Ruo B, Rumsfeld JS, Hlatky MA, Liu H, Browner WS, Whooley MA. Depressive Symptoms and Health-Related Quality of LifeThe Heart and Soul Study. JAMA. 2003;290(2):215-221. doi:10.1001/jama.290.2.215
Author Affiliations: Section of General Internal Medicine, Veterans Affairs Medical Center, San Francisco (Drs Ruo, Liu, and Whooley); Department of Medicine, University of California, San Francisco (Drs Ruo, Browner, and Whooley); Cardiology and Health Services Research, Denver Veterans Affairs Medical Center, Denver, Colo (Dr Rumsfeld); Health Research and Policy, Stanford University School of Medicine, Stanford, Calif (Dr Hlatky); Research Institute, California Pacific Medical Center, San Francisco (Dr Browner); Department of Epidemiology and Biostatistics, University of California, San Francisco (Drs Browner and Whooley).
Context Little is known regarding the extent to which patient-reported health
status, including symptom burden, physical limitation, and quality of life,
is determined by psychosocial vs physiological factors among patients with
Objective To compare the contributions of depressive symptoms and measures of
cardiac function to the health status of patients with coronary artery disease.
Design, Setting, and Participants Cross-sectional study of 1024 adults with stable coronary artery disease
recruited from outpatient clinics in the San Francisco Bay Area between September
2000 and December 2002.
Main Measures Measurement of depressive symptoms using the Patient Health Questionnaire
(PHQ); assessment of cardiac function by measuring left ventricular ejection
fraction on echocardiography, exercise capacity on treadmill testing, and
ischemia on stress echocardiography; and measurement of a range of health
status outcomes, including symptom burden, physical limitation, and quality
of life, using the Seattle Angina Questionnaire. Participants were also asked
to rate their overall health as excellent, very good, good, fair, or poor.
Results Of the 1024 participants, 201 (20%) had depressive symptoms (PHQ score
≥10). Participants with depressive symptoms were more likely than those
without depressive symptoms to report at least mild symptom burden (60% vs
33%; P<.001), mild physical limitation (73% vs
40%; P<.001), mildly diminished quality of life
(67% vs 31%; P<.001), and fair or poor overall
health (66% vs 30%; P<.001). In multivariate analyses
adjusting for measures of cardiac function and other patient characteristics,
depressive symptoms were strongly associated with greater symptom burden (odds
ratio [OR], 1.8; 95% confidence interval [CI], 1.3-2.7; P = .002), greater physical limitation (OR, 3.1; 95% CI, 2.1-4.6; P<.001), worse quality of life (OR, 3.1; 95% CI, 2.2-4.6; P<.001), and worse overall health (OR, 2.0; 95% CI,
1.3-2.9; P<.001). Although decreased exercise
capacity was associated with worse health status, left ventricular ejection
fraction and ischemia were not.
Conclusions Among patients with coronary disease, depressive symptoms are strongly
associated with patient-reported health status, including symptom burden,
physical limitation, quality of life, and overall health. Conversely, 2 traditional
measures of cardiac function—ejection fraction and ischemia—are
not. Efforts to improve health status should include assessment and treatment
of depressive symptoms.
A primary goal of therapy for patients with chronic disease is to improve
their health status, including symptoms, functional status, and quality of
life. In patients with coronary disease, cardiovascular interventions are
known to improve health status,1- 4 but
the extent to which such benefits result from changes in cardiac vs noncardiac
factors is unclear. Most studies have found only limited associations between
cardiac function and health status measures,5- 9 suggesting
that other factors may be as important as cardiac function in determining
the health status of patients with heart disease.
Depressive symptoms are known to be associated with worse health status
among patients with coronary artery disease,10- 12 but
their relative contributions compared with physiologic measures of disease
severity are unknown.13 To examine the relative
influence of depressive symptoms and cardiac function on health status, we
measured depressive symptoms, cardiac function (including left ventricular
ejection fraction, exercise capacity, and ischemia), and a range of health
status outcomes among 1024 patients with coronary artery disease. We hypothesized
that depressive symptoms would be more strongly associated with health status
than measures of cardiac function.
The Heart and Soul Study is a prospective cohort study of psychosocial
factors and health outcomes in patients with coronary disease. We used administrative
databases to identify outpatients with documented coronary artery disease
at 2 Department of Veterans Affairs Medical Centers (San Francisco Veterans
Affairs Medical Center and the Veterans Affairs Palo Alto Health Care System,
California), 1 university medical center (University of California, San Francisco),
and 9 public health clinics in the Community Health Network of San Francisco.
Patients were eligible to participate if they had at least 1 of the following:
a history of myocardial infarction, angiographic evidence of at least 50%
stenosis in 1 or more coronary vessels, prior evidence of exercise-induced
ischemia by treadmill or nuclear testing, a history of coronary revascularization,
or a diagnosis of coronary artery disease by an internist or cardiologist.
A total of 15 438 eligible patients were mailed an invitation to
participate, and 2495 responded that they would be interested. Of the 2495
patients whom we attempted to contact by telephone to schedule a study appointment,
505 could not be reached and 596 declined to participate. An additional 370
patients were excluded because they had a history of myocardial infarction
in the prior 6 months, deemed themselves unable to walk 1 block, or were planning
to move out of the local area within 3 years.
Between September 2000 and December 2002, a total of 1024 participants
enrolled, including 549 (54%) with a history of myocardial infarction, 237
(23%) with a history of revascularization but not myocardial infarction, and
238 (23%) with a diagnosis of coronary disease that was documented by their
physician (based on a positive angiogram or treadmill test in >98% of cases).
Participants completed a daylong baseline study appointment that included
a medical history interview, a physical examination, an exercise treadmill
test with a stress echocardiogram, and a comprehensive health status questionnaire.
This protocol was approved by the following institutional review boards:
the Committee on Human Research at the University of California, San Francisco;
the Research and Development Committee at the San Francisco Veterans Affairs
Medical Center; the Medical Human Subjects Committee at Stanford University;
the Human Subjects Committee at the Veterans Affairs Palo Alto Health Care
System; and the Data Governance Board of the Community Health Network of San
Francisco. All participants provided written informed consent.
Based on the model initially described by Wilson and Cleary,13 and later modified for patients with coronary disease,14,15 we used the Seattle Angina Questionnaire
to assess 3 components of health status: symptom burden (2-item angina frequency
scale), functional status (9-item physical limitation scale), and disease-specific
quality of life (3-item disease perception scale).16,17 As
a measure of generic health status, we also asked participants, "Compared
with other people your age, how would you rate your overall health?"18,19 Participants chose from responses
of "poor," "fair," "good," "very good," or "excellent."
For each subscale of the Seattle Angina Questionnaire, responses were
scored from 0 to 100, with higher scores indicating better health status (ie,
less symptom burden, less physical limitation, and better quality of life).
Although Seattle Angina Questionnaire scale scores are continuous, they can
be grouped for clinical interpretability. A priori, we divided the symptom
burden scores into categories reflecting daily (0-30), weekly (31-60), monthly
(61-90), or absent (91-100) angina; the physical limitation scores into severe
(0-24), moderate (25-49), mild (50-74), or minimal (75-100) physical limitation;
and the quality-of-life scores into severely diminished (0-24), moderately
diminished (25-49), mildly diminished (50-74), or good to excellent (75-100)
quality of life.14
Depressive Symptoms. Our primary predictor
variable was depressive symptoms as measured by the 9-item Patient Health
Questionnaire (PHQ).20 For the primary analysis,
we categorized participants as depressed if they scored 10 or greater on the
PHQ, representing the minimum number of symptoms required for a diagnosis
of major depression.21 To examine the association
between a range of depressive symptoms and health status, we further divided
participants into categories representing no to minimal depressive symptoms
(score 0-3), mild to moderate depressive symptoms (score 4-9), and symptoms
consistent with major depression (score ≥10). Participants who were found
to have high levels of depressive symptoms were informed that they may be
depressed, instructed to discuss these symptoms with their primary care physician,
and provided a list of local resources available for further evaluation and
Cardiac Function. We assessed cardiac function
using a resting echocardiogram for measurement of left ventricular ejection
fraction, an exercise treadmill test for measurement of exercise capacity,
and a stress echocardiogram for assessment of ischemia. We performed a symptom-limited,
graded exercise treadmill test according to a standard Bruce protocol. Peak
exercise capacity was defined as total number of metabolic equivalent tasks
(METs) achieved, including 3 categories defined a priori as low (<5 METs),
medium (5-7 METs), and high (>7 METs) exercise capacity. Continuous, 12-lead
electrocardiographic monitoring was performed throughout exercise.
Imaging and pulse wave Doppler echocardiography were performed using
an Acuson Sequoia Ultrasound System (Mountain View, Calif) with a 3.5-MHz
transducer. A complete resting 2-dimensional echocardiogram was performed
just before exercise. Standard 2-dimensional parasternal short-axis and apical
2-chamber and 4-chamber views obtained during held inspiration were planimetered
to determine left ventricular ejection fraction. At peak exercise, apical
2-chamber, 4-chamber, and precordial long-axis and short-axis views were obtained
to detect the development of right or left ventricular dilatation or wall
motion abnormalities during exercise.
To account for both fixed and exercise-induced wall motion defects,
we calculated the wall motion score index at peak exercise as our measure
of ischemia.22 Each of 16 wall segments in
the left ventricle was scored based on the contractility visualized at peak
exercise (1 = normal, 2 = hypokinetic, 3 = akinetic, 4 = dyskinetic, 5 = aneurysm).
The wall motion score index was defined as the sum of wall motion scores divided
by the number of segments visualized,22 with
a normally contracting left ventricle receiving a wall motion score index
of 1 (16/16 = 1) and higher wall motion scores indicating worse contractility.
We also measured inducible ischemia as a dichotomous variable, defined as
the presence of exercise-induced electrocardiographic changes or new echocardiographic
wall motion abnormalities at peak exercise.
Potential Confounding Variables. Age, ethnicity,
education, income, mari-tal status, medical history, smoking, and alcohol
use were determined by questionnaire. Participants were instructed to bring
their medication bottles to the study appointment, and study personnel recorded
all current medications, including use of β-blockers, 3-hydroxy-3-methylglutaryl
coenzyme A (HMG-CoA) reductase inhibitors (statins), renin-angiotensin system
inhibitors, and antidepressant medications (selective serotinin reuptake inhibitors,
tricyclics, or other antidepressants).
We measured stress using the 4-item Perceived Stress Scale23 and
considered participants to have stress if they scored 9 or greater on the
16-point scale, corresponding to experiencing at least 1 stressful symptom
"fairly often." We assessed social support by asking participants, "Do you
have as much contact as you would like with someone you feel close to, someone
in whom you can trust and confide (yes/no)?"24 Body
mass index was calculated as weight in kilograms divided by the square of
height in meters.
The goal of this study was to examine the contributions of depressive
symptoms and cardiac function to patient-reported health status. Differences
in characteristics between participants with and without depressive symptoms
(PHQ score ≥10) were compared using t tests (or
nonparametric equivalent) for continuous variables and χ2 tests
(or Fisher exact test if <5 expected observations in any cell) for dichotomous
variables. We also compared the unadjusted frequency of health status outcomes
among participants with and without depressive symptoms using a χ2 test for trend.
To further evaluate the association between independent variables (depressive
symptoms and cardiac function) and outcome variables (symptom burden, physical
limitation, disease-specific quality of life, and overall health), we used
multivariate ordinal logistic regression, a method that allows the outcome
variable to have more than 2 categories. Ordinal logistic regression calculates
a single odds ratio (OR) for the association between a predictor variable
(eg, presence of depressive symptoms) and each combination of higher risk
vs lower risk outcome categories (eg, severe physical limitation vs other
categories; severe or moderate physical limitation vs other categories; severe,
moderate, or mild physical limitation vs no physical limitation).
For the multivariate analyses, we entered all variables from Table 1 into forward stepwise ordinal logistic
regression models (P<.20 for inclusion in the
models) with each of the 4 health status measures as outcomes. Depressive
symptoms and the 3 measures of cardiac function (left ventricular ejection
fraction, exercise capacity, and wall motion score index) were forced into
these models as predictor variables. Continuous variables were entered per
SD change. We also examined the association of depressed left ventricular
ejection fraction and inducible ischemia (entered as dichotomous variables)
with health status outcomes. In all regression models, we tested for interactions
between sex and exercise capacity, depressive symptoms and category of inclusion
criteria, and depressive symptoms and measures of cardiac function. The proportional
odds assumption was verified for all models. Results are reported as ORs with
95% confidence intervals (CIs). Analyses were performed using SAS version
8 (SAS Institute, Inc, Cary, NC).
Of the 1024 participants, 201 (20%) had depressive symptoms (PHQ score
≥10). Compared with participants who did not have depressive symptoms,
those with depressive symptoms were younger, had lower income, and were less
likely to be male or married (Table 1).
They were more likely to have a history of myocardial infarction or diabetes
mellitus, to smoke, and to report greater stress and worse social support.
Participants with depressive symptoms had higher body mass index and lower
We observed a dose-response relationship between depression score and
all 4 measures of health status (Figure 1, Figure 2). Participants
with depressive symptoms (PHQ score ≥10) were more likely than those without
depressive symptoms to report at least mild symptom burden (60% vs 33%; P<.001), mild physical limitation (73% vs 40%; P<.001), and mildly diminished quality of life (67%
vs 31%; P<.001). They were also more likely to
report fair or poor overall health (66% vs 30%; P<.001)
In analyses adjusted for measures of cardiac function and other patient
characteristics, depressive symptoms were independently associated with all
4 measures of health status (Table 3).
Even after further adjustment for the presence of angina symptoms, depressive
symptoms remained strongly associated with worse physical limitation (OR,
2.9; 95% CI, 2.0-4.3; P<.001), worse quality of
life (OR, 2.8; 95% CI, 1.9-4.1; P<.001), and worse
overall health (OR, 1.7; 95% CI, 1.2-2.6; P = .006).
When entered as a continuous variable in the multivariate models, each
SD (5.5-point) increase in depression score was associated with greater symptom
burden (OR, 1.5; 95% CI, 1.3-1.7; P<.001), worse
physical limitation (OR, 2.1; 95% CI, 1.8-2.4; P<.001),
worse quality of life (OR, 1.9; 95% CI, 1.6-2.2; P<.001),
and worse overall health (OR, 1.6; 95% CI, 1.4-1.9; P<.001).
We did not observe any interaction between depressive symptoms and category
of inclusion criteria (all P values for interaction
>.20). Depressive symptoms were strongly associated with worse health status
in all 3 diagnostic subgroups (history of myocardial infarction, history of
revascularization but not myocardial infarction, and diagnosis of coronary
disease documented by a physician). Likewise, there were no interactions between
depressive symptoms and measures of cardiac function in any of the 4 health
status models (all P values for interaction >.20).
In particular, we observed similar associations between depression score and
worse health status in all 3 strata of exercise capacity (Figure 2).
We observed no interaction between sex and exercise capacity in any
of the health status models (all P values for interaction
>.70). In adjusted models, decreased exercise capacity by treadmill testing
was associated with greater symptom burden, greater physical limitation, worse
quality of life, and worse overall health (Table 3). However, resting left ventricular ejection fraction and
wall motion score index were not associated with any of the 4 health status
Overall, 12% of participants had a depressed left ventricular ejection
fraction (≤50%), and 33% of participants had inducible ischemia (defined
as the presence of exercise-induced electrocardiographic changes or new echocardiographic
wall motion abnormalities at peak exercise). When entered as a dichotomous
variable, depressed left ventricular ejection fraction was not associated
with symptom burden (OR, 1.1; 95% CI, 0.7-1.7; P =
.67), physical limitation (OR, 1.1; 95% CI, 0.7-1.7; P =
.66), diminished quality of life (OR, 1.2; 95% CI, 0.8-1.9; P = .34), or worse overall health (OR, 1.3; 95% CI, 0.9-2.0; P = .16). Likewise, the presence of inducible ischemia
was not associated with symptom burden (OR, 1.1; 95% CI, 0.8-1.5; P = .57), physical limitation (OR, 1.0; 95% CI, 0.8-1.4; P = .82), diminished quality of life (OR, 0.9; 95% CI, 0.7-1.2; P = .48), or worse overall health (OR, 1.1; 95% CI, 0.9-1.5; P = .32).
Among patients with coronary disease, we found that depressive symptoms
were strongly associated with health status outcomes, including symptom burden,
physical limitation, quality of life, and overall health. In contrast, 2 physiological
measures of disease severity—left ventricular ejection fraction and
ischemia—were not. Exercise capacity by treadmill testing was also predictive
of health status outcomes, but depressive symptoms remained associated with
health status in all strata of exercise capacity. Although the causal pathways
between depressive symptoms and health status outcomes cannot be determined
by this cross-sectional study and are almost certainly bidirectional, our
results suggest that depressive symptoms are an important factor in the perceived
health status of patients with coronary disease.
We found that depressive symptoms were associated with overall and disease-specific
health status, independent of cardiac function. Indeed, depressive symptoms
were as strongly associated with disease-specific health status as was exercise
capacity, one of the primary variables used to validate the Seattle Angina
Questionnaire.17 Previous studies have demonstrated
an association between depressive symptoms and health status outcomes in patients
with coronary disease,10,25- 28 but
these studies did not measure severity of cardiac disease simultaneously.
Other studies have found that symptoms of anxiety and depression lead to poor
health status, independent of the degree of angiographic stenosis, but these
studies did not assess cardiac function by measuring exercise capacity, ejection
fraction, or ischemia.11,28,29
Our results suggest that efforts to improve the health status of cardiac
patients should include assessment and treatment of depressive symptoms. Treatment
of depression leads to improvements in health status,30,31 and
improved health status is associated with better health outcomes.14,32- 36 Some
antidepressant therapies, such as selective serotonin reuptake inhibitors,
may even improve cardiovascular outcomes among patients with coronary disease.37,38 Health care professionals can easily
identify depression by administering 2 simple screening questions ("During
the past month, have you often been bothered by feeling down, depressed, or
hopeless?" and "During the past month, have you often been bothered by having
little interest or pleasure in doing things?") and a brief follow-up interview
if one of the questions is answered affirmatively.39,40 For
maximal benefit, detection and treatment of depression should be combined
with patient-support programs, such as frequent nursing follow-up and close
monitoring of adherence to therapy.41,42
Our findings demonstrate that depressive symptoms are at least as important
as cardiac function in the health-related quality of life of patients with
coronary disease. Indeed, "low-tech" measures of health, including depressive
symptoms and exercise capacity, were more strongly associated with health
status outcomes than "high-tech" measures of cardiac disease severity, including
ejection fraction and ischemia. These results are consistent with a large
body of literature demonstrating poor correlation between "high-tech" physiological
measures and health-related quality of life in patients with other chronic
diseases such as asthma,43 chronic obstructive
pulmonary disease,44,45 peptic
ulcer disease,46 diabetes,47 prostate
hypertrophy,48 and musculoskeletal disorders.49,50
Health status measures are increasingly used to assess the benefits
of the rapies in clinical trials.51 Since many
cardiac interventions can alter both physiology and mood,2,52 it
is plausible that some quality-of-life improvements found in these trials
may be due to noncardiac factors. Our results suggest that studies measuring
quality-of-life outcomes should attempt to determine whether changes are due
to cardiac or to noncardiac factors.
If improvements in depressive symptoms are responsible for changes in
quality of life, then future efforts to enhance the health status of cardiac
patients could focus on modifying depressive symptoms.30 Such
efforts would have substantial implications for care in patients with coronary
disease, where the traditional focus has been on cardiac physiology and psychosocial
factors such as depression are often overlooked.53,54
Several limitations must be considered in interpreting our results.
First, we chose to focus on depressive symptoms and coronary disease because
they are the most common chronic mental and physical disorders and the 2 leading
causes of disability in the world.55 However,
only 7% of eligible patients actually enrolled in the study, and the majority
of participants were men, so our results may not generalize to other groups
of patients. Second, our study population was recruited based on the presence
of coronary disease and did not require a diagnosis of heart failure. Thus,
the prevalence of systolic dysfunction was low (12%). However, the prevalence
of other cardiac conditions was relatively high in our sample, including a
history of myocardial infarction in over half of the participants, a history
of revascularization in over half of the participants, inducible ischemia
in a third of the participants, and a wide range of exercise capacity. Thus,
we believe our sample represents an appropriate population in which to examine
the contributions of depressive symptoms and cardiac function to health status.
Third, since the PHQ does not assess duration or recurrence of depressive
symptoms, we were not able to explore potential differences in the association
between depressive symptoms and health status by duration of depression or
number of recurrences. Finally, our cross-sectional design precludes determination
of the direction of causality between depressive symptoms and health status.
However, since health status is by definition a subjective internal experience,
a cross-sectional measurement of its association with psychological and cardiac
function provides insight that would not be achieved by assessing health status
at a subsequent time point when the patient's physiologic or psychological
state could have changed.
In summary, we found that depressive symptoms, a modifiable risk factor,
are strongly associated with symptom burden, physical function, disease-specific
quality of life, and perceived overall health among patients with coronary
disease. In contrast, 2 traditional measures of disease severity—ejection
fraction and ischemia—were not associated with health status outcomes.
Future efforts to improve the health status of patients with coronary artery
disease should include a focus on depressive symptoms.