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Blood pressure control in hypertensives—a model for the study of life events
J Chron Dis Vol. 37, No. 4, pp. 247-253, 1984 Printed in Great Britain. All rights reserved
Copyright c
0021-9681/84 $3.00+0.00 1984 Pergamon Press Ltd
BLOOD PRESSURE CONTROL IN HYPERTENSIVESA MODEL FOR THE STUDY OF LIFE EVENTS CAROL
Departments
W. BUCK’*
and
ALLAN
P.
DONNER~
of ‘Epidemiology and Biostatistics and *Family Medicine, University of Western Ontario, London, Ontario, Canada N6A 5B7 (Received in revised form 24 October 1983)
events were elicited during an average recall period of 8.5 months among 235 hypertensive patients whose blood pressure was under control just prior to the beginning of the recall period. At the end of the recall period, the 41 patients no longer under control reported a significantly higher proportion both of unfavourable and unexpected life changes compared with the 194 patients whose blood pressure was still under control. The differences persisted after allowing for potentially confounding variables. The patients were not aware of their blood pressure status at the time of the life events interview. Abstract-Life
1. INTRODUCTION THE STUDY of the relationship between life events and illness is fraught with methodological problems [ 1,2]. In retrospective studies, the recall of events may be more complete among people who are seeking an explanation of their ill health. Bias can arise if the occurrence of life events makes a person more likely to report illness or to seek health care for symptoms of illness. Nor is the sequence of life events and illness easily determined. Even in prospective studies, where the chronology of life events and illness seems clear, it is possible that early symptoms of illness make a person more vulnerable to life events which in turn exacerbate the illness. The latter is called the “proneness hypothesis” by Dohrenwend and Dohrenwend [3]. The status of blood pressure control in hypertensive patients offers a model for the study of life events that overcomes some of these difficulties. This is so for the following reasons:
(a) It is possible to obtain information on life events and on change in blood pressure status without the subject being aware of the latter. Thus recall bias can be eliminated. (b) Loss of control of blood pressure can be objectively determined among all subjects under study. Thus differential reporting and care-seeking can be eliminated. (c) If it can be assumed that loss of blood pressure control is asymptomatic, one eliminates the possibility that symptoms make the patient more prone to life events. (d) If the investigation is restricted to patients who are compliant with treatment, one can rule out the possibility of a behavioural phenomenon that leads on the one hand to non-compliance and loss of blood pressure control, and on the other to life events. Exclusion of non-compliant patients also eliminates the possibility that life events lead to loss of blood pressure control because they interfere with compliance. Thus the hypertension control model offers an attractive approach. Moreover, question of whether life events affect the control of blood pressure is interesting in its right. Monk, in a review of psychological status and hypertension, emphasized importance of studying the role of environmental and social factors [4]. Brody *Author to whom all correspondence
should be addressed.
the own the has
248
CAROL W. BUCK and ALLAN P. DONNER
provided evidence that treated hypertensives who experience psychological distress require more medication to control their blood pressure [5]. If it were true that stressful life events could cause a hypertensive patient to lose control of blood pressure, the therapeutic implications would be important. 2.
METHODS
2.1 Source of data
The present study was carried out during the course of a controlled trial of hypertension screening and compliance-enhancing management in general practice [5]. To determine the effect of strategies for improving compliance, hypertensives in the experimental and control practices were visited in their homes by trained interviewers 4 years after the initiation of the program. During the home visit, blood pressure was measured and an extensive interview was carried out. The interview included an inventory of life events, questions on the patient’s sense of well-being, personality characteristics, social support and compliance with treatment. Data concerning demographic variables and life-style were also obtained during the interview. For the study of life events in relation to blood pressure control, we pooled the data for patients in the experimental and control practices. This was done in order to obtain the maximum number of patients who were compliant and whose blood pressure was under control at the beginning of the recall period for life events. How they became compliant and achieved control of blood pressure was not a primary concern of this investigation. 2.2 Period of observation Questions about life events covered the period from January lst, 1981 to the time of the home visit. The mean interval from January 1st to the home visit was 8.5 months, with a standard deviation of 2.9 months and a range of 4-15 months. Baseline control of blood pressure was determined from the records of office visits during the period October to December 1980. The patient’s blood pressure was considered to be under control if the diastolic pressure at the last such visit was less than 90 mmHg. It has to be assumed that patients under control between October and December 1980 did not fall out of control before January lst, 198 1. 2.3 The life events instrument (see Appendix) We used the PER1 Life Events Scale developed by Dohrenwend et al. [7]. It consists of 102 events grouped according to the various facets of life. The events have been assigned weights corresponding to their presumed stressfulness. For each event reported, four additional questions were asked about the subject’s perception of the event. (a) (b) (c) (d)
Whether it was a change for the worse, the better, or neither. Whether it was expected or unexpected. The subject’s degree of control over the event, on a scale from O-4. The amount of adjustment required, on a scale from O-4.
These questions were added because reports by Streiner et al. [8] and by Suls and Mullen [9] indicate that illness is more likely to follow events that are perceived as undesirable, unexpected, beyond the subject’s control, or requiring considerable adjustment. To avoid embarrassment on the subject’s part and to elicit the most honest responses, the interviewer did not discuss with the subject any event that was reported. The subject was asked to read a numbered list of the 102 events and to indicate the number of each event that had occurred during the period of recall. The four questions about the perception of an event were handled similarly, by giving the subject a score sheet on which to check the appropriate answer for each of the selected events. Our procedure, therefore, had elements of both the self-administered questionnaire and the check-list interview. Neugebauer observes that it is not yet known if a self-administered
249
Blood Pressure Control in Hypertension
questionnaire is more or less reliable than an interview check-list of life events [lo]. But, as Neugebauer points out, unreliability would attenuate rather than increase the strength of an association between illness and life events. In making this statement, Neugebauer obviously refers to unbiased lack of reliability. In the present study biased unreliability is unlikely because an objective measurement of “illness” was used. Blood pressure was measured with a random zero sphygmomanometer. The interviewers were told that the computer would convert the recorded systolic, diastolic and random zero readings into the patient’s true blood pressure. The method of calculation was not explained to them. If a patient asked what the blood pressure was, the interviewers were instructed to say that this could not be determined until the readings had been processed by the computer. 2.4 Dejinitions Blood pressure control at the home visit. Blood pressure was designated as under control if the average of the 2nd and 3rd of three diastolic readings was less than 90 mmHg. Compliance. Compliance with therapy was defined as follows:
(a) Patient reported no missed appointments with the physician during the past year. (b) Patient reported that in the week prior to the home visit, 80% of any prescribed antihypertensive medication had been taken. Since self-reported compliance is known to overestimate true compliance, we cannot be certain that all non-compliant patients were excluded. This issue will be discussed later. 3. RESULTS
3.1 Eligible patients In the random sample of hypertensive patients visited in their homes, 235 met the two eligibility criteria for this study: (a) Blood pressure under control prior to the period of life event recall. (b) Evidence of compliance with therapy. The eligible patients ranged in age from 20-65 years, the age limits used in the clinical trial from which the data came. The majority (80%) were aged 45-65. Males made up 42:; and females 58% of the eligible group. Blood pressure had fallen out of control by the time of the home visit in 41 patients, 17% of the eligible group. Table 1 compares mean diastolic pressures at the last office visit in 1980 and at the home visit in 1981 for those under control and out of control on the second occasion. It is clear that the two groups had similar levels of diastolic pressure at the office visit just before the life events recall period. The mean recall period for life events was 9.3 months in patients whose blood pressure had fallen out of control and 8.3 months in patients still under control. The slightly greater recall period among the former would tend to reduce slightly their memory of events. 3.2 Univariate
analysis
of life events and blood pressure
control
Comparisons of life events among patients with blood pressure under control and out of control are shown in Table 2.
TABLt
Mean diastolic blood CmmHg) At last office visit At home visit N ‘i90mmHg.
pressure
I.
Diastolic blood pressure control at home visit ~ Under control’ out of control 79.7 77.0 194
80.2 96.2 41
CAROL W. BUCK and ALLAN P. DONNER
250
TABLE2.
(4
No.
of It>
events per month
Blood messwe
of obseruation
status
N
Under control Out of control
W
Ltfi
event
weight
194 41
Under control Out of control required
Blood pressure
Degree
of control
Blood pressure
over
events
0.72
N
Mean Adj.
P
N
as a change for
-.-.
N 152 37
of events
Under control Out of control
P
355.5 351 .o
152 31
Under control Out of control
Blood pressure
Mean wt
status
described
1.62 1.41
0.36
@er patient)
status
(E) Proportion of events described Blood pressure status .~_
Proportion
N 152 31
152 37
Under control Out of control
(F)
P’
0.37
@t-r patient)
status
Under control Out of control
(W
0.25 0.26
@er patient)
Blood pressure status
F-3 Adjustment
Mean No
Mean control 2.33 1.98
P
0.17
the w’orse
Mean proportion
~_.
0.22 0.34
P
0.04
as unexpected**
N” 149 36
*p-value based upon Wilcoxon Rank Sum test. l*4 patients with events did not supply information
Mean proportion 0.28 0.45
P
0.02
on this point.
The computations in the first section of Table 2 are based upon the average number of events per month in order to allow for the variable recall period. The computations in the succeeding sections are based on values averaged over the events reported. Thus the sample size in the first section is greater than in succeeding sections, because 46 patients reported no events. Table 2 shows that only two kinds of life events were significantly related to loss of blood pressure control--events that were perceived as a change for the worse and events that were unexpected.
3.3 Multivariate analysis of life events altowing for confounding variables Critics of life events research have emphasized that variables related both to life events and illness must be taken into account before concluding that life events have an independent role [l 11. Therefore we examined the following variables with respect to their relationship with loss of blood pressure control: age, sex, marital status, social class (Blishen classification of Canadian occupations) [ 121, education, coronary prone behaviour, smoking and social support. A variable was considered to be a potential confounder if it had some relationship with loss of blood pressure control, whether or not the association was statistically significant. The following variables emerged as potential confounders; age, sex, marital status, education, smoking and social support. A multiple logistic regression was performed for each life event variable in relation to blood pressure status. The results are shown in Table 3. After allowing for the potentially confounding variables, the proportion of life events described as unexpected had a highly significant relationship with loss of blood pressure control, and the proportion described as a change for the worse fell just short of significance at the 5% level (p = 0.052). Among the potential confounders, only marital status had a consistently significant relationship with loss of blood pressure control. The coding of marital status is such that a positive regression coefficient indicates a greater likelihood of loss of blood pressure control among never married patients.
Blood Pressure
Control
TABLE 3. REXJLTS OF I-HE MULTIPLE LOGLSTK
251
in Hypertension
REGREWON
ANALYSIS OF BLOOD
PRESSURE
CONTROL
Diastolic blood Dependent
variable:
Pressure
(>90mmHg=
control
I, <90mmHg=O)
Independent Variables:
Xl
X2 Xl X4 X5 X6 X7 X8 X9
X,0 Xl, X,2
X,
X? X, X4 X5
X6 X7
X8 X9 X,0 XL\
Sex (male = 1, female = 0) Age (20-44 = I, 45-65 = 0) Never married (yes = I, no = 0) Highest education level (more than high Ever smoked (yes = 1, no = 0) Social support (average score) Number of events/month Average adjustment required Average control experienced Proportion of events a change for worse Proportion of events unexpected Average event weight
2.08’ 0.18 2.94’* 0.33 0.46 - I .09 -0.52 (n = 229)’
1.64 0.06 2.86** -0.10 0.95 -0.59 - 1.06 (n = 184)
school = I. lesser education
SlImlilary Regression coefficient/standard I .79 I .94 1.91 -0.21 - 0.27 -0.14 3.05” 3.25” 2.84’* 0.06 0.30 -0.07 0.25 0.38 0.57 0.20 - 0.05 -0.23
-1.13 (n = 184)
1.94 (n = 184)
2.61** (n = 180)
X12
= 0)
erro? 1.78 -0.09 2X8** -0.01 0.84 -0.41
-0.21 (n = 184)
“A positive sign implies a positive relationship with loss of control. bBecause of missing values on some of the independent variables, the sample sizes for these analyses slightly less than for the analyses reported in Table 2. ‘p CO.05. **p
PRESSURE CONTROL
AND
SELF-REPORTED
Under control Mean no. days disability in previous 2 weeks Patient’s health compared with others of same age Better Same Worse Mean score on eight symotoms
HEALTH
are
STATUS
Out of control ~~~5 ~ ~~~
P ,o.so_._~
I .09 (I = 0.08)
“. 10
0, ‘0
30.4 50.8 18.7
24.4 53.6 22.2
1.81
I .78
> 0.50 (x2 = 0.66)
>0.50 (I =O.lOl
3.4 Is loss of blood pressure control asymptomatic?
In the introduction we referred to the importance of assuming that loss of blood pressure control does not produce symptoms which could make the patient more prone to life events. A recent report by Van Reed et al. offers evidence of a weak curvilinear relationship between diastolic pressure and symptoms [13]. Their subjects were scored according to the reported presence of 39 symptoms. The lowest average symptom score was obtained from subjects with diastolic pressures between 75 and 94. Those with pressures below or above this range had slightly higher scores. Symptoms of dizziness, chest pain and sleeplessness each showed this pattern. At the home visit, our patients were asked general questions about their health and about 8 specific symptoms (dizziness, blurred vision, headache, limb weakness, cold hands, nosebleed, constipation and dry mouth). Table 4 compares the responses of the hypertensives under control and out of control. There is no evidence that loss of blood pressure control was associated with an increase in disability, a perception of generally poorer health, or with the presence of eight specific symptoms.
252
CAROL W. BUCK and ALLAN P. DONNER
It must be recognized, however, that the information on health status was obtained crosssectionally. Therefore we cannot eliminate the possibility that symptoms associated with loss of blood pressure control occurred earlier in the recall period and precipitated life events. But if this had happened, it would be most unlikely that the symptoms would have disappeared, since the “proneness hypothesis” states that the life events exacerbate the early symptoms and thereby lead to manifest illness. 3.5 Was loss of blood pressure control a consequence of non-compliance with treatment? Although our investigation was restricted to patients who reported themselves as compliant it is likely that only 50-607; were truly so [14]. Therefore it is possible that life events reduced blood pressure control by diminishing compliance with treatment rather than by a direct influence upon the physiological determinants of blood pressure. We explored the role of compliance by examining blood pressure control among hypertensives under control at the last office visit who reported themselves as noncompliant at the home visit. A patient who reports non-compliance is almost always telling the truth [ 141.Among these patients 85% were still under control at the home visit, a proportion almost identical to the 83% under control among the compliant group. Thus it appears that compliance had little influence upon blood pressure control among patients who were already controlled 8 months (on average) previously. By contrast, among patients not under control at the last office visit, 66% of the compliant and only 54”/0of the non-compliant were under control at the home visit. This is evidence of a carry-over phenomenon which has been reported in the literature, indicating that controlled hypertensives can remain normotensive, sometimes for an extended period, after stopping drug treatment [IS, 161. Another approach to the issue of noncompliance is to restrict the comparison of life events to patients who were not under drug treatment during the period of observation. Unfortunately only a small number of patients fell into this category. Nevertheless, the differences in the proportion of unfavourable and unexpected events between those under and out of control in this subgroup were of the same magnitude and direction as in the total group of patients. 3.6 Potential bias from pooling patients from experimental and control practices It is conceivable that the counselling used to enhance compliance in the Experimental practices had a “soothing” effect on patients, making them less vulnerable both to life events and loss of blood pressure control. This was examined by introducing Practice Type into the logistic regression analyses for unfavourable and unexpected life events. Adding this variable had a negligible effect on the t and p values. 4.
DISCUSSION
The purpose of this research was to study the effect of life events upon the regulation of blood pressure in the hope of avoiding some of the methodological problems that make it so difficult to interpret observed associations between life events and illness, We have found that life events of an unfavourable or unexpected nature are associated with loss of blood pressure control in previously controlled hypertensives. These observations are in accord with the results of many other studies of life events and illness. We did not find a statistically significant association with events of an uncontrollable nature, although a weak relationship in the expected direction was observed. To what extent have we been successful in eliminating the methodological biases that we sought to avoid by choosing the blood pressure model? Recall bias and differential reporting of illness have certainly been eliminated. Given the absence of an association between self-reported health status and loss of blood pressure control, it is unlikely that the association with life events represents the reverse causal mechanism whereby illness leads to events. The possibility that life events acted upon compliance with antihypertensive therapy rather than upon the physiological mechanism of blood pressure control must be considered, since we did not use a fully accurate measure of compliance.
Blood PressureControl in Hypertension
253
We have evidence, however, that among the patients under study, compliance was of less importance than is generally the case. Thus, it seems reasonable to conclude that these results add considerable weight to the belief that life events are capable of evoking an adverse physiological reaction. In addition to the general conclusion, the results have applicability to the clinical management of hypertension. The physician would be well advised to make more frequent checks of blood pressure in a patient who is experiencing stressful life events. Acknoi~ledgements-This research was supported by Grant DM 330(b) from the Ontario Ministry of Health. We are grateful to the London Hypertension Study for allowing us to share their data, to Jane Mayberry for devising the format of the life events interview and to Peggy Baker and Nedra Salmon for assistance in the analysis of data.
REFERENCES I. 2. 3. 4. 5. 6. I. 8. 9. 10. II. 12. 13. 14. IS. 16.
Rabkin JG, Struening EL: Life events, stress and illness. Science 194: 1013-1020, 1976 Goldberg EL, Comstock GW: Life events and subsequent illness. Am J Epid 104: 146157, 1976 Dohrenwend BS, Dohrenwend BP: In Straful Life Events and Their Contexts. Dohrenwend BS, Dohrenwend BP (Eds). New York: Prodist 1981 Monk M: Psychological status and hypertension. Am J Epid 112: 200-208, 1980 Brody DS: Psychological distress and hypertension control. J Human Stress 6: 2-6, 1980 Bass MJ, Donner A, McWhinney IR: Effectiveness of the family physician in hypertension screening. Can Fam Physician 28: 255-258, 1982 Dohrenwend BS. Krasnoff L, Askenasy AR, Dohrenwend BP: Exemplification of a method for scaling life events: the PERI Life Events Scale. J Health Sot Behnv 19: 205-229. 1978 Streiner DL, Norman GR, McFarlane AH, Roy RG: Quality of life events, and their relationship to strain. Schiz Bull 7: 34-42, 1981 Suls J, Mullen B: Life events, perceived control and illness. J Human Stress 7: 30-34, 1981 Neugebauer R: The reliability of life-event reports. In Stressful Life Events aad Their Context. Dohrenwend BS, Dohrenwend BP (Eds). New York: Prodist, 1981 Goldberg EL, Comstock GW: Epidemiology of life events. Am J Epid 111: 736-752, 1980 Blishen BR, Jones FE, Naegele KD, Porter J: Canadian Society: Sociological Perspectives. Toronto: MacMillan, 197 I Van Reek J, Drederiks J, Phillipsen H, Van Zutphen W, Seelen T: Subjective complaints and blood pressure. J Psychosom Res 26: 155-166, 1982 Gordis L: Conceptual and methodologic problems in measuring patient compliance. In Compliance in Health Care. Haynes RB, Taylor DW, Sackett DL (Eds). Baltimore: Johns Hopkins University Press, 1979 Fernandez PC, Galway AB, Kim BK: Prolonged normotension following cessation of therapy in uncomplicated essential hypertension. CIin Invest Med 5: 31-37, 1982 Perry M. Wessler S, Aviolo LV: Survival of treated hypertensive patients. JAMA 210: 890-895, 1969
Copyright c
0021-9681/84 $3.00+0.00 1984 Pergamon Press Ltd
BLOOD PRESSURE CONTROL IN HYPERTENSIVESA MODEL FOR THE STUDY OF LIFE EVENTS CAROL
Departments
W. BUCK’*
and
ALLAN
P.
DONNER~
of ‘Epidemiology and Biostatistics and *Family Medicine, University of Western Ontario, London, Ontario, Canada N6A 5B7 (Received in revised form 24 October 1983)
events were elicited during an average recall period of 8.5 months among 235 hypertensive patients whose blood pressure was under control just prior to the beginning of the recall period. At the end of the recall period, the 41 patients no longer under control reported a significantly higher proportion both of unfavourable and unexpected life changes compared with the 194 patients whose blood pressure was still under control. The differences persisted after allowing for potentially confounding variables. The patients were not aware of their blood pressure status at the time of the life events interview. Abstract-Life
1. INTRODUCTION THE STUDY of the relationship between life events and illness is fraught with methodological problems [ 1,2]. In retrospective studies, the recall of events may be more complete among people who are seeking an explanation of their ill health. Bias can arise if the occurrence of life events makes a person more likely to report illness or to seek health care for symptoms of illness. Nor is the sequence of life events and illness easily determined. Even in prospective studies, where the chronology of life events and illness seems clear, it is possible that early symptoms of illness make a person more vulnerable to life events which in turn exacerbate the illness. The latter is called the “proneness hypothesis” by Dohrenwend and Dohrenwend [3]. The status of blood pressure control in hypertensive patients offers a model for the study of life events that overcomes some of these difficulties. This is so for the following reasons:
(a) It is possible to obtain information on life events and on change in blood pressure status without the subject being aware of the latter. Thus recall bias can be eliminated. (b) Loss of control of blood pressure can be objectively determined among all subjects under study. Thus differential reporting and care-seeking can be eliminated. (c) If it can be assumed that loss of blood pressure control is asymptomatic, one eliminates the possibility that symptoms make the patient more prone to life events. (d) If the investigation is restricted to patients who are compliant with treatment, one can rule out the possibility of a behavioural phenomenon that leads on the one hand to non-compliance and loss of blood pressure control, and on the other to life events. Exclusion of non-compliant patients also eliminates the possibility that life events lead to loss of blood pressure control because they interfere with compliance. Thus the hypertension control model offers an attractive approach. Moreover, question of whether life events affect the control of blood pressure is interesting in its right. Monk, in a review of psychological status and hypertension, emphasized importance of studying the role of environmental and social factors [4]. Brody *Author to whom all correspondence
should be addressed.
the own the has
248
CAROL W. BUCK and ALLAN P. DONNER
provided evidence that treated hypertensives who experience psychological distress require more medication to control their blood pressure [5]. If it were true that stressful life events could cause a hypertensive patient to lose control of blood pressure, the therapeutic implications would be important. 2.
METHODS
2.1 Source of data
The present study was carried out during the course of a controlled trial of hypertension screening and compliance-enhancing management in general practice [5]. To determine the effect of strategies for improving compliance, hypertensives in the experimental and control practices were visited in their homes by trained interviewers 4 years after the initiation of the program. During the home visit, blood pressure was measured and an extensive interview was carried out. The interview included an inventory of life events, questions on the patient’s sense of well-being, personality characteristics, social support and compliance with treatment. Data concerning demographic variables and life-style were also obtained during the interview. For the study of life events in relation to blood pressure control, we pooled the data for patients in the experimental and control practices. This was done in order to obtain the maximum number of patients who were compliant and whose blood pressure was under control at the beginning of the recall period for life events. How they became compliant and achieved control of blood pressure was not a primary concern of this investigation. 2.2 Period of observation Questions about life events covered the period from January lst, 1981 to the time of the home visit. The mean interval from January 1st to the home visit was 8.5 months, with a standard deviation of 2.9 months and a range of 4-15 months. Baseline control of blood pressure was determined from the records of office visits during the period October to December 1980. The patient’s blood pressure was considered to be under control if the diastolic pressure at the last such visit was less than 90 mmHg. It has to be assumed that patients under control between October and December 1980 did not fall out of control before January lst, 198 1. 2.3 The life events instrument (see Appendix) We used the PER1 Life Events Scale developed by Dohrenwend et al. [7]. It consists of 102 events grouped according to the various facets of life. The events have been assigned weights corresponding to their presumed stressfulness. For each event reported, four additional questions were asked about the subject’s perception of the event. (a) (b) (c) (d)
Whether it was a change for the worse, the better, or neither. Whether it was expected or unexpected. The subject’s degree of control over the event, on a scale from O-4. The amount of adjustment required, on a scale from O-4.
These questions were added because reports by Streiner et al. [8] and by Suls and Mullen [9] indicate that illness is more likely to follow events that are perceived as undesirable, unexpected, beyond the subject’s control, or requiring considerable adjustment. To avoid embarrassment on the subject’s part and to elicit the most honest responses, the interviewer did not discuss with the subject any event that was reported. The subject was asked to read a numbered list of the 102 events and to indicate the number of each event that had occurred during the period of recall. The four questions about the perception of an event were handled similarly, by giving the subject a score sheet on which to check the appropriate answer for each of the selected events. Our procedure, therefore, had elements of both the self-administered questionnaire and the check-list interview. Neugebauer observes that it is not yet known if a self-administered
249
Blood Pressure Control in Hypertension
questionnaire is more or less reliable than an interview check-list of life events [lo]. But, as Neugebauer points out, unreliability would attenuate rather than increase the strength of an association between illness and life events. In making this statement, Neugebauer obviously refers to unbiased lack of reliability. In the present study biased unreliability is unlikely because an objective measurement of “illness” was used. Blood pressure was measured with a random zero sphygmomanometer. The interviewers were told that the computer would convert the recorded systolic, diastolic and random zero readings into the patient’s true blood pressure. The method of calculation was not explained to them. If a patient asked what the blood pressure was, the interviewers were instructed to say that this could not be determined until the readings had been processed by the computer. 2.4 Dejinitions Blood pressure control at the home visit. Blood pressure was designated as under control if the average of the 2nd and 3rd of three diastolic readings was less than 90 mmHg. Compliance. Compliance with therapy was defined as follows:
(a) Patient reported no missed appointments with the physician during the past year. (b) Patient reported that in the week prior to the home visit, 80% of any prescribed antihypertensive medication had been taken. Since self-reported compliance is known to overestimate true compliance, we cannot be certain that all non-compliant patients were excluded. This issue will be discussed later. 3. RESULTS
3.1 Eligible patients In the random sample of hypertensive patients visited in their homes, 235 met the two eligibility criteria for this study: (a) Blood pressure under control prior to the period of life event recall. (b) Evidence of compliance with therapy. The eligible patients ranged in age from 20-65 years, the age limits used in the clinical trial from which the data came. The majority (80%) were aged 45-65. Males made up 42:; and females 58% of the eligible group. Blood pressure had fallen out of control by the time of the home visit in 41 patients, 17% of the eligible group. Table 1 compares mean diastolic pressures at the last office visit in 1980 and at the home visit in 1981 for those under control and out of control on the second occasion. It is clear that the two groups had similar levels of diastolic pressure at the office visit just before the life events recall period. The mean recall period for life events was 9.3 months in patients whose blood pressure had fallen out of control and 8.3 months in patients still under control. The slightly greater recall period among the former would tend to reduce slightly their memory of events. 3.2 Univariate
analysis
of life events and blood pressure
control
Comparisons of life events among patients with blood pressure under control and out of control are shown in Table 2.
TABLt
Mean diastolic blood CmmHg) At last office visit At home visit N ‘i90mmHg.
pressure
I.
Diastolic blood pressure control at home visit ~ Under control’ out of control 79.7 77.0 194
80.2 96.2 41
CAROL W. BUCK and ALLAN P. DONNER
250
TABLE2.
(4
No.
of It>
events per month
Blood messwe
of obseruation
status
N
Under control Out of control
W
Ltfi
event
weight
194 41
Under control Out of control required
Blood pressure
Degree
of control
Blood pressure
over
events
0.72
N
Mean Adj.
P
N
as a change for
-.-.
N 152 37
of events
Under control Out of control
P
355.5 351 .o
152 31
Under control Out of control
Blood pressure
Mean wt
status
described
1.62 1.41
0.36
@er patient)
status
(E) Proportion of events described Blood pressure status .~_
Proportion
N 152 31
152 37
Under control Out of control
(F)
P’
0.37
@t-r patient)
status
Under control Out of control
(W
0.25 0.26
@er patient)
Blood pressure status
F-3 Adjustment
Mean No
Mean control 2.33 1.98
P
0.17
the w’orse
Mean proportion
~_.
0.22 0.34
P
0.04
as unexpected**
N” 149 36
*p-value based upon Wilcoxon Rank Sum test. l*4 patients with events did not supply information
Mean proportion 0.28 0.45
P
0.02
on this point.
The computations in the first section of Table 2 are based upon the average number of events per month in order to allow for the variable recall period. The computations in the succeeding sections are based on values averaged over the events reported. Thus the sample size in the first section is greater than in succeeding sections, because 46 patients reported no events. Table 2 shows that only two kinds of life events were significantly related to loss of blood pressure control--events that were perceived as a change for the worse and events that were unexpected.
3.3 Multivariate analysis of life events altowing for confounding variables Critics of life events research have emphasized that variables related both to life events and illness must be taken into account before concluding that life events have an independent role [l 11. Therefore we examined the following variables with respect to their relationship with loss of blood pressure control: age, sex, marital status, social class (Blishen classification of Canadian occupations) [ 121, education, coronary prone behaviour, smoking and social support. A variable was considered to be a potential confounder if it had some relationship with loss of blood pressure control, whether or not the association was statistically significant. The following variables emerged as potential confounders; age, sex, marital status, education, smoking and social support. A multiple logistic regression was performed for each life event variable in relation to blood pressure status. The results are shown in Table 3. After allowing for the potentially confounding variables, the proportion of life events described as unexpected had a highly significant relationship with loss of blood pressure control, and the proportion described as a change for the worse fell just short of significance at the 5% level (p = 0.052). Among the potential confounders, only marital status had a consistently significant relationship with loss of blood pressure control. The coding of marital status is such that a positive regression coefficient indicates a greater likelihood of loss of blood pressure control among never married patients.
Blood Pressure
Control
TABLE 3. REXJLTS OF I-HE MULTIPLE LOGLSTK
251
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REGREWON
ANALYSIS OF BLOOD
PRESSURE
CONTROL
Diastolic blood Dependent
variable:
Pressure
(>90mmHg=
control
I, <90mmHg=O)
Independent Variables:
Xl
X2 Xl X4 X5 X6 X7 X8 X9
X,0 Xl, X,2
X,
X? X, X4 X5
X6 X7
X8 X9 X,0 XL\
Sex (male = 1, female = 0) Age (20-44 = I, 45-65 = 0) Never married (yes = I, no = 0) Highest education level (more than high Ever smoked (yes = 1, no = 0) Social support (average score) Number of events/month Average adjustment required Average control experienced Proportion of events a change for worse Proportion of events unexpected Average event weight
2.08’ 0.18 2.94’* 0.33 0.46 - I .09 -0.52 (n = 229)’
1.64 0.06 2.86** -0.10 0.95 -0.59 - 1.06 (n = 184)
school = I. lesser education
SlImlilary Regression coefficient/standard I .79 I .94 1.91 -0.21 - 0.27 -0.14 3.05” 3.25” 2.84’* 0.06 0.30 -0.07 0.25 0.38 0.57 0.20 - 0.05 -0.23
-1.13 (n = 184)
1.94 (n = 184)
2.61** (n = 180)
X12
= 0)
erro? 1.78 -0.09 2X8** -0.01 0.84 -0.41
-0.21 (n = 184)
“A positive sign implies a positive relationship with loss of control. bBecause of missing values on some of the independent variables, the sample sizes for these analyses slightly less than for the analyses reported in Table 2. ‘p CO.05. **p
PRESSURE CONTROL
AND
SELF-REPORTED
Under control Mean no. days disability in previous 2 weeks Patient’s health compared with others of same age Better Same Worse Mean score on eight symotoms
HEALTH
are
STATUS
Out of control ~~~5 ~ ~~~
P ,o.so_._~
I .09 (I = 0.08)
“. 10
0, ‘0
30.4 50.8 18.7
24.4 53.6 22.2
1.81
I .78
> 0.50 (x2 = 0.66)
>0.50 (I =O.lOl
3.4 Is loss of blood pressure control asymptomatic?
In the introduction we referred to the importance of assuming that loss of blood pressure control does not produce symptoms which could make the patient more prone to life events. A recent report by Van Reed et al. offers evidence of a weak curvilinear relationship between diastolic pressure and symptoms [13]. Their subjects were scored according to the reported presence of 39 symptoms. The lowest average symptom score was obtained from subjects with diastolic pressures between 75 and 94. Those with pressures below or above this range had slightly higher scores. Symptoms of dizziness, chest pain and sleeplessness each showed this pattern. At the home visit, our patients were asked general questions about their health and about 8 specific symptoms (dizziness, blurred vision, headache, limb weakness, cold hands, nosebleed, constipation and dry mouth). Table 4 compares the responses of the hypertensives under control and out of control. There is no evidence that loss of blood pressure control was associated with an increase in disability, a perception of generally poorer health, or with the presence of eight specific symptoms.
252
CAROL W. BUCK and ALLAN P. DONNER
It must be recognized, however, that the information on health status was obtained crosssectionally. Therefore we cannot eliminate the possibility that symptoms associated with loss of blood pressure control occurred earlier in the recall period and precipitated life events. But if this had happened, it would be most unlikely that the symptoms would have disappeared, since the “proneness hypothesis” states that the life events exacerbate the early symptoms and thereby lead to manifest illness. 3.5 Was loss of blood pressure control a consequence of non-compliance with treatment? Although our investigation was restricted to patients who reported themselves as compliant it is likely that only 50-607; were truly so [14]. Therefore it is possible that life events reduced blood pressure control by diminishing compliance with treatment rather than by a direct influence upon the physiological determinants of blood pressure. We explored the role of compliance by examining blood pressure control among hypertensives under control at the last office visit who reported themselves as noncompliant at the home visit. A patient who reports non-compliance is almost always telling the truth [ 141.Among these patients 85% were still under control at the home visit, a proportion almost identical to the 83% under control among the compliant group. Thus it appears that compliance had little influence upon blood pressure control among patients who were already controlled 8 months (on average) previously. By contrast, among patients not under control at the last office visit, 66% of the compliant and only 54”/0of the non-compliant were under control at the home visit. This is evidence of a carry-over phenomenon which has been reported in the literature, indicating that controlled hypertensives can remain normotensive, sometimes for an extended period, after stopping drug treatment [IS, 161. Another approach to the issue of noncompliance is to restrict the comparison of life events to patients who were not under drug treatment during the period of observation. Unfortunately only a small number of patients fell into this category. Nevertheless, the differences in the proportion of unfavourable and unexpected events between those under and out of control in this subgroup were of the same magnitude and direction as in the total group of patients. 3.6 Potential bias from pooling patients from experimental and control practices It is conceivable that the counselling used to enhance compliance in the Experimental practices had a “soothing” effect on patients, making them less vulnerable both to life events and loss of blood pressure control. This was examined by introducing Practice Type into the logistic regression analyses for unfavourable and unexpected life events. Adding this variable had a negligible effect on the t and p values. 4.
DISCUSSION
The purpose of this research was to study the effect of life events upon the regulation of blood pressure in the hope of avoiding some of the methodological problems that make it so difficult to interpret observed associations between life events and illness, We have found that life events of an unfavourable or unexpected nature are associated with loss of blood pressure control in previously controlled hypertensives. These observations are in accord with the results of many other studies of life events and illness. We did not find a statistically significant association with events of an uncontrollable nature, although a weak relationship in the expected direction was observed. To what extent have we been successful in eliminating the methodological biases that we sought to avoid by choosing the blood pressure model? Recall bias and differential reporting of illness have certainly been eliminated. Given the absence of an association between self-reported health status and loss of blood pressure control, it is unlikely that the association with life events represents the reverse causal mechanism whereby illness leads to events. The possibility that life events acted upon compliance with antihypertensive therapy rather than upon the physiological mechanism of blood pressure control must be considered, since we did not use a fully accurate measure of compliance.
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We have evidence, however, that among the patients under study, compliance was of less importance than is generally the case. Thus, it seems reasonable to conclude that these results add considerable weight to the belief that life events are capable of evoking an adverse physiological reaction. In addition to the general conclusion, the results have applicability to the clinical management of hypertension. The physician would be well advised to make more frequent checks of blood pressure in a patient who is experiencing stressful life events. Acknoi~ledgements-This research was supported by Grant DM 330(b) from the Ontario Ministry of Health. We are grateful to the London Hypertension Study for allowing us to share their data, to Jane Mayberry for devising the format of the life events interview and to Peggy Baker and Nedra Salmon for assistance in the analysis of data.
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