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Insomnia and Depression Prior to Myocardial Infarction
ROBERT
M.
CARNEY, PHD, KENNETH
E.
FREEDLAND,
PHD, AND
ALLAN
S.
JAFFE,
MD
Insomnia is common among patients who subsequently experience an acute myocardial
infarction (MI), and is a major symptom of psychiatric depression. The purpose of this study
was
to
determine what proportion
of
patients reporting insomnia prior
to
MI have depression.
Of 70 patients with a recent MI, 27 (39 ) reported having had insomnia for two weeks or
longer prior
to
their
MI, 13 of
whom
(48 ) met
diagnostic criteria
for a
major depressive
episode (MDE). MDE accounted for a significant proportion of the patients reporting insomnia
prior to MI (p
<
0.0001). Furthermore, those patients with insomnia who did not meet diagnostic
criteria for MDE nevertheless had three times as many depressive symptoms, excluding sleep
disturbance,
as did
those patients
who did not
experience insomnia prior
to
their
MI (p <
0.0009). The implications of this finding are discussed, as well as possible explanations for the
relationship between insomnia, depression,
and
subsequent
MI.
INTRODUCTION
Many patients who have suffered acute
myocardial infarction (MIj report insom-
nia
in the
weeks
or
months prior
to the
event (1-3). Nearly half
of
such patients
reported frequent nocturnal awakenings
during the six months prior to the event
in a recent study. This incidence is greater
than the 33 incidence reported for a
group of hospitalized patients with non-
cardiac medical illnesses or 26 for a
sample of medically healthy controls (1).
The increased frequency of insomnia was
present even after controlling
for the use
of stimulants such
as
coffee and cigarettes.
The etiology
of
this insomnia
is
unclear.
From
the
Departments
of
Psychiatry
and
Medi-
cine, Divisions of Behavioral Medicine and Cardiol-
ogy, Washington University School of Medicine, St.
Louis, Missouri.
Address reprint requests
to:
Robert
M.
Carney,
Ph.D., Jewish Hospital of St. Louis, Department of
Psychiatry, 216 S. Kingshighway Boulevard, St.
Louis, MO 63110.
Received
for
publication March
6,
1990; revision
received July 17,
1990.
It could result from episodes of nocturnal
myocardial ischemia which are known to
occur in some persons with coronary ar-
tery disease [CAD] (4). Another possibil-
ity, however, is that insomnia prior to MI
may
be a
symptom
of
clinical depression
that
we and
others have documented
to
be common
in
patients with coronary
ar-
tery disease.
A variety
of
psychological complaints,
including anxiety, dysphoric mood, vital
exhaustion, fatigue, and general malaise,
have been commonly reported prior to
acute MI (1, 2). Insomnia, fatigue, and
general malaise are classic symptoms of
psychiatric depression. Thus, it is possible
that depression could account for the high
prevalence of insomnia, vital exhaus-
tion,
and
general psychological distress
observed
in
patients prior
to
acute
myo-
cardial infarction.
The
purpose
of
this
study was to determine whether the pres-
ence of major depressive disorder ac-
counts for a significant proportion of pa-
tients reporting insomnia for two weeks
or more prior to their myocardial infarc-
tion.
Psychosomatic Medicine 52:603-609 1990)
6
0033-3174/9O/5206-O6O3 O2 00/0
Copyright © 1990 by the American Psycho
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R. M. CARNEY et al.
METHODS
Subjects
Subjects were recruited for this study from a
sequential series of patients with documented acute
myocardial infarction who were admitted to the
Barnes Hospital Coronary Care Unit. Infarction was
documented in all patients by the presence of chest
pain compatible with ischemia, electrocardiographic
changes, and a rising and falling pattern of MB-
creatine kinase (MB-CK) characteristic of acute in-
farction with at least one level above the upper
bound of the reference range (5). Patients admitted
to the study had to be: (1) under 70 years of age; (2)
without history or evidence of a previous MI; (3)
without history of angioplasty or coronary artery
bypass surgery; (4) without severe diabetes or other
chronic medical illnesses; (5) without present diag-
nosis of congestive heart failure, valvular heart dis-
ease (except mitral valve prolapse), or severe mental
impairment; (6) able to complete the psychiatric
diagnostic interview and psychological testing; (7)
permitted by the patient's cardiologist to p articipate
in the study.
The first 70 patients who met these criteria and
who agreed to participate were enrolled during the
five to seven days immediately following the acute
myocardial infarction.
Procedure
A modified version of the affective disorders sec-
tion of the Diagnostic Interview Schedule (DIS) (6)
was used to assess the presence of symptoms of
depression and determ ine the presence and d uration
of sleep complaints. The DIS is a structured inter-
view developed by the National Institutes of Mental
Health for epidemiologic studies of psychiatric dis-
order. It has been shown in previous studies to be
both reliable and valid (7-9). Modifications of the
DIS included the addition of questions to determine
the onset and duration of each symptom and ques-
tions regarding the specific type of insomnia (sleep
onset, interval, or terminal) experienced by the pa-
tient. Following the DIS, patients were asked ques-
tions regarding the presence and time of onset of
symptoms of medical and cardiovascular illnesses,
including angina. Patients were interviewed after
agreeing to be enrolled in the study. The interview
was administered by two lay interviewers with ex-
tensive training and experience in administering the
DIS. Two senior clinicians independently reviewed
the interview results for each subject and rendered
diagnoses according to DSM-II1-R criteria (10). One
hundred percent agreement was achieved between
the two clinicians. The presence of a depressive
disorder at the time of myocardial infarction was
determined from the patients' retrospective report
of the duration of the relevant symptoms that they
had experienced prior to their myocardial infarction.
All medical and demographic information was ob-
tained from the patients' medical charts.
RESULTS
Twenty-seven (39%) of the 70 patients
enrolled in the study reported insomnia
for at least two weeks prior to acute in-
farction. Sixteen (23%) of the 70 patients
met DSM-III-R criteria for a major depres-
sive episode (MDE) during the same
period. None of the patients met the di-
agnostic criteria for any of the other affec-
tive disorders described in the DSM-III-R
nosology.
Thirteen of the 16 patients with MDE
(81%) reported insomnia of at least two
weeks' duration. Seven (54%) of these pa-
tients complained of early morning awak-
ening with an inability to return to sleep
(terminal insomnia), and frequent awak-
enings during the night (interval insom-
nia),
while six (46%) complained of these
problems as well as a difficulty in falling
asleep (sleep-onset insomnia). None of the
MDE patients reported hypersomnia.
Of the 54 patients who did not meet
diagnostic criteria for MDE, 14 (26%) com-
plained of insomnia. Nine (64%) of these
patients reported interval and terminal
insomnia; four (29%) terminal, interval,
and sleep-onset; and one (7%) sleep-onset
insomnia alone. Three of the patients
without MDE complained of hypersom-
6 0 4 Psychosomatic Medicine 52:603-609 (1990)
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INSO MN IA DEPRESSION AN D MYO CAR DIAL INFARC TION
nia. All three of these patients were being
treated for coronary artery disease prior
to their myocardial infarction and were
taking beta-blockers and other medica-
tions during the period of hypersomnia.
Two of the patients were also taking anx-
iolytics during this time.
Forty-eight percent of all patients re-
porting insomnia met DSM-III-R criteria
for major depression. The difference in
the proportions of patients w ith insomnia
between the depressed and nondepressed
groups was statistically significant (x
2
=
14.65,
df= 1,
p < 0.0001). Additional anal-
yses were planned in order to identify
other potential causes of insomnia. Unfor-
tunately, we were unable to obtain relia-
ble information regarding caffeine con-
sumption in the weeks preceding myocar-
dial infarction. We were able to compare
the proportions of patients who were pre-
scribed medications or who had known
medical illnesses sometimes associated
with insomnia. Because there were only
three patients who complained of hyper-
somnia, we were unable to include them
as a separate group in these analyses.
However, since adding them to the non-
insomnia group could obscure important
differences, they were dropped from the
remaining analyses. The results of these
analyses, as well as comparisons of addi-
tional demographic and medical infor-
mation, are presented in Table 1. Demo-
graphic and medical characteristics of pa-
tients without MDE (with and without
insomnia) and for patients with MDE
were generally comparable, except for a
higher proportion of females in the MDE
group.
Unlike some other psychiatric diagnos-
tic systems (e.g., the Research Diagnostic
Criteria) (11), DSM-III-R does not include
a diagnosis of minor depression, except
for dysthymia. The criteria for dysthymia
require the presence of depressed mood
and two or more additional depressive
symptoms for at least six months. Al-
though none of the patients without MDE
met DSM-III-R criteria for dysthymia,
many reported depressive symptoms that
had been present for several weeks prior
to their myocardial infarction. The mean
number of depressive symptoms exclud-
ing sleep disturbance present for two
weeks or longer for patients without MDE
who reported insomnia was 3.36, while
those patients without insomnia reported
a mean of 0.85 depressive symptoms dur-
ing the same period (t = 3.54, df = 48, p <
0.0009). Thus, although only 48% of the
patients with insomnia met diagnostic cri-
teria for MDE, the remaining patients re-
porting insomnia had significantly more
depressive symptoms than did those w ith-
out insomnia. Furthermore, 25% of the
patients without MDE but with insomnia
reported having received psychiatric
treatment at some time in the past. In
contrast, none of the patients without in-
somnia reported ever receiving psychiat-
ric treatment (x
2
= 8.02, d/ = 1, p < 0.004).
DISCUSSION
Nearly half of the patients who com-
plained of insomnia for two weeks or
longer prior to their acute myocardial in-
farction met criteria for a major depres-
sive episode. Twenty-three percent of the
total sample of patients met the DSM-III-
R criteria for a major depressive episode.
This rate is close to the 18% prevalence
estimate of major depressive disorder re-
portedly recently by Schleifer et al. (12)
using the Research Diagnostic Criteria
(11), and to the 18% which we reported
for CAD patients without myocardial in-
farction. Patients with insomnia who did
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R M CARNEY et al
TABLE 1. Means (Standard Deviations) and Frequencies of Selected Medical and Demographic
Variables for MDE Patients and Non-MDE Patients with and with out Insomnia
Variables
Mean age
Mean number o f alcoholic
drinks weekly
Mean number
of
cigarettes
daily (current smokers)
Current smokers
Sex (% females)
History of angina
History o f hypertension
History o f diabetes
Chronic lung disease
Receiving beta-blockers
Receiving sleep medications
Receiving psychiatric medica-
tions
MDE
N 16
53.4 (8.2)
2.9 (9)
28.8(16.2)
56
50
38
38
25
6
25
6
6
Non-MDE
Insomnia
N = 14
54.7(7.9)
3.8 (5)
30.0(11.0)
43
2 1
23
58
14
0
19
3
0
Non-MDE
w/o
Insomnia
N = 37
52.1 (10.6)
4 .1 (5)'
2 7 . 8 ( 1 5 . 6 )
46
14
2 1
40
14
0
29
7
3
F =
=
=
X
2
=
x
2
=
x
2
=
x
2
=
x
2
=
0.71
1.16
0.96
=
0.7
= 8.2
= 4.5
=
1.3
= 0.5
FETt
X
2
=
FET
FET
=
0.6
P
NS*
NS
NS
NS
0.02
NS
NS
NS
NS
NS
NS
NS
* NS, not s ignificant.
t FET, Fisher's exact test.
not meet full criteria for major depression
nevertheless reported more than three
times
as
many symptoms
of
depression
than did patients with normal sleep pat-
terns.
They also were significantly more
likely
to
have received psychiatric treat-
ment in the past. Thus, many of the pa-
tients with insomnia who
did not
have
major depression may have experienced
a minor or subclinical depression that
included sleep disturbance.
Consistent with previous studies
of
MDE in patients with coronary artery dis-
ease (13), the re was a higher proportion of
women
in the
MDE group.
In
fact,
one
half of the total sample of women met
criteria
for a
major depressive episode.
Among patients without MDE, there was
no difference in the proportion of women
between those with or without insomnia.
No differences were found
in
the pres-
ence of anginal symptoms between those
with
or
without MDE,
or
between those
with
or
without insomnia. Patients with
insomnia were neither more
nor
less
likely than the other patients to be taking
medications that affect sleep. They were
also no different from other patients with
respect
to age or any
medical variable
studied. Thus, their insomnia cannot eas-
ily be explained by the presence of other
chronic m edical illnesses or m edications.
Unfortunately, we were not able to obtain
reliable estimates of caffeine intake in the
weeks preceeding the myocardial infarc-
tion. Thus, greater caffeine consumption
in the weeks prior to the acute infarction
cannot
be
excluded
as a
possible expla-
nation for insomnia in at least some of the
patients. None
of
the patients who com-
plained of insomnia had been previously
diagnosed
as
having sleep apnea. How-
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INSO MN IA DEPRESSION AN D MYO CAR DIAL INFARC TION
ever, we were unable to rule out the pos-
sibility that some patients had this disor-
der.
The use of a retrospective self-report
interview to assess the presence of depres-
sion and insomnia is a limitation of this
study. Because of the difficulty in accu-
rately predicting myocardial infarction,
even among high risk patients with
known coronary disease, it is difficult to
study this question prospectively. For this
reason, it is also difficult to use m ore
reliable means, such as sleep EEG, of doc-
umenting sleep disturbance. The DIS has
been carefully validated and has been
used in medical as well as psychiatric
populations to assess depressive symp-
toms.
Nevertheless, patients with recent
myocardial infarction may not accurately
recall symptoms that occurred just prior
to their infarction. Our data must there-
fore be interpreted with caution.
A recent study of insomnia in the gen-
eral population reported by Ford and Ka-
merow (14) showed a strong relationship
not only between insomnia and depres-
sion, but also between insomnia and anx-
iety disorders. The interview employed in
this study focused primarily on affective
disorders, so it was not possible to deter-
mine whether other psychiatric disorders
were also associated with some of the
cases of insomnia.
Ford and Kamerow (14) also found that
the risk of developing major depression
within one year after the first interview
was over 20 times greater for patients w ho
continued reporting insomnia, suggesting
that sleep disturbance in m any cases may
be an early symptom of depression, or
may reflect an underlying process of af-
fective disturbance. Unfortunately, we
did not obtain a follow-up interview of
subjects in this study and thus have no
information concerning how many of
these patients subsequently developed a
major depression. Clearly, future studies
of insomnia prior to an infarction should
evaluate pa tients for other psychiatric dis-
orders, and include a follow-up assess-
ment of psychiatric status.
Although depression may account for
many cases of insomnia in persons who
subsequently experience a myocardial in-
farction, and depression and insomnia are
highly prevalent in these patients, the na-
ture of the relationship betw een insomnia
and depression and subsequent myocar-
dial infarction remains unclear. If insom-
nia and depression play an etiologic role
in MI, it is still unclear whether depres-
sion is the crucial factor, or if sleep dis-
turbance, secondary to or independent of
depression, is of primary importance .
Depression is associated with an in-
creased risk of myocardial infarction and
other cardiac events (15, 16). Psychiatric
patients with depression have higher
rates of myocardial infarction than do pa-
tients with other psychiatric disorders
(17),
and nearly two times the expected
mortality due to cardiovascular disease
(18).
We have speculated previously that
increased sympathetic tone associated
with depression may be responsible for
this relationship by placing additional
stress on the cardiovascular system (15),
or by accelerating the progression of ath-
erosclerosis (19). It is possible, however,
that sleep disturbance associated with
depression is of primary importance .
Medically well persons with major
depression tend to begin rapid eye move-
ment (REM) sleep earlier than do nonde-
pressed persons (20-22), and they have a
greater REM density during each sleep
cycle (23). Many studies tha t have inves-
tigated the relationship between stages of
sleep and the incidence of nocturnal myo-
cardial ischemia have reported an in-
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R. M. CARNEY et al.
creased frequency of anginal episodes
during REM sleep, at least in a subset of
patients (24, 25). Although the mecha-
nisms underlying the relationship be-
tween stages of sleep and nocturnal is-
chemic episodes are not well understood
(26),
it is possible that patients with
depression are at greater risk for noctur-
nal ischemia as a result of some alteration
of REM sleep.
On the other hand, simply being awake
at night, particularly if associated with
getting out of bed, can produce silent is-
chemic episodes in patients with CAD (4).
An increased rate of ischemic episodes
could place the patient with sleep disturb-
ance at greater risk for myocardial infarc-
tion or sudden cardiac death. Thus,
depression may be significant in the etiol-
ogy of myocardial infarction only because
it is often associated with insomnia.
The possibility that ischemic episodes
may in fact be the cause of sleep disturb-
ance must also be considered, although
only a small number of patients reported
having episodes of anginal pain at any
time before their infarction. Perhaps si-
lent ischemic episodes lead to sleepless-
ness, although the study by Barry et al.
(4) suggests that being awake, and espe-
cially getting out of bed, more often pre-
cedes the ischemic event. We further can-
not definitively exclude the possibility
that some instances of insomnia could
have been related to manifestations of
congestive heart failure such as orthopnea
and paroxysmal dyspnea, but a clear his-
tory describing these symptoms was not
elicited by the clinicians caring for the
patients studied. Clearly, more research
needs to be done to explore these various
possibilities.
In summary, a major depressive episode
was diagnosed in nearly half of the pa-
tients who reported insomnia for at least
two weeks prior to an acute myocardial
infarction. The remaining cases of insom-
nia were associated with more than three
times as many symptoms of depression
than were reported by those patients
without pre-MI insomnia. The signifi-
cance of the relationship between insom-
nia and depression and subsequent acute
myocardial infarction remains unclear.
Nevertheless, the diagnosis and treatment
of major depression in patients at risk for
myocardial infarction may be especially
important. Not only can treating depres-
sion be expected to improve the quality
of life for these individuals, but it may
reduce their incidence of acute myocar-
dial infarction.
The authors wish to
acknowledge the
contributions
to this study of
aren Clark,
Adriaantje
teVeJde, Laurie Smith,
Judith
SkaJa, and Peggy Boyd.
Supported in part by
the Heart
Lung
and BJood Institute, United States Public
Health Service Grant No. 1 ROl HL42427-
01
and the National Research Demonstra-
tion Center Grant, SCOR in Ischemic Heart
Disease Grant
No.
HL1764 6 National In-
stitutes of Health Bethesda Maryland.
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