In recent years, a number of studies have that depression is a risk factor for atherosclerotic-related cardiovascular medical events. Given the high rate of cardiovascular disease (CVD) and depression in this country, it is important to examine mechanisms by which depression may contribute to cardiac pathophysiology. In this study, 70 older, non-smoking men and women at high risk for CVD (or with manifest CVD not on medications, or on medications which can be safely stopped for testing), who are also depressed, will be randomized to a cognitive-behavioral intervention or usual care. At baseline, subjects will be assessed for traditional cardiovascular risk factors (lipids, blood pressure, exercise habits) and non-traditional cardiovascular risk factors (e.g., endothelial dysfunction, urinary nitrogen oxides, platelet reactivity, cell adhesion molecules, asymmetric dimethylarginine). Hypothalamic pituitary axis (HPA) abnormalities (measured with cortisol levels, diurnal cortisol and reactivity) and sympathomedullary/parasympathetic activity (measured with respiratory sinus activity (RSA), baroreflex activity, and pre-systolic ejection period (PEP) reactivity) will also be assessed. Subjects will be randomized to an intervention )16 weeks of cognitive-behavioral therapy (CBT) for depression) to a wait-list control (followed by CBT). The above measures will be assessed at baseline, post-treatment and at 6- months follow-up. Thirty non-depressed controls matched for age, gender and cardiovascular risk level will also be assessed at the pre-treatment time period. We hypothesize that at baseline, compared to controls, depressed subjects will have significantly higher levels of HPA activity, lower RSA, higher endothelial dysfunction, but similar levels of PEP. We hypothesize that subjects in the intervention will demonstrate significant reduction in depressed mood, improve HPA activity, lower endothelial dysfunction, and lower SA, compared to control subjects and that these changes will be maintained at six-month follow-up. The study is designed to provide new information on how depression might lead to atherosclerosis and affect cardiovascular morbidity and mortality.
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