Abstract 5011: Role of Autonomic Nervous System Dysregulation and Inflammation in the Increased Risk of Depression for Cardiovascular Mortality: The Cardiovascular Health Study

The increased cardiovascular (CV) risk associated with depression is hypothesized to be explained by autonomic nervous system (ANS) dysregulation and inflammatory processes. This study determines the role of ANS dysregulation and inflammation in the predictive value of depression for CV mortality. 908 participants of the Cardiovascular Health Study (age 71±5 yrs) free of CV disease were evaluated for depression (CES-D scale), ANS dysregulation by abnormal non-linear heart rate variability (decreased short-term fractal scaling exponent), and inflammation (IL-6, CRP, fibrinogen and WBC). Predictors of CV mortality were examined using Cox regression analysis, adjusting for age, sex, race, systolic blood pressure, diabetes, subclinical disease, use of beta-blockers, smoking status, BMI, and physical activity (median follow-up=13.3 yrs). Risks were calculated for subgroups based on the presence or absence of depression, and ANS or inflammatory CV risk factors (Figure ). Depression was predictive of CV mortality (RR=1.88, CI=1.23–2.86), ANS dysregulation (p=0.014) and inflammatory markers (IL-6 p=0.072; WBC p=0.033; and fibrinogen p=0.050) were correlated with depression. The association of depression with CV mortality occurred primarily in the presence of ANS dysregulation and/or inflammation (Figure ). Addition of ANS and inflammatory markers to the multivariate model did not substantially reduce the CV mortality risk of depression (adjusted RR=1.65, CI=1.03–2.65). Depression is predictive of cardiovascular mortality, and the elevated risk is additive to autonomic nervous system dysregulation and inflammation