Systolic Hypertension in Older Persons: How Aggressive Should Treatment Be?

Systolic Hypertension in Older Persons: How Aggressive Should Treatment Be? John R. Kapoor, Sarwat Chaudry, Joseph V. Agostini, and Jo Anne Micale Foody

Systolic hypertension (SH) is a major public health concern predominantly affecting older persons. A key message of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) is that SH is a much more important cardiovascular disease risk factor than diastolic hypertension, particularly in older persons. Consequently, aggressive control of elevations of systolic blood pressure (SBP) is recommended.1 Despite increasing attention, SH is on the rise: isolated elevations of SBP in a national sampling of Veteran’s Administration patients have increased from 57% in 1990 to 1995 to 76% of patients in 1999.2 This article considers several clinically pertinent issues, including the evidence for treating older patients with elevations in SBP, treating SH in the b oldest old Q (those aged N85 years), and how aggressively these patients should be treated. In addition, issues regarding clinical decision making in older patients with SH are discussed. n 2006 Published by Elsevier Inc.

Systolic Hypertension Isolated SH (ISH) is a term that has been used for many years to describe elevated SBP with normal (or even low) diastolic blood pressure (DBP). Because of concerns that the word isolated may minimize the perceived health risk, many authors have adopted the use of SH (in place of ISH) to emphasize that this condition is an integral part of cardiovascular health.3 This shift is reflected in JNC 7, which for the first time since 1980 omitted the term ISH, replacing it with SH. Accordingly, we will use the term SH in this review to refer to the same condition traditionally referred to as ISH. Beginning in 1980, the JNC defined SH as SBP 160 mm Hg or greater with DBP less than

90 mm Hg.4 -6 Later, in 1993, the JNC lowered the definition of SH to SBP 140 mm Hg or greater with a DBP less than 90 mm Hg7,8 based largely on data from the Systolic Hypertension in the Elderly Program (SHEP) trial. For the purposes of this review, consistent with criteria from JNC 7, we define SH as SBP of at least 140 mm Hg with a DBP of less than 90 mm Hg.

Evidence Base: SH As early as the 1970s, epidemiologic studies strongly suggested that SH was a risk factor for cardiovascular disease.9 With the publication of SHEP in 1991, trial evidence supported treatment of this condition.10 The Systolic Hypertension in Europe (Syst-Eur) 11 and Systolic Hypertension in China (Syst-China)12 trials further supported the treatment of SH. The definition of SH used in all 3 trials was similar. Systolic Hypertension in the Elderly Program defined SH as SBP of 160 to 219 mm Hg with DBP of less than 90 mm Hg, whereas Syst-Eur and Syst-China defined SH as SBP 160 to 219 mm Hg and DBP less than 95 mm Hg. More recently, a substudy of the Losartan Intervention for Endpoint Reduction (LIFE)13 trial addressed the role of blood pressure (BP) reduction in

From the Department of Veterans Affairs, VA Connecticut Healthcare System, West Haven, CT, Department of Internal Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine; New Haven, CT, and Department of Internal Medicine, Yale University School of Medicine, New Haven, CT. Address reprint requests to John R. Kapoor, Department of Internal Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine; New Haven, CT. 0033-0620/$ - see front matter n 2006 Published by Elsevier Inc. doi:10.1016/j.pcad.2006.02.006

Progress in Cardiovascular Diseases, Vol. 48, No. 6 (May/June), 2006: pp 397-406

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Table 1. Studies of Treating SH With SBP Greater Than 160 mm Hg SHEP10

Syst-Eur11

Syst-China12

LIFE substudy13

n Mean age (y) % Female Primary end point

4736 72 57 Stroke

4695 70 67 Stroke

2394 66 35 Stroke

Initial mean BP (mm Hg) Mean BP reduction (mm Hg) Primary agent Secondary agents Stroke RR (95% CI) NNT Total CV events RR (95% CI) NNT Total CV mortality RR (95% CI) NNT Total mortality RR (95% CI) NNT

170/77 27/9 Chlorthalidone Atenolol, reserpine

174/85 23/7 Nitrendipine Enalapril, HCTZ

170/86 20/5 Nitrendipine Captopril, HCTZ

1326 70 59 Cardiovascular death, stroke, or myocardial infarction 174/83 28/9 Losartan F HCTZ Atenolol, HCTZ

0.63 (0.49-0.82) 45

0.58 (0.41-0.84) 72

0.69 (0.48-1.02) 62

0.60 (0.38-0.92) 70

0.68 (0.58-0.79) 19

0.71 (0.57-0.87) 42

0.72 (0.53-0.96) 43

0.75 (0.56-1.01) 44

0.80 (0.60-1.05) 109

0.73 (0.53-1.03) 112

0.68 (0.44-1.06) 81

0.54 (0.34-0.87) 72

0.87 (0.73-1.05) 83

0.86 (0.68-1.09) 120

0.68 (0.49-0.93) 44

0.72 (0.53-1.00) 43

Abbreviations: CV, cardiovascular; HCTZ, hydrochlorthiazide.

older patients with left ventricular hypertrophy (LVH) and SH—again defined as an SBP of 160 mm hg and above. The key features of these studies are discussed below and summarized in Table 1. Systolic Hypertension in the Elderly Program Systolic Hypertension in the Elderly Program was a randomized, double-blind, placebo-controlled trial conducted in 16 tertiary care centers in the United States. The study was designed to determine the effect of drug treatment on the risk of fatal and nonfatal stroke in SH. The 4736 participants ranged in age from 60 to 96 years, with a mean age of 72 years. Of the total study population, 57% were women and 14% were black. The mean BP at the time of randomization was 170/77 mm Hg. Average follow-up was 5 years. For individuals with SBP greater than 180 mm Hg, the goal was to reduce SBP to less than 160 mm Hg. For those with SBP 160 to 179 mm Hg, the goal was to reduce the SBP by at least 20 mm Hg. All participants were given the thiazide diuretic chlorthalidone (12.5-25 mg/d) or matching placebo. Atenolol (25-50 mg/d) was added next, if needed. Of the participants in the active treatment group, 46% received chlorthalidone only.

The average BP after 5 years was 155/72 mm Hg in the placebo group and 143/68 mm Hg in the active treatment group. The 5-year incidence of stroke (fatal and nonfatal combined) was 8.2% in the placebo group and 5.2% in the active treatment group, with a relative risk (RR) of 0.63 and 95% confidence interval (CI) of 0.50 to 0.82. The number needed to treat (NNT) to prevent 1 stroke was 45. There was a statistically significant 32% reduction in the incidence of cardiovascular disease (fatal and nonfatal combined). The reductions in cardiovascular mortality and all-cause mortality achieved by active treatment were not statistically significant, though the study was not powered to detect differences in these end points. The development of new cases of diabetes was not significantly greater in the active treatment group compared with the placebo group (8.6% vs 7.5%, respectively, P = .25).14 Active treatment was not found to have a negative impact on cognitive function, quality of life, or general health.15 Systolic Hypertension in Europe Systolic Hypertension in Europe was a randomized, double-blind, placebo-controlled trial conducted in 198 centers in 23 European countries. Like SHEP, the primary objective

SYSTOLIC HYPERTENSION IN OLDER PERSONS

was to determine whether active treatment of SH could reduce the risk of stroke. The 4695 participants, followed for 2 years, ranged in age from 60 to 100 years, with a mean age of 70 years and a mean BP of 174/85 mm Hg. Women comprised 67% of the study sample. Unlike SHEP, treatment goals were not based on baseline SBP. Rather, the goal was to reduce all participants’ SBP to less than 150 mm Hg. Active treatment consisted of the long-active dihydropyridine calcium channel blocker nitrendipine (10-40 mg/d), with the addition of enalapril (5-20 mg/d), then HCTZ (12.5 mg to 25 mg/d), as needed to lower the SBP to goal. After 2 years, nitrendipine was the only treatment given to 59% of the participants in the active treatment group. At the median 2-year follow-up, BP decreased to an average of 160/83 mm Hg in the placebo group and 150/78 mm Hg in the active treatment group. Treatment significantly reduced the risk of stroke by 42%, from 3.35% in the placebo group to 1.96% in the active treatment group. The NNT to prevent 1 stroke was 72. Cardiovascular disease was also significantly reduced by 30% with active treatment. Treatment did not significantly reduce cardiovascular or all-cause mortality. The active treatment group had half the incidence of dementia compared with the placebo group (7.7 cases per 1000 patient-years compared with 3.8 cases).16 An analysis of 610 patients showed that measures of depression, ambulation, physical activities related to house work, and sleep and rest were not significantly different in the active treatment group and the placebo group.17 Over the 2-year period, 15% of study participants discontinued nitrendipine, 20% discontinued enalapril, and only 6% discontinued HCTZ. The reasons for stopping nitrendipine were edema and flushing, and for enalapril, cough.18 Systolic Hypertension in China Systolic Hypertension in China was a randomized, single-blind, placebo-controlled study conducted in 31 centers in China. The trial was prematurely terminated with the publication of the Syst-Eur trial. The results of this study must therefore be interpreted within the context of these limitations. Systolic Hypertension in China

399 was designed to determine whether active treatment could reduce the incidence of stroke in older persons with SH. The 2394 patients had a mean age of 66 years and a mean BP of 170/ 86 mm Hg, and 35% were women. Patients were followed up for a median of 3 years. As in Syst-Eur, the goal in the active treatment group was to lower SBP to less than 150 mm Hg. Active treatment was started with nitrendipine (10 or 20 mg/d or 20 mg twice daily), with the possible addition of captopril (12.5 mg/d or twice daily or 25 mg twice daily) or HCTZ (in the same dosages as captopril) or both to achieve target SBP. Among participants who took study medication for at least 2 years, nitrendipine was the only medication given in 74% of the active treatment group. After 2 years, SBP fell to an average of 159/84 mm Hg in the placebo group and 150/81 mm Hg in the active treatment group. In the placebo group, the rate of stroke was 5.17%, and in the active treatment group, the rate was 3.59%. The RR for stroke was not statistically significant at 0.69 (95% CI, 0.48-1.02), and the NNT to prevent 1 stroke was 62. Significant reductions were seen in total cardiovascular events and total mortality, but not in total cardiovascular mortality. Losartan Intervention For Endpoint Reduction Substudy13 In a more recent substudy of the LIFE trial, investigators tested the hypothesis that losartan improves outcome better than atenolol in patients with ISH and electrocardiographically documented LVH (ECG-LVH). In this doubleblind, randomized, parallel-group study conducted in 1995 to 2001, 1326 men and women aged 55 through 80 years, with SBP of 160 to 200 mm Hg and DBP of less than 90 mm Hg (mean, 174/83 mm Hg) and ECG-LVH, were recruited internationally. Patients were randomized to receive once-daily losartan (n = 660) or atenolol (n = 666), with hydrochlorothiazide as the second agent in both arms, for a mean of 4.7 years. The main outcome of interest was a composite end point of cardiovascular death, stroke, or myocardial infarction. In this study, BP was reduced by 28/9 and 28/9 mm Hg in the losartan and atenolol arms, respectively. The main outcome was reduced by

400 25% with losartan compared with atenolol, 25.1 vs 35.4 events per 1000 patient-years (RR, 0.75; 95% CI, 0.56-1.01; P = .06) after adjustment for risk and degree of ECG-LVH. Patients receiving losartan had reductions in cardiovascular mortality (8.7 vs 16.9 events per 1000 patient-years; RR, 0.54; 95% CI, 0.34-0.87; P = .01), nonfatal and fatal stroke (10.6 vs 18.9 events per 1000 patient-years; RR, 0.60; 95% CI, 0.380.92; P = .02), new-onset diabetes (12.6 vs 20.1 events per 1000 patient-years; RR, 0.62; 95% CI, 0.40-0.97; P = .04), and total mortality (21.2 vs 30.2 events per 1000 patient-years; RR, 0.72; 95% CI, 0.53-1.00; P = .046). An analysis of 8 trials including 15 693 patients with ISH followed for an average of 3.8 years, with average BPs of 174 mm Hg systolic and 83 mm Hg diastolic, found that, overall, the net declines in SBP and DBP were 5.96% (95% CI, 5.63-6.28) and 4.91% (95% CI, 4.44-5.38), respectively. In the control group, 734 deaths and 835 major adverse cardiovascular events occurred, whereas in the treatment group, 656 deaths and 647 events occurred. Across all trials, treatment was associated with a 13% (95% CI, 2%-22%; P = .02) mortality difference. Finally, in yet another meta-analysis that more specifically combined data on individuals 80 years or older in SHEP, SHEP-pilot,19 SystEur, and STOP-Hypertension, active treatment was associated with 39% reduction in congestive heart failure, 34% reduction in stroke, and 22% reduction in cardiovascular disease (CVD).20 The aforementioned trials addressed the role of BP lowering in those persons with SBPs of 160 mm Hg and above. Although most uncontrolled hypertension in the United States are in fact mild (stage 1) SH in older adults,21 to date, no large-scale clinical trial has assessed the value of therapy in this group. Thus, few trial data are available to guide clinical decision making in this group. The evidence available consists primarily of observational data from the Framingham Heart and Physicians Health Studies. Framingham Analysis of participants in the Framingham Heart Study with stage 1 SH revealed a greater risk for development of cardiovascular disease (RR, 1.47; 95% CI, 1.24-1.74), coronary heart

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disease (RR, 1.44; 95% CI, 1.18-1.77), stroke (RR, 1.42; 95% CI, 1.03-1.93), and heart failure (RR, 1.60; 95% CI, 1.15-2.22) compared with those with normal BP.22 Mortality from cardiovascular disease was also greater compared with that of normotensives (RR, 1.57; 95% CI, 1.242.00). The total number of people with stage 1 SH was relatively small (N = 351), and only 90 participants were 60 years or older at the beginning of the study. This study suggests that stage 1 SH is associated with increased risk for cardiovascular disease. Physicians’ Health Study In this study, 1266 of 22 071 men had stage 1 SH at baseline, with a mean SBP of 142.3 mm Hg and a mean age of 59 years.23 All participants were physicians, and none was treated for stage 1 SH. When compared with normal BP, stage 1 SH was associated with significantly increased risks of cardiovascular disease (RR, 1.32; 95% CI, 1.09-1.59), stroke (RR, 1.42; 95% CI, 1.04-1.93), cardiovascular death (RR, 1.56; 95% CI, 1.13-2.15), and all-cause mortality (RR, 1.22; 95% CI, 1.01-1.47). Thus, based on observational data, it is reasonable to assign increased risk associated with hypertension in this group and to lower BP in this group with the understanding that randomized clinical trial data to support this approach are lacking.

What is the Evidence for Treating the Oldest Old? Patients older than 85 years are commonly considered the oldest old24 and comprise a significant proportion of the population.25 The narrowed therapeutic window of most therapies, including antihypertensives, competing risks from non–BP-related causes, as well as higher cardiovascular event rates,26 is particularly an important consideration in this group. In SHEP, the benefit of active treatment compared with placebo increased with age, reaching its maximum in the 650 patients in the oldest age group (those at least 80 years of age). The RR for stroke in actively treated patients in the oldest age group was 0.53 (95% CI, 0.32-0.88), compared with 0.74 (95% CI, 0.48-1.14) in

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the group aged 60 to 69 years.10 Although the risk reduction in the 2 groups may not actually be different, the evidence at least suggests that the older patients may still benefit from treatment. Subgroup analysis of Syst-Eur revealed that although active treatment did not postpone death in patients older than 80 years, it probably still prevented cardiovascular complications, stroke, and cardiac end points. The small size of the oldest age group (n = 441) limited its power to draw statistically significant conclusions.27 The Hypertension in the Very Elderly Trial, a large multicenter placebo-controlled trial in hypertensives 80 years and older will compare diuretic therapy with angiotensin-converting enzyme inhibitor (ACE-I) therapy and placebo. Recently released results from the (unblinded) pilot study for this trial demonstrate a clear reduction in stroke (relative hazard rate [HR], 0.47; 95% CI, 0.24-0.93), but also a possible increase in total mortality in the 13-month average follow-up (relative HR, 1.23; 95% CI, 0.75-2.01).28 Results for the main trial are likely to shed light on the risks and benefits of antihypertensive therapy in the oldest cohort of patients.

Which Antihypertensive Strategies are Preferred in the Treatment of SH? Lifestyle Modification The original Dietary Approaches to Stop Hypertension (DASH) trial demonstrated that a diet that is high in fruits, vegetables, and fiber; includes whole grains, poultry, fish, and nuts; and limits intake of red meats, sweets, total and saturated fat, and cholesterol lowers BP significantly compared with a typical American diet.29 Furthermore, the combined effects on BP reduction of the DASH diet and decreasing sodium intake to levels below 100 mmol/d are greater than the effects of either intervention alone.30 An analysis of the DASH diet in stage 1 SH demonstrated its effectiveness in lowering SBP by 11.2 mm Hg and controlling SBP to less than 140 mm Hg in 18 of the 23 participants.31 The study population was relatively small (a total of 72 individuals), and the mean age of the group receiving the DASH diet was 54.7 years. There has not been a large-scale trial of the impact of

this diet on mortality or in older adults with SH, stage 1 or otherwise. In contrast to the effectiveness of dietary modification and the effectiveness of exercise in younger patients in reducing BP,32 an 8-week aerobic exercise program did not lower BP in older adults with stage 1 SH.33 The exercise program in older adults with SH did have beneficial effects on maximal oxygen consumption and workload. Whether training programs that are more intensive or of longer duration would be more effective in lowering SBP is unknown. Medications There are many options in the treatment of hypertension in general and SH in particular. The major clinical trials of SH (discussed hereinabove) were performed more than 10 years ago, when fewer options were available and different evidence regarding risks and benefits of each treatment option was available. Based on the data and recommendations from JNC 7, it is reasonable to start pharmacologic therapy for SH with thiazide diuretics. The use of chlorthalidone as initial therapy in SHEP resulted in reduction in stroke and overall cardiovascular events, and in Syst-Eur, HCTZ was associated with fewer adverse events necessitating discontinuation compared with calcium channel blockers.18 Despite concern about the long-term metabolic effects of thiazides, the incidence of diabetes was not significantly greater in the active treatment group compared with the placebo group in SHEP.14 When treating patients with SH who also have comorbidities, such as diabetes mellitus or coronary artery disease, agents such as an ACEI or angiotensin receptor blocker (ARB) may be preferentially used. These agents were used as a second-line therapy in a substantial number of study participants in the major trials discussed above. Furthermore, results from the LIFE study demonstrated that losartan is superior to atenolol in reducing cardiovascular events in older patients with SH and LVH.13 Although b-blockers have been demonstrated to improve outcomes in older persons with cardiovascular disease, their role in older patients with uncomplicated SH is somewhat

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controversial. In a meta-analysis of 10 trials involving more than 16 000 persons 60 years or older, diuretic therapy was superior to betablockade with regard to all end points and was effective in preventing cerebrovascular events. b-blocker therapy was ineffective in preventing coronary heart disease, cardiovascular mortality, and all-cause mortality.34 b-blockers should therefore not be viewed as appropriate first-line therapy for uncomplicated hypertension in the elderly hypertensive patient. Many patients with SH will require more than 1 medication to adequately control SBP, and JNC 7 emphasizes the need for early combination therapy in most hypertensive patients.1 In selecting a second medication, it is important to choose an agent with a mechanism of action complementary to that of the first medication. For instance, b-blockers and an ACE-I or ARB both act by blocking renin release, so there is less additive benefit in using these agents together.35,36 Similarly, there is little synergy between thiazide diuretics and the dihydropyridine calcium channel blockers.37,38 Complementary combinations include thiazide diuretics with an ACE-I or ARB, and calcium channel blockers with b-blockers or ACE-I.

Treatment Gap Data from a recent community-based cohort study suggested that major gaps exist for implementation of antihypertensive therapy across age groups, and particularly in women.39 Specifically, BP control rates for those younger than 60 years, 60 to 79 years, and 80 years and older were 38%, 36%, and 38% in men ( P = .30) and 38%, 28%, and 23% in women ( P b .001), respectively. Furthermore, among participants 80 years or older, major cardiovascular events occurred in 9.5% of the normal BP group, 19.8% of the prehypertension group (HR, 1.9; 95% CI, 0.9-3.9), 20.3% of the stage 1 hypertension group (HR, 1.8; 95% CI, 0.8-3.7), and 24.7% of the stage 2 or treated hypertension group (HR, 2.4; 95% CI, 1.2-4.6). These data suggest that current rates of BP control, especially among older women with hypertension, are low and that there is a need for greater and more effective control of BP in the oldest patients considering the profound increases in

cardiovascular disease associated with incrementally higher pressures.39

Clinical Decision Making However, the decision whether to lower BP in older patients is often challenging. Although the JNC 71 states that a BP greater than 140/90 mm Hg warrants therapy irrespective of age, no clinical trial evidence is available to demonstrate that reducing a BP of 140 to 159 mm Hg (stage 1 hypertension) in older persons improves morbidity or mortality. Although data are strong, supportive of aggressive BP reduction in older persons with a BP of 160 mm Hg and above, the possibly increased risk of adverse effects and perceived lower benefits in the elderly may deter clinicians from aggressively treating SH in the elderly.39 Furthermore, the reality of applying guideline-based care to patients with multiple morbidities may be problematic. Indeed, if current relevant clinical practice guidelines for specific diseases are followed, an elderly patient with several comorbid conditions might be prescribed multiple medications with high risk of medication errors, adverse drug events, and drug interactions.40 Increasing numbers of medications are associated with an increased risk of adverse events. Moreover, likely because they are the most commonly prescribed class of drugs, cardiovascular drugs account for 25% of known adverse events.41 The long-term benefits and harm of combination therapy in patients with multiple disease states are not clear.42 Therefore, because current widely used guidelines offer little guidance to care for older patients with several chronic diseases, and all medications have the potential for harm as well as benefit, physicians must strike a balance between following practice guidelines and adjusting recommendations for individual patients’ comorbidities. Hypertension treatment decisions, particularly in older persons, must often rely on extrapolations and fall into a gray area where optimal choice for an individual patient may be unclear and people might choose differently. Compounding clinical uncertainty, long duration of therapy, complexity of the regimen, asymptomatic nature of the condition, and lack of immediate or perceived benefits are all important

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Table 2. Proposed New Definition of Hypertension

Healthy patients Stage 1 Stage 2 Stage 3

BP, CV Disease

CV Risk

Disease Markers

End-organ Damage

Approximately 115/75, no CV disease Occasional or intermittent BP elevations or early CV disease Sustained BP elevations or progressive CV disease Marked and sustained BP elevations or advanced CV disease

None/few Several Many Many

None Present Present Present

None None Present Present

Adapted from American Society of Hypertension meeting, San Francisco, Calif. Patients are divided into categories of normal and stages 1 to 3 hypertension. Cardiovascular risk factors include age, sex, abnormal cholesterol and triglyceride levels, obesity as measured by body mass index, smoking, and family history of cardiovascular diseases such as heart disease or stroke. Early markers of cardiovascular disease include microalbuminuria, exaggerated BP responses to exercise and mental stress, and impaired blood glucose tolerance. Hypertensive organ damage includes damage to the heart, arteries, brain, kidneys, and eyes. Abbreviation: CV, cardiovascular.

considerations in care decisions. Furthermore, age-related physiologic and metabolic alterations, increased prevalence of risk factors and comorbidities, and heterogeneity among older persons all complicate the decision making process for the older hypertensive patient and may cause the substantial variation in treatment rates.21 In these instances, patients must understand the probable outcomes of options, consider the personal value they place on benefits vs risks, and share decision making with their practitioners. Shared decision making (SDM) occurs when the doctor and patient share all stages of the decision making process and both agree on the final treatment decision.43 The primacy of patient-centered care has been supported by both the Institute of Medicine (Washington, DC)44 and the United States Preventive Services Task Force (Washington, DC),45 which have proposed a realignment of health care based on patient experience and values. Consideration of an older individual’s environmental, social, and cultural context as well as understanding potential physician-level determinants of care is essential to provide appropriate patient-centered care through a process of SDM. Unfortunately, the patientprovider relationship is complex, and our understanding of, and evidence about, SDM is limited. As with most other aspects of health care, a systematic approach is most likely to improve the quality of decision making as well as care.46 This approach leads health care providers through a process that first would assess the patients’ eligibility for BP control, determine their desire to participate in decision making and establish a partnership for doing so, elicit patient preferen-

ces and values, provide information on risk of hypertension and treatment, and, finally, negotiate and deliver the agreed-upon management plan. Research suggests that patients engaged in this process have improved adherence and outcomes and are more satisfied with their care.47-51 Finally, a new definition of hypertension recently proposed by leaders of the American Society of Hypertension, San Francisco, Calif, emphasizes the notion that high BP alone is only part of what makes a person hypertensive. Cardiovascular risk factors, early markers of disease, and organ damage are also integral components of the hypertensive syndrome (Table 2). It emphasizes that hypertension is a continuum of disease. The new definition challenges clinicians to treat all aspects of hypertension, as opposed to just a BP value. However, the clinical utility of such an approach remains to be determined, particularly in the elderly.

Comment There is strong evidence to guide treatment of SH in patients with SBP 160 mm Hg or greater. Guidelines have been widely disseminated, and effective readily available therapies should be advocated by physicians. Furthermore, recent work demonstrates the long-term (11-14 years) effectiveness of treating SH in reducing both cardiovascular events and overall mortality in this group.52 Despite this, health care providers often do not initiate or intensify therapy appropriately for these patients. In a large-scale study of hypertensive patients, of whom 40% had BP at least 160/90 mm Hg, increases in therapy took place during only 6.7% of visits.52-54

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The evidence behind JNC 7 guidelines regarding treatment of older patients with SBP 140 to 159 mm Hg and SH among the oldest old is less strong. No large-scale clinical trials have been performed to assess the effectiveness of treatment of SH in patients with SBP 140 to 159 mm Hg. Current evidence available suggests that physicians should not withhold therapy solely based on advanced age because this is a group of patients with especially high cardiovascular risk.55-71 Therapy in these patient populations should be determined by balancing potential benefits of treatment with individual patient preference and tolerance of therapy. Similarly, although JNC 7 states that patients should be treated to targets of less than 140 mm Hg in most cases, and less than 130 mm Hg in patients with diabetes mellitus or chronic renal disease, there are no clinical trial data to support this. Of the 3 major SH trials discussed, SHEP achieved the lowest mean SBP, at 143/68 mm Hg. There is currently no evidence from clinical trials for lowering SBP in patients with SH to targets less than 140 mm Hg. The main challenge for clinicians treating older persons with SH is to identify those older persons most appropriate for treatment, identify the most appropriate therapeutic regimen for the individual patient, and achieve BP targets that are safe for the individual patient. Given JNC 7 guidelines calling for use of SBP as the chief diagnostic and management target in older persons, older persons will be candidates for therapy. However, more clinical trials may be needed to help inform clinicians and patients in making decisions about SH in complex older persons with elevations in SBP.

Acknowledgments Dr Foody is supported by a National Institutes of Health/National Institute on Aging (NIH/NIA) (Baltimore, MD), Career Development Award (K08-AG20623-01) and an NIA/Hartford Foundation Fellowship in Geriatrics (Baltimore, MD). Dr Chaudhry is supported by the National Institutes of Health/National Heart, Lung and Blood Institute (NIH/NHBLI) RO1 (R01HL080228) (Baltimore, MD). Dr Agostini is supported by a VA Health Services Research Career Development Award (Washington, DC)

and the Claude D. Pepper Older Americans Independence Center at Yale University School of Medicine (#P30AG21342) (New Haven, CT). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs, West Haven, Conn.

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