Autonomic nervous system dysfunction and inflammation contribute to the increased cardiovascular mortality risk associated with depression.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Kop
Willem J
WJ
Department of Medicine, Division of Cardiology, University of Maryland Medical Center, Baltimore, MD 21201, USA. wkop@medicine.umaryland.edu
Stein
Phyllis K
PK
Tracy
Russell P
RP
Barzilay
Joshua I
JI
Schulz
Richard
R
Gottdiener
John S
JS
D000368:Aged; D001342:Autonomic Nervous System Diseases / Q000453:epidemiology*; D015415:Biomarkers; D002097:C-Reactive Protein; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000401:mortality* / Q000503:physiopathology; D002423:Cause of Death; D015331:Cohort Studies; D015897:Comorbidity; D003866:Depressive Disorder / Q000453:epidemiology*; D004562:Electrocardiography / Q000706:statistics & numerical data; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000453:epidemiology*; D015850:Interleukin-6 / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D012307:Risk Factors
D015415:Biomarkers; D015850:Interleukin-6; D002097:C-Reactive Protein