Published June 6, 2002
Isolated systolic hypertension (ISH) is currently defined as a systolic blood pressure (SBP) > 140 mm Hg with diastolic blood pressure (DBP) < 90 mm Hg, and not secondary to another disorder. This current definition represents a change from the earlier definition of ISH, utilized in most studies, of SBP > 160-165 mm Hg with DBP < 90-95 mm Hg. It is a disease entity that was once thought to be relatively benign. However, recent data support the view that systolic hypertension, even in the absence of diastolic hypertension, is a significant risk factor which, if left untreated, increases morbidity and mortality across populations.
Current consensus opinion regards a stable blood pressure of < 140/90 mm Hg as a general goal in an unspecified population, with different stages of hypertension corresponding to deviations from this consensus. In 1997, the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure issued guidelines 1 (JNC VI) for the definition and classification of hypertension (Tables 1 and 2):
This chapter attempts to provide an overview of the data supporting the need for prompt and aggressive treatment of ISH in populations commonly encountered in clinical practice, as well as the experience documented with various treatment regimens.
In spite of trends demonstrating an improvement in both the recognition and the treatment of this disease, hypertension remains a common affliction, with consensus estimates that approximately 50 million patients suffer from hypertension in the United States alone. Although often clinically silent, hypertension is a serious risk factor associated with stroke and cardiovascular morbidity.
The reported prevalence of ISH varies. It increases with advancing age, with recent estimates from the National Health and Nutrition Examination Survey (NHANES III) showing that ISH accounts for 54% of hypertension in patients aged 50 to 59 years and 87% in patients aged 60 years or older.2 The reason for this increase may reflect proposed pathophysiologic mechanisms involved in the generation of ISH and discussed below. For many years it was thought that ISH was not strongly associated with the sequelae linked to diastolic or combined hypertension and, as such, specific treatment goals in ISH were less emphasized. As data from landmark studies have demonstrated a link between isolated systolic hypertension and morbidity from multiple causes, the importance of addressing this form of hypertension has emerged.
In older patients with systolic hypertension, systemic arterial compliance is significantly reduced when compared with younger controls; this is thought to be due to an increased rigidity of the arterial walls. Specifically, mechanical changes in arterial walls such as atherosclerosis and gradual loss of aortic distensibility, which decrease overall arterial compliance, are more commonly encountered with advancing age.3 This decrease in compliance results in higher systolic pressures as the large vessels become less able to reduce the pressure generated by the left ventricle by means of distension. However, while increases in peripheral resistance will cause elevations in diastolic blood pressures, the loss of large-vessel elasticity does the opposite. These counteracting forces may keep the diastolic pressure normal in the setting of an increasing systolic pressure.
Because the distensibility of the ascending aorta and other major vessels fails most often due to changes seen with aging, the majority of risks for ISH and the potential benefits of treatment have been demonstrated predominantly in older populations, and the extent to which these data are applicable to younger patients remains to be seen.
Interestingly, some authors have suggested that the same pathophysiologic mechanisms discussed above result, when combined, in a more important elevation in pulse pressure, which is defined as the difference between systolic and diastolic blood pressures. Evidence is beginning to show that elevation in pulse pressure itself may be an important independent risk factor for all-cause and cardiovascular mortality, and analysis of Framington Heart Study data has revealed that neither SBP nor DBP is superior to pulse pressure in predicting coronary heart disease risk.4,5
Despite its sizable impact on morbidity and mortality, hypertension is often clinically silent, and the most crucial data obtained from the patient may come by way of taking proper sphygmomanometer readings. This is not to say that important information is not available in the history and physical examination; however, in the setting of suspected ISH, these exercises are most helpful in eliminating other causes for the elevated blood pressure and for risk stratification. As such, a detailed discussion is beyond the scope of this chapter.
As noted, the diagnosis of ISH is made by demonstrating a SBP =140 mm Hg with a DBP < 90, following current national recommendations for blood pressure monitoring (Table 3).
The diagnosis of ISH is reserved for situations in which the blood pressure has been measured on several occasions with consistent results, and after exclusion of other causes of widened pulse pressure such as arteriovenous fistulae, thyroid disease, anemia, aortic regurgitation, and intrinsic diseases of the artery such as coarctation.1 Although the possibility exists for false-positive measurements, to date indirect manometry remains acceptable for both JNC VI and most major trial purposes. If travel to the physician's office is not feasible, or if a patient's anxiety in the office is thought to be distorting results, self-measurement of blood pressure at home is an effective method of identifying patients at higher risk due to ISH.
Once hypertension is established, careful evaluation to identify risk factors, exclusion of hypertension related to a secondary problem, and evaluation of target organ damage should be undertaken as guided by clinical findings. JNC VI guidelines utilize this evaluation (Tables 4 and 5) to risk-stratify patients for treatment considerations.
Unfortunately, recent studies show that ISH remains a common and undertreated disease in the United States and abroad. A recent review by NHANES III2 found that ISH was the most common hypertension subtype in people aged 50 years and older, and that ISH patients composed the largest group of uncontrolled hypertensive patients (65%). Despite evidence that ISH is both the most common form of hypertension in elderly patients as well as evidence that ISH tends to worsen with advancing age, analysis of large populations shows that even among treated patients, blood pressure control is increasingly inadequate among older patients.1,6
In 1998, the Evaluation and Interventions for Systolic Blood pressure Evaluation: Regional and Global (EISBERG) project7 gathered and analyzed data from approximately 17,000 patients in seven countries, including the United States, in an effort to determine the adequacy of blood pressure control in hypertensive disease. The study revealed little improvement in the control of systolic blood pressure, documenting an alarming 90% of control failures. Systolic blood pressure control was achieved in less than 40% of patients who had a goal BP of < 140/90. A review of qualitative data gathered by the project revealed an overall lack of understanding of the disease on the part of patients, coupled with a reluctance on the part of general practitioners to aggressively treat ISH in elderly patients. Taken together, the data from the NHANES III and EISBERG project reveal that current practices are incongruent with the evolving picture of the importance of systolic hypertension and pulse pressure evident from population data.8
That ISH is a legitimate, independent risk factor associated with increased end-stage renal disease, cardiac disease, and stroke has been positively demonstrated in the literature.9 ISH itself is associated with two to three times the risk of cardiovascular events or mortality across ages and genders; this risk is essentially doubled in diabetic patients or smokers. Other data suggests ISH may independently increase risk for dementia.10 In fact, elevated systolic blood pressure and elevations in pulse pressures (SBP - DBP) seen in ISH are now believed to have more influence than does diastolic blood pressure on the progression of cardiac disease.
This realization required the design of new studies to directly measure the results of therapeutic interventions in ISH on outcomes. Three major trials11-13 have investigated the effects on common risk factors of lowering systolic hypertension with pharmacologic agents (Table 6).
The results of these trials were pooled into a meta-analysis,14 which concluded that active treatment did reduce risk factors associated with ISH; specifically, active treatment reduced all-cause mortality by 17%, cardiovascular mortality by 25%, all cardiovascular end points by 32%, all strokes by 37%, and all myocardial infarction by 25%.
A further demonstration of the risk reduction associated with treatment of elderly patients with ISH is apparent in another meta-analysis by Staessen et al,15 in which the data from the above three trials were pooled with data from five additional trials featuring subgroups of elderly ISH patients (patients aged 60 years or older and using SBP > 160 and DBP < 90-95 mm Hg to define ISH). The results of this meta-analysis revealed untreated ISH to be related to total and cardiovascular mortality, with a 10 mm Hg increase in SBP correlating with a nearly 10% increased risk of all measured complications except for coronary events. Conversely, active treatment of systolic hypertension to reduce a pretreatment mean of 174/83 mm Hg by -5.96% systolic and -4.91% diastolic reduced total mortality by 13% (P = 0.02), cardiovascular death by 18% (P = 0.01), all cardiovascular fatal and nonfatal events by 26% (P < 0.0001), stroke by 30% (P < 0.0001), and coronary events by 23% (P = 0.001).
The data supporting an aggressive approach toward controlling ISH in the elderly is evident; however, some reports have suggested that the practice of reducing blood pressure in elderly patients may itself lead to complications. The three landmark trials above11-13 did not generally achieve reductions in blood pressure below 140/72 mm Hg, nor did they generally segregate elderly patients into subgroups. At least one study16 has shown a statistically significant increase in elderly patients' risk of stroke when DBP falls below 65 mm Hg in patients treated for hypertension (compared with controls). Additionally, an analysis of the SHEP cohort revealed that, in treated patients, a DBP of < 70 mm Hg was associated with increased stroke, CHD, and CVD,17 although treated patients never performed worse than placebo patients in terms of CVD events. Finally, there are reports that in the very elderly patient population (eg, ages > 80-85), higher levels of blood pressure may correlate with improved mortality. However, a meta-analysis of several antihypertensive drug therapy trials in patients age > 80 years did not support withholding treatment of hypertension in this population.18 Clearly, these studies demonstrate the need for further work to clarify the goal of blood pressure reduction efforts in selected scenarios.
An approach to individual patients can incorporate the data discussed above with the current JNC VI guidelines (Table 7) in order to select an approach to therapy that maximizes benefits of blood pressure reduction in patients with ISH. What follows are broad recommendations for specific interventions that can be used in the clinical setting of patient care:
As noted previously, the risks of ISH are higher in patients with diabetes and in smokers; thus, tight control of the former and cessation of the latter are important in reducing morbidity and mortality. Interestingly, the diabetic subsegment of the SHEP trial showed almost twice the reduction in absolute risk from all major cardiovascular events compared with nondiabetic patients, although the population in this instance was limited to relatively well-controlled non-insulin-dependent patients.19 This further underscores the need to address both diseases concomitantly in order to maximize patient benefits.
A change from a sedentary lifestyle to a more active lifestyle with a formal exercise program is often recommended in patients suffering from chronic illness, and in fact may be beneficial in patients with ISH. However, one study20 of the effects of an exercise program targeting an intensity of 65% maximum predicted heart rate in elderly patients (age 64 ± 7 years old) with ISH failed to demonstrate improvements in large-artery mechanics or blood pressure over an 8-week period, suggesting that exercise alone is insufficient to treat ISH in this group. The authors suggest that longer programs, or introduction of the program at a younger age, are as-yet unproved alternatives worth exploring.
Dietary modification is important in subgroups of patients with diabetes and hyperlipidemia, and additionally there are data to support a significant mean reduction in SBP of 11.8 mm Hg in a group of patients with stage 1 ISH (SBP 140-159 mm Hg pretreatment) treated with the use of the DASH diet.21 This is an inexpensive, attractive alternative for compliant patients with mild ISH, and the magnitude of reduction in SBP is comparable with many low-dose drug regimens.
Ideal agents would target those pathophysiologic derangements that are thought to be present in ISH, and without causing serious side effects. In particular, the emergence of widened pulse pressure as a significant independent risk factor for mortality highlights the importance of avoiding agents whose actions might increase the pulse pressurefor example, agents that cause profound decreases in diastolic blood pressure. For ISH, then, a theoretic advantage would be seen in agents having a direct vasodilatory effect on the aorta and large vessels, improving arterial compliance and reversing the changes that are seen with aging and ISH.