European Heart Journal Advance Access originally published online on April 8, 2008
European Heart Journal 2008 29(9):1110-1117; doi:10.1093/eurheartj/ehn137
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Analysis of potential predictors of depression among coronary heart disease risk factors including heart rate variability, markers of inflammation, and endothelial function
1 Department of Internal Medicine, Cardioangiology, University of Bologna, Bologna, Italy
2 Section of Epidemiology and Public Health, University of Chieti, Chieti, Italy
3 University of Bologna, Bologna, Italy
4 Mario Negri Institute for Pharmacological Research, Bergamo, Italy
Received 9 November 2007; revised 21 February 2008; accepted 10 March 2008; online publish-ahead-of-print 8 April 2008.
* Corresponding author. Tel: +39 035 319888, Fax: +39 035 319331, Email: gcosta{at}marionegri.it
Aims: We investigated the relationship between autonomic nervous system balance, systemic immune activation, endothelial dysfunction, and depression in patients free of coronary heart disease (CHD) with increased CHD risk.
Methods and results: Depression status (Beck Depression Inventory, BDI), selected CHD risk factors, inflammation markers, measures of heart rate variability (HRV), and indices of endothelial function (flow-mediated dilation, FMD) were evaluated in 415 subjects free of CHD, diabetes mellitus, and other life-threatening conditions, with at least two CHD risk factors among the following: older age, male gender, current smoking, hypertension, and dislipidaemia. Overall, 51.7% of the participants were males, aged 57.6 ± 8.8 years on average (minimum 30, maximum 70). Almost half were hypertensive, 43.9% were dyslipidemic, 30.4% current smokers, and 23.1% showed a depressive symptomatology (BDI 
10). Logistic regression showed that, as compared with non-depressed individuals and after adjustment for age, gender, and hypertension, depressive subjects were significantly more likely to be smokers, to have higher total cholesterol, higher C-reactive protein, and Interleukin-6. In addition, depressed subjects were more likely to have altered HRV and their FMD was severely impaired (adjusted odds ratio of 1% increase = 0.72; 95% CI: 0.61–0.86).
Conclusion: Our data indicate an independent association between depression and impaired HRV, systemic inflammatory, and endothelial function. These mechanisms play a role not only in the complication of advanced forms of disease, but also promote and/or accelerate the early disease and connect depression and CHD.
Key Words: Depression disorders • Coronary heart disease • Autonomic nervous system • Endothelial function • Inflammation markers
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