Exploring Links Between Depression and Subclinical Atherosclerosis

A substantial body of research points to a multifaceted link between depression and cardiovascular disease, with rates of depression being 3 times higher in patients with CAD.

A substantial body of research points to a multifaceted link between depression and cardiovascular disease (CVD), with rates of depression being 3 times higher in patients with coronary artery disease (CAD) compared to the general population.1 Overall, CVD contributes to 17 million deaths worldwide each year, and CAD accounts for 42% of these deaths.

With the prevalence of both diseases increasing rapidly, there is a critical need to elucidate the relationship between CAD and depression in order to optimize treatment and outcomes in these patient populations. Research pertaining to the preclinical stages of atherosclerosis – the most common cause of CAD – indicate a positive association with depression although results have been mixed overall.1

Although the potential mechanisms driving this relationship are not yet clear, it is likely that the “physiological and behavioral changes resulting from depression support the formation of coronary atheroma,” as Sher Ali Khan, MD, from the Mel and Enid Zuckerman College of Public Health at the University of Arizona in Tucson, stated in a recent interview. “Physiological changes might include higher levels of corticosteroids in the system and higher sympathetic surge, and behavioral changes may include unhealthy lifestyle factors associated with depression, such as not sleeping well and consuming higher amounts of high calorie and high carbohydrate foods.” 

Dr Khan and colleagues from several universities conducted a systematic review of 23 studies to clarify the link between depression and subclinical coronary atherosclerosis as assessed via coronary artery calcification (CAC) scoring.1 Both longitudinal and cross-sectional studies were included in the review, with a combined total of 58,207 participants aged 36 to 73 years. Their observations, published ahead of print in the Journal of Cardiovascular Translational Research, are highlighted below.

Depression and CAC prevalence: Of 15 studies assessing CAC prevalence in depression, a positive association was observed in 4 studies. Longitudinal research published in 2017 demonstrated a significant association between depression and CAC, especially for patients with the somatic symptom cluster.2,3 Smoking was found to exert a synergistic effect on this relationship, in a dose-dependent manner based on the number of pack years.

A 2010 longitudinal study noted a 2-fold greater risk of CAC in patients with persistent depression, who were assessed at 3 points over the 10 year study period, and a 2013 cross-sectional study reported a positive correlation between depression and CAC, which was especially strong in women vs men.4,5

Depression and CAC severity: 6 of 10 studies evaluating the connection between depression and CAC severity revealed a positive association, including a large cross-sectional study of late-life depression in participants aged 60 years and older.6 Depression was assessed with the Centers for Epidemiological Studies-Depression (CES-D) and subsequently confirmed by a psychologist or psychiatrist.

Other longitudinal studies have shown significantly higher CAC severity in men vs women, which progressed in a linear fashion, and a positive association between depression and CAC severity in patients with rheumatoid arthritis.1 Additionally, a study of a biracial female sample from large urban communities demonstrated a positive association in those with a history of multiple depressive episodes but not those who had experienced 2 or less episodes.7

Depression and CAC progression: Of 5 studies that investigated the relationship between depression and CAC progression, 3 showed a positive association. Specifically, 2 analyses of data from the Study of Women’s Health Across the Nation (SWAN) revealed a positive association between depression and CAC progression as measured by change in mean-long (CAC +25) over time in patients with baseline CAC. There was a stronger association in those with recurrent vs single episode depression or those with no history of depression.8,9

Additional findings from longitudinal research also indicate a significant association between depression and CAC progression, with CAC progression increasing along with the number of pack years of smoking.2

Depression and CAC incidence: A 2012 study exploring the association between depression and CAC incidence found that the total CES-D and the depressed affect subscale were significantly associated with incident CAC independently of age, sex, race, education, and antidepressant use.10 Tobacco use and mean arterial pressure were identified as significant mediators.

In other research, only the “cumulative somatic symptom cluster by cumulative smoking exposure interaction was significantly associated with CAC >0 at year 25 (P =.028),” wrote Khan, et al.1 “Somatic symptoms appear to be a particularly relevant cluster of depressive symptomatology in the relationship between smoking and CVD risk.”

Taken together, these review findings support an association between depression and subclinical coronary atherosclerosis and suggest that depression is an independent predictor for CAD. Depression may cause CAD “through various biological pathways such as inflammation, shifting homeostasis, endothelial injury and endothelial dysfunction, platelet activation, and abnormal autonomic function,” as explained in the review.1

This implies that successfully treating depression could ultimately prevent the formation of coronary atheroma formation, according to Dr Khan. He recommends addressing “depression the same way you would manage other risk factors for CAD such as hypertension and hyperlipidemia.”

Future research in this area should aim to identify the exact physiological mechanisms by which depression may lead to CAD. “We also need to know how big a risk it confers as compared to conventional risk factors for CAD,” said Dr Khan.  


1.     Khan SA, Shahzad U, Zarak MS, Channa J, Khan I, Ghani MOA. Association of depression with subclinical coronary atherosclerosis: a systematic review. [Published online March 20, 2020.] J Cardiovasc Transl Res. doi:10.1007/s12265-020-09985-4.

2.     Carroll AJ Ms, Auer R, Colangelo LA, et al. Association of the interaction between smoking and depressive symptom clusters with coronary artery calcification: the CARDIA study. J Dual Diagn. 2017;13(1):43‐51.

3.     Carroll AJ, Carnethon MR, Liu K, et al. Interaction between smoking and depressive symptoms with subclinical heart disease in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Health Psychol. 2017;36(2):101‐111.

4.     Hamer M, Kivimaki M, Lahiri A, Marmot MG, Steptoe A. Persistent cognitive depressive symptoms are associated with coronary artery calcification. Atherosclerosis. 2010;210(1):209‐213.

5.     Ahmadi N, Vaidya N, Hajsadeghi F, Arora R. Gender-specific association of depression with high levels of C reactive protein and coronary atherosclerosis: a analysis of mesa study cohort. J Am Coll Cardiol. 2013;61(10 Suppl):E1332.

6.     Tiemeier H, van Dijck W, Hofman A, Witteman JCM, Stijnen T, Breteler MMB. Relationship between atherosclerosis and late-life depression: the Rotterdam Study. Arch Gen Psychiatry. 2004;61(4):369–376.

7.     Janssen I, Powell LH, Matthews KA, et al. Relation of persistent depressive symptoms to coronary artery calcification in women aged 46 to 59 years. Am J Cardiol. 2016;117(12):1884‐1889.

8.     Janssen I, Powell LH, Matthews KA, 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(6):1186‐1191.e1.

9.     Matthews KA, Chang YF, Sutton-Tyrrell K, Edmundowicz D, Bromberger JT. Recurrent major depression predicts progression of coronary calcification in healthy women: Study of Women’s Health Across the Nation. Psychosom Med. 2010;72(8):742‐747.

10.  Stewart JC, Zielke DJ, Hawkins MA, 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(4):410‐417.

This article originally appeared on Psychiatry Advisor