Insomnia and Depression Prior to Myocardial Infarction

8/18/2019 Insomnia and Depression Prior to Myocardial Infarction

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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

Psychosomatic Medicine 52:603-609 (1990)

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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-

Psychosomatic Medicine 52:603-609 (1990)

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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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Insomnia and Depression Prior to Myocardial Infarction

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