Atherosclerosis 212 (2010) 292–298 Contents lists available at ScienceDirect Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis Autonomic nervous system, inflammation and preclinical carotid atherosclerosis in depressed subjects with coronary risk factors Carmine Pizzi a,∗ , Lamberto Manzoli b , Stefano Mancini c , Gigliola Bedetti d , Fiorella Fontana a , Grazia Maria Costa e a Department of Internal Medicine, Aging and Nephrological Diseases, University of Bologna, Italy b Section of Epidemiology and Public Health, University “G. d’Annunzio” of Chieti, Italy c Department of Internal Medicine, University of Modena, Italy d Division of Cardiology, S. Maria della Scaletta Hospital, Imola, Italy e Department of Cardiovascular Disease, University of Bologna, Italy article info Article history: Received 30 March 2010 Received in revised form 23 April 2010 Accepted 28 April 2010 Available online 6 May 2010 Keywords: Autonomic nervous system Inflammation Intima-media thickness Depression Coronary risk factors abstract Objectives: We investigated the relationship between intima-media thickening (IMT) as an expression of preclinical atherosclerosis and coronary risk factors, including the autonomic nervous system and inflammation markers, in depressed subjects free from coronary artery disease. Methods: We studied 391 asymptomatic subjects with a cluster of risk factors, and we evaluated depres- sion using the Beck Depression Inventory. IMT of the common carotid artery was determined by B-mode ultrasound imaging. Traditional risk factors for atherosclerosis were recorded. Markers of inflammation (C-reactive protein, CRP; interleukin 6, IL-6) and heart rate variability (time domain) were determined. Results: A total of 90 (23.0%) subjects showed a depressive symptomatology. The average IMT was increased in depressed subjects (0.87 ± 0.35 mm) at risk for CHD but free from disease as compared to controls (0.77 ± 0.19 mm; p < 0.001). Heart rate variability was reduced in depressed subjects. Levels of SDNN (103 ± 14 ms) and SDANN (93 ± 20 ms) were decreased in depressed subjects as compared to non-depressed subjects (SDNN 113 ± 22 ms and SDANN 108 ± 35 ms; p < 0.001). Subjects with depression had higher CRP (1.14 ± 0.65 mg/dl) and IL-6 (2.00 ± 0.40 pg/ml) than subjects without depression (CRP: 0.79 ± 0.34 mg/dl; IL-6: 1.6 ± 0.6 pg/ml; p < 0.001, respectively). In multivariate analysis, depression was positively correlated with CRP and IL-6 and IMT, and inversely associated with levels of SDANN. Conclusions: IMT is higher in depressed subjects, indicating that atherosclerosis is accelerated in this sub- group of patients. This is mainly due to patho-physiological mechanisms which connect depression and coronary artery disease, such as inflammation and imbalance of the autonomic nervous system. © 2010 Elsevier Ireland Ltd. All rights reserved. 1. Introduction The prevalence of depression in patients with coronary heart disease (CHD) is estimated to be about of 40%, and half of these patients develop major depression [1]. Depression has appeared as a new and important cardiac risk factor and the occurrence of depression in patients with CHD leads to an unfavorable outcome. Recent evidence has suggested that a diagnosis of depression following myocardial infarction conferred a 2–2.5-fold increased independent risk of a poorer cardiovascu- lar prognosis [2]. In fact, a relationship between the symptoms of ∗ Corresponding author at: Dipartimento di Medicina Interna, dell’Invecchiamento, Malattie Nefrologiche (Padiglione 11), Università di Bologna, Via Giuseppe Massarenti 9, 40138 Bologna, Italy. Tel.: +39 51 6364911; fax: +39 51 392486. E-mail address: carmine.pizzi@unibo.it (C. Pizzi). depression and the severity of CHD has been documented [3], sug- gesting that depression disorders could accelerate atherosclerosis progression and its clinical complications. However, the cause of accelerated atherosclerosis in patients with depression and CHD remains unclear. Several potential patho- physiological mechanisms have been suggested to contribute to an adverse prognosis in CHD-depressed patients, namely the different lifestyle of depressed individuals [4], modifications in platelet func- tion [5], abnormal autonomic tone [6], systemic immune activation [7] and endothelial dysfunction [8]. Among these, altered cardiac autonomic tone has been associated with depressed patients with and without CHD [6]. Moreover, depressed patients have exhibited elevated inflammation markers [7]. The interrelationship between autonomic nervous system dysfunction and inflammation, and atherosclerosis is well documented and is one of the earliest steps in the development of atherosclerosis [9,10]. Detecting the early stage of atherosclerosis is of major clinical relevance because it may offer the possibility of identifying patients 0021-9150/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2010.04.038