"Treating Hypertension" or "Lowering Blood Pressure"? Extending the Concept

It is many years since Pickering won the debate with Platt [1, 2]. Hypertension is not a single disease entity with a bimodal distribution clearly separating the population into a normotensive majority and a hypertensive minority with clearly delineated distinguishing features [1, 2]. Rather, there is a strong and continuous relationship between usual level of blood pressure and the risk of heart attack or stroke, with no lower threshold evident, below which reduction in blood pressure is no longer associated with a reduction in risk [3]. A few years after the Pickering and Platt debate, Geoffrey Rose wrote that, “In an operational sense, hypertension should be de ned in terms of a bloodpressure level above which investigation and treatment do more good than harm” [4]. Indeed, over the past 50 years, as blood pressure-lowering drugs have improved and the evidence of bene t has accrued, we have progressively lowered the bar, for the level at which drug treatment should be recommended to lower blood pressure. Blood pressure-lowering treatment started with ganglion blockers for malignant hypertension in the 1950s, and moved to sympatholytic agents for severe hypertension in the 1960s, and gradually extended to moderate hypertension in the 1970s and to mild hypertension in the 1980s. Major trials in elderly subjects in the 1990s extended the indications further. Thus, the bar was progressively lowered from say 200/120 mmHg in the early days to 140/90 mmHg today [5–7]. The dif culty with these broad-brush de nitions is that the bene ts and risks of lowering blood pressure are not uniform across the whole population, but vary greatly in individuals according to each person’s total cardiovascular risk pro le. Geoffrey Rose’s operational de nition applies uniquely to each individual. This concept is now recognized and indeed enshrined in major guidelines for the management of hypertension including JNC (V1) [6] and the WHO-ISH 1999 Guidelines [7]. Both of these sets of recommendations for treatment remove the focus from the level of blood pressure alone to a careful assessment of the total cardiovascular risk in each individual, including the blood pressure itself, other risk factors, the presence of target organ damage, of diabetes and of associated cardiovascular conditions, such as coronary, cerebrovascular, renal and peripheral vascular disease. It follows, naturally, that the threshold for the introduction of blood pressure-lowering drugs should vary greatly between patients, and be carefully strati ed according to the individual’s total cardiovascular risk as exempli ed in the key tables of those two sets of guidelines – Table 3 in the WHO-ISH Guidelines [7] and Table 5 in JNC (VI) [6]. For example, the WHO-ISH Committee [7] recommends that individuals with blood pressures of 140–149/90–94 mm Hg (i.e. in the so-called hypertensive range), who have no other risk factors or associated conditions, may be managed with lifestyle measures alone, while others with blood pressures of 130– 139/85–89 mmHg (i.e. in the so-called normotensive range) who have diabetes or established cardiovascular disease may be treated with blood pressure-lowering drugs even though they are not “hypertensive”. The evidence to support the use of blood pressurelowering drugs in individuals who do not meet the existing de nitions of “hypertension” (blood pressure >140/90 mmHg) has grown substantially since the publication of JNC VI [6] and WHO-ISH 1999 [7]. The strongest evidence in those recommendations was gathered in diabetic subjects in whom the bene ts of blood pressure lowering were such that both guidelines recommended treatment for diabetic patients with “high normal” pressures in the range 130–139/85–89 mmHg. Since then, a number of completed studies have reinforced the evidence – the Heart Outcomes Prevention Evaluation Study (HOPE) [8], three studies in patients with type 2 diabetes and nephropathy [9–11], the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) [12] and the Heart Protection Study (HPS) [13]. Furthermore, the Framingham group [14] have recently reinforced the clear gradations of risk within the “normotensive” range, with de nite stepwise increases in the risk of cardiovascular disease as the blood pressure increases from “optimal” to “normal” to “high normal” using the WHO-ISH and JNC (VI) de nitions [6, 7]. The HOPE study, published in 2000 [8] was performed in subjects with high cardiovascular risk, 80% of whom had coronary heart disease, with an average entry blood pressure of 139/79 mmHg, so that both normotensive and hypertensive subjects were randomized. After 4.5 years of treatment with the ACE inhibitor ramipril, there was an overall 3/2 mmHg greater fall in pressure on active treatment than placebo and signi cant reduction in BLOOD PRESSURE 2002; 11: 68±70