Role of Depression

The role of depression in CHD has drawn increasing attention in recent years, not only with regard to its adverse impact on prognosis among patients with established CHD but also with regard to its potential contribution to the pathogenesis of CHD. Although several well-conducted, prospective studies have reported findings in support of an increased risk associated with depression for incident CHD events, our investigation focused specifically on the elderly, the age at which the preponderance of heart disease becomes clinically manifest. Moreover, our sample was ethnically and socioeconomically diverse and broadly representative of community-dwelling elderly participants in general. The only other study on depression and incident CHD end points in the elderly involved a secondary analysis of data from the Systolic Hypertension in the Elderly Program (SHEP) trial. The latter results, however, have more limited generalization because the participants in the SHEP trial were considerably healthier than are community-dwelling elderly individuals in general.

Our findings suggest that among older women, but not older men, depressive symptoms are associated with an increased risk for incident CHD events independent of established CHD risk factors. However, additional adjustment for impaired physical function decreased the risk for incident CHD outcomes to nonsignificant levels, with a reduction in risk estimates of about 50%. We also examined whether the risk for incident CHD events might be mostly restricted to those with unusually high symptom levels. Among men, there was no consistent relationship between symptom levels and outcomes. The relationship among women seemed more consistent with a gradient effect for increasing symptom levels rather than a threshold effect at high symptom levels, although neither effect survived adjustment for physical function. Thus, our data are not consistent with the notion that the "clinically" depressed form a special risk category for incident CHD events, although we certainly cannot dismiss this possibility entirely because of the lack of a clinical diagnosis of depression.

The findings suggest that depressive symptoms may be related to CHD risk in older women because of their correlation with impaired physical function. Impaired physical function is often considered a measure of general frail health, resulting from the cumulative burden of morbidities incurred throughout life. It is highly predictive of overall mortality in the elderly and has shown strong associations with CHD mortality, severity of MI, and post-MI survival. Impaired physical function also may be more specifically related to CHD end points as a potential marker of subclinical disease. Physical function represents mobility-related activities, such as walking a half mile or climbing stairs, and older persons may reduce these kinds of activities to prevent coronary ischemic episodes or because of other preexisting cardiovascular conditions, such as intermittent claudication or congestive heart failure. Impaired function might also result from silent ischemic events or asymptomatic MIs, the incidence of which is known to increase with age and predispose to cardiac death. Regardless of how impaired physical function affects CHD risk, it is strongly correlated with depressive symptoms and perhaps overwhelms any independent effect of these symptoms on CHD outcomes.

Although our findings seem to negate a truly independent contribution of depression to coronary risk in the elderly population in general, the results from our exploratory analysis are suggestive of an independent effect of these symptoms in a subgroup of elderly women, that is, women who are in relatively good physical health, defined in our analysis as those who survived at least 3 more years event-free or who had no mobility-related impairments. This would be consistent with the generally much stronger associations between depression and incident CHD outcomes in middle-aged populations, where the prevalence of impaired physical function, or overall frail health, is minimal. It is also consistent with the increased risk associated with depression for CHD outcomes among the relatively healthy women in the SHEP trial. In addition, there is some evidence that suggests that depression may actually precipitate a decline in physical functioning. This raises the possibility that impaired physical function is perhaps an intermediary step in the causal pathway between depression and CHD events, for example, by being a manifestation of early or subclinical disease. In this case, controlling for physical function might, in fact, have amounted to overadjustment. Thus, our findings do leave open the possibility that depressive symptoms contribute independently to risk for acute CHD events in healthier older women.

Various mechanisms have been proposed to account for the increased risk for CHD outcomes associated with depression in middle-aged populations and that may also play a role in healthier older women. For example, depression has been linked to altered neuroendocrine function involving the adrenergic and corticosteroid systems, to poor adherence to medical treatment, and to co-occurrence with established risk factors. Depression is also thought to increase coronary risk by promoting arrhythmic events through its impact on autonomic tone, especially increased sympathetic tone and decreased vagal tone. Altered autonomic tone has been shown to increase risk for ventricular arrhythmias and sudden cardiac death by a number of mechanisms, including elevated catecholamine levels, prolongation of the electrocardiographic QT interval, and reduced heart rate variability.

The lack of an association between depressive symptoms and CHD risk among older men was unexpected. Most recent studies fail either to report or to find a differential effect by sex. However, data from the SHEP trial[14] also showed no association between depression and CHD risk in older men but a positive association in older women, although the SHEP findings were limited to women who reported an increase in depressive symptoms. We also considered examining changes in depression status, but the power for this analysis was very limited, partly because of missing depression data during follow-up. A recent study using combined data from 3 EPESE sites found some evidence for an association between changes in depression status and increased risk for incident cardiovascular disease. However, this effect was, in contrast to those of the SHEP trial, limited to men, and more studies are clearly needed to establish whether changes in depression reliably increase risk for incident CHD in elderly men or women. Our approach of classifying individuals according to initial depression status is consistent with most other studies on this subject, and our findings raise doubt that a single assessment of depression is a useful predictor of incident CHD in the elderly.

In summary, similar to traditional CHD risk factors, depression does not predict CHD outcomes nearly as consistently in this older population as it does in middle-aged populations. Depression was not associated with an increased risk for incident CHD among older men, whereas among older women the increased risk is possibly limited to those who are relatively healthy or who do not have serious limitations in physical function. Except for perhaps in this latter group, our data suggest that these symptoms may not be useful for the identification of older persons at high risk for CHD, and, unlike for the secondary prevention of CHD, targeting these symptoms is unlikely to be an effective strategy for the purpose of primary prevention. However, our findings, together with those of the SHEP trial, lend some support to the notion, advocated by others, that depression is possibly a more important risk factor for CHD in women than it is in men.