Depression, Inflammation, and Incident Cardiovascular Disease in Women With Suspected Coronary Ischemia: The National Heart, Lung, and Blood Institute–Sponsored WISE Study
The purpose of this study was to examine prospectively whether inflammation explains the relationship between depression and cardiovascular disease (CVD).
Background
It is unclear whether inflammation is a mechanism linking depression to CVD.
Methods
We measured C-reactive protein (CRP) and interleukin (IL)-6 in 559 women with suspected coronary ischemia who completed the Beck Depression Inventory (BDI) at baseline and were followed over 5.9 years. We considered indicators of past and current depression to classify women into 3 groups: 1) depression, having both elevated depressive symptoms (BDI ≥10) and a previous diagnosis of depression requiring treatment; 2) possible depression, having either indicator but not both; and 3) no depression, having neither indicator of depression. The main outcome was incidence of CVD events (hospital stays for nonfatal myocardial infarction, stroke, congestive heart failure, and CVD-related mortality).
Results
Compared with women without depression, women with depression had a 70% higher CRP (p = 0.0008) and a 25% higher IL-6 (p = 0.04), whereas women with possible depression had 30% higher CRP (p = 0.02) and 28% higher IL-6 (p = 0.01). Depression was a significant predictor of CVD (hazard ratio 2.58, p = 0.0009), but possible depression was not (hazard ratio 1.12, p = 0.68). Adjustment for other patient factors did not substantially affect the results. Addition of CRP decreased the estimate for depression by 13% and addition of IL-6 decreased it by 4%. Both depression and inflammatory biomarkers remained independent predictors of outcome.
Conclusions
Despite their robust association with depression, inflammatory biomarkers explain only a small portion of the association between depression and CVD incidence.
Abbreviations and Acronyms
BDI
Beck Depression Inventory
CAD
coronary artery disease
CRP
C-reactive protein
CVD
cardiovascular disease
HR
hazard ratio
IL
interleukin
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This work was supported by contracts from the National Heart, Lung, and Blood Institute N01-HV-68161, N01-HV-68162, N01-HV-68163, and N01-HV-68164; grant K24HL077506 (to Dr. Vaccarino); a General Clinical Research Center grant M01-RR00425 from the National Center for Research Resources; and grants from the Gustavus and Louis Pfeiffer Research Foundation, The Women’s Guild, Cedars-Sinai Medical Center, the Ladies Hospital Aid Society of Western Pennsylvania, and QMED, Inc.