Download The Updated WHO/ISH Hypertension Guidelines

The Updated WHO/ISH Hypertension Guidelines
Linda Brookes, MSc
Following the announcement of the Antihypertensive and Lipid-Lowering Treatment to Prevent
Heart Attack Trial (ALLHAT)[1] results at the end of 2002, the US hypertension guidelines were
completely revised and reissued as the Seventh Report of the Joint National Committee on
Prevention, Detection, Evaluation, and the Treatment of High Blood Pressure (JNC 7) [2] in the
Spring of 2003. This was soon followed by guideline updates jointly issued from the European
Society of Hypertension (ESH) and the European Society of Cardiology (ESC). [3] The wave of
updates continued at the 2004 meeting of International Society of Hypertension (ISH), in Sao
Paulo, Brazil, where there was discussion of the recently updated World Health Organization
(WHO)/ISH guidelines for the management of hypertension.
A statement published in the November issue of the Journal of Hypertension[4] extends the
original guidelines, published in 1999,[5] in 3 specific areas:
1. Ascertainment of overall cardiovascular risk to establish thresholds of and goals for
treatment.
2. Treatment strategies
3. Cost-effectiveness
The 1999 guidelines remain current in other areas. Unlike the current US hypertension guidelines
(JNC 7) and European guidelines, the WHO/ISH guidelines are aimed at a global audience and
are intended to serve as a template for the development of national, regional, and local guidelines.
However, they resemble the European guidelines more closely than they do JNC 7.
Blood Pressure Classification
The WHO/ISH blood pressure classification includes 3 grades of hypertension (Table 1).
Table 1. WHO/ISH Classification of Hypertension
Blood Pressure Grade 1 Grade 2 Grade 3
SBP (mm Hg)
140-159 160-179 >/= 180
DBP (mm Hg)
90-99
100-109 >/= 110
DBP, diastolic blood pressure; SBP, systolic blood pressure
Unlike JNC 7, in the WHO/ISH statement, there is no "prehypertension" classification. According
to WHO/ISH Writing Group member Judith A Whitworth, DSc, MD, PhD (The Australian National
University, Canberra, ACT, Australia), who presented the guidelines in São Paulo, the guideline
authors were concerned about the implications of such a label.
Cardiovascular Risk
In the new set of WHO/ISH guidelines, factors influencing prognosis have not changed in
essence from the 1999 guidelines, ie:
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
Levels of SBP and DBP (grades 1-3)
Males aged > 55 years








Females ages > 65 years
Smoking
Total cholesterol > 61 mmol/L (240 mg/dL) or LDL-cholesterol > 4.0 mmol/L (160 mg/dL)
HDL-cholesterol < 1.0 mmol/L (< 40 mg/dL) in men, < 1.2 mmol/L (< 45 mg/dL) in women
History of cardiovascular disease in first-degree relatives before age 50 years
Obesity, physical inactivity
Target organ damage (left ventricular hypertrophy, microalbuminuria [20-300 mg/day],
radiologic or ultrasound evidence of extensive atherosclerotic plaque, hypertensive
renopathy grade III or IV)
Associated clinical conditions (diabetes, cardiovascular disease, heart disease, renal
disease, peripheral vascular disease)
The stratification of total (added) cardiovascular risk at different blood pressure levels has been
very slightly simplified from the 1999 guidelines: there is no longer any distinction between high
and very high risk (Table 2). The WHO/ISH stratification is very similar to that of the European
guidelines.
Table 2. WHO/ISH Stratification of Risk to Quantify Prognosis
Blood Pressure (mm Hg)
Grade 1
Grade 2
Grade 3
SBP 140-159 SBP 160-179 SBP >/= 180
or
or
or
Other Risk Factors and Disease History DBP 90-99 DBP 100-109 DBP >/= 110
I No other risk factors
Low
Medium
High
II 1-2 risk factors
Medium
Medium
High
III >/= 3 risk factors or TOD or ACC
High
High
High
ACC, associated clinical condition; DBP, diastolic blood pressure; SBP, systolic blood pressure;
TOD, target organ damage
Thresholds and Targets for Blood Pressure Lowering
The statement cites new observational data that support lowering the systolic threshold, since
even low-risk patients are likely to benefit from lower pressures. Trials reported since 1999 are
cited to give support to the recommendation for lowering blood pressure in high-risk patients
beginning at thresholds significantly below 160 mm Hg SBP and/or 90 mm Hg DBP.
Observational studies, limited randomized clinical trial data, and extrapolation from randomized
trial data are in agreement that the primary goal is to lower SBP to < 140 mm Hg and in high-risk
patients to < 130/80 mm Hg.
Lifestyle Modification
As in the US and European guidelines, lifestyle modifications are recommended for all patients in
the Australian guidelines:





Weight loss in the overweight
Increased physical activity
Moderation of alcohol intake
Dietary changes (more fruit, vegetables, and low saturated fat)
Reduction of dietary sodium intake and increased dietary potassium
Initial Therapy
The WHO/ISH statement cites multiple randomized clinical trials showing reductions in
morbidity/mortality compared with placebo for diuretics/beta-blockers and calcium channel
blockers (CCBs). Meta-analyses of randomized clinical trials comparing angiotensin-converting
enzyme (ACE) inhibitors or CCBs against older drugs have shown no convincing differences (but
they do not exclude the possibility of small differences in specific outcomes).
The WHO/ISH agree that the aggregate trial data suggest the morbidity/mortality benefits of
antihypertensive treatment derive largely from blood pressure reduction; at the same time, strong
evidence that specific agents benefit patients with compelling indications is cited as the basis for
recommending certain classes of drugs in such patients (Table 3).
Table 3. Compelling Indications for Specific Antihypertensive Drugs
Compelling Indication
Elderly with isolated systolic
hypertension
Preferred Drug
Primary Endpoint
Diuretic
Stroke
DHCCB
Stroke
Diabetic nephropathy type 1
ACE inhibitor
Progression of renal failure
Diabetic nephropathy type 2
ARB
Progression of renal failure
Nondiabetic nephropathy
ACE inhibitor
Progression of renal failure
Post MI
ACE inhibitor
Mortality
Left ventricular dysfunction
Beta-blocker
Mortality
ACE inhibitor
Heart failure
ACE inhibitor
Mortality
CHF (diuretics almost always
included)
Beta-blocker
Mortality
Spironolactone
Mortality
Left ventricular hypertrophy
ARB
Cardiovascular morbidity and
mortality
Cerebrovascular disease
ACE inhibitor +
diuretic
Recurrent stroke
Diuretic
Recurrent stroke
Renal disease
Cardiac disease
ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; CHF; congestive heart
failure; DHCCB, dihydropyridine calcium channel blocker; MI, myocardial infarction
For patients without compelling indications, the comparative trial data indicate that, on the basis
of availability and cost, a (low-dose) diuretic should be considered for first-line therapy.
Subsequent Therapy
The WHO/ISH guidelines point out that monotherapy will be inadequate for the majority of
patients. They note that no available comparative randomized clinical trial data on
morbidity/mortality are available to guide selection of optimal combinations, but point out that
diuretics enhance the efficacy of other classes and will most often be a component of
combination therapy. Fixed-dose combination formulations have advantages in patient adherence
and efficacy, and are not more expensive than monotherapy.
Cost-effectiveness
Because of limited resources, cost-effective treatment may not be affordable, the guidelines note.
Where resources are limited, priority for drug therapy should be given to those at higher risk,
since the return on the investment in terms of events prevented will be higher in these patients. In
many settings, thiazides are cheapest and hence most cost-effective, but for compelling
indications, classes that provide additional benefits, even if more expensive, may be more costeffective. In high-risk patients with large benefits from treatment, even expensive drugs may be
cost-effective, whereas in low-risk patients, treatment may not be cost-effective unless the drugs
are cheap.
Finally, the World Health Report 2002 reported that that population strategies to reduce blood
pressure are very cost-effective worldwide.[6] Dr. Whitworth stressed that prevention of
cardiovascular disease requires both population-based and high-risk group strategies. For
instance, one should target unhealthy lifestyle choices by recommending dietary modifications,
smoking cessation, and exercise regimens, where appropriate. Importantly, as Dr. Whitworth
emphasized, a primary strategy for the prevention of cardiovascular disease should include
treating cardiovascular risk factors, especially hypertension, glucose intolerance, and
hyperlipidemia, as well as overall cardiovascular disease management.
References
1. The ALLHAT Officers and Co-ordinators for the ALLHAT Collaborative Group. Major
outcomes in high-risk hypertensive patients randomized to angiotensin converting
enzyme inhibitor or calcium channel blocker vs diuretic. The Antihypertensive and LipidLowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288:1981-1997.
2. Chobanian AV, Bakris GL, Black HR, et al. Seventh Report of the Joint National
Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.
Hypertension. 2003;42:1206-1252.
3. Guidelines Committee. 2003 European Society of Hypertension -- European Society of
Cardiology guidelines for the management of arterial hypertension. J Hypertens.
2003;21;1011-1053.
4. World Health Organization, International Society of Hypertension Writing Group. 2003
World Health Organization (WHO)/International Society of Hypertension (ISH) statement
on management of hypertension. J Hypertens. 2003;21:1983-1992.
5. Guidelines Sub-Committee. 1999 World Health Organization – International Society of
Hypertension guidelines for the management of hypertension. J Hypertens. 1999;17:151183.
6. The World Health Report 2002: Reducing Risks, Promoting Healthy Life. Geneva,
Switzerland: World Health Organization; 1992.