Patient-reported health status is highly valued as a key measure of health care quality, yet little is known about the extent to which it is determined by subjective perception compared with objective measures of disease severity. We sought to compare the associations of depressive symptoms and objective measures of cardiac disease severity with perceived functional status in patients with stable coronary artery disease. We assessed depressive symptoms, severity of cardiovascular disease, and perceived functional status in a cross-sectional study of 1,023 patients with stable coronary artery disease. We compared the extent to which patient-reported functional status was influenced by depressive symptoms versus objective measures of disease severity. We then evaluated perceived functional status as a predictor of subsequent cardiovascular hospitalizations during 8.8 years of follow-up. Patients with depressive symptoms were more likely to report poor functional status than those without depressive symptoms (44% vs 17%; p <0.001). After adjustment for traditional risk factors and co-morbid conditions, independent predictors of poor functional status were depressive symptoms (odds ratio [OR] 2.68, 95% confidence interval [CI] 1.89 to 3.79), poor exercise capacity (OR 2.30, 95% CI 1.65 to 3.19), and history of heart failure (OR 1.61, 95% CI 1.12 to 2.29). Compared with patients who had class I functional status, those with class II functional status had a 96% greater rate (hazard ratio 1.96, 95% CI 1.15 to 3.34) and those with class III or IV functional status had a 104% greater rate (hazard ratio 2.04, 95% CI 1.12 to 3.73) of hospitalization for HF, adjusted for baseline demographic characteristics, co-morbidities, cardiac disease severity, and depressive symptoms. In conclusion, depressive symptoms and cardiac disease severity were independently associated with patient-reported functional status. This suggests that perceived functional status may be as strongly influenced by depressive symptoms as it is by cardiovascular disease severity.
Depression is particularly prevalent in patients with cardiovascular disease, and screening is recommended for all patients with coronary artery disease (CAD). Identification of depressive symptoms in patients with CAD is important because these patients have a worse prognosis. Depressive symptoms contribute to an increased burden of cardiovascular and functional impairment. Depression has a significant negative influence on self-rated functional status in CAD. Previous studies have demonstrated that functional impairment is associated with more severe symptoms and worse health in patients with CAD. Poor functional classification is also a risk factor for future cardiac events including stroke, HF hospitalization, and mortality. However, determining the degree of influence depression has in comparison with objective measures of disease on symptoms burden in patients with stable CAD is unknown. Therefore, understanding how depression and severity cardiac disease relate to quality of life and perception of symptoms is important. We sought to test the hypothesis that depressive symptoms are associated with patients’ perceived symptom burden even after adjusting for objective markers of CAD severity using a cross-sectional study of a cohort of patients with stable CAD. In addition, we evaluated the association between functional status as a predictor of subsequent cardiovascular hospitalizations both before and after adjustment for depressive symptoms.
Methods
The Heart and Soul Study is a prospective cohort study that was originally designed to investigate the effects of psychosocial factors on health outcomes in patients with stable CAD. Methods have been previously described. Patients were eligible if they had at least one of the following: history of myocardial infarction (MI), angiographic evidence of ≥50% stenosis in ≥1 coronary vessels, evidence of exercise-induced ischemia by treadmill electrocardiogram or stress nuclear perfusion imaging, a history of coronary revascularization, or a diagnosis of coronary disease. Patients were excluded if they were unable to walk at least 1 block, had an acute coronary syndrome within the previous 6 months, or were likely to move from the area within 3 years.
From September 2000 to December 2002, 1,024 subjects were recruited from 12 outpatient clinics in the San Francisco Bay Area, including 1,023 with assessment of functional status. All participants completed a full-day study including medical history and physical examination, health status questionnaires, and an exercise treadmill test with baseline and stress echocardiograms. Institutional review boards at each site approved this study protocol. All participants provided written informed consent.
The primary outcome was perceived functional status that was obtained by self-report questionnaire. Assessment of functional status was performed using a scale combining elements of the New York Heart Association functional classification and the Canadian Cardiovascular Society angina score which are both well-established prognostic tools in patients with cardiovascular disease. Participants were asked to grade the severity of their cardiac symptom burden, which could include chest discomfort, dyspnea, or fatigue, ranging from minimal (I) to mild (II) to moderate (III) to severe (IV) ( Box 1 ).
Which one of the following statements best describes the symptoms associated with your heart condition:
- I.
I have no limitation of physical activity. Ordinary physical activity does not cause fatigue, shortness of breath, or chest pain.
- II.
I have slight limitation of physical activity. Ordinary physical activity results in fatigue, shortness of breath, or chest pain.
- III.
I have marked limitation of physical activity. Less than ordinary activity causes fatigue, shortness of breath, or chest pain.
- IV.
I am unable to engage in any physical activity without discomfort. Fatigue, shortness of breath, or chest pain may be present even at rest.
To assess depressive symptoms, all participants completed the 9-item Patient Health Questionnaire (PHQ-9). The PHQ-9 is a well-studied and validated diagnostic tool for identifying depression with a score of ≥10 representing 88% specificity and 88% sensitivity. Patients were categorized as “depressed” if they scored a 10 or greater on the PHQ-9, which represented an estimate of the burden of depressive symptoms.
Participants underwent symptom-limited exercise stress testing according to a standard Bruce protocol (those unable to complete the standard protocol were converted to a manual protocol) with continuous 12-lead electrocardiogram monitoring. Immediately before and after exercise, participants underwent complete 2-dimensional echocardiograms at rest with all standard views using an Acuson Sequoia Ultrasound System (Siemens Medical Solutions, Mountain View, California) with a 3.5-MHz transducer and Doppler ultrasound examination. Left ventricular ejection fraction, diastolic function, and left ventricular mass were assessed as previously described. We defined exercise-induced ischemia as the presence of ≥1 new wall motion abnormalities at peak exercise that was not present at rest. Each of the 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. A single experienced cardiologist, who was blinded to the results of all laboratory values and clinical histories, interpreted all echocardiograms.
Demographic characteristics, medical history, and smoking status were assessed by self-report questionnaire. Alcohol use was assessed using the Alcohol Use Disorders Identification Test (AUDIT-C). We measured weight and height and calculated the body mass index (kg/m 2 ). Participants were asked to bring their medication bottles to the study appointment, and research personnel recorded all current medications. Medications were categorized using Epocrates Rx (San Mateo, California). Lipid values were measured by standard laboratory techniques. Cystatin C was measured using the Siemens assay, and estimated glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equation.
To identify hospitalizations for HF or MI, we conducted annual telephone interviews with participants or their proxies regarding recent emergency room visits, hospitalizations, or death. Two independent and blinded adjudicators each reviewed any reported events, medical records, death certificates, or coroner’s reports. If the adjudicators agreed on the outcome classification, their classification was binding. If they disagreed, a third blinded adjudicator reviewed the event and determined the outcome classification. MI was defined using standard diagnostic criteria. Hospitalization for HF has been previously defined.
Baseline characteristics between prespecified groups were compared using ANOVA for continuous variables and chi-square test for dichotomous variables. We used ordinal logistic regression for cross-sectional analyses with functional status (severe vs moderate vs mild vs minimal symptoms) as the outcome. Because there were only 49 participants with severe limitation of functional status, they were combined with participants with moderate limitation of functional status for all models. Cox proportional hazards models were used for longitudinal analyses. As a subgroup analysis, subjects with a diagnosis of HF at baseline were defined as subjects who self-reported a history of HF, had a left ventricular ejection fraction <50%, or had diastolic dysfunction (pseudonormal or restrictive pattern) on baseline echocardiogram at rest. We checked for interaction of depressive symptoms with gender, age, marital status, exercise capacity, presence of inducible ischemia, and HF. Analyses were performed using Stata (version 12.1; Statacorp, College Station, Texas).
Results
At baseline, among 1,023 participants, 199 (19.4%) had depressive symptoms (PHQ-9 score ≥10). Compared with nondepressed participants, those who were depressed were younger and less likely to be male or married ( Table 1 ). Patients with depression had lower income and were more likely to smoke than those without depression. They were also more likely to have a history of diabetes, myocardial infarction, heart failure, and/or increased body mass index. Participants with depressive symptoms had lower exercise capacity, greater left ventricular mass, and were more likely to be taking a statin medication.
| Variables ∗ | Depressive Symptoms | p value | |
|---|---|---|---|
| Yes (n=199) | No (n=824) | ||
| Age (years) | 62.6 (±11.9) | 67.8 (±10.4) | <0.001 |
| Men | 152 (76.4%) | 688 (83.4%) | 0.021 |
| White | 110 (55.3%) | 505 (61.2%) | 0.125 |
| High school graduate | 166 (83.4%) | 725 (88.1%) | 0.077 |
| Annual income <$20K | 128 (64.3%) | 370 (45.2%) | <0.001 |
| Married | 66 (33.2%) | 370 (45.0%) | 0.002 |
| Hypertension | 151 (76.3%) | 572 (69.5%) | 0.060 |
| Diabetes mellitus | 68 (34.3%) | 197 (23.9%) | 0.003 |
| Myocardial infarction | 121 (61.7%) | 426 (51.9%) | 0.013 |
| Heart failure | 49 (24.8%) | 130 (15.9%) | 0.003 |
| eGFR (ml/min) | 70.6 (±21.3) | 70.9 (±25.1) | 0.840 |
| Stroke | 33 (16.8%) | 115 (14.0%) | 0.320 |
| Coronary revascularization | 109 (55.3%) | 493 (59.8%) | 0.249 |
| LV ejection fraction (%) | 60.5 (±10.1) | 61.9 (±9.5) | 0.062 |
| Diastolic dysfunction † | 22 (12.7%) | 94 (12.8%) | 0.984 |
| LV mass (g/m 2 ) | 102.6 (±29.9) | 97.2 (±25.5) | 0.011 |
| Resting wall motion index score | 1.2 (±0.4) | 1.2 (±0.3) | 0.178 |
| Exercise capacity (METs) | 6.5 (±3.2) | 7.5 (±3.3) | <0.001 |
| Inducible ischemia | 41 (24.0%) | 187 (24.4%) | 0.904 |
| BMI (kg/m2) | 29.2 (±5.7) | 28.2 (±5.2) | 0.016 |
| Current smoker | 67 (33.8%) | 134 (16.3%) | <0.001 |
| Regular alcohol use | 55 (27.8%) | 238 (29.1%) | 0.713 |
| Anti-platelet | 145 (74.0%) | 596 (73.1%) | 0.809 |
| B-blocker | 119 (60.7%) | 474 (58.2%) | 0.514 |
| ACE-I or ARB | 104 (53.1%) | 420 (51.5%) | 0.701 |
| Statin | 113 (57.7%) | 544 (66.8%) | 0.017 |
∗ Number (percent) for dichotomous variables; mean ± standard deviation for continuous variable.
† Diastolic dysfunction = pseudonormal or restrictive pattern on echo.
Participants with depression were more likely to report poor (class III or IV) functional status than those without depression (44% vs 17%; p <0.001; Figure 1 ). Of the 199 participants with depression, 38 (17%) had minimal, 78 (39%) had mild, and 87 (44%) had moderate or severe limitation of functional status (p <0.001). Of the 824 participants without depression, 343 (42%) had minimal, 338 (41%) had mild, and 143 (17%) had moderate or severe limitation of functional status (p <0.001).
Perception of higher symptom burden was associated with greater LV mass index, higher wall motion score index, worse exercise capacity, and greater inducible ischemia ( Table 2 ). Compared with those with minimal symptoms, participants with greater functional status limitation did not have significant differences in left ventricular ejection fraction or presence of diastolic dysfunction ( Table 2 ). The prevalence of depressive symptoms ranged from 9.0% in patients with mild symptoms to 46.9% in patients with severe symptoms (p <0.001).
| Variable | Functional status classification | p value | |||
|---|---|---|---|---|---|
| Minimal I (n=347) | Mild II (n=416) | Moderate III (n=181) | Severe IV (n=49) | ||
| LV ejection fraction | 62.2 (±9.1) | 61.7 (±9.5) | 60.9 (±10.5) | 60.5 (±11.1) | 0.405 |
| Diastolic dysfunction ∗ | 36 (10.8%) | 56 (15.0%) | 18 (11.3%) | 6 (14.3%) | 0.369 |
| LV mass index (g/m 2 ) | 95.4 ± 25.0 | 98.0 ± 25.9 | 101.3 ± 27.9 | 111.6 ± 33.0 | <0.001 |
| Resting wall motion index | 1.1 (±0.3) | 1.2 (±0.4) | 1.2 (±0.4) | 1.2 (±0.4) | 0.045 |
| Exercise capacity (METs) | 9.0 (±3.6) | 6.6 (±2.7) | 5.7 (±2.6) | 5.0 (±2.6) | <0.001 |
| Inducible ischemia | 67 (18.8%) | 102 (26.7%) | 48 (26.5%) | 11 (29.7%) | 0.016 |
| Depressive symptom score | 3.2 (±4.3) | 5.3 (±5.1) | 7.9 (±6.1) | 9.6 (±6.8) | <0.001 |
| Depression (PHQ-9 score ≥10) | 34 (9.0%) | 78 (18.8%) | 64 (35.4%) | 23 (46.9%) | <0.001 |
∗ Diastolic dysfunction = pseudonormal or restrictive pattern on echocardiogram.
Multivariate analysis of the association between depression and perceived functional status was significant after adjustment for baseline demographics (age, gender, income, marital status), co-morbidities (history of diabetes, myocardial infarction, heart failure, use of statin medication, body mass index, smoking), left ventricular systolic function, and cardiac disease severity (exercise capacity, left ventricular mass, inducible ischemia, wall motion index score at rest; Table 3 ). Participants with depression had 2.7 times greater odds of having worse perceived functional status compared with those without depressive symptoms. Other predictors of worse functional status included poor treadmill exercise capacity (<5 metabolic equivalents of task [METs]), current smoking, annual income of <20,000 USD per year, and history of HF ( Table 4 ). There were no significant interactions of depression with gender, marital status, inducible ischemia, or exercise capacity.
| Model | Worse functional classification | |
|---|---|---|
| OR (95% CI) | p value | |
| Unadjusted | 3.61 (2.67, 4.87) | <0.001 |
| Model 1 | 3.32 (2.45, 4.51) | <0.001 |
| Model 2 | 2.78 (2.02, 3.82) | <0.001 |
| Model 3 | 2.68 (1.89, 3.79) | <0.001 |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
