INTRODUCCIÓN

Despite the growing awareness of the high burden associated with hypertension in terms of excess risk of morbidity and mortality worldwide,1 situation is still nasty. In the U.S., awareness of hypertension among the general population increased from 51% to 73% from years 1976-1980 to years 1986-1991, but thereafter it leveled around 68% (years 1991-1994) and 70% (years 1999-2000). Of greater concern, rate of control of hypertension (blood pressure [BP] <140/90 mm Hg), which had markedly increased from 10% (years 1976-1980) to 29% (years 1988-1991), is now unexpectedly stagnant between 27% (years 1991-1994) and 34% (years 1999-2000).2

The seventh report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), coordinated by the National Heart, Lung, and Blood Institute, has recently came to light in a short version1 and a more complete version will be published soon.3 JNC 7 is a major challenge, more than appearing on the surface. It is essentially the last major attempt and effort to bridge the gap between the current availability of potent, accurately tested and well tolerated antihypertensive strategies and their poor and inadequate current implementation in the clinical practice.

Several parts of the JNC 7 document resemble prior JNC reports. However, some crucial points of the JNC 7 report deserve mention and even some criticism.

PRE-HYPERTENSION

Subjects with systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg (the highest makes faith) are now labeled «pre-hypertensives» (Figure 1). Ironically, a perfectly healthy 19-year old subject with BP persistently 120/80 mm Hg would not be considered «normal,» but «pre-hypertensive.» The concept of «prehypertension» clearly arises from the well established evidence of a linear, graded and continuous association between BP and cardiovascular risk without any evidence of a threshold from values of 115/75 mm Hg.4 It also comes from the Framingham evidence that a high-normal blood pressure (130-139 mm Hg systolic or 85-89 mm Hg diastolic) is associated with an increased risk of cardiovascular disease and future hypertension.5 In the mind of JNC 7 experts, emphasis on «pre-hypertension» is clearly aimed to sensitize general population and health professionals to implement effective and sustained strategies for a healthier life (smoking prevention or cessation, prevention or treatment of overweight, physical activity, etc.). However, in the mind of critics, «pre-hypertension» may be viewed as an unnecessary definition of «nearly disease» even in completely healthy subjects, which might generate anger, anxiety and depression, with potential influences even in the working and family environment. Just to make a comparison with a similar document, the recent European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines6 maintained the prior classification of normotension (systolic BP 120-129 mm Hg and diastolic BP 80-84 mm Hg) and high-normal BP (systolic BP 130-139 or diastolic BP 85-89 mm Hg). Probably, the term pre-hypertension would have been more acceptable if limited to subjects with high-normal BP.

STAGES 1 AND 2 ONLY

Stage 3 has been eliminated because the therapeutic strategies in stage 2 and 3 are essentially the same. Therefore, all subjects with systolic BP≥160 mm Hg or diastolic BP≥100 mm Hg now belong to stage 2, which is the highest stage. By contrast, the ESC/ESH guidelines maintain grade 2 (systolic 160-179 or diastolic 100-109 mm Hg) and grade 3 (systolic ≥180 or diastolic ≥110 mm Hg).

ROLE OF SYSTOLIC BP

JNC 7 recognizes that systolic BP is more important than diastolic BP as a cardiovascular risk factor, except perhaps in younger subjects. Progressive stiffening of large arteries is believed to be an important basic mechanism of the rise progressive in systolic and decrease in diastolic BP after age 55, with consequent widening of pulse pressure (PP) with age.7,8 A wide PP may thus reflect already diseased arteries, with adverse prognostic implications.7,8 In cross-sectional studies, PP showed a strong direct association with carotid atherosclerosis, left ventricular mass and white matter lesions detected by magnetic resonance imaging.9-11 From a prognostic standpoint, an association has been noted in several studies between PP and risk of cardiovascular morbid events in different clinical settings and such association was independent of systolic and diastolic BP.12-14 Unfortunately, systolic BP control is more difficult to achieve than diastolic control, particularly in the elderly.

CARDIOVASCULAR RISK FACTORS

JNC 7 list several well established cardiovascular risk factors, which include also microalbuminuria or estimated glomerular filtration rate <60 ml/min. The statement is correct in view of the extensive evidence on the independent prognostic impact of microalbuminuria in patients with hypertension.5,16 However, at least in the short version published in JAMA,1 little effort seems devoted to define the level of cardiovascular risk in the individual subject (risk stratification) on the basis of the different combinations between BP levels and concomitant risk factors. In contrast, the ESC/ESH document6 defines 5 levels of risk (average risk, low-added risk, moderate added risk, high added risk and very high added risk) on the basis of such combinations. For example, subjects with stage I hypertension would be at low-added risk in the presence of no other risk factors, moderate added risk in the presence of 1-2 other risk factors, high added risk in the presence of 3 or more risk factors, diabetes or target organ damage, or very high added risk in case of associated clinical condition (prior stroke, TIA, coronary artery disease, peripheral vascular disease or retinopathy stage III or IV). As discussed below, implications for treatment seems to be scarcely dependent on concomitant risk factors (apart from the case of diabetes) and mostly oriented on BP levels.

WHO NEEDS ANTIHYPERTENSIVE DRUGS

Subjects «not at goal» with lifestyle modifications should begin drug treatment. Goal means <140/90 mm Hg, with the notable exception of <130/80 in diabetics. Fortunately, the ESC/ESH document endorses exactly the same goals. Of note, JNC 7 recommends drug treatment in non diabetic subjects with systolic BP ≥ 140 mm Hg or diastolic BP ≥90 mm Hg despite lifestyle modifications even in the complete absence of concomitant risk factors, as well as in the presence of only 1-2 risk factors. This sounds like a quite liberal approach to drug treatment. By contrast, the ESC/ESH document looks a bit more restrictive, by recommending drug treatment in subjects not at goal after at least 3 months of life-style measures in case of moderate added risk (1-2 risk factors in grade 1 hypertension, 0-2 risk factors in grade 2 hypertension), or not at goal after 3-12 months of life style measures in case of low risk (no risk factors in grade 1 hypertension).

WHICH DRUGS?

This is a crucial point. JNC 7 seems to be quite drastic on the surface, but a careful inspection of the entire document reveals flexibility. JNC 7 simply states that in subjects with stage I hypertension, thyazide diuretics should be used «as initial therapy for most patients with hypertension.» The rationale for such position comes from the low cost of diuretics and the evidence that «in most outcome trials including the recently published Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), diuretics have been virtually unsurpassed in preventing the cardiovascular complications of hypertension.» Critics may argue that «unsurpassed» does not mean «superior» and that the ALLHAT trials has several methodological shortcomings.17,18 An important shortcoming of ALLHAT was the forced association, by protocol, of lisinopril with atenolol, instead of a diuretic or a dihydropiridine calcium-antagonist (the usual choice in the clinical practice), in subjects resistant to monotherapy. Such policy inevitably led to favor chlorthalidone (which could add atenolol in a pharmacologically appropriate combination) and to punish lisinopril.

At variance with JNC7, the ESC/ESH document considers diuretics, beta-blockers, ACE-inhibitors, calcium antagonists and angiotensin II blockers as suitable drugs for the initiation and maintenance of therapy.6 Such a position is based on the lack of evidence of a clear superiority of one single class versus another in the major outcome trials. Notably, the ESC/ESH document adds the statement (box 11) that the choice of drugs will be influenced by many factors including the «cost of drugs.» Thus, the acute physician may interpret such a position (lack of superiority of one class versus another and cost of drug to be taken into account) as very similar, in its essential substance, to that expressed by the JNC 7 document in support of diuretics as first line agents.

Beyond the points of pre-hypertension and initial therapy with diuretics, JNC 7 and ESC/ESH show an apparent agreement over several points. Both recognize that combinations between two or more drugs are needed to normalize blood pressure in many patients. Here, JNC 7 introduces objective criteria by stating that if pre-treatment BP is >20/10 mm Hg above the goal, consideration should be given to begin treatment with 2 agents. Thus, JNC 7 clearly suggests that in all non-diabetic subjects with BP>160 mm Hg systolic or 100 mm Hg diastolic (as well as in diabetics with BP>150 mm Hg systolic or 90 mm Hg diastolic) treatment should begin with 2 drugs.

Another important area of substantial agreement between the JNC 7 and ESC/ESH guidelines regards the preferential indication for specific drugs even for initial therapy. As shown in figure 2, the «compelling indications» for specific antihypertensive drug mentioned by JNC 72 are not substantially dissimilar from the «conditions favoring the use»6 of specific drugs mentioned in the ESC/ESH document.

From a purely scientific, and not diplomatic, perspective, it is encouraging to realize that most positions on the diagnosis and treatment of patients with hypertension are not substantially different on the two sides of the ocean.

In conclusion, JNC 7 is an updated and well equipped arsenal of formidable weapons against hypertension and its complications. The stage is now set for a hard task: their effective implementation in the clinical practice.

Correspondence: Dr. Paolo Verdecchia.
Ospedale R. Silvestrini. Dipartimento Malattie Cardiovascolari.
Vía S. Andrea Delle Fate, s/n. Perugia. Italy.
E-mail: verdec@tin.it