Noninvasive assessment of subclinical atherosclerosis in persons with symptoms of depression


      • Depression and depressive symptoms are globally prevalent and a medically treatable condition.
      • Early screening of patients with depression for subclinical atherosclerosis can provide assessment of CVD burden.
      • CAC provides a noninvasive method for assessment of CVD burden and can be used for risk stratification of patients.
      • Those with higher burden of CVD can be offered preventive treatment in order to halt progression of atherosclerosis.


      Background and aims

      Depression is a mood disorder characterized by persistent feelings of loss of interest along with a cluster of clinical symptoms. It is a significant public health concern affecting 350 million people worldwide. Depression has an association with increased risk of cardiovascular disease. The World Health Organization estimates both depression and coronary artery disease to be the two major causes of disability-adjusted life years by year 2020. Early identification of subclinical cardiovascular disease in people suffering from depression may significantly impact risk stratification of these patients.


      An electronic search of MEDLINE database was carried out using PubMed and OvidSP. Subclinical atherosclerosis was identified by coronary artery calcium (CAC). A total of 24 studies were identified to be included in the review.


      In this review of twenty-four studies, we found that twelve studies identified a positive association between depression and subclinical atherosclerosis. Ten studies found no significant association between depressive symptoms and coronary calcification. Whereas, two studies showed negative association.


      There is mixed evidence assessing the relationship between depression and CAC. Depressive symptoms may represent a potentially modifiable risk factor for early prevention of cardiovascular disease especially in younger patients with moderate to severe depression.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Marcus M.
        • Yasamy M.T.
        • van Ommeren M.
        • et al.
        Depression: a Global Public Health Concern. vol. 1. WHO Department of Mental Health and Substance Abuse, 2012: 6-8
        • Nicholson A.
        • Kuper H.
        • Hemingway H.
        Depression as an aetiologic and prognostic factor in coronary heart disease: a meta-analysis of 6362 events among 146 538 participants in 54 observational studies.
        Eur. Heart J. 2006; 27: 2763-2774
        • Murray C.
        • Lopez A.
        The Global Burden of Disease. vol. 1. 1996 (WHO/Harvard School of Public Health/World Bank, In, Harvard University Press, Boston)
        • Association, AP
        Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR Fourth Edition (Text Revision).
        • Greenberg P.E.
        • Kessler R.C.
        • Birnbaum H.G.
        • et al.
        The economic burden of depression in the United States: how did it change between 1990 and 2000?.
        J. Clin. psychiatry. 2003; 64: 1465-1475
        • Kessler R.C.
        • Chiu W.T.
        • Demler O.
        • et al.
        Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the national comorbidity survey replication.
        Arch. Gen. Psychiatry. 2005; 62: 617-627
        • Kessler R.C.
        • Berglund P.
        • Demler O.
        • et al.
        The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R).
        Jama. 2003; 289: 3095-3105
      1. National Institute of Mental Health 12th International Conference on Mental Health Problems in the General Health Care Sector. Baltimore, Maryland, USA. July 13-14, 1998. Abstracts, Int J Psychiatry Med,1998;28:379–406.

        • Hoyert D.L.
        • Kung H.C.
        • Smith B.L.
        Deaths: preliminary data for 2003.
        Natl. Vital Stat. Rep. 2005; 53: 1-48
        • Robinson J.G.
        • Fox K.M.
        • Bullano M.F.
        • et al.
        Atherosclerosis profile and incidence of cardiovascular events: a population-based survey.
        BMC Cardiovasc Disord. 2009; 9: 46
        • Erbel R.
        • Mohlenkamp S.
        • Moebus S.
        • et al.
        Coronary risk stratification, discrimination, and reclassification improvement based on quantification of subclinical coronary atherosclerosis: the Heinz Nixdorf Recall study.
        J. Am. Coll. Cardiol. 2010; 56: 1397-1406
        • Piers L.H.
        • Salachova F.
        • Slart R.H.
        • et al.
        The role of coronary artery calcification score in clinical practice.
        BMC Cardiovasc Disord. 2008; 8: 38
        • Wilson P.W.
        • D'Agostino R.B.
        • Levy D.
        • et al.
        Prediction of coronary heart disease using risk factor categories.
        Circulation. 1998; 97: 1837-1847
        • O'Malley P.G.
        • Jones D.L.
        • Feuerstein I.M.
        • et al.
        Lack of correlation between psychological factors and subclinical coronary artery disease.
        N. Engl. J. Med. 2000; 343: 1298-1304
        • Tiemeier H.
        • van Dijck W.
        • Hofman A.
        • et al.
        Relationship between atherosclerosis and late-life depression: the Rotterdam Study.
        Arch. Gen. Psychiatry. 2004; 61: 369-376
        • Agatisa P.K.
        • Matthews K.A.
        • Bromberger J.T.
        • et al.
        Coronary and aortic calcification in women with a history of major depression.
        Arch. Intern Med. 2005; 165: 1229-1236
        • Kop W.J.
        • Berman D.S.
        • Gransar H.
        • et al.
        Social network and coronary artery calcification in asymptomatic individuals.
        Psychosom. Med. 2005; 67: 343-352
        • Taylor A.J.
        • Arora N.S.
        • Bindeman J.
        • et al.
        Conventional, emerging, heredity, lifestyle, and psychosocial coronary risk factors: relationships to subclinical atherosclerosis.
        Prev. Cardiol. 2006; 9: 25-32
        • Diez Roux A.V.
        • Ranjit N.
        • Powell L.
        • et al.
        Psychosocial factors and coronary calcium in adults without clinical cardiovascular disease.
        Ann. Intern Med. 2006; 144: 822-831
        • Smith T.W.
        • Uchino B.N.
        • Berg C.A.
        • et al.
        Associations of self-reports versus spouse ratings of negative affectivity, dominance, and affiliation with coronary artery disease: where should we look and who should we ask when studying personality and health?.
        Health Psychol. 2008; 27: 676-684
        • Greco C.M.
        • Kao A.H.
        • Sattar A.
        • et al.
        Association between depression and coronary artery calcification in women with systemic lupus erythematosus.
        Rheumatol. Oxf. 2009; 48: 576-581
        • Lewis T.T.
        • Everson-Rose S.A.
        • Colvin A.
        • et al.
        Interactive effects of race and depressive symptoms on calcification in African American and white women.
        Psychosom. Med. 2009; 71: 163-170
        • Hamer M.
        • Kivimaki M.
        • Lahiri A.
        • et al.
        Persistent cognitive depressive symptoms are associated with coronary artery calcification.
        Atherosclerosis. 2010; 210: 209-213
        • Matthews K.A.
        • Chang Y.F.
        • Sutton-Tyrrell K.
        • et al.
        Recurrent major depression predicts progression of coronary calcification in healthy women: study of Women's Health across the Nation.
        Psychosom. Med. 2010; 72: 742-747
        • Janssen I.
        • Powell L.H.
        • Matthews K.A.
        • et al.
        Depressive symptoms are related to progression of coronary calcium in midlife women: the Study of Women's Health across the Nation (SWAN) Heart Study.
        Am. Heart J. 2011; 161 (e1181): 1186-1191
        • Rozanski A.
        • Gransar H.
        • Kubzansky L.D.
        • et al.
        Do psychological risk factors predict the presence of coronary atherosclerosis?.
        Psychosom. Med. 2011; 73: 7-15
        • Low C.A.
        • Matthews K.A.
        • Kuller L.H.
        • et al.
        Psychosocial predictors of coronary artery calcification progression in postmenopausal women.
        Psychosom. Med. 2011; 73: 789-794
        • Stewart J.C.
        • Zielke D.J.
        • Hawkins M.A.
        • et al.
        Depressive symptom clusters and 5-year incidence of coronary artery calcification: the coronary artery risk development in young adults study.
        Circulation. 2012; 126: 410-417
        • Greco C.M.
        • Li T.
        • Sattar A.
        • et al.
        Association between depression and vascular disease in systemic lupus erythematosus.
        J. Rheumatol. 2012; 39: 262-268
        • Wolff E.F.
        • He Y.
        • Black D.M.
        • et al.
        Self-reported menopausal symptoms, coronary artery calcification, and carotid intima-media thickness in recently menopausal women screened for the Kronos early estrogen prevention study (KEEPS).
        Fertil. Steril. 2013; 99: 1385-1391
        • Devantier T.A.
        • Norgaard B.L.
        • Sand N.P.
        • et al.
        Lack of correlation between depression and coronary artery calcification in a non-selected Danish population.
        Psychosomatics. 2013; 54: 458-465
        • Hernandez R.
        • Allen N.B.
        • Liu K.
        • et al.
        Association of depressive symptoms, trait anxiety, and perceived stress with subclinical atherosclerosis: results from the Chicago Healthy Aging Study (CHAS).
        Prev. Med. 2014; 61: 54-60
        • Liu Y.L.
        • Szklo M.
        • Davidson K.W.
        • et al.
        Differential association of psychosocial comorbidities with subclinical atherosclerosis in rheumatoid arthritis.
        Arthritis Care Res. Hob. 2015; 67: 1335-1344
        • Bellettiere J.
        • Kritz-Silverstein D.
        • Laughlin G.A.
        • et al.
        Relation of depressive symptoms with coronary artery calcium determined by electron-beam computed tomography (from the rancho bernardo study).
        Am. J. Cardiol. 2016; 117: 325-332
        • Cheong E.
        • Lee J.Y.
        • Lee S.H.
        • et al.
        Lifestyle including dietary habits and changes in coronary artery calcium score: a retrospective cohort study.
        Clin. Hypertens. 2015; 22: 5
        • Janssen I.
        • Powell L.H.
        • Matthews K.A.
        • et al.
        Relation of persistent depressive symptoms to coronary artery calcification in women aged 46 to 59 years.
        Am. J. Cardiol. 2016; 117: 1884-1889
        • Santos I.S.
        • Bittencourt M.S.
        • Rocco P.T.
        • et al.
        Relation of anxiety and depressive symptoms to coronary artery calcium (from the ELSA-brasil baseline data).
        Am. J. Cardiol. 2016; 118: 183-187
        • Serrano Jr., C.V.
        • Setani K.T.
        • Sakamoto E.
        • et al.
        Association between depression and development of coronary artery disease: pathophysiologic and diagnostic implications.
        Vasc. Health Risk Manag. 2011; 7: 159-164
        • Laghrissi-Thode F.
        • Wagner W.R.
        • Pollock B.G.
        • et al.
        Elevated platelet factor 4 and beta-thromboglobulin plasma levels in depressed patients with ischemic heart disease.
        Biol. Psychiatry. 1997; 42: 290-295
        • Bruce E.C.
        • Musselman D.L.
        Depression, alterations in platelet function, and ischemic heart disease.
        Psychosom. Med. 2005; 67: S34-S36
        • Watkins L.L.
        • Grossman P.
        Association of depressive symptoms with reduced baroreflex cardiac control in coronary artery disease.
        Am. Heart J. 1999; 137: 453-457
        • Bivanco-Lima D.
        • Souza Santos I.
        • Vannucchi A.M.
        • et al.
        Cardiovascular risk in individuals with depression.
        Rev. Assoc. Med. Bras. 2013; 59: 298-304
        • Carroll B.J.
        • Curtis G.C.
        • Davies B.M.
        • et al.
        Urinary free cortisol excretion in depression.
        Psychol. Med. 1976; 6: 43-50
        • Sachar E.J.
        • Hellman L.
        • Fukushima D.K.
        • et al.
        Cortisol production in depressive illness. A clinical and biochemical clarification.
        Arch. Gen. Psychiatry. 1970; 23: 289-298
        • Hajat A.
        • Diez-Roux A.V.
        • Sanchez B.N.
        • et al.
        Examining the association between salivary cortisol levels and subclinical measures of atherosclerosis: the Multi-Ethnic Study of Atherosclerosis.
        Psychoneuroendocrinology. 2013; 38: 1036-1046
        • Stewart J.C.
        • Janicki D.L.
        • Muldoon M.F.
        • et al.
        Negative emotions and 3-year progression of subclinical atherosclerosis.
        Arch. Gen. Psychiatry. 2007; 64: 225-233
        • Haas D.C.
        • Davidson K.W.
        • Schwartz D.J.
        • et al.
        Depressive symptoms are independently predictive of carotid atherosclerosis.
        Am. J. Cardiol. 2005; 95: 547-550
        • Piwonski J.
        • Piwonska A.
        • Sygnowska E.
        Is there an association between depressive symptoms and coronary artery disease in the Polish adult population?.
        Kardiol. Pol. 2014; 72: 50-55
        • Rudisch B.
        • Nemeroff C.B.
        Epidemiology of comorbid coronary artery disease and depression.
        Biol. Psychiatry. 2003; 54: 227-240
        • Frasure-Smith N.
        • Lesperance F.
        Depression and coronary artery disease.
        Herz. 2006; 31: 64-68
        • O'Malley P.G.
        • Taylor A.J.
        • Jackson J.L.
        • et al.
        Prognostic value of coronary electron-beam computed tomography for coronary heart disease events in asymptomatic populations.
        Am. J. Cardiol. 2000; 85: 945-948
        • Sangiorgi G.
        • Rumberger J.A.
        • Severson A.
        • et al.
        Arterial calcification and not lumen stenosis is highly correlated with atherosclerotic plaque burden in humans: a histologic study of 723 coronary artery segments using nondecalcifying methodology.
        J. Am. Coll. Cardiol. 1998; 31: 126-133