The Updated WHO/ISH Hypertension Guidelines

Linda Brookes, MSc

Disclosures

March 18, 2004

Editorial Collaboration

Medscape &

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:

  • 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
Other Risk Factors and Disease History Blood Pressure (mm Hg)
Grade 1
SBP 140-159
or
DBP 90-99
Grade 2
SBP 160-179
or
DBP 100-109
Grade 3
SBP ≥ 180
or
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 Preferred Drug Primary Endpoint
Elderly with isolated systolic hypertension Diuretic Stroke
DHCCB Stroke
Renal disease
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
Cardiac disease
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
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 cost-effective. 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 Lipid-Lowering 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;17:151-183.

  6. The World Health Report 2002: Reducing Risks, Promoting Healthy Life. Geneva, Switzerland: World Health Organization; 1992.

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