Is depression a major risk factor for coronary disease? A systematic review of the epidemiologic evidence

My objective is to examine systematically the status of the current evidence for and against depression as an independent major risk factor for coronary disease. From English-language reports on depression and coronary disease in MEDLINE (1966-2002) and PsycINFO (1967-2002), and from informal searches, I selected all studies that addressed the specific questions related to the established criteria for risk-factor status: (1) strength of association, (2) prediction, (3) specificity, (4) consistency, (5) dose-response effect, (6) biological plausibility, and (7) response to treatment. I find that the evidence for depression as a coronary disease risk factor is good for four criteria: strength of association, prediction, consistency, and dose-response effect. The evidence on specificity and biological plausibility is fair. Due to the lack of definitive studies, there is currently insufficient evidence for cardiac risk reduction in response to treatment for depression. My conclusion is that the evidence for depression's role as an independent major risk factor for coronary disease is good in four areas, but not yet conclusive in three, pointing to the need for three types of studies: (1) prospective, observational studies that address specificity questions, (2) studies of biological mechanisms linking depression and coronary disease, and (3) clinical trials of treatments for depression in people with coronary disease or at high risk for developing coronary disease.