Clinical Significance of Systolic and Pulse Pressure

Long ignored as precursors to cardiovascular events, elevated systolic pressure and widening pulse pressure are now being recognized as accurate diagnostic predictors, particularly in older persons.

By Arun Malhotra, MD, and Raymond R. Townsend, MD

Dr. Malhotra is a senior fellow in the nephrology, renal, electolyte, and hypertension division of the department of medicine, and Dr. Townsend is an associate professor of medicine and director of the hypertension program at the University of Pennsylvania, Philadelphia.

Since the invention of the sphygmomanometer in 1896, the assumption that diastolic blood pressure was the paramount prognostic indicator in patients with hypertension went virtually unchallenged for nearly a century. Physiology textbooks universally emphasized the key role of diastolic pressure in reflecting the severity of hypertension, often without any mention of systolic pressure or pulse pressure. Likewise, antihypertensive therapy studies from 1960 through the 1980s, as well as the Joint National Committee (JNC) guidelines prior to 1993, defined the severity of hypertension solely in terms of diastolic pressure.

Actuarial tables, which are used by insurance companies to estimate risk of death, also relied on diastolic pressure, although actuarial analyses dating as far back as 1914 recognized the importance of both systolic and pulse pressures as predictors of death. Even today, the United States Food and Drug Administration (FDA) regards reduction in diastolic pressure as the primary measure of antihypertensive drug efficacy.

For years, medical students were taught that an acceptable level of systolic pressure was determined by adding 100 mm Hg to a patient's age. Until the early 1990s, however, the value of treating elevated systolic pressure in patients with diastolic pressure less than 90 mm Hg remained unproved.

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Prognostic Indicators of Cardiovascular Risk

Only during the last 10 years have systolic blood pressure and pulse pressure been recognized as significant prognostic indicators of cardiovascular risk. As with so many trends in medicine, however, this change has occurred largely as a result of a greater appreciation of research data that were clearly recognized as important by others in the past.

Results of the ongoing Framingham study, for example, repeatedly disclosed that systolic pressure is a better predictor of cardiovascular events than is diastolic pressure. Yet not until 1991, when the results of the Systolic Hypertension in the Elderly Program (SHEP) clearly demonstrated a reduction in morbidity and mortality, was the benefit of treating elevated systolic pressure accompanied by normal diastolic pressure recognized.

These findings were further supported by the results of the Systolic Hypertension in Europe (Syst-Eur) Trial and other hypertension studies, culminating in the incorporation of systolic blood pressure into the JNC classification guidelines. The World Health Organization/ International Society of Hypertension (WHO/ISH) guidelines also now include systolic pressure in classifications of blood pressure.

According to the latest JNC-VI guidelines, the staging of blood pressure severity is determined by whichever value-systolic or diastolic-is higher (see table below).

For example, a patient with a blood pressure of 164/96 mm Hg has stage 1 diastolic hypertension but stage 2 systolic hypertension. Because the systolic reading is higher, this patient's hypertension would be correctly classified as stage 2 hypertension. As these classification guidelines become more widely accepted, the accuracy of diagnosis and classification of hypertension will likely improve, as demonstrated by results of the Framingham cohort study (see figure below).

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Evaluating Pulse Pressure

An inverse relationship between diastolic blood pressure and the risk of cardiovascular disease was first recognized in the 1980s. However, diastolic pressure must always be interpreted in the context of the third measure of blood pressure, the pulse pressure, which is simply the difference between the systolic and diastolic values. Higher pulse pressures have been correlated with an increased occurrence of cardiovascular events.

According to the Framingham study, for example, a 65-year-old-man with a blood pressure of 170/70 mm Hg has a risk of stroke, heart failure, or another cardiovascular event that is twice as high as that of another man of the same age whose blood pressure is 170/110 mm Hg (Circulation, vol. 100, p. 354, 1999). The reason is that although the first man's diastolic pressure is low, his pulse pressure (100 mm Hg) is higher than the other man's (60 mm Hg).

More recent studies, in fact, suggest that pulse pressure is a more accurate predictor of cardiovascular events than is systolic or diastolic blood pressure alone. This finding, however, must be considered in the context of a patient's age, which has overriding significance in the interpretation of blood pressure readings. In younger people, particularly those younger than 45 years of age, diastolic pressure is a better predictor of cardiovascular risk than is systolic or pulse pressure. Keep in mind, however, that cardiovascular events typically do not occur until age 65 or later. As a patient ages, the character of the blood pressure changes, and diastolic pressure becomes less significant as a predictor of cardiovascular events.

Epidemiologic studies have shown a close correlation between pulse pressure and the incidence of cardiovascular disease. In a large cross-sectional prospective study by Benetos and others of 19,083 patients 40 to 69 years of age, the pulse pressure alone was shown to be an independent predictor of cardiac risks as judged by the degree of cardiac hypertrophy (Hypertension, vol. 30, p. 1410, 1997).

In the United States, investigators have examined the prognostic value of pretreatment pulse pressure and found it to be an accurate predictor of myocardial infarction. Results of several longitudinal studies in older patients with hypertension indicate that a high pulse pressure is a sensitive marker for carotid artery stenosis, which increases the risk of stroke, coronary heart disease, and sudden death.

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Role of Increase Arterial Stiffness

The preponderance of current data underscores the role of increased arterial stiffness in the development of cardiovascular events. As hypertension develops, early changes in the circulation tend to affect primarily the systemic vascular resistance at the level of the smaller vessels. In younger people, the increase in vascular resistance is reflected by an elevation in both systolic and diastolic pressure (see figure below). In time, however, the relative contribution of increased vascular resistance to elevated blood pressure lessens, and the role of large-vessel stiffness increases.

As the large vessels age, the elastic elements in their walls fracture and, over many years, degrade with repeated stress. At the same time, inelastic elements such as collagen tend to accumulate. The large vessels thus become less compliant, and a greater initial pressure is necessary to pack the cardiac stroke volume into them. The result is increased systolic pressure.

Another sign of aging in the circulatory system is reduced recoil in the smaller vessels as a result of the loss of elastic elements. The result is a decrease in diastolic pressure. The diastolic pressure tends to peak between the ages of 55 and 60 and decreases after that, whereas systolic pressure continues to increase. Thus, pulse pressure tends to widen as a person ages. Similar changes occur in patients with hypertension, although effective antihypertensive therapy will retard the increase in systolic pressure.

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Increase in Pulse Wave Velocity

Every cardiac contraction emits a pulse wave into the circulation that travels throughout the peripheral vasculature and, in younger people, returns to the heart as the aortic valve is closing. This returning wave contributes to the slight hump seen in the blood pressure waveform after the aortic valve shuts (see figure below, left). As a person ages and large-vessel stiffness occurs, the velocity of the pulse wave increases, causing the wave to return to the heart when the aortic valve is still open, which increases the systolic blood pressure. This change creates the shoulderlike configuration in the plot of the blood pressure waveform and further increases systolic pressure (see figure, below right).

When the systolic blood pressure burden or load on the left ventricle increases, so does the degree of stress on the heart wall, creating a greater demand for oxygen and nutrients. Unfortunately, the decrease in diastolic pressure associated with aging may compromise coronary perfusion, which occurs only during diastole. This combination of changes significantly increases the likelihood of a supply-and-demand imbalance.

In short, the widening in pulse pressure that occurs with aging and antecedent hypertension reflects several pathologic processes, including increased vascular resistance, reduced large-vessel compliance caused by increased vascular stiffness, and accelerated pulse wave velocity with faster wave reflection. Simply put, widening pulse pressure incorporates the well-known risks of increased systolic pressure and reduced diastolic pressure. It also reconciles the seemingly paradoxical research findings that indicate decreased cardiovascular risk in older patients who have higher diastolic blood pressure.

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Data from the SHEP and Syst-Eur Studies

Currently, no clinical trials have been conducted that address treatment of hypertension for the express purpose of decreasing pulse pressure. Consequently, the effects of drug therapy on pulse pressure are largely inferred from clinical trials of antihypertensive treatment. These data come mainly from the SHEP and Syst-Eur hypertension studies.

The value of diuretic therapy in older patients who have isolated systolic hypertension was demonstrated in the SHEP study. In this trial, average enrollment blood pressure in both the treatment group (which received a diuretic, along with beta-blockers or reserpine as needed) and placebo group was 170/77 mm Hg, resulting in an initial pulse pressure of 93 mm Hg. During the five years of the study, blood pressure readings in the treatment group averaged 143/68 mm Hg, yielding a pulse pressure of 75 mm Hg (a reduction of 18 mm Hg). Blood pressure readings in the placebo group averaged 155/72 mm Hg, yielding a pulse pressure of 83 mm Hg (a reduction of only 10 mm Hg).

In the Syst-Eur trial, in which the long-acting dihydropyridine calcium channel blocker nitrendipine (not available in the United States) was administered with additional therapy if needed, pulse pressure was reduced 16 mm Hg in the treatment group but only 11 mm Hg in the placebo group, a difference that was considered statistically significant.

Both of these studies showed remarkable improvement in stroke outcomes in the treatment groups. It is reasonable to conclude, therefore, that therapy based on either diuretic agents or dihydropyridine calcium channel blockers has salutary effects on elevated pulse pressure in older patients. An interesting review of the SHEP data noted that there may be a practical lower limit for diastolic pressure reduction during such treatments: the benefits of systolic pressure reduction were diminished when diastolic pressure fell below approximately 55 mm Hg.

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Serious Harbinger

The recognition of widening pulse pressure as a serious harbinger of cardiovascular events has followed on the heels of an increasing awareness of the serious consequences of elevated systolic pressure, particularly in older patients. The processes that elevate pulse pressure center on changes in the blood vessel wall that occur with aging and antecedent hypertension, especially in cases in which blood pressure control has been difficult to achieve or maintain.

In the coming months, it is likely that older antihypertensive treatment trials will be resurrected and reevaluated in terms of patients' pulse pressure at the time of study entry. Perhaps more important, the response of pulse pressure to intervention during these trials may help indicate the optimal approach to antihypertensive therapy.

Suggested Reading Benetos A, et al.: Pulse pressure and cardiovascular mortality in normotensive and hypertensive subjects. Hypertension 32:560, 1998. Domanski MJ, et al.: Isolated systolic hypertension: prognostic information provided by pulse pressure. Hypertension 34:375, 1999. Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure: The Sixth Report. Arch Intern Med 157:2413, 1997. Kannel WB, et al.: Systolic versus diastolic blood pressure and the risk of coronary heart disease. Am J Cardiol 27:335, 1971. Lloyd-Jones DM, et al.: Differential impact of systolic and diastolic blood pressure level on JNC-VI staging. Hypertension 34:381, 1999. Mitchell GF, et al.: Sphygmomanometrically determined pulse pressure is a powerful independent predictor of recurrent events after myocardial infarction in patients with impaired left ventricular function. Circulation 96:4254, 1997. Somes GW, et al.: The role of diastolic blood pressure when treating isolated systolic hypertension. Arch Intern Med 159:2004, 1999. Staessen JA, et al., for the Systolic Hypertension in Europe (Syst-Eur) Trial Investigators: Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. Lancet 350:757, 1997. Systolic Hypertension in the Elderly Program (SHEP) Study Group: Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: Final results. JAMA 265:3255, 1991.

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