This is a competitive renewal application for a study of cardiovascular autonomic dysregulation as a mechanism linking depression to mortality after acute myocardial infarction (MI). Pinpointing the mechanism is an important goal because it is one of the key steps in developing a treatment for post-MI depression that improves the chances for cardiac event-free survival. During the first 4 years of the study, a cohort of 356 depressed and 411 non-depressed post-MI patients were recruited and followed for up to 30 (mean = 24) months, during which time 47 deaths and 57 recurrent non-fatal MIs were documented. This cohort includes far more depressed patients than any other study of depression and mortality after MI, is highly diverse (40% women, 25% minorities), and very well characterized medically, with 100% follow-up. The original hypotheses were that both depression and low HRV predict mortality in post-MI patients, depressed post-MI patients have lower HRV than do non-depressed patients, and low HRV mediates the relationship between depression and mortality. The findings provide robust support for the first two hypotheses and partial support for the third. The proposed renewal will extend the follow-up of this unique cohort in order to increase the number of endpoints and derive new, state-of-the-art measures from the existing Holter monitor tapes, including QT interval measures and nonlinear and wavelet indices of HRV. These variables have recently been shown to be highly sensitive to specific components of cardiac autonomic modulation, and there is growing evidence that they are better predictors of mortality and other cardiac events than the traditional HRV indices.
The specific aims of the study are (1) to determine whether novel nonlinear and wavelet indices of HRV and QT interval variability are associated with depression and with mortality after acute myocardial infarction, (2) to determine whether they mediate the effect of depression on mortality after acute MI, and (3) to determine whether nighttime cardiovascular autonomic dysregulation in depressed post-MI patients is a stronger predictor of mortality than is daytime dysregulation.
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