The Benefits of Detecting and Treating Mild Hypertension: What We Know, and What We Need to Learn

This issue includes 2 systematic reviews dealing with the diagnosis and management of hypertension. In the first, Sundstrm and colleagues assess the evidence on the effects of blood pressure reduction on cardiovascular outcomes in patients with stage 1 hypertension (1). In the second, Piper and associates evaluate methods used to identify persons with elevated blood pressure (2) Sundstrm and colleagues combined data from a previous systematic review of 3 trials (3) with patient-level data from participants with stage 1 hypertension in the BPLTTC (Blood Pressure Lowering Treatment Trialists' Collaboration) database (4). The earlier review reported no significant reduction in cardiovascular events, death, or stroke with treatment of stage 1 hypertension but acknowledged that data were limited. Sundstrm and colleagues' analysis included patients at a mean age of 63.5 years who had baseline blood pressures of 140 to 160/90 to 99 mm Hg, had no previous clinical cardiovascular disease or renal failure, and were followed for at least 1 year. In contrast to the earlier review, most of the BPLTTC participants (96%) were diabetic, and 61% were receiving antihypertensive medications at baseline. The addition of these patients increased the number of participants from 8912 to 15266, the number of cardiovascular events from 165 to 661, the number of strokes from 30 to 154, and the number of deaths from 167 to 665 compared with the previous review. Both placebo and less intensive treatment were compared with intensive treatment. The more aggressive drug treatment resulted in a modest average blood pressure reduction of 3.6/2.4 mm Hg and was associated with significant reductions in stroke (28%), cardiovascular deaths (25%), and total deaths (22%), but no difference in total cardiovascular outcomes. The findings did not differ between BPLTTC and non-BPLTTC studies or by diabetes status or age. The results are consistent with those of prior analyses in hypertension clinical outcome trials that showed that blood pressure reductions, even within this lower range, are associated with favorable cardiovascular outcomes (47). Sundstrm and colleagues' work is timely in light of a recent guideline that recommended relaxing blood pressure goals in patients older than 60 years (the population at highest risk) (8, 9). In addition, although all other U.S. and international guidelines continue to recommend antihypertensive drug treatment to achieve blood pressure targets less than 140/90 mm Hg at least up to age 80 years, the National Committee for Quality Assurance has relaxed its target blood pressure quality metric from less than 140/90 mm Hg to less than 150/90 mm Hg in patients older than 60 years. Of note, the strength of evidence in Sundstrm and colleagues' review is not equivalent to that in a prospective trial comparing treatment versus no treatment of stage 1 hypertension. None of the included studies specifically enrolled patients with stage 1 hypertension, and because washout of antihypertensive agents was not required in all studies, some participants may have been enrolled with higher blood pressures. In addition, the primary objective of several of the trials in the review was to compare the effect of specific drug regimens rather than the effects of different blood pressures on clinical outcomes, and blood pressure targets in these trials were not uniformly defined. A trial specifically designed to assess the benefit of initiating treatment in this population was considered by the National Heart, Lung, and Blood Institute, but preference was given to trials assessing the effect of the even lower blood pressure targets (systolic blood pressure <140 mm Hg vs. <120 mm Hg) in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial and SPRINT (Systolic Blood Pressure Intervention Trial). Analyses based on achieved blood pressure reductions in clinical outcome trials have pitfalls, even if carefully done (5, 6). Differences in outcomes in patients achieving a lower blood pressure may be explained by factors besides the blood pressure reduction. Some of these confounding factors may be known or anticipated; others may be more subtle (or unknown) and more difficult to adjust for. Furthermore, Sundstrm and colleagues' review does not inform whether treatment of hypertension in this range benefits patients older than 60 years because data from such patients were excluded. Although a prospective clinical outcome trial will be needed to provide a definitive answer, Sundstrm and colleagues' results are consistent with the benefits of treating patients younger than 60 years with stage 1 hypertension. The fact that modest blood pressure reduction in this younger population without clinical cardiovascular disease significantly reduces hard clinical outcomes, such as stroke and death, shows promise for even greater absolute event reduction in higher-risk populations, such as older persons, those with cardiovascular disease, and high-risk racial or ethnic subgroups. This report also reinforces the tight correlation between blood pressure reduction in this blood pressure range and stroke reduction seen in other studies. Previous analyses of the effect of blood pressure reduction on clinical outcomes have shown no difference in response by age (4). Still, a critical void remains in the evidence base to document the optimal blood pressure goal in hypertensive patients of all ages. The review by Piper and associates, which was conducted to inform an updated U.S. Preventive Services Task Force recommendation on screening for hypertension, provides insight into methods of identifying persons with elevated blood pressure, including those with modest elevation who would nonetheless benefit from treatment, especially if a trial were to confirm the findings of Sundstrm and colleagues' analysis (10). It documents the accuracy of ambulatory blood pressure monitoring (ABPM) in ascertaining blood pressures associated with adverse clinical outcomes, thus supporting ABPM as the reference standard for confirming elevated office readings in identifying the need for hypertension treatment. It also found that persons with blood pressure in the high-normal range, older persons, those with an above-normal body mass index, and African Americans are at higher risk for hypertension on rescreening within 6 years than are persons without these risk factors. Although the data are limited, home blood pressure monitoring seemed to provide accuracy similar to that of ABPM. The findings are consistent with those of the systematic review conducted by the British National Institute for Health and Care Excellence that resulted in the British hypertension guideline being the only national guideline to recommend confirmation of elevated office readings by ABPM before initiation of antihypertensive drug treatment (10). Availability of this diagnostic method in the United States is currently hindered by the reluctance of insurers to reimburse for it. This review for the U.S. Preventive Services Task Force will hopefully lead to greater availability of ABPM.