Heartache and heartbreak--the link between depression and cardiovascular disease.

The close, bidirectional relationship between depression and cardiovascular disease is well established. Major depression is associated with an increased risk of coronary artery disease and acute cardiovascular sequelae, such as myocardial infarction, congestive heart failure, and isolated systolic hypertension. Morbidity and mortality in patients with cardiovascular disease and depression are significantly higher than in patients with cardiovascular disease who are not depressed. Various pathophysiological mechanisms might underlie the risk of cardiovascular disease in patients with depression: increased inflammation; increased susceptibility to blood clotting (owing to alterations in multiple steps of the clotting cascade, including platelet activation and aggregation); oxidative stress; subclinical hypothyroidism; hyperactivity of the sympatho-adrenomedullary system and the hypothalamic-pituitary-adrenal axis; reductions in numbers of circulating endothelial progenitor cells and associated arterial repair processes; decreased heart rate variability; and the presence of genetic factors. Early identification of patients with depression who are at risk of cardiovascular disease, as well as prevention and appropriate treatment of cardiovascular disease in these patients, is an important and attainable goal. However, adequately powered studies are required to determine the optimal treatment regimen for patients with both depression and cardiovascular disorders.