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Assessing the Impact of Antihypertensive Therapy on Quality of Life in the Elderly
Hypertension
Assessing the Impact of Antihypertensive Therapy on Quality of Life in the Elderly
Philip G . Weiler, MD, MPH*
During the past 12 years, quality of life has become increasingly accepted as an important measure of the impact of medical care. With the escalating costs of medical care, it has been argued by some that more emphasis is needed on the impact of medical technology on quality of life. Some believe that, especially in treating elderly persons, care that only increases the burden of chronic illness and extends life but does not offer significant improvement in the quality of life should not be provided.' The term quality of l$e has been widely used both in the vernacular and scientific literature and usually encompasses several different concepts. This term is used in different ways by research scientists, policymakers, health care practitioners, and others; it is frequently used interchangeably with health status or functional status. A lack of consensus exists on its definition with inadequate conceptualization of its ~ o m p o n e n t s .Yet, ~~ despite these problems, the emphasis that it places on measuring the quality or value of time and not just its quantity is important. This emphasis is particularly important in evaluating the impact of therapy for hypertension in elderly persons because the disease is frequently asymptomatic, and the elderly may have several concomitant illnesses and limitation^.'^. 20
DEFINING THE CONCEPT It helps in focusing our consideration to make a distinction between the concept of quality in the term quality of life as referring to a person's worth based on some comparative external social standard versus quality based on the inherent health and well-being of a person in comparison with his or her own potential and goals. Quality based on some external *Director, Center for Aging and Health, Department of Community Health, School of Medicine, University of California, Davis, California Clinics in Geriatric Medicine-Vol.
5, No. 4, November 1989
703
standard presents considerable ethical and medical issues, and is not necessarily related to health or medical care. It is also important to emphasize that the larger institutional or social issues related to quality of life such as working conditions, income, pollution, crime, housing, satisfaction with government and vublic services. and environmental conditions are not directly responsiveto health or medical interventions. Objective measures of quality of life include employment status, marital status, material possessions, socioeconomic status, which can be used and may be easier to measure, but their actual association with personal happiness and satisfaction with life may be relatively low. Therefore, it is the healthrelated quality-of-life measures and their subjective indicators that are important in medical literature and are relevant to studies of treatment of hypertension of elderly persons. These measures usually involve some measurement of physical function, social function, emotional state, and perceptions of well-being. Quality of life can be assessed from several different perspectives. First of all, it can be studied as a direct outcome of therapy or a consequence of a cardiovascular event. Particularly with conditions such as mild hypertension or elevated cholesterol, in the short term, the therapy can be worse than the disease if the medication causes symptoms or disability. When evaluating cardiovascular events such as stroke or a mvocardial infarction. the imDaZt on a ~ e r s o n ' sclualitv of life as an outcom'e of these diseases * . brings different issues into consideration than just considering mortality and health care costs such as the use of the "quality-adjusted years of life" index.37Additionally, both pharmacologic and nonpharmacologic therapies may impact on quality of life and should be considered when weighing the various risks and benefits of theravy. Second.. clualitv , of life can be studied as a risk factor for the subsequentdevelopment of cardiovascular events or complications of hypertension. For example, people with a poor quality of life may be more likely to develop a stroke or a myocardial infarction. Lastly, quality of life may be a risk modifier by mediating the effect of other risk factors (for example, hypertension or compliance with treatment) or subsequent cardiovascular disease. A poor quality of life may increase the chances of having elevated blood pressure. It may also decrease the chances of a person complying with medical treatment. Figure 1 summarizes the inter-relationship of quality of life, therapy, hypertension, and cardiovascular disease and shows the various ways it can be studied. To assess quality of life as a primary outcome of therapy, clinicians need to be mindful of the possible effects on quality of life of the major drugs used in the treatment of hypertension. All of the major therapies for the treatment of hypertension can have some impact on the quality of life." This includes both pharmacologic and nonpharmacologic measures.'* Although most of these effects are medical symptoms, it is these very symptoms that consequently impact on the broader domains of quality of life such as social and emotional functioning as well as cognitive status. The reason quality of life has become increasingly important in hypertension is because we are not dealing with the treatment of symptoms but t change the natural historv of a disease. It is the risk of some an a t t e m ~ to future event (for example, cardiovascular disease or stroke) that one tries
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Therapy
Hypertension
Quality of Life
Cardiovascul-ar Disease
Figure 1. Relationship of antihypertensive therapy to quality of life. Quality of life may be an outcome measure of therapy, an effect modifier of other risk factors, or a risk factor itself.
to prevent by treating hypertension. The reduction of this future risk needs to be balanced against the present impact on a person's lifestyle and enjoyment. It has been said that because hypertension is usually an asymptomatic disease, it is difficult to make an asymptomatic person feel better and, therefore, quality-of-life considerations are particularly important if we want to improve the patient's status in both the short and long term. It is interesting to note that physicians can have a biased perspective of how patients are doing on therapy if they do not look at issues related to quality of life. In one a survey was performed on 75 consecutive patients from an English group practice, who had hypertension controlled by the usual antihypertensive drugs, including diuretics, P-blockers, and methyldopa. A series of questions about quality of life was asked of the patients, their closest relatives, and the physicians. One hundred per cent of the physicians surveyed thought the patients had improved after therapy, whereas only 48 per cent of the patients believed they had improved after therapy. One per cent of relatives thought the patients had improved, whereas 99 per cent of the relatives believed the patients had become worse. The relatives described such symptoms in the patients as loss of memory (33 per cent), more irritability (45 per cent), depression (46 per cent), more hypochondriasis (55 per cent), and decreased sexual interest (64per cent). This study demonstrates that hypertensive therapy often may interfere with patients' enjoyment of life in ways of which neither the physician nor the patient is aware. Other factors bear on this issue as well. Hypertension, although usually asymptomatic, may itself have an impact on behavior and quality of life. Hypertension has been shown to affect neuropsychological performance. Untreated patients with essential hypertension showed a slight functional impairment on tests of sensory-perceptual, cognitive, and psychomotor
abilities when compared with matched normotensive controls.34 Performance was most marked for those tests requiring speed and psychomotor coordination. In addition, in a follow-up study, those hypertensive patients who were treated and their blood pressured lowered had an improvement in performance scores that approached those of the normotensive control subjects. Hypertensives not on therapy remained deficient in their test performance. Therefore the authors conclude that the behavioral deficits resulting from the effects of mild hypertension on the central nervous system may be rever~ible.~' Although emphasis in assessing therapy is usually on the possible negative effects on quality of life, it is important to make sure that both negative and positive aspects are e ~ a l u a t e d . ~For ' example, it has been ~~ reported that captopril may have a mood-elevating effect. Z ~ b e n k ofound that the use of captopril was associated with substantial mood elevation in three depressed patients. He concluded that angiotensin-converting enzyme (ACE) inhibitors may alter neuropeptide synthesis or degradation and be therapeutic for these problems. Gengo and associate^'^ reported the results of a double-blind, three-way crossover study measuring the influence of Pblocker treatment on drowsiness and mental test performance in older hypertensive patients. The data showed greater improvement in mental testing performance associated with treatment (metaprolol) compared with placebo. Therefore some medications may actually improve quality of life and be of benefit through mechanisms other than their antihypertensive effect. Another interesting study2 examined the possibility of negative effects by determining the frequency with which tricyclic antidepressants were used in a large sample of Medicaid recipients (n = 143,253) taking any one of seven commonly used antihypertensive medications, insulin, or oral hypoglycemic agents. Tricyclic antidepressant use was significantly higher in patients taking p-blockers (23 per cent) than patients taking hydralazine or hypoglycemic patients, both 15 per cent. Patients on methyldopa and reserpine both showed a lower frequency of tricyclic antidepressant use (about 10 per cent each). The authors conclude that P-blockers may be more likely to cause depression in patients being treated for hypertension.
QUALITY-OF-LIFE MEASURES The development of quality-of-life measures is an exciting new area in the assessment of the impact of various therapies, particularly the evaluation of antihypertensive therapy. Quality-of-life measures need to be tailored to the specific disease or treatment being studied such as hypertension, myocardial infarction, or congestive heart failure. Each illness has its own implications for quality of life. For myocardial infarction measures, for example, need to evaluate critically ill patients and long-term rehabilitation. Chronic congestive heart failure may have severe impact on functional status, and measurements must emphasize self-care functions. Hypertension presents a different set of problems. No one class of hypertensive medication is effective in more than 50 per cent of the patients,' so frequently patients
need to be on one or more medications, each of which may have some impact on the quality of life. It is important to know how different drugs with different pathways affect quality of life. Centrally acting adrenergic inhibitors may have a different effect on quality of life then peripheral adrenergic inhibitors or direct vasodilators. Table 1 lists the components of quality of life and gives examples of certain measures that can be used to measure each domain. These are only examples, and several other measures can be used for each of these areas. One component of quality of life is social functioning that measures a person's ability to give and receive support. It also looks at the quality and quantity of social linkages. Many instruments can measure these connections. Two examples are the Interpersonal Support Evaluation Listx6and the Lubben Social Network Scale.26The Interpersonal Support Evaluation List assesses the amount of social support people feel they receive in four major domains: tangible aid, appraisal, belonging, and self-esteem. Respondents are asked to indicate the extent to which the 16 items apply to them. The instrument has been widely used with adult populations of all ages and has excellent psychometric properties. Some have demonstrated the instrument to have a strong relationship with health behaviors and morbidity in elderly pop~lations.'~ A composite social network scale that addresses the issue of the size, quality, and reciprocity of social relationships has been developed by Lubben, which is a modification of the Berkman-Syme social network index.3,26 The Lubben Social Network Scale consists of 10 weighted items in three areas: family networks, friends networks, and interdependent social supports, with scores ranging from 0 to 50. Both of these scales are easy to use and score, and are currently being used in a large study of community-dwelling elderly persons. Physical functioning is an important component of quality of life and relates to subjective feelings about health status and illness. It too can be Table I . Domains of Quality of Lqe and Measures DOMAINS
EXAMPLES OF MEASURES
Social functioning Feelings of support Family network Friends network
Interpersonal Support Evaluation List Lubben Social Network Scale
Physical functioning Health status Well-being Symptomslburden Mobility
Sickness Impact Profile Instrumental activities of daily living/ activities of daily living
Emotional functioning Affect Mood Sense of well-being
Center for Epidemiological Studies Depression Scale General Psychological Well-Being
Cognitive functioning Memory Visual-spatial Hvvothesis testing
Mini-Mental State Digit Symbol Substitution Test Letters Set Test
i
measured in many ways. A widely used measure of subjective health status and the burden of illness is the Sickness Impact Profile (SIP).4The SIP is a self-administered behavioral-based measure of sickness-related dysfunction rather than disease. The SIP was intended to provide a descriptive profile of changes in a person's behavior because of sickness and to measure universal patterns of limitations owing to particular types of medical conditions or disability. It contains 136 statements describing changes in behavior, attributable to sickness by the patient. The items represent 12 day-to-day activities including sleep and rest, work, eating, home management, alertness, emotional behavior, and communication. The items can be clustered into three major dimensions: physical, psychosocial, and independent categories. The major strengths of the SIP are its attempts to be universally applicable in its use as a comprehensive behavioral indicator of sickness-related dysfunction. The activities of daily living (ADL) by KatzZ3and the instrumental activities of daily living (IADL)= are types of instruments that are designed to measure two different categories of a person's functioning that may affect quality of life. The ADL functions are self-care tasks, such as bathing, feeding, dressing, and transferring, essential to personal maintenance. IADL functions are more complex activities that require fine motor coordination and include complex activities such as shopping, housekeeping, paying bills, and use of transportation. Both ADL and IADL are gross measures of rudimentary behavior, but are prerequisites for independence and most recreational activities. Emotional functioning is another component of quality of life, and is important because it reflects one's interaction with the environment and sense of well-being. A widely used self-report measure of presence and persistence of depressive symptoms is the Center for Epidemiological Studies Depression Scale (CESD).29In addition to depression, the many epidemiologic and clinical studies that have used the CESD have found it useful for evaluating aspects of self-esteem as well as state and trait anxiety. The CESD consists of 20 items that can be scored 0 to 3, depending on the frequency within the past week. It is a useful scale and it has been widely used in studies of the elderly population; it is currently being used in the Systolic Hypertension in the Elderly Program (SHEP) study.5 The General Psychological Well-Being Scale was developed as an index of well-being, based on self-representations of positive and negative effect and emotional states, and it was designed for use in community surveys.12 It is a self-administered questionnaire first used for Health and Nutrition Examination Survey (HANES-1). The scale has 22 items, which are organized in six subscales: anxiety, depressed mood, positive well-being, self-control, general health, and vitality. The psychometric properties of the scale are good, and it appears to be sensitive to changes in a person's general psychologic well-being. Cognitive functioning is the final component of quality of life, and perhaps the most important. The Mini-Mental State is a 30-item, widely used measure of cognitive function that evaluates concentration, attention, memory, orientation, and speech.14 The Mini-Mental State also tests attention and calculation, recall, registration, and orientation. It has been
well standardized in its application to elderly persons, and is currently ' being used in SHEP5 and other studies of the elderly p ~ p u l a t i o n . ~The Digit Symbol Substitution TesP9~40 requires sustained attention, visualspatial skills, and response shifting and has been used in many hypertension trials including the SHEP5 study. It is part of the Wechsler Adult Intelligence Scale,39,40 which is one of the most widely used measures of intelligence. The Digit Symbol Substitution Test requires that the participant fill in the series of symbols that have been paired with designated numbers, and the score recorded is the number of symbols correctly coded, within 90 seconds. The Letter Sets Test is a subtle test of abstract inductive reasoning, which has been used widely with elderly subjects and is part of a factored referenced test." It requires hypothesis formation and testing to discern the pattern that makes four sets of letters alike and one set different. The hypothesis has to be formed about what has come into the set and then the hypothesis must be tested against each of the sets to determine which one does not fit; this abstract level of thinking represents a subtle test of cognitive function. The test also penalizes for guessing. It is sensitive to cognitive changes resulting from high blood pressure. This set of measures of the components of quality of life is by no means conclusive, but represents some widely accepted ones that are currently being used and are applicable to the study of hypertension in elderly persons. Other areas that may be included are sexual functioning or intimacy,18 personal productivity, and role fulfillment at work,lg home, or in the community. Newer concepts such as locus of control and opportunity for choices are important, especially for nursing home patients.24Currently, a plethora of instruments already seems to be available that are well validated and reliable for use in studies. The Clearinghouse on Health Indexesg publishes a quarterly bibliography of health indexes that contains information or various measures for quality of life. Although many instruments measure each of these com~onents.one onlv needs to choose a few to cover the areas adequately and operationalize the concept of quality of life.6. 37
REVIEW OF RECENT STUDIES Few studies have specifically looked at quality of life as a prestudy construct. Table 2 shows some of the recent studies that have looked at the impact of antihypertensive therapy on quality of life and the results of these studies. Seven of the nine studies listed involved evaluation of an ACE inhibitor as one of the therapies. All of the studies used multiple medications and compared their effects on the quality of life. Only the Croog study,1° however, had quality of life as a primary outcome for the study. In the others, quality of life was a covariant or a secondary outcome of the study. Most of the measures of quality of life also center around medical side effects and tap into one or two domains of quality of life, without a multidimensional approach. One prospective study, without an interven-
Table 2 . Results of Recent Studies Examining Impact of Antihypertensive Therapy on Quality of Life AUTHORS
Aranda, 1986l
TYPE OF STUDY
THERAPY
Randomized crossover; group Captopril, metoprolol 1 received captopril and group 2 metoprolol (n = 20)
QUALITY OF LIFE MEASURES
OUTCOME
Subjective Questions of WellBeing
Both drugs equally effective in lowering blood pressure; captopril group showed greater improvement in quality of life, but both drug groups showed improvement
Diuretics, p-blockers, Rosenthal, 1986=' Multicenter open trial; other drugs withdrawn and methyldopa, clonidine, vasodilators replaced with captopril (n = 100; ages 29-73 years)
Self-administered questionnaire including items on well-being, vivid dreams, depression, dizziness, headaches
Side effects reduced in 36% of the patients on captopril
Yadfat, 198642
Treatment-control groups matched by age and sex (n = 106; ages 45-70 years)
Self-administered questionnaire on side effects (e.g., sexual dysfunction, fatigue, vivid dreams) and general feeling of well-being, mood, concentration
Significant reduction in side effects and improvement in quality of life in captopril group
Croog, 19861°
Multicenter, randomized, Captopril methyldopa, double-blind trial (n = 626; propranolol, ages 21-65 years) hydrochlorothiazide
Five domains: (1)sense of wellbeing and satisfaction with life, (2) physical state, (3) emotional state, (4) intellectual functioning, (5) ability to perform in social roles and degree of satisfaction derived from those roles
Captopril patients had significantly better scores in general well-being and life satisfaction, and were least likely tn withdraw from treatment because of adverse effects
Captopril, thiazides
Captopril group had few complaints vs. methyldopa group; no significant difference in activity index or depression between groups; oxprenolol was associated with increase in depression scores
Hill, 1985"
Multicenter, single-blind, randomized clinical trial (n = 567; age >50)
Captopril, methyldopa plus hydrochlorothiazide or oxprenolol with chlorthalidone
Complaint rate, activity index, psychiatric morbidity (depression)
Siegrist, 198734
Prospective study; subjects screened for cardiovascular risk factors (n = 416 middle-aged men)
No intervention
Untreated (refused) hypertensives Physical symptoms, mental alertness, emotional well-being, experienced a lower rate of sleep disturbances compared role performance at work with treated patients
Williams, 198741 Multi-center, double-blind, randomized trial (n = 626)
Captopril, methyldopa, propranolol, hydrochlorothiazide added in 2 months if goal blood pressure not reached
General well-being, physical symptoms, depression, sexual dysfunction, work performance
No differences in quality of life between those patients on diuretics and those not at 8 weeks; at 24 weeks, patients on diuretics had significant worsening of well-being compared with those not on diuretics
Lichter, 1986"
Randomized, single-blind, placebo-controlled trial (n = 25)
Atenolol, enalapril, placebo
Memory tests of recall
Patients treated with enalapril showed no change in memory function, but consistent and mild deficit in atenolol group
Patel, 198730
Randomized, controlled trial Group relaxation, stress (n = 192; ages 35-64 years) management
General health, enjoyment of life, Treatment group did better on personal and family relationships at work, general relationships health, enjoyment of life, personal relationships
tion, found that untreated hypertensive patients experienced fewer problems with quality of life than treated hypertensives. Although the ACE inhibitors in general seem to have a positive effect on the quality of life, the findings on other medications seem to be conflicting. Some studies, for example, find a decrease in mental capacity for patients on P-blockers, and others find impr~vement.'~. 32 Some also find increased problems with patients on diuretics42.43 and others found no difference in patients being treated with diuretics. Solomon36found that verbal memory was impaired in both hypertensive and normotensive patients taking methyldopa or propanolol, but hypertensive patients taking a diuretic did not demonstrate a deficit in this area. No change in visual memory occurred in any of the groups tested. Another problem with studies on the quality of life is the relevance of the findings. One study on the effects of relaxation and stress management on blood pressure and quality of life3' found a significant difference in favor of the treatment group in reference to four areas of quality of life. These significant differences in quality of life, however, may not be clinically significant. Problems with comparability also exist between treatment and control groups because several of the studies do not have a randomized desigm3'. 43 Some of the measures of quality of life in the reported studies do not use previously validated instruments but were developed ad hoc for the study.'. " Although the Croog study is extremely important because it recognizes quality of life as an outcome and as a multidimensional construct and used a randomized, double-blind design that had quality of life as the primary outconle, several questions exist regarding the rate of attrition, the choice of drugs, and the use of univariate statistical analyses with multiple dependent measures.'O An ongoing study that is looking at quality of life in hypertensives is the SHEP study,5 a clinical trial funded by the National Heart, Lung, and Blood Institute (NHLBI). The main purpose of the SHEP study is to evaluate the effects of treating isolated systolic hypertension (ISH) on mortality and morbidity in elderly persons. It is the first major NHLBl study to look at the issue of quality of life as it bears on the question of whether to treat or not to treat ISH. Factors used to evaluate quality of life in SHEP include side effects to medication, measures of cognitive status, affective state, ability to perform activities of daily living, satisfaction with life in general, and subjective well-being. It also looks at a person's social network. The quality of life component of SHEP was designed to answer questions on the effects of untreated ISH on the quality of life of elderly participants, and the effects of lowering systolic blood pressure on quality of life in elderly patients. <>
CONCLUSION It is not possible to answer fully the question of whether to treat or not treat hypertension in elderly persons without looking at the impact of treatment on the quality of life. Increasingly the issue of whether we are adding quality to the years of life, or just extending life is becoming more
important. It also seems evident that although the conceptualization and theory relevant to quality of life is not fully developed, we already have a sufficient understanding of the concept to develop a hierarchy of possible data-gathering instruments that fit within the overall framework. The ~ r o b l e mis not having too few instruments, but too many so that it frequently bewilders the clinician and researcher. A few instruments in each of the major domains of the quality of life, as previously described, are all that are needed to carry out significant research in this area. More studies need to be done that have quality of life as the target outcome. In addressing this issue, however, certain problem areas need further attention: (1)It is becoming increasingly more difficult to justify the inclusion of a placebo group in any clinical trial, particularly in the area of hypertension. Except for the unanswered question of isolated systolic hypertension in elderly persons, it has been well documented that hypertension is a significant risk factor for cardiovascular events and should receive some intervention. Because of this it may be increasingly difficult to compare quality of life in an untreated group of hypertensives versus those receiving some form of pharmacologic or nonpharmacologic intervention. In comparing multiple pharmacologic interventions the issue arises as to which drug(s) should be in the comparison group and which one should be used as a standard. Without a gold standard for measurement, it is difficult to develop criterion validity measures for scales used to measure the quality of life.37(2) Additional testable theories and systematic models would provide an overall conceptual framework for quality-of-life evaluations, such as the Health Belief which exists to explain behavior related to preventive health practices. (3) Another issue that may come up in the measurement of quality of life is whether a profile of scores (index) or battery of tests should be used. The latter is the most common strategy, but, with increasing numbers of variables in such a strategy, it increases the likelihood that a significant difference will be found by chance alone. Therefore, it is important to state specific hypotheses before a clinical trial begins, determine what the primary outcome will be and be parsimonious in the selection of quality-of-life measures. Another problem to avoid is the relabeling of variables such as quality of life after a study is over. Measures should reflect some prior concept of quality of life before the study begins. (4) Lastly, the meaningfulness of the quality-of-life data in reference to treatment of hypertension in elderly persons has not been fully evaluated. It is difficult to determine what a few points difference, for example, in a cognitive function test or affective evaluation test mean clinically. Several of the studies evaluating quality of life either looked at it undimensionally, but did not interpret related to medical symptoms, or multidimen~ionall~, the clinical significance of the differences found in the quality-of-life measures. Despite these problems, however, the type of future treatment of hypertension in elderly persons will depend as much on the impact of such treatment on the quality of life as it does on blood pressure readings and mortality.
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27. Miller RE, Shapiro AP, King HE, et al: Effect of antihypertensive treatment on the behavioral consequences of elevated blood pressure. Hypertension 6:202-208, 1984 28. O'Malley K: Lifestyle and quality of life in patients with hypertension. Irish Med J 11:304305, 1987 29. Orme J, Reis J, Herz E: Factorial and indiscriminate validity of the center for epidemiological studies depression (CES-D) scale. J Clin Psycho1 42:28-33, 1986 30. Patel C, Marmot MG: Stress management, blood pressure and quality of life. J Hyperten 5(suppl 1):521-528, 1987 31. Rosenthal T, Algom M, Chagnac A, et al: Captopril as a replacement therapy in hypertension improving quality of life-a multicenter study. Postgrad Med J 62(suppl 1):114-115, 1986 32. Rosenstock IM, Strecher VJ, Becker MH: Social learning theory and the health belief model. Health Educ Q 15:175-183, 1988 33. Rosow I, Breslau H: A Guttman health scale for the aged. J Gerontol 21:556-559, 1966 34. Shapiro AP, Miller RE, King HE, et al: Behavioral consequences of mild hypertension. Hypertension 4:355-360, 1982 35. Siegrist J, Matschinger H, Motz W: Untreated hypertensives and their quality of life. J Hypertens S(supp1 1):15-20, 1987 36. Solomon S, Hotchkiss E, Saravay SM, et al: Impairment of memory function by antihypertensive medication. Arch Gen Psychiatry 40:1109-1112, 1983 37. Spritzer WO: State of science 1986: Quality of life and functional status as target variables for research. J Chronic Dis 40:465-471, 1987 38. Watters K, Campbell B: Can an antihypertensive agent be both effective and improve the quality of life? A multi-center study with indapamide. Br J Clin Pract 40239-244, 1986 39. Wechsler D: The Measurement and Appraisal of Adult Intelligence, ed 4. Baltimore, Williams & Wilkins, 1958 40. Wechsler D: Wechsler Adult Intelligence Scale Manual. New York, Psychological Corporation, 1958 41. Wenger N, Mattson M, Furberg C, et al: Overview: Assessment of quality of life in clinical trials of cardiovascular therapies. In Wenger N, Mattson M, Furberg C, et al (eds): Assessment of Quality of Life in Cardiovascular Therapies. Washington, DC, Le Jacq, 1984 42. Williams GH, Croog SH, Levine S, et al: Impact of antihypertensive therapy on quality of life: Effect of hydrochlorothiazide. J Hypertens 5(suppl 1):29-35, 1987 43. Yadfat Y, Fidd J, Bloom D: Captopril as a replacement for standard multiple therapy in hypertension and quality of life. Postgrad Med J 62(suppl 1):116, 1986 44. Zubenko GS, Nixon RA: Mood elevating effect of captopril in depressed patients. Am J Psychiatry 141:llO-111, 1984 Department of Community Health, TB 168 School of Medicine University of California Davis, CA 95616
Assessing the Impact of Antihypertensive Therapy on Quality of Life in the Elderly
Philip G . Weiler, MD, MPH*
During the past 12 years, quality of life has become increasingly accepted as an important measure of the impact of medical care. With the escalating costs of medical care, it has been argued by some that more emphasis is needed on the impact of medical technology on quality of life. Some believe that, especially in treating elderly persons, care that only increases the burden of chronic illness and extends life but does not offer significant improvement in the quality of life should not be provided.' The term quality of l$e has been widely used both in the vernacular and scientific literature and usually encompasses several different concepts. This term is used in different ways by research scientists, policymakers, health care practitioners, and others; it is frequently used interchangeably with health status or functional status. A lack of consensus exists on its definition with inadequate conceptualization of its ~ o m p o n e n t s .Yet, ~~ despite these problems, the emphasis that it places on measuring the quality or value of time and not just its quantity is important. This emphasis is particularly important in evaluating the impact of therapy for hypertension in elderly persons because the disease is frequently asymptomatic, and the elderly may have several concomitant illnesses and limitation^.'^. 20
DEFINING THE CONCEPT It helps in focusing our consideration to make a distinction between the concept of quality in the term quality of life as referring to a person's worth based on some comparative external social standard versus quality based on the inherent health and well-being of a person in comparison with his or her own potential and goals. Quality based on some external *Director, Center for Aging and Health, Department of Community Health, School of Medicine, University of California, Davis, California Clinics in Geriatric Medicine-Vol.
5, No. 4, November 1989
703
standard presents considerable ethical and medical issues, and is not necessarily related to health or medical care. It is also important to emphasize that the larger institutional or social issues related to quality of life such as working conditions, income, pollution, crime, housing, satisfaction with government and vublic services. and environmental conditions are not directly responsiveto health or medical interventions. Objective measures of quality of life include employment status, marital status, material possessions, socioeconomic status, which can be used and may be easier to measure, but their actual association with personal happiness and satisfaction with life may be relatively low. Therefore, it is the healthrelated quality-of-life measures and their subjective indicators that are important in medical literature and are relevant to studies of treatment of hypertension of elderly persons. These measures usually involve some measurement of physical function, social function, emotional state, and perceptions of well-being. Quality of life can be assessed from several different perspectives. First of all, it can be studied as a direct outcome of therapy or a consequence of a cardiovascular event. Particularly with conditions such as mild hypertension or elevated cholesterol, in the short term, the therapy can be worse than the disease if the medication causes symptoms or disability. When evaluating cardiovascular events such as stroke or a mvocardial infarction. the imDaZt on a ~ e r s o n ' sclualitv of life as an outcom'e of these diseases * . brings different issues into consideration than just considering mortality and health care costs such as the use of the "quality-adjusted years of life" index.37Additionally, both pharmacologic and nonpharmacologic therapies may impact on quality of life and should be considered when weighing the various risks and benefits of theravy. Second.. clualitv , of life can be studied as a risk factor for the subsequentdevelopment of cardiovascular events or complications of hypertension. For example, people with a poor quality of life may be more likely to develop a stroke or a myocardial infarction. Lastly, quality of life may be a risk modifier by mediating the effect of other risk factors (for example, hypertension or compliance with treatment) or subsequent cardiovascular disease. A poor quality of life may increase the chances of having elevated blood pressure. It may also decrease the chances of a person complying with medical treatment. Figure 1 summarizes the inter-relationship of quality of life, therapy, hypertension, and cardiovascular disease and shows the various ways it can be studied. To assess quality of life as a primary outcome of therapy, clinicians need to be mindful of the possible effects on quality of life of the major drugs used in the treatment of hypertension. All of the major therapies for the treatment of hypertension can have some impact on the quality of life." This includes both pharmacologic and nonpharmacologic measures.'* Although most of these effects are medical symptoms, it is these very symptoms that consequently impact on the broader domains of quality of life such as social and emotional functioning as well as cognitive status. The reason quality of life has become increasingly important in hypertension is because we are not dealing with the treatment of symptoms but t change the natural historv of a disease. It is the risk of some an a t t e m ~ to future event (for example, cardiovascular disease or stroke) that one tries
-
Therapy
Hypertension
Quality of Life
Cardiovascul-ar Disease
Figure 1. Relationship of antihypertensive therapy to quality of life. Quality of life may be an outcome measure of therapy, an effect modifier of other risk factors, or a risk factor itself.
to prevent by treating hypertension. The reduction of this future risk needs to be balanced against the present impact on a person's lifestyle and enjoyment. It has been said that because hypertension is usually an asymptomatic disease, it is difficult to make an asymptomatic person feel better and, therefore, quality-of-life considerations are particularly important if we want to improve the patient's status in both the short and long term. It is interesting to note that physicians can have a biased perspective of how patients are doing on therapy if they do not look at issues related to quality of life. In one a survey was performed on 75 consecutive patients from an English group practice, who had hypertension controlled by the usual antihypertensive drugs, including diuretics, P-blockers, and methyldopa. A series of questions about quality of life was asked of the patients, their closest relatives, and the physicians. One hundred per cent of the physicians surveyed thought the patients had improved after therapy, whereas only 48 per cent of the patients believed they had improved after therapy. One per cent of relatives thought the patients had improved, whereas 99 per cent of the relatives believed the patients had become worse. The relatives described such symptoms in the patients as loss of memory (33 per cent), more irritability (45 per cent), depression (46 per cent), more hypochondriasis (55 per cent), and decreased sexual interest (64per cent). This study demonstrates that hypertensive therapy often may interfere with patients' enjoyment of life in ways of which neither the physician nor the patient is aware. Other factors bear on this issue as well. Hypertension, although usually asymptomatic, may itself have an impact on behavior and quality of life. Hypertension has been shown to affect neuropsychological performance. Untreated patients with essential hypertension showed a slight functional impairment on tests of sensory-perceptual, cognitive, and psychomotor
abilities when compared with matched normotensive controls.34 Performance was most marked for those tests requiring speed and psychomotor coordination. In addition, in a follow-up study, those hypertensive patients who were treated and their blood pressured lowered had an improvement in performance scores that approached those of the normotensive control subjects. Hypertensives not on therapy remained deficient in their test performance. Therefore the authors conclude that the behavioral deficits resulting from the effects of mild hypertension on the central nervous system may be rever~ible.~' Although emphasis in assessing therapy is usually on the possible negative effects on quality of life, it is important to make sure that both negative and positive aspects are e ~ a l u a t e d . ~For ' example, it has been ~~ reported that captopril may have a mood-elevating effect. Z ~ b e n k ofound that the use of captopril was associated with substantial mood elevation in three depressed patients. He concluded that angiotensin-converting enzyme (ACE) inhibitors may alter neuropeptide synthesis or degradation and be therapeutic for these problems. Gengo and associate^'^ reported the results of a double-blind, three-way crossover study measuring the influence of Pblocker treatment on drowsiness and mental test performance in older hypertensive patients. The data showed greater improvement in mental testing performance associated with treatment (metaprolol) compared with placebo. Therefore some medications may actually improve quality of life and be of benefit through mechanisms other than their antihypertensive effect. Another interesting study2 examined the possibility of negative effects by determining the frequency with which tricyclic antidepressants were used in a large sample of Medicaid recipients (n = 143,253) taking any one of seven commonly used antihypertensive medications, insulin, or oral hypoglycemic agents. Tricyclic antidepressant use was significantly higher in patients taking p-blockers (23 per cent) than patients taking hydralazine or hypoglycemic patients, both 15 per cent. Patients on methyldopa and reserpine both showed a lower frequency of tricyclic antidepressant use (about 10 per cent each). The authors conclude that P-blockers may be more likely to cause depression in patients being treated for hypertension.
QUALITY-OF-LIFE MEASURES The development of quality-of-life measures is an exciting new area in the assessment of the impact of various therapies, particularly the evaluation of antihypertensive therapy. Quality-of-life measures need to be tailored to the specific disease or treatment being studied such as hypertension, myocardial infarction, or congestive heart failure. Each illness has its own implications for quality of life. For myocardial infarction measures, for example, need to evaluate critically ill patients and long-term rehabilitation. Chronic congestive heart failure may have severe impact on functional status, and measurements must emphasize self-care functions. Hypertension presents a different set of problems. No one class of hypertensive medication is effective in more than 50 per cent of the patients,' so frequently patients
need to be on one or more medications, each of which may have some impact on the quality of life. It is important to know how different drugs with different pathways affect quality of life. Centrally acting adrenergic inhibitors may have a different effect on quality of life then peripheral adrenergic inhibitors or direct vasodilators. Table 1 lists the components of quality of life and gives examples of certain measures that can be used to measure each domain. These are only examples, and several other measures can be used for each of these areas. One component of quality of life is social functioning that measures a person's ability to give and receive support. It also looks at the quality and quantity of social linkages. Many instruments can measure these connections. Two examples are the Interpersonal Support Evaluation Listx6and the Lubben Social Network Scale.26The Interpersonal Support Evaluation List assesses the amount of social support people feel they receive in four major domains: tangible aid, appraisal, belonging, and self-esteem. Respondents are asked to indicate the extent to which the 16 items apply to them. The instrument has been widely used with adult populations of all ages and has excellent psychometric properties. Some have demonstrated the instrument to have a strong relationship with health behaviors and morbidity in elderly pop~lations.'~ A composite social network scale that addresses the issue of the size, quality, and reciprocity of social relationships has been developed by Lubben, which is a modification of the Berkman-Syme social network index.3,26 The Lubben Social Network Scale consists of 10 weighted items in three areas: family networks, friends networks, and interdependent social supports, with scores ranging from 0 to 50. Both of these scales are easy to use and score, and are currently being used in a large study of community-dwelling elderly persons. Physical functioning is an important component of quality of life and relates to subjective feelings about health status and illness. It too can be Table I . Domains of Quality of Lqe and Measures DOMAINS
EXAMPLES OF MEASURES
Social functioning Feelings of support Family network Friends network
Interpersonal Support Evaluation List Lubben Social Network Scale
Physical functioning Health status Well-being Symptomslburden Mobility
Sickness Impact Profile Instrumental activities of daily living/ activities of daily living
Emotional functioning Affect Mood Sense of well-being
Center for Epidemiological Studies Depression Scale General Psychological Well-Being
Cognitive functioning Memory Visual-spatial Hvvothesis testing
Mini-Mental State Digit Symbol Substitution Test Letters Set Test
i
measured in many ways. A widely used measure of subjective health status and the burden of illness is the Sickness Impact Profile (SIP).4The SIP is a self-administered behavioral-based measure of sickness-related dysfunction rather than disease. The SIP was intended to provide a descriptive profile of changes in a person's behavior because of sickness and to measure universal patterns of limitations owing to particular types of medical conditions or disability. It contains 136 statements describing changes in behavior, attributable to sickness by the patient. The items represent 12 day-to-day activities including sleep and rest, work, eating, home management, alertness, emotional behavior, and communication. The items can be clustered into three major dimensions: physical, psychosocial, and independent categories. The major strengths of the SIP are its attempts to be universally applicable in its use as a comprehensive behavioral indicator of sickness-related dysfunction. The activities of daily living (ADL) by KatzZ3and the instrumental activities of daily living (IADL)= are types of instruments that are designed to measure two different categories of a person's functioning that may affect quality of life. The ADL functions are self-care tasks, such as bathing, feeding, dressing, and transferring, essential to personal maintenance. IADL functions are more complex activities that require fine motor coordination and include complex activities such as shopping, housekeeping, paying bills, and use of transportation. Both ADL and IADL are gross measures of rudimentary behavior, but are prerequisites for independence and most recreational activities. Emotional functioning is another component of quality of life, and is important because it reflects one's interaction with the environment and sense of well-being. A widely used self-report measure of presence and persistence of depressive symptoms is the Center for Epidemiological Studies Depression Scale (CESD).29In addition to depression, the many epidemiologic and clinical studies that have used the CESD have found it useful for evaluating aspects of self-esteem as well as state and trait anxiety. The CESD consists of 20 items that can be scored 0 to 3, depending on the frequency within the past week. It is a useful scale and it has been widely used in studies of the elderly population; it is currently being used in the Systolic Hypertension in the Elderly Program (SHEP) study.5 The General Psychological Well-Being Scale was developed as an index of well-being, based on self-representations of positive and negative effect and emotional states, and it was designed for use in community surveys.12 It is a self-administered questionnaire first used for Health and Nutrition Examination Survey (HANES-1). The scale has 22 items, which are organized in six subscales: anxiety, depressed mood, positive well-being, self-control, general health, and vitality. The psychometric properties of the scale are good, and it appears to be sensitive to changes in a person's general psychologic well-being. Cognitive functioning is the final component of quality of life, and perhaps the most important. The Mini-Mental State is a 30-item, widely used measure of cognitive function that evaluates concentration, attention, memory, orientation, and speech.14 The Mini-Mental State also tests attention and calculation, recall, registration, and orientation. It has been
well standardized in its application to elderly persons, and is currently ' being used in SHEP5 and other studies of the elderly p ~ p u l a t i o n . ~The Digit Symbol Substitution TesP9~40 requires sustained attention, visualspatial skills, and response shifting and has been used in many hypertension trials including the SHEP5 study. It is part of the Wechsler Adult Intelligence Scale,39,40 which is one of the most widely used measures of intelligence. The Digit Symbol Substitution Test requires that the participant fill in the series of symbols that have been paired with designated numbers, and the score recorded is the number of symbols correctly coded, within 90 seconds. The Letter Sets Test is a subtle test of abstract inductive reasoning, which has been used widely with elderly subjects and is part of a factored referenced test." It requires hypothesis formation and testing to discern the pattern that makes four sets of letters alike and one set different. The hypothesis has to be formed about what has come into the set and then the hypothesis must be tested against each of the sets to determine which one does not fit; this abstract level of thinking represents a subtle test of cognitive function. The test also penalizes for guessing. It is sensitive to cognitive changes resulting from high blood pressure. This set of measures of the components of quality of life is by no means conclusive, but represents some widely accepted ones that are currently being used and are applicable to the study of hypertension in elderly persons. Other areas that may be included are sexual functioning or intimacy,18 personal productivity, and role fulfillment at work,lg home, or in the community. Newer concepts such as locus of control and opportunity for choices are important, especially for nursing home patients.24Currently, a plethora of instruments already seems to be available that are well validated and reliable for use in studies. The Clearinghouse on Health Indexesg publishes a quarterly bibliography of health indexes that contains information or various measures for quality of life. Although many instruments measure each of these com~onents.one onlv needs to choose a few to cover the areas adequately and operationalize the concept of quality of life.6. 37
REVIEW OF RECENT STUDIES Few studies have specifically looked at quality of life as a prestudy construct. Table 2 shows some of the recent studies that have looked at the impact of antihypertensive therapy on quality of life and the results of these studies. Seven of the nine studies listed involved evaluation of an ACE inhibitor as one of the therapies. All of the studies used multiple medications and compared their effects on the quality of life. Only the Croog study,1° however, had quality of life as a primary outcome for the study. In the others, quality of life was a covariant or a secondary outcome of the study. Most of the measures of quality of life also center around medical side effects and tap into one or two domains of quality of life, without a multidimensional approach. One prospective study, without an interven-
Table 2 . Results of Recent Studies Examining Impact of Antihypertensive Therapy on Quality of Life AUTHORS
Aranda, 1986l
TYPE OF STUDY
THERAPY
Randomized crossover; group Captopril, metoprolol 1 received captopril and group 2 metoprolol (n = 20)
QUALITY OF LIFE MEASURES
OUTCOME
Subjective Questions of WellBeing
Both drugs equally effective in lowering blood pressure; captopril group showed greater improvement in quality of life, but both drug groups showed improvement
Diuretics, p-blockers, Rosenthal, 1986=' Multicenter open trial; other drugs withdrawn and methyldopa, clonidine, vasodilators replaced with captopril (n = 100; ages 29-73 years)
Self-administered questionnaire including items on well-being, vivid dreams, depression, dizziness, headaches
Side effects reduced in 36% of the patients on captopril
Yadfat, 198642
Treatment-control groups matched by age and sex (n = 106; ages 45-70 years)
Self-administered questionnaire on side effects (e.g., sexual dysfunction, fatigue, vivid dreams) and general feeling of well-being, mood, concentration
Significant reduction in side effects and improvement in quality of life in captopril group
Croog, 19861°
Multicenter, randomized, Captopril methyldopa, double-blind trial (n = 626; propranolol, ages 21-65 years) hydrochlorothiazide
Five domains: (1)sense of wellbeing and satisfaction with life, (2) physical state, (3) emotional state, (4) intellectual functioning, (5) ability to perform in social roles and degree of satisfaction derived from those roles
Captopril patients had significantly better scores in general well-being and life satisfaction, and were least likely tn withdraw from treatment because of adverse effects
Captopril, thiazides
Captopril group had few complaints vs. methyldopa group; no significant difference in activity index or depression between groups; oxprenolol was associated with increase in depression scores
Hill, 1985"
Multicenter, single-blind, randomized clinical trial (n = 567; age >50)
Captopril, methyldopa plus hydrochlorothiazide or oxprenolol with chlorthalidone
Complaint rate, activity index, psychiatric morbidity (depression)
Siegrist, 198734
Prospective study; subjects screened for cardiovascular risk factors (n = 416 middle-aged men)
No intervention
Untreated (refused) hypertensives Physical symptoms, mental alertness, emotional well-being, experienced a lower rate of sleep disturbances compared role performance at work with treated patients
Williams, 198741 Multi-center, double-blind, randomized trial (n = 626)
Captopril, methyldopa, propranolol, hydrochlorothiazide added in 2 months if goal blood pressure not reached
General well-being, physical symptoms, depression, sexual dysfunction, work performance
No differences in quality of life between those patients on diuretics and those not at 8 weeks; at 24 weeks, patients on diuretics had significant worsening of well-being compared with those not on diuretics
Lichter, 1986"
Randomized, single-blind, placebo-controlled trial (n = 25)
Atenolol, enalapril, placebo
Memory tests of recall
Patients treated with enalapril showed no change in memory function, but consistent and mild deficit in atenolol group
Patel, 198730
Randomized, controlled trial Group relaxation, stress (n = 192; ages 35-64 years) management
General health, enjoyment of life, Treatment group did better on personal and family relationships at work, general relationships health, enjoyment of life, personal relationships
tion, found that untreated hypertensive patients experienced fewer problems with quality of life than treated hypertensives. Although the ACE inhibitors in general seem to have a positive effect on the quality of life, the findings on other medications seem to be conflicting. Some studies, for example, find a decrease in mental capacity for patients on P-blockers, and others find impr~vement.'~. 32 Some also find increased problems with patients on diuretics42.43 and others found no difference in patients being treated with diuretics. Solomon36found that verbal memory was impaired in both hypertensive and normotensive patients taking methyldopa or propanolol, but hypertensive patients taking a diuretic did not demonstrate a deficit in this area. No change in visual memory occurred in any of the groups tested. Another problem with studies on the quality of life is the relevance of the findings. One study on the effects of relaxation and stress management on blood pressure and quality of life3' found a significant difference in favor of the treatment group in reference to four areas of quality of life. These significant differences in quality of life, however, may not be clinically significant. Problems with comparability also exist between treatment and control groups because several of the studies do not have a randomized desigm3'. 43 Some of the measures of quality of life in the reported studies do not use previously validated instruments but were developed ad hoc for the study.'. " Although the Croog study is extremely important because it recognizes quality of life as an outcome and as a multidimensional construct and used a randomized, double-blind design that had quality of life as the primary outconle, several questions exist regarding the rate of attrition, the choice of drugs, and the use of univariate statistical analyses with multiple dependent measures.'O An ongoing study that is looking at quality of life in hypertensives is the SHEP study,5 a clinical trial funded by the National Heart, Lung, and Blood Institute (NHLBI). The main purpose of the SHEP study is to evaluate the effects of treating isolated systolic hypertension (ISH) on mortality and morbidity in elderly persons. It is the first major NHLBl study to look at the issue of quality of life as it bears on the question of whether to treat or not to treat ISH. Factors used to evaluate quality of life in SHEP include side effects to medication, measures of cognitive status, affective state, ability to perform activities of daily living, satisfaction with life in general, and subjective well-being. It also looks at a person's social network. The quality of life component of SHEP was designed to answer questions on the effects of untreated ISH on the quality of life of elderly participants, and the effects of lowering systolic blood pressure on quality of life in elderly patients. <>
CONCLUSION It is not possible to answer fully the question of whether to treat or not treat hypertension in elderly persons without looking at the impact of treatment on the quality of life. Increasingly the issue of whether we are adding quality to the years of life, or just extending life is becoming more
important. It also seems evident that although the conceptualization and theory relevant to quality of life is not fully developed, we already have a sufficient understanding of the concept to develop a hierarchy of possible data-gathering instruments that fit within the overall framework. The ~ r o b l e mis not having too few instruments, but too many so that it frequently bewilders the clinician and researcher. A few instruments in each of the major domains of the quality of life, as previously described, are all that are needed to carry out significant research in this area. More studies need to be done that have quality of life as the target outcome. In addressing this issue, however, certain problem areas need further attention: (1)It is becoming increasingly more difficult to justify the inclusion of a placebo group in any clinical trial, particularly in the area of hypertension. Except for the unanswered question of isolated systolic hypertension in elderly persons, it has been well documented that hypertension is a significant risk factor for cardiovascular events and should receive some intervention. Because of this it may be increasingly difficult to compare quality of life in an untreated group of hypertensives versus those receiving some form of pharmacologic or nonpharmacologic intervention. In comparing multiple pharmacologic interventions the issue arises as to which drug(s) should be in the comparison group and which one should be used as a standard. Without a gold standard for measurement, it is difficult to develop criterion validity measures for scales used to measure the quality of life.37(2) Additional testable theories and systematic models would provide an overall conceptual framework for quality-of-life evaluations, such as the Health Belief which exists to explain behavior related to preventive health practices. (3) Another issue that may come up in the measurement of quality of life is whether a profile of scores (index) or battery of tests should be used. The latter is the most common strategy, but, with increasing numbers of variables in such a strategy, it increases the likelihood that a significant difference will be found by chance alone. Therefore, it is important to state specific hypotheses before a clinical trial begins, determine what the primary outcome will be and be parsimonious in the selection of quality-of-life measures. Another problem to avoid is the relabeling of variables such as quality of life after a study is over. Measures should reflect some prior concept of quality of life before the study begins. (4) Lastly, the meaningfulness of the quality-of-life data in reference to treatment of hypertension in elderly persons has not been fully evaluated. It is difficult to determine what a few points difference, for example, in a cognitive function test or affective evaluation test mean clinically. Several of the studies evaluating quality of life either looked at it undimensionally, but did not interpret related to medical symptoms, or multidimen~ionall~, the clinical significance of the differences found in the quality-of-life measures. Despite these problems, however, the type of future treatment of hypertension in elderly persons will depend as much on the impact of such treatment on the quality of life as it does on blood pressure readings and mortality.
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