Depression and cardiovascular disease: an update on how course of illness may influence risk.

Depression constitutes a novel and independent risk factor for cardiovascular disease, which despite extensive support in the literature has been underappreciated. While much of the evidence for depression as a risk factor for cardiovascular disease is based on studies following myocardial infarction, the elevated vascular risk conveyed by depression is not confined to periods following acute coronary syndromes. For that matter, the risk appears across mood disorders with evidence for even greater risk in bipolar disorder. This review summarizes the literature linking depressive disorders to cardiovascular mortality with a focus on how the course of illness of mood disorders may influence this risk. Mood disorders may influence risk over decades of illness in a dose-response to symptom burden, or the persistence of affective symptomatology. This may be mediated through changes in the activity of the autonomic nervous system, the hypothalamic-pituitary-adrenal axis, and inflammatory cytokines. Whether treatment of depression can mitigate this risk is not established although there are suggestions to support this contention, which could be better studied with more effective treatments of depression and larger standardized samples. Directions for future study of mechanisms and treatment are discussed. Regardless of causal mechanisms, persons with depressive disorders and other risk factors for vascular disease represent a neglected, high-risk group for cardiovascular events. In addition to the appropriate treatment for depression, screening and optimized management of traditional risk factors for cardiovascular diseases is necessary.