Abstract
To investigate prospectively whether autonomic nervous system (ANS) dysfunction and inflammation play a role in the increased cardiovascular disease (CVD)-related mortality risk associated with depression. Participants in the Cardiovascular Health Study (n = 907; mean age, 71.3 ± 4.6 years; 59.1% women) were evaluated for ANS indices derived from heart rate variability (HRV) analysis (frequency and time domain HRV, and nonlinear indices, including detrended fluctuation analysis (DFA(1)) and heart rate turbulence). Inflammation markers included C-reactive protein, interleukin-6, fibrinogen, and white blood cell count). Depressive symptoms were assessed, using the 10-item Centers for Epidemiological Studies Depression scale. Cox proportional hazards models were used to investigate the mortality risk associated with depression, ANS, and inflammation markers, adjusting for demographic and clinical covariates. Depression was associated with ANS dysfunction (DFA(1), p = .018), and increased inflammation markers (white blood cell count, p = .012, fibrinogen p = .043) adjusting for covariates. CVD-related mortality occurred in 121 participants during a median follow-up of 13.3 years. Depression was associated with an increased CVD mortality risk (hazard ratio, 1.88; 95% confidence interval, 1.23-2.86). Multivariable analyses showed that depression was an independent predictor of CVD mortality (hazard ratio, 1.72; 95% confidence interval, 1.05-2.83) when adjusting for independent HRV and inflammation predictors (DFA(1), heart rate turbulence, interleukin-6), attenuating the depression-CVD mortality association by 12.7% (p < .001). Autonomic dysfunction and inflammation contribute to the increased cardiovascular mortality risk associated with depression, but a large portion of the predictive value of depression remains unexplained by these neuroimmunological measures.
Highlights
Depression is associated with an increased risk of cardiovascular disease (CVD) [1,2,3,4]
We examined the magnitude of change in the association between depression and CVD mortality when continuous heart rate variability (HRV) and inflammation markers were added to the Cox regression models
Depression was not associated with traditional CVD risk factors or subclinical disease (p > .2)
Summary
Depression is associated with an increased risk of cardiovascular disease (CVD) [1,2,3,4]. The pathophysiological mechanisms accounting for the relationship between depression and CVD risk remain unclear. These mechanisms may involve autonomic nervous system (ANS) dysfunction and inflammation. Prior cross-sectional studies have shown that depression is associated with autonomic dysfunction [5,6,7] and elevated inflammation markers [8,9,10,11], but the mediating role of these purported mechanisms has not been consistently established [12,13,14,15,16]. Elevated parasympathetic nervous system activity is associated with attenuated immune system responsiveness to inflammatory stimuli [27]. Additional research is needed to examine whether these autonomic and inflammation-related processes are involved in the relationship between depression and CVD progression
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
