Contents lists available at ScienceDirect Maturitas journal homepage: www.elsevier.com/locate/maturitas Exploring the path between depression, anxiety and 10-year cardiovascular disease incidence, among apparently healthy Greek middle-aged adults: The ATTICA study Natasa Kollia a , Demosthenes Panagiotakos a, ⁎ , Ekavi Georgousopoulou a , Christina Chrysohoou b , Mary Yannakoulia a , Christodoulos Stefanadis b , Somnath Chatterji c , Josep Maria Haro d , Charalabos Papageorgiou e , Christos Pitsavos b , for the ATTICA Study investigators a Department of Science of Dietetics and Nutrition, School of Health Science and Education, Harokopio University, Athens, Greece b First Cardiology Clinic, School of Medicine, University of Athens, Athens, Greece c Information, Evidence and Research, World Health Organization, Geneva, Switzerland d Parc Sanitari Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain e Department of Psychiatry, School of Medicine, University of Athens, Athens, Greece ARTICLE INFO Keywords: Depression Anxiety Psychological distress Cardiovascular disease CVD risk factors Mediation ABSTRACT Objectives: Although there is substantial evidence that psychological factors play an important role in the onset and course of cardiovascular disease (CVD), less is known about their combined effect and the pathways by which they affect cardiovascular health. The present work aimed to prospectively explore the effects of de- pression and anxiety on the 10-year CVD incidence, in relation to other lifestyle determinants, as linking factors in the context of the ATTICA study. Study design/Main outcome measures: The ATTICA study is a population- based, health and nutrition prospective cohort study (2002–2012), during which 853 middle-aged participants without a history of CVD [453 men (aged 45 ± 13 years) and 400 women (aged 44 ± 18 years)], underwent psychological evaluations at enrollment. The latent trait of depression and anxiety combined measure was es- timated and referred as “Psychological distress”; path analysis was applied to describe the relationships among the different factors. Results: “Psychological distress” was positively associated with the 10-year CVD incidence (adjusted OR per 10 units: 1.4, 95% CI: 1.1, 1.7). Three linking pathways were revealed: sedentariness, inflammation and metabolic syndrome. Moreover, “Psychological distress” mediated the association between socioeconomic status (SES) and CVD, with participants of low SES scoring higher on the psychological measure (adjusted linear regression coefficient b: -7.1, 95% CI: -9.7, -4.5). Conclusions: Lifestyle and clinical factors seem to link psychological distress with CVD development. Joint psychological assessments should be considered for inclusion in CVD preventive strategies, which should in- corporate interventions for interrupting the linking pathways. 1. Introduction Although there is evidence of declining rates of Cardiovascular Disease (CVD) mortality in several European countries, according to the recent European CVD Statistics (2017), CVD remains the leading cause of death in Europe with an age-adjusted death rate up to 500 per 100,000 individuals (45% of all deaths; responsible for over 4 million deaths per year) [1]. Moreover, mental disorders, such as depression and anxiety, are now considered on the top-5 of main causes of disability and morbidity in both genders in the developed world [2]. Several narrative and quantitative reviews of dozens of descriptive epidemiological studies have concluded that psychological factors predict CVD morbidity and mortality at primary and secondary level (i.e., in individuals with or without previous cardiovascular history) and relate to chronic diseases of adulthood [3]. In addition, depression and anxiety have been both linked to two of the identified CVD risk factors; socioeconomic inequalities [4] and the adaptation of unhealthy lifestyle including unhealthy dietary habits [5]. Although, many http://dx.doi.org/10.1016/j.maturitas.2017.09.005 Received 11 July 2017; Received in revised form 10 September 2017; Accepted 15 September 2017 ⁎ Corresponding author at: Harokopio University, 70 Eleftheriou Venizelou Ave, Athens, Attica, 176 61, Greece. E-mail addresses: d.b.panagiotakos@usa.net, dbpanag@hua.gr (D. Panagiotakos). Abbreviations: CVD, cardiovascular disease; SES, socioeconomic status; IRT, Item response theory; IPAQ, international physical activity questionnaire; ZDRS, Zung self-rating depression scale; STAI, state anxiety sub-scale of the Spielberger state-trait anxiety inventory; CRP, C-reactive protein; MetS, metabolic syndrome Maturitas 106 (2017) 73–79 0378-5122/ © 2017 Elsevier B.V. All rights reserved. MARK