Recent studies demonstrate that the immune system plays an important role in coronary artery disease (CAD). Research also shows that psychological factors such as major depressive disorder and acute mental stress are involved in the clinical progression of CAD. Depression is associated with higher levels of immune parameters that play a role in CAD (cytokines, markers of low grade inflammation, infectious pathogen burden, and adhesion molecules), and most of these measures also increase in response to acute physical and mental stress. The pathophysiological mechanisms linking depression and mental stress with adverse cardiovascular outcomes may therefore be mediated by immunological factors. The proposed research will examine clinical outcomes in patients who undergo percutaneous coronary revascularization, because a major problem remains the frequent (20 percent-40 percent) occurrence of coronary restenosis and new cardiac events in the 6 months after the intervention. These adverse outcomes have substantial impact on the costs of medical care and patients' quality of life. Since previous research has not examined the role of behaviorally-induced changes in immune parameters in the prediction of CAD progression, the following immunological measures will be examined: cytokines (IL-1B, IL-4, IL-6, IFNy, TNFa), acute phase proteins (CRP, fibrinogen), lymphocyte counts and differential, adhesion molecules (ICAM-1, LFA, L-selectin), and a composite measure of pathogen burden (CNV, H. pylori, C. pneumoniae). Using a longitudinal design, this project will determine the time course of changes in depression and changes in immune parameters. Moreover, the present study will determine the contribution of behavioral and immunological factors in the clinical progression of coronary disease following coronary angioplasty. These data may therefore improve the identification of patients at risk for recurrent cardiac events and restenosis after coronary angioplasty, and provide further understanding of the pathophysiological mechanisms involved in coronary disease progression.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL066149-04
Application #
6745571
Study Section
Special Emphasis Panel (ZRG1-RPHB-2 (01))
Program Officer
Czajkowski, Susan
Project Start
2001-07-06
Project End
2006-05-31
Budget Start
2004-06-01
Budget End
2005-05-31
Support Year
4
Fiscal Year
2004
Total Cost
$569,593
Indirect Cost
Name
Henry M. Jackson Fdn for the Adv Mil/Med
Department
Type
DUNS #
144676566
City
Rockville
State
MD
Country
United States
Zip Code
20817
Kop, Willem J; Stein, Phyllis K; Tracy, Russell P et al. (2010) Autonomic nervous system dysfunction and inflammation contribute to the increased cardiovascular mortality risk associated with depression. Psychosom Med 72:626-35
Kop, Willem J; Kuhl, Emily A; Barasch, Eddy et al. (2010) Association between depressive symptoms and fibrosis markers: the Cardiovascular Health Study. Brain Behav Immun 24:229-35
Kop, Willem J; Weinstein, Ali A; Deuster, Patricia A et al. (2008) Inflammatory markers and negative mood symptoms following exercise withdrawal. Brain Behav Immun 22:1190-6
Kop, Willem J; Weissman, Neil J; Zhu, Jianhui et al. (2008) Effects of acute mental stress and exercise on inflammatory markers in patients with coronary artery disease and healthy controls. Am J Cardiol 101:767-73
Kop, Willem J; Gottdiener, John S (2005) The role of immune system parameters in the relationship between depression and coronary artery disease. Psychosom Med 67 Suppl 1:S37-41
Kop, Willem J (2003) The integration of cardiovascular behavioral medicine and psychoneuroimmunology: new developments based on converging research fields. Brain Behav Immun 17:233-7
Kop, Willem J; Gottdiener, John S; Tangen, Catherine M et al. (2002) Inflammation and coagulation factors in persons > 65 years of age with symptoms of depression but without evidence of myocardial ischemia. Am J Cardiol 89:419-24