Hostname: page-component-76fb5796d-x4r87 Total loading time: 0 Render date: 2024-04-25T15:50:38.329Z Has data issue: false hasContentIssue false
  • English
  • Français

The associations of high levels of C-reactive protein with depression and myocardial infarction in 9258 women and men from the HUNT population study

Published online by Cambridge University Press:  06 May 2010

O. Bjerkeset ,
U. Romild ,
G. Davey Smith  and
K. Hveem
O. Bjerkeset*
Affiliation:
Department of Research and Development (RaD), Levanger Hospital, Health Trust Nord-Trøndelag, Norway Department of Neuroscience, Unit for Psychiatry and Behavioural Science, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
U. Romild
Affiliation:
Department of Research and Development (RaD), Levanger Hospital, Health Trust Nord-Trøndelag, Norway Swedish National Institute of Public Health, Östersund, Sweden
G. Davey Smith
Affiliation:
Department of Social Medicine, University of Bristol, UK
K. Hveem
Affiliation:
Department of Research and Development (RaD), Levanger Hospital, Health Trust Nord-Trøndelag, Norway Department of Public Health and General Practise, Norwegian University of Science and Technology, Trondheim, Norway
*
*Address for correspondence: Dr O. Bjerkeset, Department of Research and Development (RaD), Levanger Hospital, Kirkegt, 2, 7600Levanger, Norway. (Email: ottar.bjerkeset@ntnu.no)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Elevated levels of circulating C-reactive protein (CRP) have been associated with coronary heart disease and, in some studies, depression. Most studies have been of populations selected by age and/or gender. We investigate these associations with depression, myocardial infarction (MI), or both, in a large general population sample.

Method

A cross-sectional population study of 9258 women and men aged ⩾20 years. The study included clinical examination, self-report of MI and depression and factors known to confound their associations. The Hospital Anxiety and Depression Scale was used to assess severity of depressive symptoms. Elevated high sensitive-CRP was defined as values >2.2 mg/l.

Results

The association of elevated CRP with depression was attenuated towards the null [from odds ratio (OR) 1.28, p=0.001 to OR 1.08, p=0.388] following extensive adjustment, while associations with MI (adjusted OR 1.42, p=0.032) and co-morbid MI and depression (adjusted OR 2.66, p=0.003) persisted. Confounders associated with elevated CRP levels were smoking (OR 1.66; p<0.001), chronic physical illness (OR 1.34, p<0.001), BMI ⩾30 (OR 1.13, p<0.001), employment (OR 0.70, p<0.001) and high coffee consumption (OR 0.83, p=0.017). Interaction tests indicated a lower effect of old age (OR 0.54, p<0.001) and smoking (OR 0.63, p<0.001) on elevated CRP levels in women compared with men.

Conclusions

CRP levels were raised in those with MI and co-morbid MI and depression; the positive association with depression was explained by confounding factors. We found new evidence that might help understand gender-specific patterns. Future studies should explore the neurobiological mechanisms underpinning these interrelations and their relevance for treatment of these conditions.

Keywords

AnxietyCRPdepressiongeneral populationinflammationMI
Type
Original Articles
Information
Psychological Medicine , Volume 41 , Issue 2 , February 2011 , pp. 345 - 352
Copyright
Copyright © Cambridge University Press 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Ajani, UA, Ford, ES, Mokdad, AH (2004). Prevalence of high C-reactive protein in persons with serum lipid concentrations within recommended values. Clinical Chemistry 50, 1618–1622.Google Scholar
Almeida, OP, Norman, P, Hankey, GJ, Jamrozik, K, Flicker, L (2007). The association between C-reactive protein concentration and depression in later life is due to poor physical health: results from the Health in Men Study (HIMS). Psychological Medicine 37, 1775–1786.CrossRefGoogle ScholarPubMed
Bjelland, I, Dahl, AA, Haug, TT, Neckelmann, D (2002). The validity of the Hospital Anxiety and Depression Scale. An updated literature review. Journal of Psychosomatic Research 52, 69–77.Google Scholar
Bremmer, MA, Beekman, AT, Deeg, DJ, Penninx, BW, Dik, MG, Hack, CE, Hoogendijk, WJ (2008). Inflammatory markers in late-life depression: results from a population-based study. Journal of Affective Disorders 106, 249–255.Google Scholar
Broadley, AJ, Korszun, A, Jones, CJ, Frenneaux, MP (2002). Arterial endothelial function is impaired in treated depression. Heart 88, 521–523.Google Scholar
Capuron, L, Ravaud, A, Gualde, N, Bosmans, E, Dantzer, R, Maes, M, Neveu, PJ (2001). Association between immune activation and early depressive symptoms in cancer patients treated with interleukin-2-based therapy. Psychoneuroendocrinology 26, 797–808.CrossRefGoogle ScholarPubMed
Danner, M, Kasl, SV, Abramson, JL, Vaccarino, V (2003). Association between depression and elevated C-reactive protein. Psychosomatic Medicine 65, 347–356.Google Scholar
De, BD, Campanella, D, Gambi, F, La, RR, Carano, A, Conti, CM, Sivestrini, C, Serroni, N, Piersanti, D, Di, GB, Moschetta, FS, Cotellessa, C, Fulcheri, M, Salerno, RM, Ferro, FM (2006). The role of C-reactive protein in mood disorders. International Journal of Immunopathology and Pharmacology 19, 721–725.Google Scholar
Elovainio, M, Keltikangas-Jarvinen, L, Pulkki-Raback, L, Kivimaki, M, Puttonen, S, Viikari, L, Rasanen, L, Mansikkaniemi, K, Viikari, J, Raitakari, OT (2006). Depressive symptoms and C-reactive protein: the Cardiovascular Risk in Young Finns Study. Psychological Medicine 36, 797–805.Google Scholar
Empana, JP, Sykes, DH, Luc, G, Juhan-Vague, I, Arveiler, D, Ferrieres, J, Amouyel, P, Bingham, A, Montaye, M, Ruidavets, JB, Haas, B, Evans, A, Jouven, X, Ducimetiere, P (2005). Contributions of depressive mood and circulating inflammatory markers to coronary heart disease in healthy European men: the Prospective Epidemiological Study of Myocardial Infarction (PRIME). Circulation 111, 2299–2305.CrossRefGoogle ScholarPubMed
Ford, DE, Erlinger, TP (2004). Depression and C-reactive protein in US adults: data from the Third National Health and Nutrition Examination Survey. Archives of Internal Medicine 164, 1010–1014.Google Scholar
Gimeno, D, Kivimaki, M, Brunner, EJ, Elovainio, M, De, VR, Steptoe, A, Kumari, M, Lowe, GD, Rumley, A, Marmot, MG, Ferrie, JE (2009). Associations of C-reactive protein and interleukin-6 with cognitive symptoms of depression: 12-year follow-up of the Whitehall II study. Psychological Medicine 39, 413–423.Google Scholar
Hestad, KA, Aukrust, P, Tonseth, S, Reitan, SK (2009). Depression has a strong relationship to alterations in the immune, endocrine and neural system. Current Psychiatry Reviews 5, 287–297.CrossRefGoogle Scholar
Holmen, J, Midthjell, K, Kruger, Ø, Langhammer, A, Holmen, TL, Bratberg, GH, Vatten, L, Lund-Larsen, PG (2003). The Nord-Trøndelag Health Study 1995–97 (HUNT 2): Objectives, content, methods and participation. Norsk Epidemiologi 13, 19–32.Google Scholar
Howren, MB, Lamkin, DM, Suls, J (2009). Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosomatic Medicine 71, 171–186.Google Scholar
Kiecolt-Glaser, JK, Glaser, R (2002). Depression and immune function: central pathways to morbidity and mortality. Journal of Psychosomatic Research 53, 873–876.CrossRefGoogle ScholarPubMed
Kojima, M, Kojima, T, Suzuki, S, Oguchi, T, Oba, M, Tsuchiya, H, Sugiura, F, Kanayama, Y, Furukawa, TA, Tokudome, S, Ishiguro, N (2009). Depression, inflammation, and pain in patients with rheumatoid arthritis. Arthritis and Rheumatism 61, 1018–1024.Google Scholar
Kuo, HK, Yen, CJ, Chang, CH, Kuo, CK, Chen, JH, Sorond, F (2005). Relation of C-reactive protein to stroke, cognitive disorders, and depression in the general population: systematic review and meta-analysis. Lancet Neurology 4, 371–380.Google Scholar
Lawlor, DA, Smith, GD, Rumley, A, Lowe, GD, Ebrahim, S (2005). Associations of fibrinogen and C-reactive protein with prevalent and incident coronary heart disease are attenuated by adjustment for confounding factors. British Women's Heart and Health Study. Thrombosis and Haemostasis 93, 955–963.Google ScholarPubMed
Lesperance, F, Frasure-Smith, N, Theroux, P, Irwin, M (2004). The association between major depression and levels of soluble intercellular adhesion molecule 1, interleukin-6, and C-reactive protein in patients with recent acute coronary syndromes. American Journal of Psychiatry 161, 271–277.Google Scholar
Lestage, J, Verrier, D, Palin, K, Dantzer, R (2002). The enzyme indoleamine 2,3-dioxygenase is induced in the mouse brain in response to peripheral administration of lipopolysaccharide and superantigen. Brain, Behavior, and Immunity 16, 596–601.Google Scholar
Liukkonen, T, Silvennoinen-Kassinen, S, Jokelainen, J, Rasanen, P, Leinonen, M, Meyer-Rochow, VB, Timonen, M (2006). The association between C-reactive protein levels and depression: results from the northern Finland 1966 birth cohort study. Biological Psychiatry 60, 825–830.Google Scholar
McCaffery, JM, Frasure-Smith, N, Dube, MP, Theroux, P, Rouleau, GA, Duan, Q, Lesperance, F (2006). Common genetic vulnerability to depressive symptoms and coronary artery disease: a review and development of candidate genes related to inflammation and serotonin. Psychosomatic Medicine 68, 187–200.Google Scholar
Miller, GE, Freedland, KE, Carney, RM, Stetler, CA, Banks, WA (2003). Pathways linking depression, adiposity, and inflammatory markers in healthy young adults. Brain, Behavior, and Immunity 17, 276–285.CrossRefGoogle ScholarPubMed
Miller, GE, Freedland, KE, Duntley, S, Carney, RM (2005). Relation of depressive symptoms to C-reactive protein and pathogen burden (cytomegalovirus, herpes simplex virus, Epstein-Barr virus) in patients with earlier acute coronary syndromes. American Journal of Cardiology 95, 317–321.Google Scholar
Okura, Y, Urban, LH, Mahoney, DW, Jacobsen, SJ, Rodeheffer, RJ (2004). Agreement between self-report questionnaires and medical record data was substantial for diabetes, hypertension, myocardial infarction and stroke but not for heart failure. Journal of Clinical Epidemiology. 57, 1096–1103.Google Scholar
Raison, CL, Capuron, L, Miller, AH (2006). Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends in Immunology 27, 24–31.Google Scholar
Rajagopalan, S, Brook, R, Rubenfire, M, Pitt, E, Young, E, Pitt, B (2001). Abnormal brachial artery flow-mediated vasodilation in young adults with major depression. American Journal of Cardiology. 88, 196–198, A7.Google Scholar
Ridker, PM, Buring, JE, Cook, NR, Rifai, N (2003). C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14 719 initially healthy American women. Circulation 107, 391–397.Google Scholar
Rodriguez-Moran, M, Guerrero-Romero, F (1999). Increased levels of C-reactive protein in non-controlled type II diabetic subjects. Journal of Diabetes and Its Complications 13, 211–215.Google Scholar
Serebruany, VL, Glassman, AH, Malinin, AI, Sane, DC, Finkel, MS, Krishnan, RR, Atar, D, Lekht, V, O'Connor, CM (2003). Enhanced platelet/endothelial activation in depressed patients with acute coronary syndromes: evidence from recent clinical trials. Blood Coagulation and Fibrinolysis 14, 563–567.Google Scholar
Skala, JA, Freedland, KE, Carney, RM (2006). Coronary heart disease and depression: a review of recent mechanistic research. Canadian Journal of Psychiatry 51, 738–745.Google Scholar
Snaith, RP, Zigmond, AS (1986). The hospital anxiety and depression scale. British Medical Journal (Clinical Research Edition) 292, 344.CrossRefGoogle ScholarPubMed
Tiemeier, H, Hofman, A, van Tuijl, HR, Kiliaan, AJ, Meijer, J, Breteler, MM (2003). Inflammatory proteins and depression in the elderly. Epidemiology 14, 103–107.Google Scholar
Whooley, MA, Caska, CM, Hendrickson, BE, Rourke, MA, Ho, J, Ali, S (2007). Depression and inflammation in patients with coronary heart disease: findings from the Heart and Soul Study. Biological Psychiatry 62, 314–320.Google Scholar