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The 1999 WHO-ISH hypertension guidelines stratifiying the risk to treat the patient

John Chalmers, MD

Chairman of WHO-ISH Guidelines Sub-Committee
Professor of Medicine, University of Sydney
Chairman of Research, Royal North Shore Hospital Sydney NSW

The Highlights of the 1999 Guidelines
The 1999 WHO-ISH Guidelines in a Regional Context
Classification, Definitions and Targets
Recommendations for Management


The Highlights of the 1999 Guidelines

The new "1999 World Health Organisation – International Society of Hypertension (WHO-ISH) Guidelines for the Management of Hypertension" (1) bring many new approaches and recommendations to guide the practising doctor, as summarised in Box 1 below:

Box 1 – Highlights of 1999 Guidelines

  • The definition and classification of hypertension (Table 1) are made congruent with the 1997 American recommendations ("JNC VI";2) so as to provide more consistent advice to practitioners.
  • The emphasis is placed on the assessment and reduction of the total cardiovascular risk (Table 2) in each patient rather than on blood pressure levels alone, with stratification of patients into low, medium, high, and very high risk groups (Table 3).
  • Lower blood pressure targets are set (<130/85mmHg) for young, middle aged, and diabetic patients with hypertension.
  • The need to individualise the initiation and maintenance of drug treatment in each patient, choosing from among the six major drug classes (Diuretic, Blockers, ACE Inhibitors, Calcium Antagonists, Alpha Blockers and Angiotensin II Receptor Antagonists).
  • The emphasis on the use of 2 or more drugs in combination so as to achieve blood pressure goals, without impairing quality of life.
  • The provision of a much shorter, simpler set of practice guidelines which will become available for practising clinicians in May this year, in recognition that the main guidelines will only be read by interested experts.


The 1999 WHO-ISH Guidelines in a Regional Context

The 1999 WHO-ISH Guidelines recognise the importance of regional diversity, with widely differing cultural and economic conditions. This is particularly important for the implementation of their recommendations as indicated in Box 2 below:

Box 2 – Guide to the 1999 Guidelines

  • These Guidelines provide recommendations that are based on the collective expert interpretation by the WHO-ISH Guidelines Sub-Committee of the available evidence from epidemiological studies and from clinical trials.
  • The primary aim is to offer balanced information to guide clinicians, rather than rigid rules that would constrain their judgement about the management of individual patients, who will differ in their personal, medical, social, ethnic and cultural characteristics.
  • The WHO-ISH Guidelines are written for a global audience from communities that vary widely in the nature of their health system and in the availability of resources.
  • It is hoped that national and regional experts will use them as a basis for drawing up recommendations that are specifically designed for the management of patients in their own region.

Classification, Definitions and Targets

The new classification of hypertension puts greater emphasis on levels of normality, emphasising the fact that the strong and continuous relationship between cardiovascular risk and blood pressure starts from very low levels of pressure (3). The new guidelines differentiate between "optimal" (<120/80mmHg), "normal" (<130/85mmHg), and "high normal" (<140/90mmHg) levels of blood pressure.

Table 1 Definitions and Classification of Blood Pressure Levels










High – Normal



Grade 1 Hypertension ("mild")



Subgroup: Borderline



Grade 2 Hypertension ("moderate")



Grade 3 Hypertension ("severe")



Isolated Systolic Hypertension

> 140


Subgroup: Borderline



When a patients’ systolic and diastolic blood pressures fall into different categories, the higher category should apply.


These new definitions of normality are central to one of the key planks in the 1999 WHO-ISH Guidelines - the setting of stringent blood pressure targets for young, middle aged and diabetes patients, for whom a target of "normal" blood pressure (<130/85mmHg) is recommended, rather than the more traditional target of <140/90mmHg or "high normal" levels which is advocated for older subjects.

These recommendations are based on the totality of the evidence, which includes the epidemiological evidence that there is no blood pressure level below which a lower pressure is not associated with a lower cardiovascular risk (3), the evidence that the achieved blood pressure is the best predictor of risk in treated hypertensive patients (4,5), the evidence from randomised clinical trials (6,7), that the risk of coronary heart disease is not reduced to the levels predicted by epidemiological evidence (3), and the repeated evidence from population surveys that, at best, blood pressure is only normalised in 25% of hypertensive subjects (8,9).

The evidence for a lower target pressure in diabetic patients is particularly strong, with the recent publication of the Hypertension Optimal Treatment (HOT) Study (10) and the United Kingdom Prospective Diabetes Study (UKPDS:11) both of which demonstrated that "tight" control of blood pressure to below 85mmHg conferred additional reduction in the risk of major cardiovascular events.

Recommendations for Management

The guidelines insist that appropriate lifestyle measures be instituted and maintained wherever they apply, particularly stopping smoking, regular exercise, weight reduction, moderation of alcohol intake, and reduction of dietary salt and saturated fat. These measures may be sufficient in a minority of patients with low cardiovascular risk, but they will enhance the efficacy of antihypertensive drugs in all patients, and combat a number of the other major cardiovascular risk factors present.

The guidelines advocate the stratification of the total cardiovascular risk in each patient (Tables 2 and 3), into 4 categories – low, medium, high and very high risk – which are used to determine the prognosis and the need for drug treatment, as well as the speed and intensity with which drug treatment is introduced.


Table 2 Factors Influencing Prognosis

Risk Factors For Cardiovascular Diseases

I Used for risk stratification

  • Levels of systolic and diastolic blood pressure (Grades 1-3)
  • Men >55 years
  • Women >65 years
  • Smoking
  • Total cholesterol >6.5 mmo/l (250 mg/dl)
  • Diabetes
  • Family history of premature cardiovascular disease

II Other factors adversely influencing prognosis

  • Reduced HDL cholesterol
  • Raised LDL cholesterol
  • Microalbuminuria in diabetes
  • Impaired glucose tolerance
  • Obesity
  • Sedentary lifestyle
  • Raised fibrinogen
  • High risk socioeconomic group
  • High risk ethnic group
  • High risk geographic region

Target Organ Damage1

  • Left ventricular hypertrophy
  • (electrocardiogram, echocardiogram or radiogram)

  • Proteinuria and/or slight elevation of plasma creatinine concentration (1.2 - 2.0 mg/dl)
  • Ultrasound or radiological evidence of atherosclerotic plaque (carotid, iliac and femoral arteries, aorta)
  • Generalised or focal narrowing of the retinal arteries
Associated Clinical Conditions2

Cerebrovascular disease

  • ischaemic stroke
  • cerebral haemorrhage
  • transient ischaemic attack

Heart disease

  • myocardial infarction
  • angina
  • coronary revascularisation
  • congestive heart failure

Renal disease

  • diabetic nephropathy
  • renal failure (plasma creatinine concentration >2.0 mg/dl)

Vascular disease

  • dissecting aneurysm
  • symptomatic arterial disease

Advanced hypertensive retinopathy

  • haemorrhages or exudates
  • papilloedema

1. "Target Organ Damage" corresponds to previous WHO Stage 2 hypertension 6
2. "Associated Clinical Conditions" corresponds to previous WHO Stage 3 hypertension.6


Table 3 Stratification of Risk to Quantify Prognosis and Influence Treatment

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Risk strata (typical 10 year risk of stroke or myocardial infarction): Low risk = less than 15%; medium risk = about 15-20% risk; high risk = about 20-30%; very high risk = 30% or more
1. TOD – Target Organ Damage (Table 2)
2. ACC – Associated Clinical Conditions, including clinical cardiovascular disease or renal disease (Table 2)

The guidelines also stress the use of effective drug combinations to normalise the blood pressure and achieve effective hypertension control in a greater proportion of patients, as shown in the HOT Study (10) in which combination therapy reduced the diastolic pressure below 90mmHg in over 90% of patients. The guidelines emphasise the use of low doses of the drugs used to build a combination and advocate the use of low doses of each of the drugs used in a combination in preference to increasing the dose of one particular class of drugs. This is because appropriate combinations will not only maximise hypotensive efficacy, they will also minimise side effects, improve quality of life, and in turn improve hypertension control in populations.
Finally, the Guidelines "mainstream" the management of hypertension in elderly subjects and the treatment of systolic hypertension, but have separate sections dealing with hypertension in special populations including ethnic minorities, subjects with diabetes, co-existing cerebrovascular disease, cardiac disease or renal disease, pregnant women, and "very elderly subjects".
While the 1999 WHO-ISH Guidelines are too long and comprehensive for most general practitioners, the companion set of "Practice Guidelines" extract the main messages from the parent set and are designed for use in general practice.



1. Guidelines Subcommittee. 1999 World Health Organisation – International Society of Hypertension Guidelines for the Management of Hypertension. J Hypertens 1999; 17:151-183
2. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The sixth report on the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Arch Intern Med 1997; 157: 2413-2446
3. MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J, et al. Blood pressure, stroke and coronary heart disease, part 1. Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 1990; 335: 765-774
4. Isles CG, Walker LM, Beevers DG et al. Mortality in patients of the Glasgow Blood Pressure Clinic. J Hypertens 1989; 4:141-156
5. Lindholm L, Ejlertsson G, Schersten B. High risk of cerebrocardiovascular morbidity in well treated male hypertensives: a retrospective study of 40-59 year old hypertensives in a Swedish primary care district. Acta med Scand 1984; 216: 251-259
6. Collins R, Pet R, MacMahon S, Hebert P, Fiebach NH, Eberlein KA et al. Blood pressure, stroke and coronary heart disease, Part 2 short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 1990; 335:827-838
7. Collins R, MacMahon S. Blood pressure, antihypertensive drug treatment and the risks of stroke and coronary heart disease. BR Med Bull 1994; 50:272-298
8. Burt VL, Cutler J A, Higgins M, et al. Trends in the prevalence, awareness, treatment and control of hypertension in the US adult population: data from the health examination surveys 1960 to 1991. Hypertension 1995; 26:60-69
9. Marques-Vidal P, Tuomilehto J. Hypertension awareness, treatment and control in the community: is the ‘rule of halves’ still valid? J Hum Hyperten 1997; 11:213-220
10. Hansson L, Zanchetti A, Carruthers SG, et al. 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; 1755-1762
11. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998; 317: 703-713




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