Mind the gap: pulse pressure, cardiovascular risk, and isolated systolic hypertension.

Hypertension is an age-old problem, and the importance of arterial blood pressure as a determinant of cardiovascular risk has been clearly demonstrated by a number of major studies since the introduction of the mercury sphygmomanometer nearly 100 years ago. Similarly, the benefits of treating hypertension have been equally well established by randomized, controlled trials. However, many of these studies focused almost exclusively on diastolic pressure, as convention dictated that this was the best predictor of risk. Moreover, despite repeated protests, data from the Framingham study in particular, demonstrating that systolic blood pressure is probably more important than diastolic pressure in defining cardiovascular risk, were largely ignored in favor of the “conventional view.” However, much recent evidence has challenged the preeminence of diastolic pressure, emphasizing the importance of systolic and, latterly, pulse pressure as more accurate predictors of cardiovascular risk. Essential hypertension is characterized by increased peripheral vascular resistance and, therefore, an increased mean arterial pressure, which is more closely related to diastolic pressure. However, pulse pressure—the “gap” between systolic and diastolic pressure—is defined mainly by the compliance of the large arteries and the cardiac output as, indeed, noted by Bramwell and Hill in 1922: “Hence the difference between systolic and diastolic pressure, that is the pulse pressure, other things being equal will vary directly as the rigidity of the arterial walls.” Aging is associated with stiffening of the large arteries and a widening of the pulse pressure in almost all populations: a consequence of arteriosclerosis. The most recent data from the Framingham study have not only confirmed the increase in systolic and decrease in diastolic pressure associated with the normal aging process, but indicate that this increase in pulse pressure, at least in the persons aged more than 50 years, is a better predictor of a cardiovascular event than systolic or diastolic pressure in isolation. Similar findings have been reported from epidemiologic studies in normotensive and hypertensive individuals, and in those surviving a myocardial infarction. Together, these data suggest that arterial stiffness is a better predictor of cardiovascular risk than peripheral vascular resistance, at least in the middle-aged and older subjects. This view is supported by more direct assessment of arterial stiffness, using aortic pulse wave velocity measurement, in patients with renal failure and hypertension. Isolated systolic hypertension, defined as an increased systolic (.160 mm Hg) but normal diastolic pressure (,90 mm Hg) affects almost half of those aged more than 60 years; a burden that is likely to grow with increasing life expectancy. It is a consequence of the age-related stiffening of the large arteries and, therefore, isolated systolic hypertension may be considered as an exaggeration of the natural aging process—something that we might all develop should we live long enough. Moreover, in contrast to essential hypertension, it is not associated with any appreciable change in peripheral vascular resistance. Therefore, isolated systolic hypertension and essential hypertension can no longer be viewed as the same condition. Historically, isolated systolic hypertension was viewed Received August 4, 2000. Accepted September 5, 2000. From the Clinical Pharmacology Unit (IBW), University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK; and Department of Cardiology (JRC), Wales Heart Research Institute, University Wales College of Medicine, Heath Park, Cardiff, UK. Address correspondence and reprint requests to Dr. John Cockcroft, Department of Cardiology, Wales Heart Research Institute, University Wales College of Medicine, Heath Park, Cardiff, UK. AJH 2000;13:1315–1317