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The Clinical Significance of Systolic Hypertension AJH 1998;11:182S–185S The Clinical Significance of Systolic Hypertension William C. Cushman Downloaded from https://academic.oup.com/ajh/article/11/S8/182S/151642 by guest on 28 September 2021 Large-scale epidemiologic studies and clinical trials Blood Pressure (JNC VI) recommends drug therapy have contributed to an increased recognition of the for all patients with stage 1 (140 to 159 mm Hg) or importance of systolic hypertension. Data from stage 2–3 (> 160 mm Hg) systolic hypertension, landmark epidemiologic studies such as the whether it occurs in isolation or in conjunction Multiple Risk Factor Intervention Trial screenee with diastolic hypertension. The sixth JNC report follow-up and the Framingham Heart Study have identified diuretics as the initial therapy of choice, demonstrated that elevated systolic blood pressure with a long-acting dihydropyridine calcium dramatically increases the risk of cardiovascular channel blocker as an alternative if diuretics are events. Of particular concern is the extremely high ineffective or not well tolerated. More research is risk associated with isolated systolic hypertension needed to evaluate other classes of drugs in this (ISH), which is much more common in the elderly setting. Regardless of the choice of therapy, than in young adults. Clinical trials have identified patients should be encouraged to adopt lifestyle significant risk reductions after treatment with modifications such as weight loss, exercise, sodium diuretics or the dihydropyridine calcium antagonist restriction, and reduced alcohol consumption. nitrendipine in older individuals with ISH. Beta Am J Hypertens 1998;11:182S–185S blockers have not been associated with such benefits. The recently released sixth report of the Joint National Committee on Prevention, KEY WORDS: Cardiovascular risk, systolic Detection, Evaluation, and Treatment of High hypertension. raditionally, the management of hyperten- SYSTOLIC HYPERTENSION AS A RISK sion has focused on diastolic blood pressure FACTOR FOR CORONARY HEART DISEASE (DBP). However, insurance companies rec- The increased focus on systolic hypertension was ognized the importance of elevated systolic Tblood pressure (SBP) as early as the 1920s. Neverthe- prompted, in part, by data from more than 300,000 men who were screened for the Multiple Risk Factor less, medical epidemiology only began to appreciate 1 the importance of SBP to cardiovascular risk in the Intervention Trial (MRFIT) during the 1970s. These 1960s, and not until the 1990s did clinical trials con- subjects were not enrolled in the intervention study, firm the benefits of treating elevated SBP. but were followed over time. MRFIT demonstrated that the risk of death from coronary heart disease (CHD) increased gradually as DBP progressed from lower to higher levels (Figure 1). However, the SBP From the University of Tennessee College of Medicine and Vet- erans Affairs Medical Center, Memphis, Tennessee. curve increased to a greater extent, indicating that Address correspondence to William C. Cushman, MD, Professor even a small elevation in SBP (eg, 140 to 159 mm Hg) of Preventive Medicine, University of Tennessee College of Medi- cine, VA Medical Center, Chief, Preventive Medicine (111Q), 1030 confers significant CHD risk. This risk is even greater Jefferson Avenue, Memphis, TN 38104. when SBP reaches levels of 160 mm Hg or more. Of 0895-7061/98/$0.00 Published by Elsevier Science, Inc. PII S0895-7061(98)00197-6 AJH–NOVEMBER 19982VOL. 11, NO. 11, PART 2 CLINICAL SIGNIFICANCE OF SYSTOLIC HYPERTENSION 183S 179 mm Hg), the chlorthalidone was doubled; 25 mg/ day atenolol or 0.05 mg/day reserpine if atenolol was contraindicated, was added if needed for BP control. Doses of the latter therapies could also be doubled if necessary. As shown in Figure 2, the incidence of stroke at 5 years was 8.2% in the placebo group versus 5.2% in the active treatment group, a difference that was highly statistically significant (P 5 .0003). The relative risk reduction with active therapy was 36%. The curves began to separate fairly early and continued to separate, suggesting that the treatment benefits might Downloaded from https://academic.oup.com/ajh/article/11/S8/182S/151642 by guest on 28 September 2021 be even greater over time. The SHEP analysis also revealed that active therapy reduced the occurrence of total CHD by 25%, nonfatal myocardial infarction (MI) FIGURE 1. Age-adjusted coronary heart disease (CHD) death by 27%, and total cardiovascular disease by 32%; all rates (per 10,000 person-years) by systolic (SBP) and diastolic decreases were statistically significant. A nonsignifi- blood pressure (DBP) for men in the Multiple Risk Factor Inter- cant, 13% reduction in total mortality was also ob- vention Trial (MRFIT): 12-year follow-up. Reprinted with per- served. In a more recent analysis, the investigators mission from Neaton JD, et al: Serum cholesterol, blood pressure, reported that diuretic-based therapy produced a 50% cigarette smoking, and death from coronary heart disease: overall reduction in the incidence of heart failure, and this findings and differences by age for 316,099 white men. Arch Intern 1 figure reached 80% among patients who had previ- Med 1992;152:56–64. © 1992 American Medical Association. ously suffered coronary events.5 In the United Kingdom, the Medical Research Council6 trial enrolled 4396 patients, age 65 to 74 particular concern is the presence of systolic pres- years, who had SBP ranging from 160 to 209 mm Hg sure $ 160 mm Hg in conjunction with DBP , 70 mm and DBP # 115 mm Hg. Patients were randomized to Hg. This form of stage 2 isolated systolic hypertension receive therapy with diuretics (2.5 mg/day amiloride (ISH) is more apt to appear with aging as the vessels plus 25 mg/day hydrochlorothiazide [HCTZ]), a become stiffer, and is associated with an extremely b-blocker (50 mg/day atenolol), or placebo. If the high risk of fatal cardiovascular events. target SBP of 150 or 160 mm Hg (depending on the Data from the Framingham Heart Study2 have also demonstrated that, compared with DBP, SBP is a stronger predictor of adverse cardiovascular events and total mortality. In fact, in patients older than age 65, elevated DBP is no longer an independent predic- tor of risk. In the overall Framingham cohort aged 45 to 74 years, the risk of cardiovascular events was increased by 50% in those with SBP of 140 to 159 mm Hg, as opposed to less than 140 mm Hg. Other data from Framingham have shown that a 20-mm Hg in- crease in SBP is a more potent risk factor than a 10-mg/dL increase in serum cholesterol.3 BENEFITS OF TREATING SYSTOLIC HYPERTENSION Several large-scale trials have now demonstrated the benefits of treating SBP in the elderly population. In the Systolic Hypertension in the Elderly Program FIGURE 2. Cumulative fatal plus nonfatal stroke rate per 100 (SHEP),4 ISH was defined as SBP of 160 to 219 mm Hg participants in the active treatment (solid line) and placebo (broken line) groups during the Systolic Hypertension in the Elderly with DBP less than 90 mm Hg. A total of 4736 patients Program. P 5 .0003. Reprinted with permission from SHEP 60 years old or older were randomized to receive 12.5 Cooperative Research Group: Prevention of stroke by antihyper- mg/day chlorthalidone or placebo. If patients in the tensive drug treatment in older persons with isolated systolic active treatment group did not achieve the goal SBP hypertension. Final results of the Systolic Hypertension in the (160 mm Hg for individuals with SBP . 180 mm Hg; Elderly Program (SHEP). JAMA 1991;265:3255–3264.4 © 1991 20 mm Hg reduction for individuals with SBP 160 to American Medical Association. 184S CUSHMAN AJH–NOVEMBER 19982VOL. 11, NO. 11, PART 2 TABLE 1. RISK REDUCTION WITH ACTIVE RECOMMENDATIONS FOR TREATING THERAPY VERSUS PLACEBO IN THE SYST-EUR ISOLATED SYSTOLIC HYPERTENSION TRIAL (FROM STAESSEN7) As specified in the sixth report of the Joint National % Risk Reduction, Fatal and Nonfatal 95% CI Committee on Prevention, Detection, Evaluation, and 8 Endpoints Combined (Active v Placebo) P Treatment of High Blood Pressure (JNC VI) in 1997, hypertension is classified as SBP of 140 to 159 mm Hg Stroke 42 .003 or DBP 90 to 99 mm Hg (stage 1), SBP 160 to 179 mm Cardiac endpoints* 26 .03 Hg or DBP 100 to 109 mm Hg (stage 2), or SBP greater Heart failure 29 .12 Myocardial infarction 30 .12 than or equal to 180 mm Hg or DBP 110 mm Hg or All fatal and nonfatal more (stage 3). The JNC VI guidelines recommend cardiovascular endpoints 31 .001 that all patients with stage 1 hypertension should Downloaded from https://academic.oup.com/ajh/article/11/S8/182S/151642 by guest on 28 September 2021 eventually be considered for antihypertensive drug * Included fatal and nonfatal heart failure, fatal and nonfatal MI, and sudden death. therapy in addition to lifestyle modifications. One con- CI, confidence interval. cern regarding this recommendation is the large size of the target population; for example, in the United States (US), 27% of individuals $ 60 years of age have stage 1 ISH and another 10% have stage 2–3 ISH.9 The initial level) was not achieved after 6 months, the dose JNC VI guidelines are based on the best currently was doubled. If further control was needed, the other available evidence; however, definitive proof is still study drug was added. needed to confirm that the risk of adverse outcomes Diuretic therapy significantly reduced the incidence can be reduced by drug therapy for stage 1 systolic of stroke by 31% and CHD by 44%. Mortality was hypertension. Nonetheless, the epidemiologic and decreased by 16%, which was of borderline signifi- clinical trial evidence suggests that patients with ele- cance. Perhaps even more notably, this was the first vated SBP should receive treatment.
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