New issues in the treatment of isolated systolic hypertension.

Before commenting on the findings in this article, I will provide a bit of background. ISH is the most common form of hypertension in those older than 65 years.2 Because this segment of the population is expanding so rapidly, ISH will soon be the most prevalent form of hypertension. Over the last few years, a paradigm shift has occurred, away from the prior concern over an elevation of diastolic pressure to our current awareness that an elevation of systolic pressure and, to an even greater extent, the combination of higher systolic and lowered diastolic pressures (ie, a widening of the pulse pressure) are the major determinants of cardiovascular risk in the elderly.3 This should come as no surprise because the widening pulse pressure reflects atherosclerotic stiffening of the aorta and large capacitance vessels.4 This provides a smaller, rigid reservoir wherein systolic inflow raises pressure and diastolic emptying lowers pressure to a greater degree than occurs with more compliant, elastic vessels. In addition, pulse-wave velocity is faster through stiff vessels, so that the usual reflection of the pressure wave back from the periphery occurs in midsystole rather than diastole, augmenting the already elevated systolic pressure and removing a major support of diastolic pressure. Therefore, the widened pulse pressure so typically found in the elderly reflects both a rise in systolic levels and a fall in diastolic levels. The dangers of high systolic pressure are well known, and unequivocal evidence shows that the treatment of ISH provides significant protection against cardiovascular mortality and morbidity.5 Attention must obviously be paid to expanding the number of elderly patients with ISH whose blood pressure is well controlled. Such control will prolong life a bit and, more importantly, it will reduce the strokes, heart attacks, and episodes of heart failure that are so burdensome to the elderly. In one of the trials of ISH treatment, the onset of dementia was also reduced,6 holding promise for even more benefit from such therapy. However, lower diastolic pressure is also dangerous. In the analysis of the course of .7500 elderly patients with ISH who were left on placebo during multiple randomized controlled trials (RCTs), a continually higher death rate was seen, as expected, with progressively higher systolic pressures on entry but, surprisingly, similar increases in mortality were seen with progressively lower diastolic pressures on entry.5 When diastolic pressures are lowered too much by antihypertensive therapy, similar increases in events have also been seen. Therefore, the high systolic pressure must be lowered, but caution is needed not to lower the already low diastolic pressure much further. Therefore, as more attention is directed toward the control of ISH, the following 3 questions must be addressed: