Putative mechanisms for a contribution of depression to atherogenesis and adverse cardiovascular events include both behavioral and biological effects. Depression is associated with poor compliance with risk factor modification strategies and with poor adherence to prescribed medication regi- mens.460,462 Patients diagnosed with this disorder are 2- to 4-fold less likely to adhere to medications and lifestyle recommendations, engage in self-management practices, or Fihn et al Stable Ischemic Heart Disease: Full Text e401 comply with recommendations for testing and follow- up.462,675,685 691 Alternatively, some studies suggest the pos- sibility of more direct pathophysiological links, including platelet activation,692 695 endothelial dysfunction,696 reduced heart rate variability,697 699 and inflammation.700 Despite the association of depression with adverse cardio- vascular outcomes, no clinical trials have established a reduction in cardiovascular risk with either counseling or antidepressant therapy. In the ENRICHD (Enhancing Recov- ery in Coronary Heart Disease) trial, 2481 patients with depression or low social support after MI were randomized to usual care or cognitive behavioral therapy, supplemented by a selective serotonin reuptake inhibitor when indicated. Ac- tive therapy was associated with improvements in depression and low social support but with no improvement in event-free survival after a mean 24 months of follow-up.237 A secondary analysis, however, demonstrated a significantly lower risk of death or MI in patients treated with a selective serotonin reuptake inhibitor.676 The safety and efficacy of sertraline in patients with a recent ACS were demonstrated in SADHART (Sertraline Antidepressant Heart Attack Randomized Trial). Patients were randomized to sertraline or placebo for 24 weeks. Sertraline resulted in improved depressive symptoms and no change in LVEF, ventricular ectopy, or QT interval. 