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Journal of Psychosomatic ResearchBehavioural Science, 12th Floor Redmond Barry Building, University of

Melbourne, Victoria 3010, Australia. Tel.: +61 3 9568 1090; fax: +61 3Introduction

Coronary artery disease (CAD) is the major cause of

disability in many developed countries and, by 2020,

is forecast to be the major cause of disease burden world-

wide [1]. Depression is disproportionately common in

patients with CAD: 17% to 27% evidence major depres-

sion [211] and 20% to 45% report depressive symptoms

[5,1015]. Patients with comorbid depression and CAD

have a two- to threefold increased risk for future cardiac

events [35,10,12,16,17]. However, despite the availability

of effective therapies for depression, there is little evidence

that these interventions improve cardiac or all-cause mortal-

ity for depressed CAD patients [11,1820]. Regardless of

mortality benefit, the recognition and treatment of depres-

sion in patients with CAD are important. Depression results

in substantial disability for both depressed individuals and

their families [21,22], and the treatment thereof has

significant potential benefits for health-related quality of

life (HRQOL) [23,24].

In this article, we review the results of recent studies of

the impact of depression and its treatment on the HRQOL

of patients with CAD. A brief introduction to the concept of4 Corresponding author. Department of Psychology, School ofKeywords: Coronary artery disease; Depression; Quality of lifeObjective: This article reviews recent studies relating to the

impact of depression and its treatment on the health-related quality

of life (HRQOL) of patients with coronary artery disease (CAD).

Methods: Articles for the primary review were identified via

MEDLINE and PsycINFO (19952006). Results: Evidence

suggests that depression has an aversive impact on the HRQOL

of patients with stable CAD as well as on patients hospitalized for

acute myocardial infarction and coronary artery bypass graft

surgery. Unfortunately, there are few depression treatment studies

in patients with CAD that make use of standardized HRQOL0022-3999/07/$ see front matter D 2007 Elsevier Inc. All rights reserved.

doi:10.1016/j.jpsychores.2006.12.009

9827 9583.

E-mail address: lesley.liebowitz@bigpond.com (L. Stafford).measures, but the limited evidence suggests that successful

treatment has positive implications for HRQOL in these patients.

The mechanisms through which depression impacts on HRQOL

require further study but are likely to be behavioral. Conclusions:

Depressive symptoms significantly undermine HRQOL in patients

with CAD despite successful medical and surgical management.

Although successful treatment of depression has not been shown to

reduce mortality rates in patients with CAD, further study may find

that the HRQOL benefits of such treatment are equally valuable.

D 2007 Elsevier Inc. All rights reserved.AbstractComorbid depression and health

with coronary

Lesley Stafforda,4, Michael Berkb,c,

aDepartment of Psychology, School of Behavioural Sc

University of MelbobBarwon Health and The Geelong Clinic, Univ

cORYGEN Youth Health,dMental Health Research Inst

Receivedrticle

lated quality of life in patients

rtery disease

rasuna Reddya, Henry J. Jacksona,c

Faculty of Medicine, Dentistry and Health Sciences,

Victoria, Australia

of Melbourne, Melbourne, Victoria, Australia

ville, Victoria, Australia

Parkville, Victoria, Australia

arch 2006

62 (2007) 401410the PsycINFO andquality of life is also provided. Artic

review were identified by searchingMEDLINE (19952006) databases using the terms dquality

mobi

al rea

cts of

ife, se

rk

ical fu

ity/fat

tation

itatio

ulate

eep an

creat

nt, so

l beh

for p

ysical

l fun

ptom

sical

uency

se per

ual fu

hold

hosomof life and depression and coronary diseaseT and dhealth

Table 1

Instruments used to measure HRQOL in patients with CAD

Instrument Type Components

Nottingham Health Profile [30] Generic 45 items, two parts: Part 1:

pain, energy, sleep, emotion

social isolation. Part 2: effe

on work, social life, home l

hobbies, holidays, housewo

SF-36 [31] Generic 36 items, eight scales: phys

emotional functioning, vital

social functioning, role limi

emotional problems, role lim

physical problems. Can calc

PCS and MCS scores

Sickness Impact Profile [32] Generic 136 items, 12 categories: sl

work, home management, re

mobility, body care/moveme

alertness behavior, emotiona

Can obtain aggregate scores

psychosocial dimensions

MacNew Heart Disease

HRQOL Instrument [33]

Specific 27 items, three domains: ph

social functioning, emotiona

five items inquire about sym

SAQ [35] Specific 19 items; five domains: phy

angina stability, angina freq

treatment satisfaction, disea

Duke Activity Status Index [36] Specific 12 items: personal care, sex

recreational activities, house

L. Stafford et al. / Journal of Psyc402status and depression and coronary disease.T Referencesections of these articles were also used to identify additional

studies that had not been identified by the database searches.

Definition, measurement, and interpretation of HRQOL

HRQOL has been defined as dthe functional effect of anillness and its consequent therapy upon a patient, as

perceived by the patientT [25]. This subjective focus meansthat HRQOL is concerned with illness experience rather

than the disease itself [26]. Most conceptualizations of

HRQOL are multidimensional and include domains of

physical functioning, social functioning, role functioning,

and mental health and general health perceptions [27].

HRQOL instruments can be generic, allowing for compar-

isons between groups of patients with different conditions

and characteristics, or disease specific, which tend to be

more responsive to changes in HRQOL [28,29]. Examples

of measures of HRQOL in patients with CAD are provided

in Table 1.

Unfortunately, a unified approach to the measurement

and definition of the concept of quality of life is lacking

[37]. These methodological issues are reviewed elsewhere

[27,3840], but it should be noted that the lack of

standardization in the reporting of effects on HRQOL and

the use of diverse HRQOL measures may result in findings

that are difficult to interpret. A large multisite study is

currently underway to develop a core heart disease HRQOLquestionnaire that will allow for meaningful comparisons

Comments

lity,

ctions,

health

x life,

Self-administered, takes 10 min, useful to track

large changes but less sensitive to small changes

and possibly inappropriate for evaluative

studies [28]

nctioning,

igue, pain,

s due to

ns due to

aggregate

Self-administered, takes 510 min,

valid, reliable, some scales possibly

inappropriate for evaluative studies [28],

considered superior generic measure for CAD

patients, widely used

d rest, eating,

ion, ambulation,

cial interaction,

avior, communication.

hysical and

Interviewer- or self-administered,

takes 2030 min, should not be separated into

12 scales, rather obtain a total score or scores

for physical and psychosocial dimensions when

used in evaluative studies

limitations,

ctioning;

s

Self-administered, takes 510 min, valid,

reliable, sensitive to change following various

cardiac interventions [34], considered

superior disease-specific instrument [28]

limitations,

,

ception

Self-administered, psychometrically sound,

useful for clinical trials with patients who have

angina or chest pain/tightness

nction,

tasks

Self-administered, emphasis on

physical capacities

atic Research 62 (2007) 401410between studies [41].

In terms of interpretation, HRQOL measurements are

limited in several ways. HRQOL may change over time,

perhaps being at its best soon after an intervention and

deteriorating in the long term [42]. Alternatively, how

patients evaluate their HRQOL may change over time [39].

Evidence suggests that as an individual comes to terms with

the fact of long-term illness, psychological adaptations

occur, which preserve life satisfaction [43]. Thus, changes in

HRQOL over time need not necessarily derive from actual

changes in health or symptoms.

The impact of depression on the HRQOL of patients

with CAD

In physically healthy individuals, both cross-sectional

[44,45] and longitudinal [46] studies have shown that the

effect of depression on HRQOL is equal to or greater than

that of most common chronic medical conditions. Moreover,

functional limitations due to depression are additive to the

limitations from the medical conditions [45]. These findings

have been confirmed in another large primary care sample

[47] and a community sample [48], and similar effects have

been reported for health care service utilization [49] and

days off from work [50]. Studies of primary care outpatients

have shown that HRQOL status changes in accordance with

changes in depressive symptoms [5153], a phenomenon

described as dsynchrony of changeT [53].

hosomIn patients with CAD, both cross-sectional and prospec-

tive studies have examined the effect of depression on

HRQOL. Few of these studies made use of structured

clinical interviews for diagnosing depression, and most

refer to depressive symptoms as measured by self-report

instruments. An overview of these studies is provided

in Table 2.

Cross-sectional studies of the effect of depression on the

HRQOL of CAD patients

Patients with stable CAD. Ruo et al. [54] compared the

effects of cardiac disease severity and depressive symptoms

on the HRQOL in a cross-sectional study of 1204 patients

with stable CAD. Depressive symptoms were strongly

associated with greater symptom burden, worse HRQOL

on the Seattle Angina Questionnaire (SAQ), greater physical

limitation, and poorer overall health, whereas measures of

cardiac severity (ejection fraction and presence of ischemia)

did not show a significant association.

Patients hospitalized for acute coronary syndrome. Cross-

sectional studies of patients with acute myocardial infarc-

tion (AMI) and unstable angina have yielded similar

results: in a substudy [55] of the Sertraline Antidepressant

Heart Attack Randomized Trial (SADHART) [56], a

randomized controlled trial of sertraline pharmacotherapy

in 369 patients hospitalized with acute coronary syndrome

(ACS) and major depression, multivariate analysis showed

that depression on the Hamilton Depression Scale (HAM-

D) was the strongest predictor of impaired baseline

HRQOL. Disease variables such as ejection fraction and

Killip class had little effect on HRQOL scores. Another

study of 1957 patients hospitalized with ACS found that a

history of depression was a significant predictor of HRQOL

7 months after hospitalization for ACS [57]. Although

active depressive symptoms were not investigated, the

presence of depression at index hospitalization was a

significant predictor of angina burden, physical limitation,

and HRQOL on the SAQ, even after adjusting for a range

of cardiac, demographic, and comorbid disease variables.

Similar findings were reported in a study of the HRQOL of

1660 patients hospitalized with ACS, which was also

assessed 7 months following discharge [58]. Using the

Medical Outcomes Study Short-Form 36 Health Status

Questionnaire (SF-36), this study found that a history of

depression (documented in medical record or self-reported)

was the dominant predictor of 7-month mental health

status, alone accounting for 80% of the explanatory power

of the multivariate risk model. History of depression was

also an independent predictor of physical health status,

together with other comorbid medical conditions. A recent

study of 181 patients with ACS showed that 16 months

after hospitalization, gender and depressive symptoms were

independent predictors of the mental component summary

L. Stafford et al. / Journal of Psyc(MCS) score of the SF-36, and the physical componentsummary (PCS) score of the SF-36 was independently

predicted by gender, baseline PCS, level of education, and

prior cardiovascular events [59].

Prospective studies of the effect of depression on the

HRQOL of patients with CAD

Several prospective studies have also shown that

symptoms of depression and anxiety predict diminished

HRQOL in CAD patients.

Patients with stable CAD. Among patients with stable CAD,

depression and anxiety are significant predictors of a variety

of HRQOL indices. One study of 198 patients who

underwent elective catheterization [60] found that depres-

sion and anxiety independently predicted diminished self-

reported physical function and activity interference at 6- and

12-month follow-up. This effect persisted despite changes in

anxiety and depression that would be expected over the time

period of the study and after adjusting for demographic,

cardiac, and comorbid conditions. In contrast, no significant

correlation between number of coronary arteries stenosed

N70% at catheterization and self-reported physical functionat 12 months was observed. Spertus et al. [61] reported on

the HRQOL of 1282 patients with stable CAD and found a

significant doseresponse relationship between depressive

symptoms and HRQOL, such that the more frequently

participants endorsed the item ddown-hearted and blue,T theworse their outcome on the SAQ. In another prospective

study, a 5-year follow-up of 111 patients with stable CAD

showed that the impact of depression on perceived physical

health (PCS score of the SF-36) was significantly mediated

by physical symptoms of angina and fatigue and was both

mediated and moderated by personality states and traits

(positive affect and novelty seeking) [62]. Positive affect

and novelty seeking had more marked effects on physical

health in the presence of more depression. Thus, a broad

range of psychological and physical factors beyond the

severity of the ischemia itself would need to be considered

in assessing indices of HRQOL.

Patients undergoing coronary artery bypass graft surgery.

Investigations of the impact of depression on HRQOL in

coronary artery bypass graft (CABG) patients have yielded

similar results to studies of other CAD patients. Presurgical

depression has been found to be an independent predictor of

HRQOL indices such as self-reported functional status [63],

symptom burden [64], and return to work [65]. In a study of

89 CABG patients followed up 6 months after surgery, Burg

et al. [66] reported that presurgical depression on the Beck

Depression Inventory (BDI) independently predicted car-

diac hospitalization, continued surgical pain, failure to

return to previous activity levels, and depressed affect.

Similarly, a study of 963 CABG patients assessed at

baseline and, again, at 6 months after surgery found that

atic Research 62 (2007) 401410 403baseline depression scores on the Geriatric Depression Scale

Table 2

Studies of depression and HRQOL in patients with CAD

Authors Design Population n

Depression

measure HRQOL measure Effect of depression on HRQOL

Beck et al. [72] Prospective

(12 months)

AMI 587 BDI SF-36, EuroQoL Depression independently predicted lower MCS, PCS, and

EuroQoL scores at 6 months (b=3.7,1.6, and5.4; 95% CI, 2.9 to 0.4, 5.3 to 2.2, 7.7 to 3.2,respectively) but independently predicted only low MCS at

12 months (b=3, 95% CI, 5 to 2)Burg et al. [66] Prospective

(6 months)

CABG 89 BDI Cardiac

hospitalization,

failure to return to

previous activities,

surgical pain

Depression had an independent effect on hospitalization

(v2=4.21, Pb.04), surgical pain (v2=6.36, Pb.01), and failureto return to activity (v2=15.04, Pb.0001)

De Jonge et al. [74] Prospective

(12 months)

AMI 468 CIDI BDI SF-36 Post-AMI depression was independently related to poor

HRQOL (b=5.74 to 20.44, 95% CI, Pb.001),more cardiac complaints (b=2.082.68, 95% CI, Pb.001),and more disability (b=3.864.56, 95% CI, Pb.001).Post-AMI depression had a greater impact on health

status than pre-AMI depression. Severity, not duration of

depressive symptoms, contributed to a further reduction

in HRQOL

Fauerbach et al. [73] Prospective

(4 months)

AMI 196 SCID BDI SF-36 Depression was independently associated with reduced

general health ( F=7.45, df=5, Pb.01), vitality ( F=9.83,df=5, Pb.01), mental health ( F=6.53, df=5, Pb.01), andsocial function ( F=7.00; df=5, 196; Pb.01) and withincreased role interference from psychological

problems ( F=7.27, df=5, Pb.01)Goyal et al. [68] Prospective

(6 months)

CABG 90 BDI SF-36 Presurgical depression was significantly related to poorer

6-month physical functioning (b=0.575, Pb.001).Two-month increases in depression predicted poorer

6-month physical functioning (b=0.438, Pb.001) andpsychosocial functioning (b=0.337, Pb.001)

Lane et al. [70] Prospective

(12 months)

AMI 288 BDI Dartmouth

COOP Scales

Depression was the dominant predictor of HRQOL

(r=.32, P=.001), but living alone (r=.30, Pb.05),Peel Index score (r=.29, P=.001), and state anxiety

(r=.38, P=.001) were also important

Mallik et al. [67] Prospective

(6 months)

CABG 963 Geriatric

Depression

Scale

SF-36 Depressive symptoms were a stronger inverse risk factor

for functional improvement (RR=0.62; 95% CI, 0.190.82)

than traditional measures of disease severity such as

previous AMI (RR=0.86; 95% CI, 0.701.02), heart failure

(RR=0.70; 95% CI, 0.450.96), diabetes (RR=0.78;

95% CI, 0.630.93), and LVEF, which was not associated

with functional improvement (RR=1.09; 95% CI, 0.951.25)

Mayou et al. [71] Prospective

(12 months)

AMI 347 HADS SF-36 Depression and anxiety predicted poorer HRQOL

on all subscales ( Pb.05) and more impairment ondaily routine ( P=.0008), social activity ( P=.0001),

and leisure activity ( P=.006)

Perski et al. [63] Prospective

(12 months)

CABG 149 dPsychologicalwell-being

indexT

NHP Presurgical distress was associated with increased

complaints of residual angina (v2=7.9, df=3, Pb.048)and more frequent use of nitrates (v2=4.5, df=1, Pb.033)

Spertus et al. [61] Prospective

(3 months)

Stable

CAD

1282 Mental

Health

Inventory

SAQ Depression was associated with more physical

limitation ( Pb.001), more frequent angina ( Pb.001),less satisfaction with treatment for CAD ( Pb.001),and lower perceived HRQOL ( Pb.001)

Sullivan et al. [60] Prospective

(12 months)

Stable

CAD

198 HAM-D Multidimensional

Pain Inventory

(activity

interference)

Baseline HRQOL measures differed significantly by

the number of vessels stenosed N70% ( Pb.03),anxiety ( P=.001), and depression ( P=.001); 12-month

measures were not associated with number of stenosed

vessels but significantly associated with baseline anxiety

( Pb.0001) and depression ( P=.01) quartilesBeth Israel/UCLA

Functional Status

Questionnaire

(physical

functioning)

L. Stafford et al. / Journal of Psychosomatic Research 62 (2007) 401410404

QOL

36

36

Q

36

Q

hosomAuthors Design Population n

Depression

measure HR

Sullivan et al. [62] Prospective

(5 years)

Stable

CAD

111 HAM-D SF-

Dias et al. [59] Cross-sectionala ACS 181 BDI SF-

Rumsfeld et al. [57] Cross-sectional ACS 1957 Documented

history of

depression

SA

Rumsfeld et al. [58] Cross-sectional ACS 1660 BDI SF-

Ruo et al. [54] Cross-sectional Stable

CAD

1024 PHQ SA

Table 2 (continued)

L. Stafford et al. / Journal of Psycwere a significant independent predictor of lack of func-

tional improvement (PCS score of the SF-36) after adjust-

ment for CAD severity, angina class, baseline PCS, and

medical history [67]. The authors concluded that depression

was a stronger predictor of poor functional improvement

after CABG than traditional measures of cardiovascular

disease severity.

A recent prospective study evaluated the impact of the

severity and course of depressive symptoms using the BDI

on 2 and 6 months postsurgical HRQOL measured with the

SF-36 (n=90) [68]. Higher levels of preoperative depressive

symptoms predicted poorer 6-month physical functioning

independently of and more powerfully than all other

preoperative variables. Postoperative increases in depression

from baseline assessment to 2-month follow-up significantly

predicted both poorer physical and psychosocial functioning

at 6 months, even after adjusting for presurgical depression

and other traditional predictors. However, in contrast to

other findings [63,69], this study did not find a significant

relationship between preoperative depression and postoper-

ative psychological and social functioning.

Patients hospitalized for AMI. A prospective study of 288

patients hospitalized for AMI found that depressive symp-

toms on the BDI provided the best independent prediction

Swenson et al. [55] Cross-sectionala ACS 369 HAM-D Q-LES-Q

CIDI, Composite International Diagnostic Interview; Dartmouth COOP Scales, D

EuroQoL Visual Analogue Scale; HADS, Hospital Anxiety and Depression Scale

PHQ, Patient Health Questionnaire.a Study was prospective, but data cited here were from a cross-sectional commeasure Effect of depression on HRQOL

Five regression models were constructed to predict PCS from

depression only (R2=.22); depression plus angina and fatigue

(R2=.53); depression plus positive affect and novelty seeking

and their interaction (R2=.48); depression plus spousal support

(R2=.27); and depression, angina, fatigue, positive affect,

and novelty seeking (overall model; R2=.65). Depression

remained significant in each model, but the proportion of

variance it predicted was diminished in the presence of the

other variables (bivariate r=.39, partial r=.37.13)

Depression was an independent predictor of MCS

but not of PCS

History of depression was independently associated with

more frequent angina (OR=2.40; 95% CI, 1.863.10;

Pb.001), greater physical limitation (OR=2.89; 95% CI,2.173.86; Pb.001), and worse HRQOL (OR=2.84; 95% CI,2.163.72; Pb.001) 7 months post-ACSDepression was the dominant predictor of MCS ( Pb.0001)and an independent predictor of PCS ( P=.003)

7 months post-ACS

Depressive symptoms were strongly associated with

greater symptom burden (OR=1.8; 95% CI, 1.32.7; P=.002),

greater physical limitation (OR=3.1; 95% CI, 2.14.6; Pb.001),worse HRQOL (OR=3.1; 95% CI, 2.24.6; Pb.001), andworse overall health (OR=2.0.95% CI 1.32.9, Pb.001).Measures of cardiac severity were not associated

atic Research 62 (2007) 401410 405of HRQOL on the Dartmouth COOP Scales during a

12-month follow-up [70]. Other predictive factors included

living alone, state anxiety at index hospitalization, and the

severity of infarction. Similarly, clinically significant levels

of anxiety and depressive symptoms predicted poorer

HRQOL on all dimensions of the SF-36, as well as more

impairment on measures of daily activity and frequency of

chest pain at 3 and 12 months after infarct (n=347) [71].

Beck et al. [72] reported that the presence of baseline

depression on the BDI predicted poorer HRQOL of 587

AMI patients followed up 6 and 12 months after infarct.

Other important predictors were baseline HRQOL, age, and

previous bypass surgery.

One study has specifically examined the particular

functional domains of HRQOL that are negatively impacted

by the presence of depression as well as the issue of whether

poor HRQOL prior to infarct accounts for this relationship

[73]. One hundred ninety-six patients hospitalized for AMI

were assessed at baseline using the Structured Clinical

Interview for DSM-IV (SCID) to evaluate depression before

hospitalization and both the BDI and Beck Anxiety

Inventory to measure post-AMI depression and anxiety,

respectively, which were present since admission. HRQOL

was measured using the SF-36 at baseline by asking patients

to rate their HRQOL prior to infarct, and the SF-36 was

with HRQOL

, SF-36 Depression was the strongest predictor of poor baseline

HRQOL (partial r=.37, P=.001)artmouth Primary Care Cooperative Information Project Scales; EuroQoL,

; LVEF, left ventricular ejection fraction; NHP, Nottingham Health Profile;

ponent.

hosomadministered again at 4-month follow-up. Baseline assess-

ment was used to assign subjects to a depressed or non-

depressed group. After adjusting for preinfarct HRQOL,

in-hospital anxiety, and demographic variables, depression

was prospectively and independently related to reduced

general health at 4 months as well as reduced overall

mental healthincluding vitality, psychological health and

social function, and increased role interference from

psychological problems. Aggregated MCS scores of both

groups improved significantly over the follow-up period,

and while significant changes in the aggregated PCS

scores were not evident, physical function tended to decline

for the depressed group and improve slightly for the

nondepressed group. This study extends on previous work

by detecting the same pattern of poorer perceived general

health and psychological and social outcomes but at an

earlier time point and with baseline anxiety and preinfarct

HRQOL controlled.

The impact of the severity and duration of depressive

symptoms on a range of health status variables including

HRQOL, cardiac symptoms, and disability was prospec-

tively investigated in 468 patients 3 and 12 months

postinfarct [74]. ICD-10 diagnostic criteria were used to

assess the presence and duration of depression, and severity

of symptoms was measured using the BDI. In multivariate

analyses adjusting for baseline cardiac condition, history of

depression, health status at 3 months, age, and sex, post-

AMI depression remained a strong predictor of poorer

health status including HRQOL on the SF-36. Thus, post-

AMI depression had a greater impact on health status than

pre-AMI depression. Furthermore, severity, but not duration

of depressive symptoms, contributed to a further reduction

in HRQOL, more disability, and increased reporting of

angina. These findings suggest that depression not only is

associated with poor health status but also predicts changes

in aspects of health status: while the addition of 3-month

health status reduced the effects of post-AMI depression on

most 12-month health status indicators, the effect remained

for HRQOL and disability outcomes. Since the effects of

post-AMI depression were attenuated by depressive symp-

toms still present at follow-up, the authors conclude that

previous reports that did not adjust for baseline health status

(e.g., Refs. [54,70]) may have overestimated the prospective

effects of depression on HRQOL because participants were

suffering from a concurrent depression that affected health

status and/or the assessment thereof.

Effect of treatment of depression on the HRQOL of patients

with CAD

Therapeutic options for the treatment of depression

include depression-focused psychotherapies, antidepressant

drugs, and a combination of these. Although the data are

limited and are primarily from open or comparator trials, the

tricyclic (TCAs) and selective serotonin reuptake inhibitors

L. Stafford et al. / Journal of Psyc406have been shown to be effective for the treatment ofdepression in patients with CAD, with response rates

comparable to those reported in depressed patients without

CAD [75]. As a point of reference, treatment with sertraline

[76] and venlafaxine [77] has been associated with improve-

ment in multiple domains of HRQOL in large samples of

depressed general practice patients and outpatients.

In terms of psychotherapeutic treatment of depression,

cognitive behavior therapy (CBT) and interpersonal therapy

are effective as both acute and maintenance treatments

[78,79]. However, the efficacy of these evidence-based

psychotherapies in depressed patients with CAD has only

been investigated in a small number of studies, and none

have included HRQOL as an outcome. The Enhancing

Recovery in Coronary Heart Disease (ENRICHD) trial

enrolled 2481 patients with AMI and depression and/or low

perceived social support in 6 to 12 sessions of individual

CBT, group therapy (if feasible), and antidepressant

medication, if indicated, versus usual care [20]. Results of

the ENRICHD trial were mixed: the findings showed small,

statistically significant improvements in depressive symp-

toms and small, significant increases in perceived social

supportthe two main outcomes other than mortality and

recurrent infarct. Psychological outcomes for the interven-

tion group were better than the control group at the 6-month

mark, but these effects did not persist to the 30-month

evaluation. There was no difference in event-free survival

between the two groups.

Unfortunately, there is a paucity of depression treatment

studies in the CAD population that make use of standardized

HRQOL measures beyond the usual depressive symptom

scales [80]. One such study is the SADHART in which

369 patients hospitalized with ACS, who also met criteria

for major depressive disorder, were randomized to 24 weeks

of double-blind treatment with sertraline or placebo [56]. In

a substudy of SADHART, HRQOL was assessed using the

SF-36 and the Quality of Life Enjoyment and Satisfaction

Scale (Q-LES-Q) [55]. Two groups were analyzed: the

full intent-to-treat sample and a subgroup of patients with

recurrent depression (defined as a history of two or more

major depressive episodes before the current hospitaliza-

tion). At 24 weeks, the SF-36 PCS and MCS scores showed

clinically meaningful improvement with sertraline and

placebo in the total randomized group, but there was no

significant drugplacebo difference. However, in the recur-

rent depression subgroup, sertraline showed greater

improvement on the SF-36 MCS score than did placebo

and was more effective in producing clinically meaning-

ful changes on the emotional role limitations and mental

health subscales.

Another recent study that investigated the clinical and

functional outcomes of depression treatment in patients with

(n=235) and without (n=204) chronic medical illness

included a cohort with CAD (n=68) [81]. Depression

(measured with the SCID and Hopkins Symptom Check-

list), disability, and functional outcome (using the SF-36

atic Research 62 (2007) 401410subscales assessing functional impairment) were assessed at

indirect effect on global HRQOL both at baseline and at

hosombaseline and at 2 and 6 months after index prescription.

Significant improvements in clinical outcomes of depression

were found, which, in turn, were associated with robust

improvements in disability measures and those SF-36

subscales that were responsive to limitations in social and

emotional functioning. There was minimal improvement in

those SF-36 scales that were more responsive to limitations

in physical functioning. Thus, despite indications that

physical limitations remain unchanged, disability improved

as depression improved, which implies that depression may

be a stronger determinant of disability than a comorbid

medical condition.

Possible mechanisms linking depression to poor HRQOL in

patients with CAD

The mechanisms that explain the effect of depression on

HRQOL in patients with CAD may be related to those

behavioral factors underlying increased cardiac mortality

and morbidity in this population. Cardiac rehabilitation

programs that are designed to reduce mortality and morbidity

by promoting adherence to medication and healthy lifestyle

regimens have been shown to improve HRQOL [8284].

Depression has a negative impact on participation in these

programs [85]. Depressed patients with CAD have also been

found to be less adherent to medication regimens [86,87] and

recommended lifestyle modifications intended to reduce

cardiovascular risk [71,8890]. For instance, depression is

associated with increased rates of smoking in CAD patients

[91] and may lower the success rates of smoking cessation

programs [92]. Depression is also associated with increased

alcohol use and physical inactivity [93]. Furthermore,

depression is bidirectionally associated with social isolation,

a factor that contributes to poor treatment adherence [94] and

which constitutes another well-established indicator of poor

cardiac prognosis [9599].

Finally, the cognitiveaffective symptoms of depression

may impact on HRQOL scores not only by impairing actual

functioning but also by encouraging a negative perception of

health status [27]. This raises the possibility that impaired

HRQOL and depression are not necessarily distinct con-

structs and that the link between the two is related to negative

affectivity (NA), a general disposition to experience sub-

jective distress including aversive mood states [100,101].

This predisposition may explain the high comorbidity of

depressive and anxiety disorders. Individuals high in NA

consistently report worse self-perceived health and more

symptoms, although their underlying physical health is not

always found to be worse [102,103]. High-NA individuals

are more likely to perceive or complain about health

concerns [100], a heightened sensitivity that could lead to

inflated health-related complaints and worse self-reported

HRQOL. Kressin et al. [104] reported on the effect of NA on

HRQOL in 1843 veterans, controlling for the effects of

depression, age, and chronic medical conditions. The results

L. Stafford et al. / Journal of Psycshowed that NAwas consistently negatively associated with3 months. This depression effect had almost disappeared at

1 month after initial treatment but recurred after 3 months.

This result suggests that subjective evaluation of global

HRQOL shortly after treatment is influenced more by the

perception of physical functioning, but later on, the indirect

effects of variables such as depression regain an influence

on HRQOL perception. The authors concluded that assess-

ment of HRQOL is distinct from that of depression but that

depression represents the most important indirect influence

on the course of HRQOL in patients with CAD.

Conclusions

HRQOL, the assessment of the patients subjective

experience of disease and treatment, is now widely

acknowledged as an important health care outcome. How-

ever, the wide variety of HRQOL instruments and the lack

of standardization in the reporting of effects on HRQOL

mean that the conceptual and methodological issues under-

lying this work require more attention. A core heart disease

HRQOL questionnaire is being developed to allow for

meaningful comparisons between studies [41]. Others [107]

have recommended the use of item response theory,

dichotomization, minimal important difference, and propor-

tions to optimize the interpretation of HRQOL outcomes in

clinical trials.

CAD has been shown to have an adverse effect on

HRQOL, which, in turn, has been associated with increased

morbidity and mortality among CAD patients. It is well

established that the prevalence of depression is dispropor-

tionately high in patients with CAD relative to the general

population and that the presence of depression confersall SF-36 subscales, even after controlling for depression and

physical illness. When adjusting for depression, the remain-

ing variance uniquely attributable to NA ranged between

0.24% and 13.9%, suggesting that insofar as depression is

correlated with NA and also has an effect on HRQOL, its

removal attenuated the independent effect of NA.

Other research, however, has shown that depression is

distinct from NA [106] and from HRQOL [105,106]. One

study used structural equation modeling to test a conceptual

model of generic and disease-specific HRQOL in 465 CAD

patients at baseline evaluation of chest pain and, again, at 1-

and 3-month follow-up [105]. The model included bio-

medical factors as well as environmental and individual

characteristics and was tested at each of the three time

points. Among the individual variables, anxiety and

depressive symptoms showed the greatest effect on the

linked variables in the model. Although depression signifi-

cantly influenced the emotional aspect of HRQOL, it had no

significant direct effect on global HRQOL. However,

depression had a major and constant effect on the perception

of physical functioning and general health, exerting a major

atic Research 62 (2007) 401410 407an increased risk of mortality. Comorbid depression in

[5] Connerney I, Shapiro PA, McLaughlin JS, Bagiella E, Sloan RP.

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176671.

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62733.

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1992;69:112834.

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[10] Rudisch B, Nemeroff CB. Epidemiology of comorbid coronary

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Gender, depression, and one-year prognosis after myocardialCAD patients has been shown to produce an additive

decrement in their HRQOL and appears to have a greater

impact on their subjective well-being than on their actual

cardiac functioning.

Additionally, the severity and course of depressive

symptoms may significantly undermine HRQOL despite

successful medical and surgical management. The mecha-

nisms through which depression impacts on HRQOL

require further study, as does the issue of optimal timing

for assessment of depressive symptoms. This information

would inform treatment decisions and facilitate the identi-

fication of interventions to improve HRQOL. It seems

that since depression is associated with poor treatment

adherence in CAD patients, the effective treatment of

depression may result in improved adherence, healthier

lifestyles, and, consequently, improved HRQOL. Although

successful treatment of depression has not yet been shown

to reduce mortality rates in patients with CAD, further study

may find that the HRQOL benefits of such treatment are

equally valuable.

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www.hqlo.com/com/content/4/1/62].related quality of life and increased disability and cardiac complaints

Comorbid depression and health-related quality of life in patients with coronary artery diseaseIntroductionDefinition, measurement, and interpretation of HRQOLThe impact of depression on the HRQOL of patients with CADCross-sectional studies of the effect of depression on the HRQOL of CAD patientsPatients with stable CADPatients hospitalized for acute coronary syndrome

Prospective studies of the effect of depression on the HRQOL of patients with CADPatients with stable CADPatients undergoing coronary artery bypass graft surgeryPatients hospitalized for AMI

Effect of treatment of depression on the HRQOL of patients with CADPossible mechanisms linking depression to poor HRQOL in patients with CAD

ConclusionsReferences