There is considerable debate about whether the association of depression with adverse cardiovascular outcomes is confounded by worse baseline cardiac disease severity in depressed patients. In a sample of 1020 patients with stable CHD, we found no evidence that major depression is associated with systolic dysfunction, diastolic dysfunction, inducible ischemia, or cardiac wall motion abnormalities. Similarly, we found little evidence of an association between depressive symptoms and CHD severity, with the exception of worse systolic function in patients with PHQ-9 scores of ≥10. Overall, however, the lack of association we observed between major depression and cardiac disease severity suggests that greater underlying cardiac disease severity is unlikely to explain the increased risk of CHD events associated with depression.
As shown in the analyses controlling for age only, the univariate associations we observed between depression and better cardiac function were due, in large part, to the inverse relationship between depression and age, such that depressed participants were significantly younger than the nondepressed participants in our sample. This inverse association between depression and age is a common finding in both population (42
) and CHD samples (43
). The association between depression and cardiac function was no longer significant in the multivariate models controlling for age and other demographic and clinical risk factors.
The association between PHQ-9 depressive symptoms and worse systolic function raises the possibility that currently elevated depressive symptoms and past month clinical depression may be differentially related to cardiac function. It is possible that the frequency and recency of depressive symptoms captured by the continuous PHQ score may be more strongly associated with cardiac function than the number of criteria required for a clinical diagnosis of major depression within the past month. Nonetheless, these results should be interpreted with caution. Not only was there no association between systolic function and depression in the primary analysis using the CDIS-IV but the primary analysis actually suggested a nonsignificant trend in the opposite direction. Thus, any differences in the association of cardiac function with depressive symptoms versus a clinical diagnosis of depression would need confirmation in other studies.
Consistent with our present results, previous longitudinal studies have reported no significant association between depression and baseline measures of cardiac disease severity, such as LVEF and Killip Class (15
), although some have reported a significant association (21
). Our study adds to this literature by evaluating the association of depression with comprehensive measures of systolic function, diastolic function, inducible ischemia, and wall motion abnormalities. It should be noted, however, that although our study suggests there is no relationship between major depression and objective measures of disease severity, these findings do not necessarily reflect patients’ perceptions of the severity of their illness. Depression may be related to cardiac function via patient perceptions unrelated to objective physiological measures. For example, Knol et al. (44
) found that patients with Type 2 diabetes who were aware of their illness had increased rates of depression, whereas those unaware of their illness did not, highlighting the importance of patient perceptions over objective disease severity.
Our study is unique in utilizing multivariate models and comprehensive measures of both depression and cardiac disease severity to examine the relationship between depression and cardiac disease severity. In addition, our study included only patients with stable CHD, whereas prospective studies generally have included patients hospitalized with acute CHD events, such as patients pre CABG, post AMI, or post revascularization. Depression detected in our sample of patients with stable CHD may be more likely to reflect true clinical depression, rather than transient distress in response to an acute event.
An important limitation of the present study is that only 184 women were included in the primary analysis. This calls into question the generalizability of these results to women. However, we found no consistent evidence for a sex by depression interaction. The significant interaction between sex and diastolic dysfunction, such that major depression was associated with better diastolic function for women, should be interpreted with caution due to the small number of women (n = 184) in the analyses and the large number of tests in our secondary analyses. However, the large sample size, complete statistical control, and use of comprehensive measures of both depression and cardiac disease severity are notable strengths of this study.
If depression does not serve as a marker for cardiac disease severity, then it is important to identify the mechanisms that link depression with subsequent CHD events. There are several plausible biobehavioral mechanisms for which there is initial empirical support, including lifestyle factors like diet, exercise, tobacco use, heavy use of alcohol, and nonadherence to treatment; traditional risk factors like hypertension, diabetes, obesity, and insulin resistance; other physiological factors associated with depression, such as platelet activation, autonomic nervous system dysregulation, endothelial dysfunction, and inflammation; and genetic factors associated with both depression and CHD (6
). It is also possible that depression increases the risk of acute cardiac events, but not chronic atherosclerosis (47
). These are important areas for additional study, as identifying mechanisms may help to guide interventions for patients with CHD who are at increased risk due to depression.
In sum, the results of the present study found little evidence for an association between depression and cardiac disease severity in patients with stable CHD. This suggests that it is unlikely that depression is confounded with disease severity in prospective studies of depression and stable CHD outcomes.