Part 1 | Vascular risk factors for depression and apathy 39 2 contractions,38 as well as behavioral pathways, such as poorer compliance with cardiac treatment and a less healthy lifestyle 39. At the same time, the vascular depression hypothesis suggests that subclinical underlying cerebrovascular disease can cause depression in cardiac patients 13. The relationship between depression and vascular diseases seems to be reciprocal 40 41. This reciprocal relationship could be synergistic in cardiac patients but not in patients without cardiac disease. This would explain the interaction between cardiac disease and depression found in our study. An alternative explanation for our findings is that depressive symptoms are an indicator of a poor prognosis in cardiac patients because the number of depressive symptoms is (partly) associated with the severity of underlying cardiovascular disease 42. We chose to use the CES-D to score depressive symptoms because, when LASA was designed, studies showed that the overlap with physical illness was limited 43 44. A more recent study 45 of patients undergoing cardiac surgery showed that the CES-D detected change after this intervention, not only shortly after surgery but also later during follow-up, which suggests that depressive symptoms, as measured with the CES-D, benefit from an improvement in cardiovascular status. Moreover, trials of antidepressants in depressed patients after myocardial infarction do not consistently report less long-term depression or a better cardiac prognosis, which suggests that depressive symptoms may in part be due to the severity of the underlying cardiac disease 46 47 48 49. In conclusion, cardiac disease moderates the association between CRDSs and incident stroke. This moderating effect of cardiac disease could be explained not only by a synergistic effect of the reciprocal mechanisms between vascular disease and depression but also by depressive symptoms being an indicator of the severity of underlying cardiac disease. Both explanations deserve more attention in further research because they have implications for targeting effective interventions. At least, depression in cardiac patients seems to be an indicator of a poorer prognosis to some extent because of the higher incidence of stroke among these patients, as this study showed. Funding/Support: This study is based on data collected in the context of LASA, which is largely funded by the Dutch Ministry of Health, Welfare and Sports. Additional Contributions: T. Feuth, MSc, Department of Epidemiology, Biostatistics and High Technology Assessment, and M. Lappenschaar, PhD, Department of Psychiatry, Radboud University Nijmegen Medical Centre, advised us on using extended Cox proportional hazards modeling with time-dependent variables.
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