Objective: To examine the relationship of depression severity to circulating endothelin-1 (ET-1), which has previously been linked to plaque rupture and postacute coronary syndrome (ACS) survival. Depression carries an independent two- to four-fold increased risk of early morbidity and mortality after ACS. The pathway(s) linking depression to event-free survival remains to be determined.
Methods: Patients with documented history of coronary artery disease (n = 101) provided a resting morning blood sample that was assayed for ET-1, and they completed the Beck Depression Inventory (BDI). ET-1 was treated as a log-transformed continuous variable (logET-1), and as a dichotomous variable using a post-ACS risk threshold previously reported (≥1.16 fmol/mL).
Results: BDI score was related to logET-1 in both unadjusted and adjusted models. In addition, unadjusted and adjusted logistic regression models with dichotomous ET-1 revealed that, for each point increase in BDI score, there was approximately a 14% increased likelihood of being at or above ET-1 risk threshold. Secondary logistic regression models demonstrated a >3.5-fold likelihood of being at or above this risk threshold in association with a BDI score of ≥10.
Conclusions: Depression symptom severity predicts ET-1 elevation that has previously been linked to post-ACS survival, with the greatest risk of elevation among those patients with worse depression symptoms. This link may identify a vulnerability to triggered ACS and poorer survival associated with depression. Future research should establish whether the observed relationship of depressive symptoms to ET-1 level mediates the link between depression and survival.
ACS = acute coronary syndrome; BDI = Beck Depression Inventory; β blocker = beta-blocking medication; CAD = coronary artery disease; ET-1 = endothelin-1; logET-1 = log transformed endothelin-1; SAS = statistical analysis software; TNF-α = tumor necrosis factor-α.
From the Cardiovascular Medicine (M.M.B., R.S.), Yale University School of Medicine, New Haven, Connecticut; VA Connecticut Healthcare System (M.M.B., D.C., R.S.), West Haven Campus, West Haven, Connecticut; Behavioral Cardiovascular Health Center (M.M.B.), Columbia University School of Medicine, New York City, New York; and CORPS (E.J.M.), Tilburg University, Tilburg, Netherlands.
Address correspondence and reprint requests to Matthew M. Burg, PhD, Section of Cardiovascular Medicine, Yale University School of Medicine/VA Connecticut, 950 Campbell Avenue, 111B, West Haven, CT 06516. E-mail: email@example.com
Received for publication May 24, 2010; revision received September 15, 2010.
This work was supported, in part, by Grants R01 HL59619-01 and HL071116-01 (R.S.) and HL84438 (M.M.B.) from the National Heart, Lung and Blood Institute of the National Institutes of Health, and by Merit Review RS#010 (R.S.) from the Department of Veterans Affairs.
The authors have not disclosed any potential conflicts of interest.