Insomnia and Depression Prior to Myocardial Infarction

ROBERT M. CARNEY, PHD, KENNETH E. FREEDLAND, P H D , 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 insomnia 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 noncardiac 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 Medicine, Divisions of Behavioral Medicine and Cardiology, 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.

Psychosomatic Medicine 52:603-609 (1990)

0033-3174/9O/5206-O6O3$O2 00/0
Copyright 1990 by the American Psycho

It could result from episodes of nocturnal

myocardial ischemia which are known to
occur in some persons with coronary artery disease [CAD] (4). Another possibility, 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 artery 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 exhaustion," and general psychological distress
observed in patients prior to acute myocardial infarction. The purpose of this
study was to determine whether the presence of major depressive disorder accounts for a significant proportion of patients reporting insomnia for two weeks
or more prior to their myocardial infarction.
603

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 MBcreatine kinase (MB-CK) characteristic of acute infarction 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 diagnosis of congestive heart failure, valvular heart disease (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 participate
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 section of the Diagnostic Interview Schedule (DIS) (6)
was used to assess the presence of symptoms of
depression and determine the presence and duration
of sleep complaints. The DIS is a structured interview developed by the National Institutes of Mental
Health for epidemiologic studies of psychiatric disorder. 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 questions regarding the specific type of insomnia (sleep
onset, interval, or terminal) experienced by the patient. Following the DIS, patients were asked questions 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

604

was administered by two lay interviewers with extensive 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 obtained 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 infarction. Sixteen (23%) of the 70 patients
met DSM-III-R criteria for a major depressive episode (MDE) during the same
period. None of the patients met the diagnostic criteria for any of the other affective 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 patients complained of early morning awakening with an inability to return to sleep
(terminal insomnia), and frequent awakenings during the night (interval insomnia), 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%) complained 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 hypersomPsychosomatic Medicine 52:603-609 (1990)

INSOMNIA, DEPRESSION AND MYOCARDIAL INFARCTION

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 medications during the period of hypersomnia.
Two of the patients were also taking anxiolytics during this time.
Forty-eight percent of all patients reporting insomnia met DSM-III-R criteria
for major depression. The difference in
the proportions of patients with insomnia
between the depressed and nondepressed
groups was statistically significant (x2 =
14.65, df= 1, p < 0.0001). Additional analyses were planned in order to identify
other potential causes of insomnia. Unfortunately, we were unable to obtain reliable information regarding caffeine consumption in the weeks preceding myocardial infarction. We were able to compare
the proportions of patients who were prescribed medications or who had known
medical illnesses sometimes associated
with insomnia. Because there were only
three patients who complained of hypersomnia, we were unable to include them
as a separate group in these analyses.
However, since adding them to the "noninsomnia" group could obscure important
differences, they were dropped from the
remaining analyses. The results of these
analyses, as well as comparisons of additional demographic and medical information, are presented in Table 1. Demographic and medical characteristics of patients 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 diagnostic 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
Psychosomatic Medicine 52:603-609 (1990)

require the presence of depressed mood

and two or more additional depressive
symptoms for at least six months. Although 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 excluding 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 during the same period (t = 3.54, df = 48, p <
0.0009). Thus, although only 48% of the
patients with insomnia met diagnostic criteria for MDE, the remaining patients reporting insomnia had significantly more
depressive symptoms than did those without 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 insomnia reported ever receiving psychiatric treatment (x2 = 8.02, d/= 1, p < 0.004).
DISCUSSION

Nearly half of the patients who complained of insomnia for two weeks or
longer prior to their acute myocardial infarction met criteria for a major depressive episode. Twenty-three percent of the
total sample of patients met the DSM-IIIR criteria for a major depressive episode.
This rate is close to the 18% prevalence
estimate of major depressive disorder reportedly recently by Schleifer et al. (12)
using the Research Diagnostic Criteria
(11), and to the 18% which we reported
for CAD patients without myocardial infarction. Patients with insomnia who did
605

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 without Insomnia

Variables

Mean age
Mean number of alcoholic
drinks weekly
Mean number of cigarettes
daily (current smokers)
Current smokers
Sex (% females)
History of angina
History of hypertension
History of diabetes
Chronic lung disease
Receiving beta-blockers
Receiving sleep medications
Receiving psychiatric medications

MDE
N= 16

Non-MDE
Insomnia
N = 14

Non-MDE
w/o
Insomnia
N = 37

53.4 (8.2)
2.9 (9)

54.7(7.9)
3.8 (5)

52.1 (10.6)
4.1 (5)'

F =

1.16

NS*
NS

28.8(16.2)

30.0(11.0)

27.8(15.6)

F =

0.96

NS

46%
14%
21%
40%
14%
0%
29%
7%
3%

X ==
x 2 ==
x 2 ==
x 2 ==
x 2 ==
FETt
X 2 ==
FET
FET

56%
50%
38%
38%
25%
6%
25%
6%
6%

43%
21%
23%
58%
14%
0%
19%
3%
0%

F = 0.71

0.7
8.2
4.5
1.3
0.5
0.6

NS
0.02
NS
NS
NS
NS
NS
NS
NS

* NS, not significant.

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 patterns. They also were significantly more
likely to have received psychiatric treatment in the past. Thus, many of the patients 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 disease (13), there 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 pres606

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 easily be explained by the presence of other
chronic medical illnesses or medications.
Unfortunately, we were not able to obtain
reliable estimates of caffeine intake in the
weeks preceeding the myocardial infarction. Thus, greater caffeine consumption
in the weeks prior to the acute infarction
cannot be excluded as a possible explanation for insomnia in at least some of the
patients. None of the patients who complained of insomnia had been previously
diagnosed as having sleep apnea. HowPsychosomatic Medicine 52:603-609 (1990)

INSOMNIA, DEPRESSION AND MYOCARDIAL INFARCTION

ever, we were unable to rule out the possibility that some patients had this disorder.
The use of a retrospective self-report
interview to assess the presence of depression and insomnia is a limitation of this
study. Because of the difficulty in accurately 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 more
reliable means, such as sleep EEG, of documenting sleep disturbance. The DIS has
been carefully validated and has been
used in medical as well as psychiatric
populations to assess depressive symptoms. Nevertheless, patients with recent
myocardial infarction may not accurately
recall symptoms that occurred just prior
to their infarction. Our data must therefore be interpreted with caution.
A recent study of insomnia in the general population reported by Ford and Kamerow (14) showed a strong relationship
not only between insomnia and depression, but also between insomnia and anxiety disorders. The interview employed in
this study focused primarily on affective
disorders, so it was not possible to determine 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 who
continued reporting insomnia, suggesting
that sleep disturbance in many cases may
be an early symptom of depression, or
may reflect an underlying process of affective disturbance. Unfortunately, we
did not obtain a follow-up interview of
subjects in this study and thus have no
information concerning how many of
Psychosomatic Medicine 52:603-609 (1990)

these patients subsequently developed a

major depression. Clearly, future studies
of insomnia prior to an infarction should
evaluate patients for other psychiatric disorders, and include a follow-up assessment of psychiatric status.
Although depression may account for
many cases of insomnia in persons who
subsequently experience a myocardial infarction, and depression and insomnia are
highly prevalent in these patients, the nature of the relationship between insomnia
and depression and subsequent myocardial infarction remains unclear. If insomnia and depression play an etiologic role
in MI, it is still unclear whether depression is the crucial factor, or if sleep disturbance, secondary to or independent of
depression, is of primary importance.
Depression is associated with an increased risk of myocardial infarction and
other cardiac events (15, 16). Psychiatric
patients with depression have higher
rates of myocardial infarction than do patients 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 atherosclerosis (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 movement (REM) sleep earlier than do nondepressed persons (20-22), and they have a
greater REM density during each sleep
cycle (23). Many studies that have investigated the relationship between stages of
sleep and the incidence of nocturnal myocardial ischemia have reported an in607

R. M. CARNEY et al.

creased frequency of anginal episodes

during REM sleep, at least in a subset of
patients (24, 25). Although the mechanisms underlying the relationship between stages of sleep and nocturnal ischemic episodes are not well understood
(26), it is possible that patients with
depression are at greater risk for nocturnal 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 ischemic episodes in patients with CAD (4).
An increased rate of ischemic episodes
could place the patient with sleep disturbance at greater risk for myocardial infarction or sudden cardiac death. Thus,
depression may be significant in the etiology of myocardial infarction only because
it is often associated with insomnia.
The possibility that ischemic episodes
may in fact be the cause of sleep disturbance must also be considered, although
only a small number of patients reported
having episodes of anginal pain at any
time before their infarction. Perhaps silent ischemic episodes lead to sleeplessness, although the study by Barry et al.
(4) suggests that being awake, and especially getting out of bed, more often precedes the ischemic event. We further cannot 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 patients who reported insomnia for at least
two weeks prior to an acute myocardial
infarction. The remaining cases of insomnia were associated with more than three
times as many symptoms of depression
than were reported by those patients
without pre-MI insomnia. The significance of the relationship between insomnia 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 depression be expected to improve the quality
of life for these individuals, but it may
reduce their incidence of acute myocardial infarction.
The authors wish to acknowledge the
contributions to this study of Karen 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 HL4242701, and the National Research Demonstration Center Grant, SCOR in Ischemic Heart
Disease, Grant No. HL17646, National Institutes of Health, Bethesda, Maryland.

REFERENCES
1. Falgar P, Schouten E, Appels A: Sleep complaints, vital exhaustion and depression, and myocardial
infarction. Washington DC, Proceedings of the Eighth Annual Scientific Session of The Society of
Behavioral Medicine, March 19-22, 1987, 58-59
2. Kuller L: Prodromata of sudden death and myocardial infarction. Adv Cardiol 2561-72, 1978

608

Psychosomatic Medicine 52:603-609 (1990)

INSOMNIA, DEPRESSION AND MYOCARDIAL INFARCTION

3. Thiel H, Parker D, Bruce T: Stress factors and the risk of myocardial infarction. J Psychosom Res 17:4345, 1973
4. Barry J, Campbell S, Yeung A, Raby K, Selwyn A: Waking, rising, and nocturnal ischemia. New Orleans,
LA, Proceedings of the 62nd Scientific Session of The American Heart Association, November 13-16,
1989, 81
5. Jaffe AS: Biochemical detection of acute myocardial infarction. In Gersh B, Rahimtoola S (eds), Acute
Myocardial Infarction. New York, Elsevier Science Publishing Company, Inc., in press
6. Robins LN, Helzer JE, Croughan J, Williams JBW, Spatzer RL: The NIMH Diagnostic Interview Schedule:
Version III. Public Health Service (HSS), (publication ADM-T-42-3), 1981
7. Robins LN, Helzer JE, Ratcliff KS, Seyfried W: Validity of the diagnostic interview schedule, Version II:
DSM-1II diagnoses. Psychol Med 12:850-870, 1982
8. Anthony JC, Folstein MF, Romanoski AJ: Comparison of the lay diagnostic interview schedule and a
standardized psychiatric diagnosis: experience in eastern Baltimore. Arch Gen Psychiatry 42:667-675,
1985
9. Helzer JE, Spitznagel EL, McEvoy L: The predictive validity of lay Diagnostic Interview Schedule
diagnoses in the general population. Arch Gen Psychiatry 44:1069-1077, 1987
10. American Psychiatric Association: Committee on Nomenclature and Statistics, Third Edition-Revised,
(DSM-III-R). Washington DC, American Psychiatric Association, 1987
11. Spitzer RL, Endicott J, Robins E: Research diagnostic criteria: Rationale and reliability. Arch Gen
Psychiatry 35:773-782, 1978
12. Schleifer SJ, Macari-Hinson MM, Coyle DA, Slater WR, Kahn M, Gorlin R, Zucker HD: The nature and
course of depression following myocardial infarction. Arch Int Med 149:1785-1789, 1989
13. Carney RM, Rich M, TeVelde A, Saini J, Clark K, Jaffe A: Major depressive disorder in coronary artery
disease. Am J Cardiol 60:1273-1275, 1987
14. Ford DE, Kamerow DB: Epidemiologic study of sleep disturbances and psychiatric disorders: An
opportunity for prevention'? JAMA 262:1479-1484, 1989
15. Carney RM, Rich M, teVelde A, Saini J, Clark K, Freedland K: The relationship between heart rate,
heart rate variability and depression in patients with coronary artery disease. J Psychosom Res 32:159164, 1988
16. Booth-Kewley S, Friedman HS: Psychologic predictors of heart disease: A quantitative review. Psychol
Bull 101:343-359, 1987
17. Dreyfuss F, Dasberg H, Assael MI: The relationship of myocardial infarction to depressive illness.
Psychother Psychosom 17:73-81, 1969
18. Rabins PV, Harvis K, Koven S: High fatality rates of late life depression associated with cardiovascular
disease. J Affective Disord 9:165-167,1985
19. Beere PA, Glagou S, Zarins CK: Retarding effect of lowered heart rate on coronary atherosclerosis.
Science 22:180-182, 1984
20. Feinberg M, Gillin JC, Carroll BJ, Greden JF, Zis AP: EEG studies of sleep in the diagnosis of depression.
Biol Psychiatry 17:305-316,1982
21. Kupfer D, Foster FG, Coble P, McPartland RJ, Ulrich RF: The application of EEG sleep for the differential
diagnosis of affective disorders. Am J Psychiatry 135:69-74, 1978
22. Rush AJ, Giles DE, Roffwarg HP, Parker CR: Sleep EEG and dexamethasone suppression test findings in
outpatients with unipolar major depressive disorders. Biol Psychiatry 17:327-341,1982
23. King D, Akiskal HS, Lemmi H, Wilson W, Belluomini J, Yerevanian BI: REM density in the differential
diagnosis of psychiatric from medicalneurologic disorders: a replication. Psychiatry Res 5:267-276,
1981
24. Nowlin J, Troyer W, Collins W, Silverman G, Nichols C, Mclntosh H, Estes E, Bogdonoff M: The
association of nocturnal angina pectoris with dreaming. Ann Intern Med 63:1040, 1965
25. Murao S, Harumi K, Katayama S, Mashima S, Shimomura K, Matsuo H, Yamamoto H, Kato R, Chen C:
All-night polygraphic studies of nocturnal angina pectoris. Jpn Heart J 13:295, 1972
26. Motta J, Guilleminault C: Cardiac dysfunction during sleep. Ann Clin Res 17:190-198, 1985

Psychosomatic Medicine 52:603-609 (1990)

609