of prospectively-designed overviews of randomised trials.
Lancet 2003;362:1527-1545
Dickerson JE, Hingorani AD, Ashby MJ, Palmer CR, Brown MJ. Optimisation of antihypertensive treatment by crossover rotation of four major
classes. Lancet 1999;353:2008-13.
Materson BJ, Reda DJ, Cushman WC. Department of veterans affairs
single-drug therapy of hypertension study. Revised figures and new data.
Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. Am J Hypertens 1995;8:189-92.
Dahlöf B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, et al.
LIFE Study Group. Cardiovascular morbidity and mortality in the Losartan Intervention for Endpoint reduction in hypertension study (LIFE): A
randomised trial against atenolol. Lancet 2002;359:995-1003.
Heart Protection Study Group. MRC/BHF heart protection study of
cholesterol lowering with simvastatin in 20,536 high-risk individuals: a
randomised placebo-controlled trial. Lancet 2002;360:7–22.
Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M;
ASCOT investigators. Prevention of coronary and stroke events with
atorvastatin in hypertensive patients who have average or lower-thenaverage cholesterol concentrations, in the Anglo Scandinavian Cardiac
Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): A multicentre
randomised controlled trial. Lancet 2003;361:1149-58.
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Papers
Odds ratios with 95% confidence intervals for outcome variables according to pertussis
vaccination status
Outcome variable
Non-vaccinated*
Partially vaccinated†
Fully vaccinated‡
P value
Asthma at age 69-81 months (1024/8240)
Prevalence in %
(No/total)
8.2 (12/146)
Competing interests: None declared.
Ethical approval: Avon Longitudinal Study of Parents and
Children Ethics and Law Committee.
1
20.3 (14/69)
12.4 (998/8025)
Unadjusted
1.00
2.84 (1.24 to 6.53)
2.05 (0.8 to 5.23)
Adjusted
1.00
1.59 (0.88 to 2.97)
1.06 (0.58 to 1.95)
2
0.05
>0.1
3
Periods of wheeze at age 69-81 months (798/8114)
Prevalence in %
(No/total)
9.0 (13/144)
16.2 (11/68)
9.8 (774/7902)
4
Unadjusted
1.00
1.95 (0.82 to 4.6)
1.09 (0.62 to 1.94)
0.2
Adjusted
1.00
1.55 (0.55 to 4.37)
0.94 (0.50 to 1.78)
0.2
Doctor diagnosed asthma at age 91 months (1597/7850)
Prevalence in %
(No/total)
15.8 (23/146)
36.2 (21/58)
5
Odent MR, Kimmel T. Pertussis vaccination and asthma: is there a link?
JAMA 1994;272:592-593.
Kemp T, Pearce N, Fitzharris P, Crane J, Fergusson D, St George I,
Wickens K, Beasley R. Is infant immunization a risk factor for childhood
asthma or allergy? Epidemiology 1997;8:678-680.
Nilsson L, Kjellman N-IM, Björksten B. A randomised controlled trial of
the effect of pertussis vaccines on atopic disease. Arch Pediatr Adolescent
Med 1998;152:734-738.
Henderson AJ, North K, Griffiths M, Harvey I, Golding J, ALSPAC Study
Team. Pertussis vaccination and wheezing illnesses in young children:
prospective cohort study. BMJ 1999;318:1173-1176.
Golding J, Pembrey M, Jones R., ALSPAC Study Team. ALSPAC—the
Avon longitudinal study of parents and children I. Study methodology.
Paediatr Perinatal Epidemiol 2001;15:74-87.
(Accepted 8 December 2003)
20.3 (1553/7667)
Unadjusted
1.00
3.03 (1.51 to 6.09)
1.36 (0.87 to 2.13)
0.005
Adjusted
1.00
1.93 (0.86 to 4.33)
0.98 (0.61 to 1.58)
0.1
doi 10.1136/bmj.38045.858889.EB
Atopy at age 7 years (1324/6463)
Prevalence in % (No)
15.4 (6/39)
20.6 (1296/6300)
Unadjusted
17.7 (22/124)
1.00
0.84 (0.32 to 2.26)
1.20 (0.75 to 1.91)
0.6
Adjusted
1.00
1.05 (0.35 to 3.21)
1.18 (0.69 to 2.03)
0.8
*No primary vaccinations, including pertussis.
†Diphtheria and tetanus ≥3 doses and no pertussis.
‡Triple (diphtheria, tetanus, and pertussis) vaccine ≥3 doses.
69-81 months, P = 0.05; doctor diagnosed asthma, 91
months, P = 0.005), it should be noted that, because of
small numbers in some groups, the confidence intervals
were wide and the results did not support the
hypothesis. When we adjusted for potential confounding factors we detected no significant associations
(P = 0.1-0.8).
Comment
These findings confirm and extend our previous observations of the lack of an independent association
between pertussis vaccination in infancy with inactivated, whole cell vaccine and the subsequent development of asthma or atopy during later childhood.
Acknowledgments: We thank the mothers and children who
took part and the midwives for their cooperation and help in
recruitment. The whole ALSPAC study team comprises
interviewers, computer technicians, laboratory technicians,
clerical workers, research scientists, volunteers, and managers
who continue to make the study possible. The ALSPAC study is
part of the European Longitudinal Study of Parents and
Children initiated by the World Health Organization.
Contributors: MG had the original idea. AM, AS, JH did the
analysis. All authors contributed to the interpretation of the
data. AM wrote the paper. JH will act as guarantor.
Funding: Core funding for the long term follow up of the cohort
came from the Medical Research Council, the Wellcome Trust,
the UK Department of Health, the Department of the Environment, DfEE, the National Institutes of Health, and a variety of
medical research charities. No specific funding was obtained for
this analysis.
Corrections and clarifications
British Hypertension Society guidelines for hypertension
management 2004 (BHS-IV): summary
An error occurred in the order of the reference list
in this Education and Debate article by Bryan
Williams et al (13 March, pp 634-40). Reference 8
in the published version (Williams et al) should
have been reference 3; and the references
published as 3 (Ramsay et al) to 7 (O’Brien et al) in
the reference list should then have been
renumbered and become references 4 to 8. The
two references cited in the footnote to table 1
should be renumbered as 6 (European Society of
Hypertension-European Society of Cardiology)
and 7 (WHO-International Society of
Hypertension); but the other references cited in the
text of the article are correct. The pdf (but not the
HTML) version on bmj.com has been amended.
Recent developments in secondary prevention and
cardiac rehabilitation after acute myocardial infarction
As a result of technology problems, some
amendments from the authors did not make it into
this clinical review by Hasnain Dalal and colleagues
(20 March, pp 693-7). In box 2, we should have
added the website address for SEARCH (the study
of additional reductions in cholesterol and
homocysteine): www.ctsu.ox.ac.uk/projects/
search.shtml. And the penultimate sentence of the
subsection “Angiotensin converting enzyme
inhibitors” should have said that rates of
revascularisation (not rates of readmission for heart
failure) were reduced in patients who took ramipril.
Obituary: Leonard (“Johnnie”) Walker
Our weekly quest to squeeze in as many obituaries
as possible led to the last minute deletion of an
important sentence from this obituary (BMJ
2003;327:1291). We omitted to say “Christianity
was an abiding passion and his faith directed his
life.” We have apologised to Dr Walker’s wife.
Is Dad mad, doctor?
I had just put away the pleural aspiration kit and labelled the
samples, and had returned to the patient, whose family had now
arrived, to check that he was comfortable.
One of the adult children greeted me with the question, “Do
you think Dad’s mad, doctor?”
“Mad?” I was a little bemused as to where this had come from.
926
“Yes. He said you are going to send off the fluid from his lungs
for psychology.”
After a few puzzled moments, the penny dropped: “No, not
psychology, cytology.”
James S Dawson senior house officer, Queen’s Medical Centre,
Nottingham
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