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The Updated WHO/ISH Hypertension Guidelines

Linda Brookes, MSc

Mar 18, 2004

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) DBP (mm Hg) 140-159 160-179 90-99 100-109 180 110

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 So 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 Other Risk Factors and Disease History I No other risk factors II 1-2 risk factors III 3 risk factors or TOD or ACC DBP 90-99 Low Medium High or or

DBP 100-109 DBP 110 Medium Medium High 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
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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 Stroke Stroke Primary Endpoint

Elderly with isolated systolic hypertension Diuretic DHCCB Renal disease Diabetic nephropathy type 1 Diabetic nephropathy type 2 Nondiabetic nephropathy Cardiac disease Post MI Left ventricular dysfunction ACE inhibitor Beta-blocker ACE inhibitor ACE inhibitor CHF (diuretics almost always included) Beta-blocker Spironolactone Left ventricular hypertrophy Cerebrovascular disease ARB ACE inhibitor ARB ACE inhibitor

Progression of renal failure Progression of renal failure Progression of renal failure

Mortality Mortality Heart failure Mortality Mortality Mortality Cardiovascular morbidity and mortality

ACE inhibitor + diuretic Recurrent stroke Diuretic Recurrent stroke

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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 costeffective, 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 costeffective 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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Medscape Cardiology 2004

Cite this article: Linda Brookes. The Updated WHO/ISH Hypertension Guidelines. Medscape. Mar 16, 2004.

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