The Heart and Soul Study is a prospective cohort study of psychosocial factors and health outcomes in patients with CAD. Methods have been described previously.1
In brief, we used administrative databases to identify outpatients with stable CAD at 2 Department of Veterans Affairs Medical Centers, 1 university medical center, and 9 public health clinics in San Francisco. Between September 2000 and December 2002, 1,024 participants completed a baseline study appointment that included a medical history interview, a physical examination, and a comprehensive health status questionnaire. Of these, 80 were not able to perform the exercise treadmill test, leaving 944 participants for analysis. This protocol was approved by the appropriate institutional review boards, and all participants provided written, informed consent.
Each participant underwent a symptom-limited, graded exercise treadmill test according to a standard Bruce protocol. To achieve maximum heart rate, participants who were unable to continue the standard Bruce protocol (for orthopedic or other reasons) were switched to slower settings on the treadmill and encouraged to exercise for as long as possible. Maximum exercise capacity was calculated as the total number of METs achieved. Beforehand, we categorized participants into those with poor (<5 METs) and normal (≥5 METs) exercise capacity.2
To calculate percent maximum heart rate achieved, the maximum heart rate achieved was divided by (220 − age).
Our primary predictor variable was depressive symptoms as measured by the 9-item Patient Health Questionnaire (PHQ). The PHQ is a self-administered validated questionnaire with a sensitivity of 88% and a specificity of 88% for major depressive disorders using a cutpoint of ≥10.3
For the primary analysis, we categorized participants as depressed if they scored ≥10 on the PHQ, representing the minimum number of symptoms required for a diagnosis of major depression.4
To examine the association between a range of depressive symptoms and exercise capacity, we further divided participants into categories representing no to minimal depressive symptoms (score 0 to 3), mild to moderate depressive symptoms (score 4 to 9), and symptoms consistent with major depression (≥10).
We assessed cardiac function using 3 measures: a self-report measure of angina frequency, an echocardiogram at rest for assessment of left ventricular ejection fraction, and a stress echocardiogram for evaluation of ischemia. To assess angina frequency, we asked participants: “Over the past 4 weeks, on average, how many times have you had chest pain, chest tightness, or angina?” Participants chose from the following responses: none, <1 time/week, 1 to 2 times/week, ≥3 times/week but not every day, 1 to 3 times/day, or ≥4 times/day.5
We classified participants as having no angina (none) versus any angina (all other responses).
We performed imaging and pulse-wave Doppler echocardiography with an Acuson Sequoia Ultrasound System (Mountain View, California) using a 3.5-MHz transducer. A complete 2-dimensional echocardiogram at rest was performed just before exercise. Standard 2-dimensional parasternal short-axis and apical 2- and 4-chamber views obtained during held inspiration were planimetered to determine left ventricular ejection fraction. At peak exercise, apical 2- and 4-chamber, and precordial long- and short-axis views were obtained to detect the development of right or left ventricular dilation or wall motion abnormalities during exercise.
To account for fixed and exercise-induced wall motion defects, we calculated the wall motion score index at peak exercise as our measure of ischemia. 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,6
with a normally contracting left ventricle receiving a wall motion score index of 1 (16/16 = 1) and higher scores indicating worse contractility.
Age, ethnicity, education, income, marital status, medical history, smoking history, 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. 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 association between depressive symptoms and treadmill exercise capacity, an objective measure of functional status. Differences in characteristics between participants with poor exercise capacity (METs <5) and those with normal exercise capacity (METs ≥5) were compared using t tests (or nonparametric equivalent) for continuous variables and chi-square tests for dichotomous variables. We compared the unadjusted association between categories of depressive symptoms and poor exercise capacity by using a chi-square test for trend. We used analysis of covariance to compare mean exercise capacity in participants with and without depressive symptoms and adjusted for potential confounding variables.
To further evaluate the association between depressive symptoms and exercise capacity, we used multivariable logistic regression. For the multivariable analyses, we entered all variables listed in into a backward elimination logistic regression model (with p <0.10 for retention in the model). We tested for interactions of depressive symptoms with angina, ejection fraction, and ischemia. Results are reported as odds ratios with 95% confidence intervals. Analyses were performed with SAS 8 (SAS Institute, Inc., Cary, North Carolina).
Characteristics of 944 Participants With Coronary Artery Disease Grouped by Exercise Capacity
Characteristics of participants are presented in . Of the 944 participants, 172 (18%) had depressive symptoms (PHQ score ≥10), and 229 (24%) had poor exercise capacity (METs <5). Participants with depressive symptoms were more likely than those without depressive symptoms to have poor exercise treadmill capacity. The proportion of participants with poor exercise capacity ranged from 21% in those with no or minimal depressive symptoms (PHQ score 0 to 3) to 34% in those with a depression score ≥10 (). In analyses adjusted for measures of cardiac function and other patient characteristics, the presence of depressive symptoms remained independently associated with worse exercise capacity (). Each SD (5.4 points) increase in depression score was associated with a 20% increased odds of poor exercise capacity (adjusted odds ratio 1.2, 95% confidence interval 1.0 to 1.5, p = 0.02).
Proportion of participants with poor exercise capacity (METs <5) stratified by depression score (p for trend <0.001)
Factors Associated With Poor Exercise Capacity in Participants With Coronary Artery Disease
When examining exercise capacity as a continuous variable, participants with depressive symptoms had significantly lower mean exercise capacity than did those who were not depressed (6.5 ± 3.2 METs vs 7.5 ± 3.3 METs; p <0.001). This difference persisted after adjustment for ejection fraction, age, ethnicity, income, body mass index, stroke, diabetes, β-blocker use, statin use, and current smoking (6.6 vs 7.5 METs; p <0.001).
In adjusted models, decreased left ventricular ejection fraction was associated with worse exercise capacity, but angina and ischemia were not associated with exercise capacity. Even when ischemia was entered as dichotomous variable (presence or absence of inducible wall motion abnormalities), it was not associated with poor exercise capacity (adjusted odds ratio 0.8, 95% confidence interval 0.6 to 1.2, p = 0.24).
Depressed participants achieved lower mean percent maximum heart rate than did participants without depressive symptoms (78 ± 16 vs 86 ± 15; p <0.0001), and adjusting for percent maximum heart rate achieved appeared to eliminate the association between depressive symptoms and poor exercise capacity (odds ratio 1.3, 95% confidence interval 0.8 to 2.1, p = 0.25). We did not observe any significant interactions between depressive symptoms and ejection fraction, ischemia, percent maximum heart rate achieved, or angina (all p values for interaction >0.20).