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Evaluating Longitudinal Associations Between Depressive Symptoms, Smoking, and Biomarkers of Cardiovascular Disease in the CARDIA Study

Carroll, Allison J., PhD; Huffman, Mark D., MD, MPH; Zhao, Lihui, PhD; Jacobs, David R. Jr, PhD; Stewart, Jesse C., PhD; Kiefe, Catarina I., MD, PhD; Liu, Kiang, PhD; Hitsman, Brian, PhD

doi: 10.1097/PSY.0000000000000667

Objective The aim of the study was to evaluate associations between 15-year trajectories of co-occurring depressive symptoms and smoking with biomarkers of cardiovascular disease at year 15.

Methods In the Coronary Artery Risk Development in Young Adults study, we modeled trajectories of depressive symptoms (Center for Epidemiologic Studies-Depression scale [CES-D]) and smoking (cigarettes per day [CPD]) among 3614 adults followed from year 0 (ages 18–30 years) through year 15 (ages 33–45 years). Biomarkers of inflammation (high-sensitivity C-reactive protein), oxidative stress (superoxide dismutase, F2-isoprostanes), and endothelial dysfunction (soluble intercellular adhesion molecule 1, soluble P-selectin) were assessed at year 15. We conducted separate linear regression analyses with CES-D trajectory, CPD trajectory, and their interaction with each of the five biomarkers.

Results The sample was 56% women, 47% black, and 40 years old on average at year 15. The CES-D trajectory by CPD trajectory interaction was not associated with any of the biomarkers (all p's > .01). Removing the interaction term, CES-D trajectory was associated with inflammation: higher levels of high-sensitivity C-reactive protein were observed in the subthreshold (β = 0.57, p = .004) and increasing depressive symptoms (β = 1.36, p < .001) trajectories compared with the no depression trajectory. CPD trajectory was associated with oxidative stress and endothelial dysfunction: compared with never smokers, heavy smokers had significantly higher levels of F2-isoprostanes (β = 6.20, p = .001), soluble intercellular adhesion molecule 1 (β = 24.98, p < .001), and soluble P-selectin (β = 2.91, p < .001).

Conclusions Co-occurring depressive symptoms and smoking do not seem to synergistically convey risk for cardiovascular disease via processes of inflammation, oxidative stress, or endothelial dysfunction. Nonetheless, these results advance our understanding of the complex relationships between modifiable risk factors and chronic disease.

From the Department of Preventive Medicine (Carroll, Huffman, Zhao, Liu, Hitsman), Northwestern University Feinberg School of Medicine, Chicago, Illinois; Division of Epidemiology and Community Health (Jacobs), School of Public Health, University of Minnesota, Minneapolis, Minnesota; Department of Psychology (Stewart), Indiana University-Purdue University Indianapolis, Indiana; and Department of Population and Quantitative Health Sciences (Kiefe), University of Massachusetts Medical School, Boston, Massachusetts.

Address correspondence to Allison J. Carroll, PhD, 680 N Lake Shore Dr Ste 1400, Chicago IL 60611. E-mail:

Received for publication May 2, 2018; revision received October 18, 2018.

Copyright © 2019 by American Psychosomatic Society
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