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CLINICAL RESEARCH: CORONARY ARTERY DISEASE

Depression, Inflammation, and Incident Cardiovascular Disease in Women With Suspected Coronary Ischemia

The National Heart, Lung, and Blood Institute–Sponsored WISE Study

Viola Vaccarino, MD, PhD^_*,_*, B. Delia Johnson, PhD, David S. Sheps, MD, MSPH, Steven E. Reis, MD, FACC, Sheryl F. Kelsey, PhD, Vera Bittner, MD, FACC^||, Thomas Rutledge, PhD^¶, Leslee J. Shaw, PhD^_*, George Sopko, MD^_** and C. Noel Bairey Merz, MD, FACC^#

^_* Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia
Department of Epidemiology
Cardiovascular Institute, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
Department of Medicine, Division of Cardiovascular Medicine, University of Florida, Gainesville, Florida
^|| Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama
^¶ University of California, San Diego, California
^# Department of Medicine, Division of Cardiology, Cedars-Sinai Research Institute, Cedars-Sinai Medical Center, Los Angeles, California
^_** National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland

Manuscript received May 2, 2007; revised manuscript received July 12, 2007, accepted July 30, 2007.

^_* Reprint requests and correspondence: Dr. Viola Vaccarino, Emory University School of Medicine, Department of Medicine, Division of Cardiology, 1256 Briarcliff Road NE, Suite-1 North, Atlanta, Georgia 30306. (Email: viola.vaccarino{at}emory.edu).

Objectives: 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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