TREATMENT TARGETS: SYSTOLIC OR DIASTOLIC PRESSURE?

Myron H. Weinberger, M.D.
Hypertension Research Center
Indiana University School of Medicine

For decades physicians have focused on diastolic blood pressure as the major cause of vascular disease and the events associated with elevated blood pressure. This obsession with diastolic pressure frequently caused practitioners to ignore the individual in whom only the systolic pressure was elevated. Indeed, until very recently the WHO guidelines for antihypertensive therapy, adopted by many of the health bodies outside of the United States, began with levels of 160/90-95. This tendency to ignore primary systolic elevation of blood pressure, frequently occurring in the absence of diastolic elevation (hence the description of Isolated Systolic Hypertension) and found more often in individuals over the age of 60 years, has been commonplace until the reports of several clinical trials completed largely in the last decade.

The Systolic Hypertension in the Elderly Program (SHEP) was the first large-scale trial directed specifically at determining whether it was beneficial to lower an isolated elevation of systolic pressure in elderly individuals. Over 447, 000 Americans over the age of 60 were screened in order to enroll 4, 736 qualified subjects with systolic pressures between 160-220 and diastolic <90 mm Hg. Individuals were randomly assigned to treatment with diuretics and beta blockers as initial therapy or placebo with the option of adding additional agents to all subjects at the discretion of the investigator. The "active" treatment group had average blood pressure levels that were approximately 10 mm Hg lower systolic and 3 mm Hg diastolic over the 5 years of the trial than that of the placebo group. Initial average pressure before randomization was roughly 170/80 and at the end of the study the "active" group had an average systolic pressure of roughly 146 mm Hg. The most impressive finding was a cumulative 36% (P=0.0003) reduction in fatal and non-fatal stroke in the group with the lower systolic pressure. There was also about 50% (P<0.001) reduction in congestive heart failure in the active group.

A similar striking benefit was seen in the Swedish Trial of Old Patients (STOP-Hypertension), which included 1627 individuals between 70 and 84 years of age with systolic pressures 180-230, and diastolic less than 90 OR 105-120 mm Hg. Thus this smaller trial included those with systolic-diastolic blood pressure elevation as well as those with isolated systolic hypertension. Initial therapy for the active group consisted of a thiazide + potassium-sparing diuretic combination and a beta blocker. However in both the active and placebo groups other agents could be added at the discretion of the investigator. Again, a significant (P<0.01) reduction in stroke and total deaths was seen in the "active" treatment group.

The Systolic Hypertension in Europe (SYST-EUR) trial, using a long-acting dihydropyridine calcium channel blocker and a similar trial in China (SYST-China) demonstrated striking benefit of blood pressure reduction in those with isolated systolic elevation despite the differences in population and type of antihypertensive drug therapy. The SYST-EUR trial also showed a unique reduction in the incidence of dementia, known to be influenced by elevated blood pressure in the elderly, in the active treatment group. Subsequent smaller trials have shown similar benefits with other forms of conventional antihypertensive therapy. Taken together, all of these trials have provided a mandate for treating even an isolated elevation of systolic pressure with the current targets being to maintain systolic pressure at levels below 140 mm Hg in uncomplicated individuals.

Recent observations from the Framingham Study have shown that isolated systolic pressure, often manifest by an increased pulse pressure, is a major risk factor for cardiovascular events and our own prospective studies have demonstrated that pulse pressure predicts mortality even among initially normotensive subjects. Thus both epidemiologic evidence and interventional data provide a compelling rationale for aggressive treatment of systolic pressures above 140 mm Hg particularly in the elderly population. How well has this evidence been translated into clinical practice? The most current information with which to address that question comes from the United States. A recent analysis of the NHANES-III Survey indicated that among more than 16,000 adults, 27% of whom were hypertensive, only 23% had blood pressure levels less than 140/90. The majority of the uncontrolled hypertensives had diastolic pressure less than 90, indicating that it was the systolic elevation that persisted. Moreover, the majority of the uncontrolled hypertensives were over age 65. Finally, the survey demonstrated that two reasons that are often offered to explain inadequate blood pressure control, lack of financial resources and inadequate access to medical care did not appear to apply to these individuals since the majority had health insurance and had visited a physician an average of three times the preceding year. These findings imply that physicians may not be aggressive enough, particularly with older subjects, in treating systolic pressure to currently recommended targets. These findings have broad relevance to populations all over the world in the face of increasing life spans.