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Major Depression, C-Reactive Protein, and Incident Ischemic Heart Disease in Healthy Men and Women

From the Strangeways Research Laboratory and University of Cambridge Department of Public Health and Primary Care (P.G.S., N.W.J.W., R.N.L.), Wort’s Causeway, Cambridge, UK; Department of Cardiology (S.M.B.), Academic Medical Center, Amsterdam, Netherlands; MRC Epidemiology Unit (N.J.W.), Institute of Metabolic Science, Cambridge, UK; and Clinical Gerontology Unit (K.-T.K.), University of Cambridge School of Clinical Medicine, Addenbrooke’s Hospital, Cambridge, UK.

Address correspondence and reprint requests to Paul Surtees, Strangeways Research Laboratory, Wort’s Causeway, Cambridge, CB1 8RN, UK. E-mail: paul.surtees{at}srl.cam.ac.uk

Objective: To investigate how C-reactive protein (CRP) and major depressive disorder (MDD) relate to each other and to incident ischemic heart disease (IHD). Studies have shown that both depression and raised CRP concentration predict IHD and that elevated CRP is linked with increased risk of depression.

Methods: A prospective case-control study of healthy men and women, aged 45 to 79 years, was undertaken within the United Kingdom European Prospective Investigation into Cancer (EPIC)-Norfolk study. CRP concentration was measured for 726 (fatal or nonfatal) IHD cases and 1688 matched controls who completed a baseline MDD self-assessment, defined by restricted Diagnostic and Statistical Manual of Mental Disorders, 4th Edition diagnostic criteria.

Results: Past-year MDD was associated with increased CRP concentration levels (4.31 mg/L for participants who reported episodes of MDD in the past year versus 3.65 mg/L for those who did not; p = .003), and the odds ratio for incident IHD associated with higher CRP concentration was 2.02 (comparing the top versus bottom quartile of CRP; 95% Confidence Interval (CI) = 1.52–2.68), adjusted for cigarette smoking, diabetes, systolic blood pressure, body mass index, and cholesterol. The association between past-year MDD and IHD was independent of CRP (odds ratio = 1.55; 95% CI = 1.01–2.37, with adjustments as above, and additionally for CRP).

Conclusions: Evidence from this study is supportive of an association between MDD and CRP although it suggests that CRP does not account for the association between MDD and future IHD.

Key Words: coronary disease • depressive disorder • epidemiology • inflammation

Abbreviations: BMI = body mass index; CRP = C-reactive protein; CVD = cardiovascular disease; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; EPIC-Norfolk = European Prospective Investigation into Cancer-Norfolk study; HLEQ = Health and Life Experiences Questionnaire; IHD = ischemic heart disease; MDD = major depressive disorder; MI = myocardial infarction; PRIME = Prospective Epidemiological Study of Myocardial Infarction; SBP = systolic blood pressure.