High Blood Pressure Treatment in the Elderly

HEALTH PROMOTION AND DISEASE PREVENTION

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HIGH BLOOD PRESSURE TREATMENT IN THE ELDERLY William B. Applegate, MD, MPH

According to some estimates, over 50% of all elderly persons have high blood pressure.69Such estimates, however, have two problems in terms of definition. First, there are two forms of high BP in older persons: isolated systolic hypertension (ISH), which is conventionally defined as a systolic blood pressure (SBP) 3160 mm Hg and a diastolic blood pressure (DBP) <90 mm Hg. Systolic-diastolic hypertension (SDH) is conventionally defined as a systolic level >I40 mm Hg and a diastolic pressure >90 to 95 mm H g 7 Data from the European Working Party on Hypertension in the Elderly (EWPHE)Trial indicate that 95 mm Hg is a suitable cutoff for SDH in elderly persons because there was no difference in subsequent cardiovascular disease rates between the treatment and control groups for participants in this study with a baseline DBP of 90 to 95 mm H g 4 Second, both the prevalence of high blood pressure of either type and the accuracy of the diagnosis are contingent on the number of occasions that blood pressure is measured.15 When blood pressure readings are averaged over two or three visits, the prevalence of SDH above age 65 is about 15% in whites and 20% to 25% in blacks.24The prevalence of ISH is age-dependent; about 10% of persons over age 70 and 20% of persons over age 80 have ISH.26Therefore, approximately one third of whites and 40% of blacks over age 65 have either ISH or SDH.7 Recent studies indicate that in many locations 50% or more of older persons are currently taking one or more antihypertensive medication^.^^ Therefore, it is quite possible that too many elderly persons are being treated for high blood pressure. PATHOPHYSIOLOGY

The pathophysiology of both SDH and ISH in the elderly involves an increase in peripheral vascular resistance.748AS humans age, structural changes From the University of Tennessee School of Medicine, Memphis, Tennessee

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in blood vessels account for some of the change in peripheral re~istance.~~ It is also possible that functional changes in the vascular smooth muscle contribute to these changes.', a-adrenergic responsiveness of the vascular smooth muscle does not greatly change with age.l The P-adrenergic responsiveness of vascular smooth muscle declines with age with a consequent decrease in the relaxation of vascular smooth muscle.' Therefore, the increase in peripheral resistance in elderly hypertensives may in part be due to diminished P-adrenergic-mediated vasodilation while a-adrenergic-mediated vasoconstriction continues unabated.' The overall pathophysiology of hypertension in black and elderly persons exhibits a similar p r ~ f i l e . ~ Both ,~~ black , ~ ~and elderly hypertensives tend to be sodium sensitive, have low renin levels, and increased vascular resistance. It has been suggested that black hypertensives are particularly likely to conserve sodium in their bodies with an expansion of extracellular volume and consequent development of h y p e r t e n ~ i o n73. ~ ~ BURDEN

Several epidemiologic studies indicate that average SBP increases throughout the life span in most countries, and average DBP rises until age 55 to 60 and then levels off.39This increase occurs in persons who have previously been classified as either hypertensive or normotensive. Data from the Framingham Study and other studies indicate that not all individuals experience the agerelated increase in blood pressure, however.39In addition, population studies from nonindustrialized societies indicate that average blood pressure does not tend to rise with age.55 Estimates of the true prevalence of hypertension vary greatly depending on the age and race of the population, the blood pressure cutoff point used for the definition of hypertension, and the number of measurements made.15The prevalence of both SDH and ISH is considerable in persons over age 50. Because levels of DBP tend to level off around age 55, the prevalence of SDH tends to be constant at ages r50.24Therefore, although some authors speak in general terms of the rise in prevalence of hypertension with age, the prevalence of SDH rises little with age.54Actually it is the rise in ISH that accounts for most of the overall increase in the prevalence of hypertension with advancing age.24 Unfortunately, only a limited amount of data is available to estimate the rate of onset of new cases of hypertension in the elderly. Follow-up analyses of the National Health and Nutrition Examination Survey (NHANES I) data indicate that the incidence of hypertension (defined as SBP >I60 mm Hg or DBP >95 mm Hg, based on only one blood pressure measurement) increases by about 5% for each 10-year interval of age18 and peaks about age 55 to 64. The incidence rates over an average of 9.5 years of follow-up were approximately 20% for white men and women over age 55 and 30% and 40% for black males and females, respectively. These rates include both SDH and ISH and are inflated estimates because they are based on single readings of blood pressure over 9 years apart. Analysis of the Framingham Study data (based on one reading, but biennial measures) indicates that the cumulative incidence of ISH, starting at age 40, is about 418 per 1000 in men and 533 per 1000 in women.78 Because of differences in definition, frequency, and the interval between measurements, these data are difficult to interpret. Nonetheless, it appears that new cases of hypertension continue to occur in elderly persons. Although the clinical treatment of hypertension has classically focused on

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DBP levels, epidemiologic data indicate that for middle-aged and older adults SBP level is more predictive of future cardiovascular morbidity and mortality than DBP.13,38 Both SBP and DBP remain independently predictive of future vascular events, however. Analyses of the Framingham Study data indicate that 42% of strokes in elderly men and 70% of strokes in elderly women are .~~ SBP appears to be slightly more directly attributable to h y p e r t e n s i ~ n Again, predictive than DBP, and the risk gradients for SBP do not wane with advancing age. When all cardiovascular risk factors are taken into account in the elderly, it is clear that an increased level of SBP is the single greatest risk factor for increased cardiovascular disease in persons over age 50.39It is also clear that increased blood pressure interacts with other cardiovascular risk factors to compound the risks. For instance, although total serum cholesterol declines somewhat as a cardiovascular risk factor in the elderly, it still confers some element of risk and compounds the risk for hypertensive^.^^ Also, the development of left ventricular hypertrophy is itself an independent cardiovascular risk factor.37 Recent reports from the Framingham Study indicate that left ventricular hypertrophy is more prevalent in older persons and highly correlated with increased SBP.'j3Also left ventricular hypertrophy in hypertensives confers increased risk of ventricular arrhythmia^.^^ Finally, data from the National Center for Health Statistics indicate that coronary heart disease (CHD) is the most common cause of mortality and morbidity in persons over age 50 and cerebrovascular disease is the third most common cause of mortality and morbidity.2352 Even as age advances into the 70s and 80s, CHD and cerebrovascular disease continue to be among the three most common causes of both mortality and morbidity.23,52 These diseases account for a majority of the disability seen in the population aged 50 to 75. After age 75, degenerative processes such as arthritis and dementia begin to account for approximately an equivalent amount of disability as CHD and cerebrovascular disease. Also, cardiac and circulatory disorders are responsible for over 50% of disease-related disability and health care expenditures in persons over age 50.55 Therefore, it is clear that the epidemiologic burden associated with elevated SBP and DBP levels in elderly persons is substantial. It does not necessarily follow that all older persons with elevated SBP or DBP require treatment, however. TREATMENT Benefits of Treatment

A series of randomized, controlled clinical trials has shown definitively that SDH should be treated in persons over age 65, although there are inadequate data to make a strong statement about persons over age 80.3,33. 53, 73 Table 1 compares the relative reduction in terms of cardiovascular morbidity or mortality for persons under age 50 and over age 60 for three major multicenter trials of the treatment of SDH: the Veterans Administration (VA) Cooperative S t ~ d i e s the , ~ ~Hypertension Detection and Follow-up Program (HDFP)," and . ~ ~ of these trials had subgroups the Australian Trial on Mild H y p e r t e n ~ i o nEach of patients aged 60 to 69. In each study over periods of follow-up varying from 4 to 7 years, the persons over 60 experienced the same relative reduction in cardiovascular morbidity or mortality as did patients under 50. When the

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Table 1. IMPACT OF ANTIHYPERTENSIVE THERAPY ON CARDIOVASCULAR MORBIDITY AND MORTALITY BY AGE GROUP

Relative Reduction*

w)

Study Veterans Administration Cooperative (morbidity) Hypertension Detection and Follow-up Program (mortality) Australian Trial on Mild Hypertension (cardiovascular trial end points)

Absolute Reduction* (per 1000 person-years) < 50 Years > 60 Years

< 50 Years

> 60 Years

55

59

21

100

6

16

2

25

20

26

5

10

'Relative reduction is the percentage of decline in the event rate in the intervention group compared with the placebo group. ?Absolute reduction is the total number of events prevented in the treatment group versus the comparison group per 1000 person-years of treatment.

absolute benefit in terms of number of events prevented per 1000 person-years is analyzed, however, more events in the short-term are prevented by treating those over 60 because they had more event^.^ Because most major hypertension trials studied only selected groups of "young old persons," the EWPHE Trial was designed to study whether medication treatment of SDH in older individuals reduced morbidity or mort a l i t ~ This . ~ ~ trial enrolled persons over age 60 (mean age 72) to either a treatment or placebo group. After an 8-year follow-up, analysis revealed no effect on all-cause mortality, but a significant 27% reduction in cardiovascular mortality. There was also a statistically significant 38% reduction in cardiac mortality and a nonsignificant (p = 0.12) but impressive 32% reduction in cerebrovascular mortality. Overall, the treatment group experienced a reduction of cardiovascular morbidity and mortality of 29 events per 1000 person-years of treatment. Treatment appeared to be effective at all levels of entry-level SBP from 160 to 239 mm Hg, but the treatment did not appear to have an impact on participants with entry-level DBP in the range of 90 to 95 mm Hg.>, The reduction in end points seen in the intervention group seemed to disappear in persons over age 80, suggesting that treatment might not be effective in persons of advanced age. There was a small number of participants over age 80, however, so these subgroup data are not definitive. Therefore, persons over age 80 with SDH who are relatively biologically "young" could be treated. Treating biologically frail persons over age 80, particularly those with substantial comorbid problems, is less compelling. It is important for the clinician to realize the level of actual absolute benefit a patient may receive over a period of time from therapy. Basically, if older persons with mild SDH (DBP 90 to 105 mm Hg) are treated with drugs and their blood pressure is controlled, a reduction of about five to eight morbid and mortal events per 1000 patient-years of treatment can be e ~ p e c t e dIf. ~their SDH is moderate to severe (DBP 105-115 mm Hg), a reduction of 20 to 30 events per 1000 patient-years of treatment can be e ~ p e c t e d . ~ The Systolic Hypertension in the Elderly Program (SHEP), a 5-year, doubleblind, placebo-controlled trial with 4736 participants with ISH demonstrated

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benefits of pharmacologic treatment (a stepped-care regimen including chlorthalidone, 12.5-25 mg, and atenolol, 25-50 mg, or reserpine, 0.05-0.1 mg) on .~~ stroke (35% reduction) and cardiovascular events (31% r e d ~ c t i o n ) Overall, the treatment group experienced a reduction of 50 cardiovascular morbid and mortal events per 1000 person-years of treatment. This confirms preliminary indications from the SHEP pilot study and the Hypertension in Elderly Patients in Primary Care (HEP) trials, which suggested that lowering elevations of SBP subsequently decreased the rate of stroke.17,31 The observed benefit of pharmacologic treatment of ISH suggests that all patients with SBP in that range (SBP 160-219 mm Hg) should be treated. Despite the fact that the first-step drug was a diuretic, the intervention group experienced an impressive and significant 21% reduction in combined fatal and nonfatal CHD events. Subgroup analyses showed that benefit from treatment was seen in persons over age 80 at entry. Finally, the magnitude of the benefit from treatment seen in this trial is actually somewhat greater than that seen in trials treating SDH. As a result of the SHEP study, it is no longer tenable for clinicians to focus exclusively on DBP when treating elderly patients with hypertension. It is clear that treatment goals should target both SBP and DBP. Potential Types of Overtreatment

There are three types of potential overtreatment for hypertension: (1) older persons may be inappropriately classified as hypertensive when they are truly normotensive; (2) some older persons are treated for hypertension without an adequate comparison of the potential benefits with the side effects and may actually experience side effects that are so serious that antihypertensive therapy is not warranted; (3) observational studies of treated hypertensives indicate that there may be a J-shaped curve relationship between treated blood pressure and subsequent cardiovascular mortality.1°20,62 Observational studies show that for both SDP and DBP treatment below a certain level of blood pressure, cardiovascular mortality may actually rise. Inappropriate Labeling of Normotensive Older Persons as Hypertensive

Several studies have shown that the casual office blood pressure measurement is strongly predictive of subsequent cardiovascular and cerebrovascular events." Recent analyses of data collected in national multicenter clinical trials, such as the HDFP,32however, indicate that the average of multiple measurements of blood pressure over several different visits is more likely to approximate a person's true blood pressure.60The office measurement of blood pressure may consistently overestimate real blood pressure in certain persons who are In addition, values for ambulatory known to have "white coat hyperten~ion."~~ blood pressure measured in middle-aged persons may be more predictive of end-organ damage than casual office measurements of blood pressure.76 Although the issue of overdiagnosis of hypertension has not been systematically studied in older persons, unpublished data from the author's clinical center indicate that many older persons may have been labeled as hypertensive by their physicians based on only one or two occasions of blood pressure measurement. Because the prevalence of older persons taking antihypertensive medicines is greater than the actual prevalence of hypertension found in older persons in population-based studies, it is possible that overtreatment based on

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an inadequate measurement of blood pressure may be a p r ~ b l e m ."'t~ , is known that both SBP and DBP levels tend to be more labile in older than younger persons. If the diagnosis of hypertension is based on only one occasion of measurement, there is a great likelihood that some of the persons labeled as hypertensive are simply individuals whose pressure happens to be fluctuating upwards at that particular time. This is the primary biologic phenomenon underlying the regression to the mean seen with blood pressure measurement. Specifically, when blood pressure is measured in groups of older persons, the average is usually higher on the first occasion of the measurement than it is when it is averaged over three occasions of measurement. Therefore, physicians in their offices who detect mild or modest elevations of SBP or DBP on one or two occasions of measurement may be simply catching some individuals who are fluctuating for a period of time above their own mean blood pressure but who are actually normotensive over an extended period of time. Unpublished data from the author's clinical center indicate that, when persons over age 60 were taken off antihypertensive medicine to establish if they were hypertensive, approximately 20% of these persons never went back on antihypertensive medication. Therefore, it is entirely conceivable that a significant minority of older persons receiving antihypertensive therapy are currently being mislabeled and, therefore, overtreated. The accuracy of the blood pressure measurement is also critical in order to prevent overtreatment. The current standard indicates that measurements should be taken with the patient in the seated position with both the arm and the back supported, using a cuff size appropriate to the circumference of the patient's arm.69The patient should be at rest for 5 minutes prior to the measurement of blood pressure, and the pressure should be taken with a calibrated mercury sphygmomanometer. Failure to consistently follow any of these basic steps in blood pressure measurement can result in the misdiagnosing of normotensive persons as hypertensive. For instance, if blood pressures are taken in the seated position without having the back supported, blood pressures are falsely elevated. Recent studies also have raised the issue whether some older persons have relatively rigid arteries, which results in falsely high blood pressure readings known as pse~dohypertension.~~, 71 It is clear from studies that some older individuals do have falsely elevated blood pressure when measured by the sphygmomanometer compared with the intra-arterial pressure measurement. Most of the studies that examined this phenomenon studied small selected cohorts thought to be likely to have pse~dohypertension.~~, 64, 70 Epidemiologic investigation of this phenomenon is underway, but most experts currently feel that the prevalence of pseudohypertension is relatively small even in persons of advanced age. Nevertheless, pseudohypertension should be suspected when older persons present with modest elevations of blood pressure without any evidence of end-organ damage. Also, pseudohypertension should be suspected in persons being treated for high blood pressure who have symptoms of hypotension but apparently normal blood pressure. One simple screening method for pseudohypertension is Osler's maneuver.47In this maneuver, the sphygmomanometer pressure is pumped above peak systolic pressure and the examiner then determines if the nonpulsatile brachial or radial artery can be palpated. If the artery is palpable, this often means that the artery is somewhat rigid; this is presumptive evidence that pseudohypertension may be present. In such cases, if there are no other cardiovascular risk factors and no sign of end-organ damage, physicians should allow the patient's blood pressure to run as high as an average of 180 to 185 mm Hg/100 to 105 mm Hg before considering treatment.

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It appears that multiple office blood pressure measurements or, in selected situations, ambulatory blood pressure measurement are highly predictive of subsequent cardiovascular risk.75Office and ambulatory blood pressure monitoring are both sufficiently sensitive and specific as screening tests for the assessment of the presence of true hypertension as long as the proper guidelines are followed. Tradeoff Between the Side Effects and Potential Benefit of Antihypertensive Therapy

Concern about the toxicity of antihypertensive therapy has caused clinicians to use restraint or even to practice therapeutic nihilism in the treatment of 77 There are good reasons why the risk-tohypertension in elderly patients.735, benefit ratio for the treatment of either systolic or diastolic hypertension may increase with age. The elderly are particularly susceptible to many of the side effects of antihypertensive medication^.^^, 77 For instance, elderly patients are more likely to develop hyponatremia and hypokalemia when treated with patients are more likely to become depressed standard doses of di~retics.~Wlder and confused when treated with antihypertensive medications that affect the central nervous system.ll The baroreceptor reflex becomes less sensitive with AS a result, elderly patients with age and also less active as SBP increases.2843 ISH or SDH could be more sensitive to the postural hypotensive effects of antihypertensive medications and have an increased propensity for falls and fractures.43 Although some have argued that elderly persons actually need higher BP to adequately perfuse vital organs such as the brain and kidney,36most studies have not shown that judicious use of antihypertensive medications in patients with hypertension has a significant adverse effect on either renal or cerebral perfusion.12,65, 67 There are few data from large-scale clinical trials to definitively determine the degree of toxicity of antihypertensive regimens in the elderly. Investigators from the HDFP have reported that the total rate of adverse effects in the treatment of mild to moderate SDH was less for the subgroup aged 60 to 69 at entry than for those under age 50.21Although these data are helpful, it should be remembered that persons in the age range from 60 to 69 should really be classified as "young-old" and may not be as susceptible to side effects as the "old-old" (?age 75). The most data available on the toxicity of antihypertensive therapy come from the EWPHE Trial. Reports from this trial indicate that treatment with a thiazide-triamterene combination resulted in mild increases in glucose intolerance, serum creatinine, and uric acid, and a mild decrease in serum potassium in the treatment group.2 In middle-aged persons, trials of SDH have tended to show that treatment reduces subsequent rates of stroke and congestive heart failure but has either Interestingly, studies in the a neutral or negative effect on rates of CHD.22,M elderly, including EWPHE and SHEP, show a beneficial effect of stepped-care treatment of hypertension in the elderly in reducing future CHD.368 One potential explanation for the failure of hypertension clinical trials in middleaged persons to show that medication reduces the rate of subsequent development of CHD is that the diuretics most frequently used as the first-step medication partially offset the beneficial impact of blood pressure lowering by adversely affecting other cardiovascular risk factors, particularly serum lipids, glucose homeostasis, and serum potassium. Recent hypertension studies have

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tended to reemphasize the fact that an interaction between two or more cardiovascular risk factors is a powerful predictor of subsequent CHD mortalIn fact, Samuelsson and colleagues have shown that a reduction of SBP or DBP not accompanied by a reduction in cholesterol (if elevated) has less impact than when both risk factors are improved. Similarly, in the Australian Trial on Mild Hypertension, treatment of hypertension had the greatest impact on patients with low initial serum c h ~ l e s t e r o l .Unfortunately, ~~ it has not definitely been established whether lipid lowering in elderly patients really lowers subsequent cardiovascular morbidity and mortality. Results of the EWPHE Trial indicate that diuretic treatment of elderly hypertensives may not have a prolonged significant impact on serum lipids5 At the end of 3 years in the EWPHE Trial, the placebo group had experienced an average fall in total serum cholesterol of 5.9 mgI100 mllyear while the treatment group experienced an average decline in total serum cholesterol of 5.0 mg1100 r n L / ~ e a r .It~ is problematic to attribute the lack of impact of antihypertensive treatment on subsequent CHD to the lipid effects of the diuretics alone. Reaven has recently pointed out that glucose homeostasis impairment with subsequent increases in serum insulin levels may play a more significant deleterious role than has been appreciated, but data to substantiate this point are currently lackings9There are not enough incriminating data to negate the use of diuretics in the elderly (particularly in light of the positive findings in SHEP). Patients who develop significant and persistent alterations of lipid levels or glucose homeostasis should be prescribed other medications. Clinicians are generally concerned that elderly patients may be particularly susceptible to hypokalemia from diuretic^.^^ Although scant data exist on the effects of hypokalemia in the elderly, it is pertinent to review some of the existing data available on middle-aged individuals because the issue is of great importance, particularly because diuretics are frequently advocated as the drug of first choice for the treatment of hypertension in the elderly. Results from the Multiple Risk Factor Intervention Trial (MRFIT) raised the question of whether hypokalemia may indeed be one of the primary reasons that the treatment of hypertension to date has seemed to have little impact on CHD rates.51Possibly, diuretic-induced adverse effects led to the MRFIT finding that hypertensive males who had electrocardiogram (ECG) abnormalities at baseline and were treated with a diuretic had a higher CHD death rate.51Certainly diuretics can induce hypokalemia, which in turn can lead to cardiac arrhythm i a ~Analysis .~~ of the MRFIT data shows no relationship between either the participant's most recent potassium level or the presence of ventricular premature beats and CHD mortality.41Also, it is curious that the increased mortality attributed to diuretic treatment occurred only in the subset of participants treated with hydrochlorothiazide rather than chl~rthalidone.~~ Further doubts about the significance of the MRFIT findings include the fact that this was a analysis after the fact and, therefore, the results could well be due to chance alone. The most striking result of this trial is not that hypertensive males with baseline ECG abnormalities treated with drugs had such a high CHD mortality but rather that the corresponding usual care group had such a low CHD mortality.51 Also, the HDFP group reanalyzed their data and concluded that there was no evidence that treatment of hypertensives with baseline ECG abnormalities with a diuretic caused an adverse CHD death rate.34This conclusion is indeed warranted for the entire HDFP cohort of both blacks and whites, males and females. When these data are closely scrutinized, however, it is clear that white males who were hypertensive and had resting ECG abnormalities did have higher CHD death rates in the special care group. Also, follow-up analysis of

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the Oslo trial on the treatment of mild hypertension (a study of middle-aged white males) indicated that participants with baseline ECG abnormalities had somewhat higher total CHD event rates.30It is possible that, for some reason, white males are particularly likely to have an adverse effect of diuretic treatment of hypertension if they have baseline ECG abnormalities. At least for elderly patients with ISH, the SHEP trial seems to put this issue to rest because those participants with ECG abnormalities at entry demonstrated as much benefit from treatment as those without baseline ECG changes. Questions still remain about the possible degree of negative impact that antihypertensive therapy may have on the quality of life of elderly patients.70 Two recent multicenter trials, however, have shown that judicious use of common antihypertensive regimens tends to have minimal negative impact on quality of life in elderly hypertensive patients. A recent VA Cooperative Study compared the impact of high- and low-dose diuretics as first-step agents and alphamethyldopa, reserpine, hydralazine, and metaprolol as second-step drugs in the treatment of elderly persons with SDH.27,45 Basically, there were no differences in any of these treatments on overall quality of life.27In another randomized, multicenter trial conducted by Applegate and colleagues, atenolol, diltiazem, and enalapril were compared in elderly women with SDH.9Although there were more drug withdrawals due to side effects in the atenolol group, there were no differences in the impact of the three treatment regimens on overall quality of life. There are a number of side effects that can substantially impair an individual older person's quality of life, however. First the mild lethargy caused by many antihypertensive agents can reduce the level of social functioning of an older person who may become lethargic and lack the initiative to leave the home. Central nervous system side effects from the use of many antihypertensive agents may lead over time to depression, some memory impairment, and a decline in overall vitality. Also, the prevalence of urinary incontinence is fairly high in community-dwelling elderly persons. The prescription of any antihypertensives that have a natriuretic effect (diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors) may cause subclinical or subtle incontinence to become much worse. Older people, if they are healthy and have a sexual partner, often continue sexual activity into late life. A wide variety of antihypertensive agents can have a negative impact on sexual desire or sexual performance. Therefore, clinicians should inquire specifically about this potential problem. Studies have shown that older people are more likely than younger people to continue taking a medication in the face of disabling side effects.57Usually, it is possible to find an antihypertensive medicine that does not cause disabling side effects, often after a process of trial and error. For some elderly patients, however, it is very difficult to find an antihypertensive medication that has very few side effects and also can be afforded on a limited, fixed income. The clinician always must weigh the side effects or risks and costs of medications against the potential benefits to be gained from long-term treatment. J-Shaped Curve

It is possible that too great a lowering of DBP may actually result in impaired coronary artery blood flow, particularly to the subendocardial layer during diastole.66Several studies have raised the question whether too great a lowering of DBP or SBP increases rates of myocardial infarction (MI). Cruickshank reported a prospective descriptive 10-year follow-up study of 902 treated

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patients (mean age 54) with SDH.ZnAlthough treated SBP was strongly correlated with subsequent death from MI and treated DBP was weakly correlated with MI deaths, there appeared to be a J-shaped curve relationship between the level of treated DBP and mortality from MI. In other words, MI mortality declined as treated DBP levels declined to 85 mm Hg, but mortality then rose again as DBP fell further. The authors noted that this pattern was true for patients with overt ischemic heart disease at the time of entry into the study and was not true for persons without signs of ischemic heart disease. Similar data suggesting a J-shaped curve relationship between DBP and cardiovascular mortality have been reported by two other prospective descriptive studies.ln,62 Samuelsson's study of 686 middle-aged hypertensive males treated with either a p-blocker or thiazide diuretic reveals a threshold below which the lowering of blood pressure is harmful (SBP <140-150 mm Hg or DBP = 85-90 mm Hg)." Applegate and colleagues also conducted a large cohort study in which elderly persons with treated SDH had higher mortality if their SBP was either always above or below the treatment goal (160 mm Hg).7 Neither study was designed to prove cause and effect, but it is possible that excessively vigorous blood-pressure lowering could be harmful. On the other hand, some epidemiologic data show a J-shaped curve relationship between DBP and mortality regardless of treatment.7 A recent randomized controlled trial of the treatment of hypertension in an elderly cohort sheds particular light on this subject.16,l7 Coope performed a randomized trial of drug treatment (atenolol and bendrofluazide) or observation on 884 elderly patients with SBP >I70 mm Hg or DBP >I05 mm Hg.16Patients were followed up to 8 years and there was a significantly greater reduction in both SBP and DBP in the treatment group. This group experienced a 30% reduction in the rate of fatal strokes, but there were no differences in the rates of fatal MI or total mortality between the two groups. Further analysis of these data revealed that there was indeed a Jshaped curve relationship between entry DBP and subsequent rates of fatal and nonfatal MI, but this relationship was true for both the treatment and control groups.17In light of these findings and the fact that some epidemiologic studies also have demonstrated a J-shaped curve relationship between DBP and coronary artery mortality, the most likely explanation is that these epidemiologic and descriptive results are confounded by the fact that individuals with the lowest DBP have a higher prevalence of serious prior cardiovascular disease with a consequent reduction of the heart's ability to generate a higher DBP. Nonetheless, caution about overly vigorous treatment of hypertension in the elderly is warranted. The conservative approach is to not lower SBP much below 135 to 140 mm Hg or DBP much below 85 mm Hg.1n*62 To date the SHEP data have not been analyzed with regard to the J-shaped curve issue.

General Guidelines for Managing Elderly Persons with Possible High Blood Pressure

General principles for managing older patients with high blood pressure include the following: 1. SDH should be treated with medication if the average blood pressure on at least two visits (three measurements per visit) is SBP >I40 to 160 mm Hg and DBP >I00 mm Hg. 2. Mild SDH (SBP 140-160 mm Hg and DBP 90-100 mm Hg) should be first treated conservatively with nonpharmacologic interventions. If

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over time the average DBP remains above 95 mm Hg, pharmacologic intervention should be initiated. 3. ISH (SBP >I60 mm Hg and DBP <90 mm Hg) should be treated. 4. Treatment goals should be SBP of 135 to 140 mm Hg and DBP 85 mm Hg. 5. For elderly persons with mild SDH, the absolute benefit of drug treatment, in terms of mortal and morbid events reduced per thousand person-years of treatment, is significant but possibly not so great that individual patients need always be treated in the face of disabling side effects from antihypertensive medications. 6. In using pharmacologic therapy, the initial daily dose should be half that recommended as the starting dose for middle-aged patients. 7. A diuretic is the drug of first choice for the treatment of hypertension in older patients. Diuretic dosages equivalent to 12.5 to 25 mglday of hydrochlorothiazide appear to be most effective. The risks associated with toxicity outweigh efficacy once the dosage increases above the equivalent of 25 mglday. 8. The choice of an alternative first-step drug or a second-step drug should be based on individual patient characteristics. 9. Pharmacologic therapy should not be continued for elderly patients with mild SDH or ISH in whom significant side effects persist despite therapy with a variety of pharmacologic agents. 10. After blood pressure has been controlled for 6 months, the dosage of the drug should be stepped down if possible. In general, the author does not recommend drugs for patients with DBP below 95 mm Hg because the EWPHE Trial Study was unable to show benefit in elderly persons enrolled in the trial whose DBP was between 90 and 95 mm H P.~ - -0. Recent studies have indicated that older persons with mild to moderate hypertension do respond to weight loss, sodium restriction, and mild aerobic exercise. Therefore, nonpharmacologic treatment should be used possibly for several months before a decision is made to institute drug therapy. Although there are few data with regard to the efficacy of nonpharmacologic interventions in older people, a recent randomized trial conducted by the author's group indicated that a combination of weight loss (in overweight persons), sodium restriction, and mild increases in aerobic exercise reduced SBP about 6 mm Hg and DBP about 5 mm Hg in persons with baseline DBP between 85 and 100 mm H g 8 A major problem with nonpharmacologic interventions is recidivism, but these interventions should be tried and also used as adjuvant therapy for persons taking medications. An important concept in treating older persons with antihypertensive medicines is to "start low and go slow." As a general rule, the physician should start with half the recommended daily starting dose and take twice as long to increase the dose until the target pressure is reached. Particular attention must be placed during the initiation phase on assessing postural hypotension and the risk of falls. In addition, a careful side effect history must be taken. It is beyond the scope of this article to discuss the different medications that can be used for older hypertensive patients. The reader is referred to a recent re vie^.^ It should be noted, however, that once successful antihypertensive drug therapy has been instituted and maintained for 6 months, it is often possible to lower an older person's drug dose. If the patient was truly hypertensive and the blood pressure was truly in a hypertensive range when the patient was initially diagnosed, it is likely that drugs cannot be discontinued

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unless t h e patient successfully adopts nonpharmacologic lifestyle interventions. It is probably worth trying to remove persons from medication for a period of time w h o did not have signs of overt cardiovascular disease a n d w h o h a d borderline hypertension at the outset of treatment (DBP of 90 to 100 m m Hg). Recently Lernfeldt a n d colleagues studied a representative population sample of 719 70-year-old individuals." Twenty-six percent were taking antihypertensive treatment; 20% of these showed n o signs of cardiovascular disease o r h a d a blood pressure 4 7 5 1 9 5 m m Hg. Treatment w a s withdrawn in 25 of these 32 patients. A t clinical follow-up 4 years later, however, only 8 of the .~~ although judicious withoriginal 25 patients were n o r m ~ t e n s i v e Therefore, drawal from medications can b e useful, the proportion w h o stay off medication for extended periods of time (unless they undertake vigorous nonpharmacologic therapy) remains limited.

SUMMARY Clinicians should clearly understand t h e magnitude of t h e clinical benefits attributable t o t h e treatment of hypertension in t h e elderly s o that appropriate tradeoffs can b e m a d e between benefits a n d side effects. Potential types of overtreatment of elevated blood pressure i n older persons include inaccurate measurement technique, insufficient numbers of readings, a n d too great a lowering of blood pressure.

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