Part 1 | Vascular risk factors for depression and apathy 31 2 Introduction Depression is highly prevalent among elderly individuals, with a reported prevalence in the community of 1.8% for major depression, 9.8% for minor depression, and 13.5% for clinically relevant depressive symptoms (CRDSs)1. Although cross-sectional studies2 3. have shown depression to be associated with poor health, functional impairment, decreased quality of life, and greater use of health services, prospective studies4 have shown depression and depressive symptoms to be independent determinants of mortality. Recently, myocardial infarction was shown to be a mediator of the higher mortality of depressed individuals5 6. The biological pathways hypothesized to link depression with cardiovascular disease include sympathetic nervous system activation, dysregulation of the hypothalamic-pituitary-adrenocortical axis, platelet aggregation dysfunction, and inflammation7 8. Studies investigating whether depression is also a risk factor for the development of cerebrovascular events have yielded mixed results. The recent consensus guideline of the American Heart Association and the American Stroke Association for the prevention of cerebrovascular events does not mention depression as a possible risk factor for stroke9. In a recent meta-analysis,5 the pooled relative risk of stroke in those with a depressed mood was 1.4 (range, 1.2-1.8), but this estimated risk was influenced by the methodologic shortcomings and heterogeneity of the studies included. In particular, most of the early studies used limited measures of depression, with only 2 using the DSM-IV to diagnose depression. The first of these studies used self-reported data on the occurrence of stroke, and the second used physician-reported ICD-10–classified cardiovascular disease10 11. Neither study documented the chronicity and severity of depression. Another source of heterogeneity in studies of the relationship between depressive symptoms and stroke is the possible moderating effect of cardiac disease. Because cardiac disease is an important predictor of stroke, stratifying by cardiac disease divides the population into low- and high-risk populations. If one assumes that the pathophysiologic mechanisms are comparable to those leading to cardiovascular disease in depressed individuals, depression in cardiac patients could aggravate the existing atherosclerotic disease, ultimately leading to stroke. Furthermore, the prevalence and incidence of depression would be expected to be higher in cardiac patients based on the vascular depression hypothesis, which states that subclinical underlying cerebrovascular disease may cause depression12 13 14 15 16. According to this hypothesis, underlying atherosclerotic disease could give rise to both stroke and depression in cardiac patients. Bearing in mind these sources of heterogeneity in earlier studies, we investigated whether the presence, severity, and chronicity of depressive symptoms and major depressive disorder (MDD) are independently associated with incident stroke in elderly patients with or without cardiac disease during a 9-year follow-up.
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