of course it does , but the focus of concern varies according to one 's perspective . blood pressure is a physical sign that reflects the pressure exerted on the arterial wall , and is determined by the circulatory volume , the force of cardiac contraction , and the tonic state of the arterial vessels . genes and environment , operating through a variety of neuronal , hormonal , and cellular mechanisms , together determine the status of each of these components . the integrated product of these multiple factors is a blood pressure level that reflects the sum total of a variety of individual mechanisms . moreover , many of these mechanisms are also involved both in blood pressure control and in the maintenance of vascular structure and function . thus , perturbation of these mechanisms may either elevate blood pressure or stimulate vascular disease , or both . presumably , the strokes and heart attacks that occur with greater frequency in those with elevated blood pressure are most likely to occur when both blood pressure and vasculotoxic mechanisms are affected . from a clinical perspective , the salient point is that the height of pressure directly relates to cardiovascular disease occurrence . in fact , there is a quantitatively predictable , linear relationship between the height of the pressure and the likelihood of both heart attack and stroke . this has perhaps best been described through the meta - analysis of multiple observational studies presented by macmahon et al . most authorities , but not all , now accept the reality that there is no threshold level by which it is possible to separate persons with normal from those with abnormal pressures , but the observed relationship is best understood as reflecting a continuous risk . nevertheless , on the basis of clinical trial experience , and by convention , an arbitrary divide has been applied to invent the condition we term ' hypertension ' . a growing consensus also supports the view that levels of blood pressure alone should not determine the need for therapy . it is but one component of many that defines absolute risk , which is the appropriate foundation on which to base therapeutic decisions . availability of orally effective antihypertensive agents made it possible to test , and ultimately confirm the hypothesis that a reduction in pressure could prevent cardiovascular events . early trials , almost always comparing treatment with diuretics and/or -blockers with placebo , consistently showed that the decline in strokes ( for a given reduction in either systolic or diastolic blood pressure , expected by virtue of the epidemiologic evidence ) was actually achieved . disappointingly , however , only about half of the epidemiologically predicted benefit with regard to heart attack occurred . to my way of thinking , the failure to realize the reduction in heart attack anticipated by the blood pressure change is important evidence that the treatment of hypertension is about more than simply a change in blood pressure . the fact that , in these trials , the same drugs produced different results in two blood pressure - related outcomes lends further weight to the argument that methods of blood pressure lowering may affect risk . perhaps there are adverse consequences of pharmacologic agents that are unrelated to their blood pressure - lowering effect , which may be observed and/or unrecognized . diuretics , for example , have an impact on electrolyte balance , lipid and uric acid metabolism , and glucose economy , in addition to their intended hemodynamic effect . the net effect of any particular class of antihypertensive agents may be the sum of the benefit produced by a lower blood pressure and the harmful consequences of its metabolic disturbances . for example , diuretics act in part by depleting blood volume . at the same time , they tend to stimulate the renin - angiotensin system . there is strong experimental and epidemiologic evidence that an activated renin - angiotensin system not only tends to increase blood pressure , but is also vasculotoxic . thus , a diuretic may simultaneously produce opposing effects . by virtue of its hypotensive property , a diuretic might prevent heart attacks . at the same time , by activating the renin - angiotensin system , there might be an increase in heart attacks . in this case , there would be a dissociation between the blood pressure effect and the vascular effects . the unpredictable net health impact would therefore be the sum of these conflicting effects . diuretics provide but one example of how disparate the actions of these pharmacologic probes may be . new and anticipated classes of antihypertensive agents are now characterized according to their unique and vastly differing effects on vascular structure and function , as well as according to their hypotensive potential . it seems almost inevitable that clinical outcomes will also differ in response to these agents . recognition that equal blood pressure reduction may not always deliver equal cardioprotection has led to formal comparisons of individual antihypertensive agents . the largest of these , the national heart , lung , and blood institute - sponsored allhat ( antihypertensive and lipid - lowering treatment to prevent heart attack trial ) , began in 1993 and has recruited 42 000 persons over 55 years . the outcome of interest is not blood pressure control , but the effect on stroke and heart attack . recently , the doxazosin arm of that study was prematurely terminated because patients randomized to receive doxazosin experienced significantly and substantially more cardiovascular disease events than did chlorothalidone - treated subjects . this result , unanticipated by many , particularly in view of the apparently favorable profile of metabolic effects associated with this -blocker , confirms that equal blood pressure response does not ensure equal cardiovascular benefit . to this important experience the stop ( swedish trial in old patients with hypertension)-2 study   was a comparison of conventional diuretic - based therapy with angiotensin - converting enzyme ( ace ) inhibitors and calcium channel blockers ( ccbs ) . overall , there were no differences in cardiovascular disease event rates between the conventional and newer therapies . the latter produced greater prevention against total cardiovascular events , and particularly against congestive heart failure , than did ccbs . a similar advantage of ace inhibitors over ccbs has been demonstrated in the abcd ( trial of antihypertensive therapy in diabetic subjects ) trial . finally , there is the recently reported hope ( heart outcomes prevention evaluation ) trial . in that study , it was found that , in older persons at high risk for cardiovascular events , the addition of an ace inhibitor to suitable conventional therapy generated substantially greater cardioprotection than did the comparison placebo treatment . again , the increment in protection against cardiovascular events could not be explained by difference in blood pressure . an attractive candidate to explain the observed outcome might be vasculoprotection produced by ace inhibitor - induced blockade of the renin - angiotensin system . regardless of the explanation , it is clear that ace inhibition in hope resulted in benefits that were independent of blood pressure . together , the results of these studies add up to overpowering evidence that it does matter which drugs are used to treat hypertension . at risk of over - simplification , an analogy can be drawn to the story of fever . at first , an elevated temperature was itself a disease . ultimately , advances in microbiology and pharmacology made it possible to match individual therapies with specific infections . in short , the physical sign of blood pressure no more defines a homogeneous subgroup than does a particular level of temperature . ultimately , however , it seems reasonable to expect that biomedical science will someday be able to identify the biologic heterogeneity that is obscured behind a blood pressure level . there are several practical consequences of the realization that it matters how pressure is reduced . first of all , it will be difficult for physicians and patients to adopt any antihypertensive agent simply on the premise that blood pressure reduction will inevitably translate into cardioprotection . second , in clinical trials , it can be expected that active antihypertensive controls will replace placebo control . nevertheless , although the realization that it matters how pressure is reduced is important , it will probably not revolutionize clinical practice . instead , this awareness is more likely to signal the beginning of simply another , but more productive chapter in story of blood pressure management . superiority of one pharmacologic approach over another in an aggregate study tells us the average affect . however , patients are a heterogeneous group of nonaverage individuals . within this group , not only therapeutic decisions will still be based on a wise application of an amalgam of knowledge gained from physiology and vascular biology , experimentation , and clinical trial results . ultimately , ability to both phenotype and genotype , coupled with a growing armamentarium of functionally distinct drugs , will make the match of treatment to patient both more precise , and more effective .
whether it matters how pressure is lowered has been debated since antihypertensive drugs proved to prevent cardiovascular events . 
 however , in clinical trials , while the stroke benefit predicted by a given difference in blood pressure was achieved , the results for myocardial infarction were roughly half that expected . 
 this suggested that adverse drug effects of diuretics and -blockers might have detracted from their hypotensive effects . 
 trials with newer antihypertensive classes have revealed superior effects on outcomes associated with converting enzyme inhibitor use , and that -blockers are less cardioprotective than diuretics . 
 these studies establish that simple blood pressure reduction is an inadequate guide to therapy . 
 the challenge now will be to determine the optimal therapy for each hypertensive patient .