It is reasonable to consider screening SIHD patients for depression and to refer or treat when indi- cated.237,239,323,457,463,674,675 (Level of Evidence: B) Class IIb 1. Treatment of depression has not been shown to improve cardiovascular disease outcomes but might be reasonable for its other clinical benefits.237,238,676 (Level of Evidence: C) Depression is a major cause of disability in developed countries and often coexists with SIHD.677,678 About 20% of patients with angiographic evidence of CAD and a similar percentage of those recovering from AMI have comorbid Multiple observational studies have demonstrated an asso- ciation between depression and cardiovascular events. In several studies involving $1000 outpatients with SIHD, those with symptoms of depression had more physical limi- tation, more frequent angina, and lower perceived quality of life than patients without depressive symptoms.239,683 One meta-analysis examined 21 prospective studies in healthy populations and 34 studies in patients with existing IHD.684 The studies in healthy cohorts demonstrated an 81% greater incidence of ischemic events (MI or fatal IHD) among patients with symptoms of depression over an average follow-up period of 10.8 years. A similarly increased risk was observed in patients with established IHD who had symptoms of depression. Relatively few studies, however, have reported estimates of risk that have been adjusted for traditional risk factors or severity of CAD. Although in aggregate the observational cohort studies suggest that depression confers a significant risk for adverse cardiovascular outcomes, con- founding by other risk factors or by disease severity is difficult to exclude. Moreover, most studies in patients with CAD have enrolled patients after recent MI or CABG, and the relevance to patients with SIHD is uncertain. Putative mechanisms for a contribution of depression to atherogenesis and adverse cardiovascular events include both behavioral and biological effects. 