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Original article

Vol. 152 No. 5152 (2022)

Preoperative depression and anxiety as predictors of postoperative C-reactive protein levels in patients undergoing cardiac surgery: a prospective observational study

  • Roland von Känel
  • Kim Rosselet
  • Katharina Gessler
  • Achim Haeussler
  • Jessica Aschmann
  • Hector Rodriguez
  • Omer Dzemali
DOI
https://doi.org/10.57187/smw.2022.40018
Cite this as:
Swiss Med Wkly. 2022;152:40018
Published
20.12.2022

Summary

AIM OF THE STUDY: In patients undergoing cardiac surgery, preoperative depressive and anxiety symptoms and increased postoperative C-reactive protein (CRP) levels have been associated with adverse outcomes. We tested the hypothesis that preoperative depressive and anxiety symptoms predict elevated in-hospital CRP levels after cardiac surgery.

METHODS: The study participants were 96 consecutive patients (mean age [SD], 67.6 [10.3] years, 78.1% men) from a single cardiac surgery centre who underwent either isolated coronary artery bypass grafting (CABG) (n = 34), isolated valve surgery (n = 29), combined procedures (including different combinations of CABG, valve surgery, aortic surgery, and others) (n = 30), or other cardiac surgical procedures (n = 3). Participants self-rated depressive and anxiety symptoms using the Patient Health Questionnaire (PHQ-9) and the General Anxiety Disorder (GAD-7) questionnaire before undergoing elective surgery. CRP levels were measured every 24 h up to 10 days post-surgery. Linear mixed (random effects) regression analysis examined the association between preoperative depressive and anxiety symptoms and CRP levels over time, adjusting for pre-surgery CRP levels, demographics, cardiovascular risk factors, medications, and surgery-related variables.

RESULTS: Before surgery, 32.2% of patients had clinically relevant depressive symptoms (PHQ-9 score ≥5) and 32.2% of patients had clinically relevant anxiety symptoms (GAD-7 score ≥5). More severe depressive symptoms (estimate [95% CI]: 0.081 [0.023, 0.139], p = 0.007) and more severe anxiety symptoms (0.059 [0.005, 0.113], p = 0.032) predicted CRP levels over 10 days, independent of covariates. Furthermore, CRP levels were higher in patients with than in those without clinically relevant depressive symptoms (0.697 [0.204, 1.191], p = 0.006) and were predicted by both more severe somatic (0.132 [0.035, 0.229], p = 0.008) and cognitive (0.128 [0.014, 0.242], p = 0.029) depressive symptoms.

CONCLUSIONS: Preoperative depressive and anxiety symptoms were independent predictors of elevated CRP levels up to 10 days post-surgery. Such a mechanism may help explain the increased morbidity and mortality risk in patients with depression and anxiety who undergo cardiac surgery.

References

  1. Correa-Rodríguez M, Abu Ejheisheh M, Suleiman-Martos N, Membrive-Jiménez MJ, Velando-Soriano A, Schmidt-RioValle J, et al. Prevalence of Depression in Coronary Artery Bypass Surgery: A Systematic Review and Meta-Analysis. J Clin Med. 2020 Mar;9(4):909. https://doi.org/10.3390/jcm9040909 DOI: https://doi.org/10.3390/jcm9040909
  2. Horne D, Kehler S, Kaoukis G, Hiebert B, Garcia E, Duhamel TA, et al. Depression before and after cardiac surgery: do all patients respond the same? J Thorac Cardiovasc Surg. 2013 May;145(5):1400–6. https://doi.org/10.1016/j.jtcvs.2012.11.011 DOI: https://doi.org/10.1016/j.jtcvs.2012.11.011
  3. Takagi H, Ando T, Umemoto T; ALICE (All-Literature Investigation of Cardiovascular Evidence) Group. Perioperative depression or anxiety and postoperative mortality in cardiac surgery: a systematic review and meta-analysis. Heart Vessels. 2017 Dec;32(12):1458–68. https://doi.org/10.1007/s00380-017-1022-3 DOI: https://doi.org/10.1007/s00380-017-1022-3
  4. Flaherty LB, Wood T, Cheng A, Khan AR. Pre-existing psychological depression confers increased risk of adverse cardiovascular outcomes following cardiac surgery: A systematic review and meta-analysis. J Thorac Cardiovasc Surg. 2017 Nov;154(5):1578–1586.e1. https://doi.org/10.1016/j.jtcvs.2017.06.052 DOI: https://doi.org/10.1016/j.jtcvs.2017.06.052
  5. Tully PJ, Baker RA. Depression, anxiety, and cardiac morbidity outcomes after coronary artery bypass surgery: a contemporary and practical review. J Geriatr Cardiol. 2012 Jun;9(2):197–208. https://doi.org/10.3724/SP.J.1263.2011.12221 DOI: https://doi.org/10.3724/SP.J.1263.2011.12221
  6. Laffey JG, Boylan JF, Cheng DC. The systemic inflammatory response to cardiac surgery: implications for the anesthesiologist. Anesthesiology. 2002 Jul;97(1):215–52. https://doi.org/10.1097/00000542-200207000-00030 DOI: https://doi.org/10.1097/00000542-200207000-00030
  7. Tomic V, Russwurm S, Möller E, Claus RA, Blaess M, Brunkhorst F, et al. Transcriptomic and proteomic patterns of systemic inflammation in on-pump and off-pump coronary artery bypass grafting. Circulation. 2005 Nov;112(19):2912–20. https://doi.org/10.1161/CIRCULATIONAHA.104.531152 DOI: https://doi.org/10.1161/CIRCULATIONAHA.104.531152
  8. Ayala J, Smith A, Farrar D. C-reactive protein levels following cardiac surgery in adults. Eur J Anaesthesiol. 2006 Jun;23 Supplement 37:196. https://doi.org/10.1097/00003643-200606001-00703 DOI: https://doi.org/10.1097/00003643-200606001-00703
  9. Holm J, Cederholm I, Alehagen U, Lindahl TL, Szabó Z. Biomarker dynamics in cardiac surgery: a prospective observational study on MR-proADM, MR-proANP, hs-CRP and sP-selectin plasma levels in the perioperative period. Biomarkers. 2020 May;25(3):296–304. https://doi.org/10.1080/1354750X.2020.1748716 DOI: https://doi.org/10.1080/1354750X.2020.1748716
  10. Min JJ, Nam K, Kim TK, Kim HJ, Seo JH, Hwang HY, et al. Relationship between early postoperative C-reactive protein elevation and long-term postoperative major adverse cardiovascular and cerebral events in patients undergoing off-pump coronary artery bypass graft surgery: a retrospective study [Erratum in: Br J Anaesth. 2014 Nov;113] [5] [:895. PMID: 24829443]. Br J Anaesth. 2014 Sep;113(3):391–401. https://doi.org/10.1093/bja/aeu099 DOI: https://doi.org/10.1093/bja/aeu099
  11. Nakamoto S, Hirose M. Prediction of early C-reactive protein levels after non-cardiac surgery under general anesthesia. PLoS One. 2019 Dec;14(12):e0226032. https://doi.org/10.1371/journal.pone.0226032 DOI: https://doi.org/10.1371/journal.pone.0226032
  12. Kouvelos GN, Milionis HJ, Arnaoutoglou EM, Chasiotis G, Gartzonika C, Papa NK, et al. Postoperative levels of cardiac troponin versus CK-MB and high-sensitivity C-reactive protein for the prediction of 1-year cardiovascular outcome in patients undergoing vascular surgery. Coron Artery Dis. 2011;22(6):428–34. https://doi.org/10.1097/MCA.0b013e3283487d96 DOI: https://doi.org/10.1097/MCA.0b013e3283487d96
  13. Osimo EF, Pillinger T, Rodriguez IM, Khandaker GM, Pariante CM, Howes OD. Inflammatory markers in depression: A meta-analysis of mean differences and variability in 5,166 patients and 5,083 controls. Brain Behav Immun. 2020 Jul;87:901–9. https://doi.org/10.1016/j.bbi.2020.02.010 DOI: https://doi.org/10.1016/j.bbi.2020.02.010
  14. Smith KJ, Au B, Ollis L, Schmitz N. The association between C-reactive protein, Interleukin-6 and depression among older adults in the community: A systematic review and meta-analysis. Exp Gerontol. 2018 Feb;102:109–32. https://doi.org/10.1016/j.exger.2017.12.005 DOI: https://doi.org/10.1016/j.exger.2017.12.005
  15. Mac Giollabhui N, Ng TH, Ellman LM, Alloy LB. The longitudinal associations of inflammatory biomarkers and depression revisited: systematic review, meta-analysis, and meta-regression. Mol Psychiatry. 2021 Jul;26(7):3302–14. https://doi.org/10.1038/s41380-020-00867-4 DOI: https://doi.org/10.1038/s41380-020-00867-4
  16. Costello H, Gould RL, Abrol E, Howard R. Systematic review and meta-analysis of the association between peripheral inflammatory cytokines and generalised anxiety disorder. BMJ Open. 2019 Jul;9(7):e027925. https://doi.org/10.1136/bmjopen-2018-027925 DOI: https://doi.org/10.1136/bmjopen-2018-027925
  17. Liu CH, Hua N, Yang HY. Alterations in Peripheral C-Reactive Protein and Inflammatory Cytokine Levels in Patients with Panic Disorder: A Systematic Review and Meta-Analysis. Neuropsychiatr Dis Treat. 2021 Dec;17:3539–58. https://doi.org/10.2147/NDT.S340388 DOI: https://doi.org/10.2147/NDT.S340388
  18. Glaus J, von Känel R, Lasserre AM, Strippoli MF, Vandeleur CL, Castelao E, et al. The bidirectional relationship between anxiety disorders and circulating levels of inflammatory markers: results from a large longitudinal population-based study. Depress Anxiety. 2018 Apr;35(4):360–71. https://doi.org/10.1002/da.22710 DOI: https://doi.org/10.1002/da.22710
  19. Frasure-Smith N, Lespérance F, Irwin MR, Sauvé C, Lespérance J, Théroux P. Depression, C-reactive protein and two-year major adverse cardiac events in men after acute coronary syndromes. Biol Psychiatry. 2007 Aug;62(4):302–8. https://doi.org/10.1016/j.biopsych.2006.09.029 DOI: https://doi.org/10.1016/j.biopsych.2006.09.029
  20. Munkhaugen J, Otterstad JE, Dammen T, Gjertsen E, Moum T, Husebye E, et al. The prevalence and predictors of elevated C-reactive protein after a coronary heart disease event. Eur J Prev Cardiol. 2018 Jun;25(9):923–31. https://doi.org/10.1177/2047487318768940 DOI: https://doi.org/10.1177/2047487318768940
  21. Poole L, Kidd T, Leigh E, Ronaldson A, Jahangiri M, Steptoe A. Depression, C-reactive protein and length of post-operative hospital stay in coronary artery bypass graft surgery patients. Brain Behav Immun. 2014 Mar;37(100):115–21. https://doi.org/10.1016/j.bbi.2013.11.008 DOI: https://doi.org/10.1016/j.bbi.2013.11.008
  22. Gao Q, Mok HP, Zhang HY, Qiu HL, Liu J, Chen ZR, et al. Inflammatory indicator levels in patients undergoing aortic valve replacement via median sternotomy with preoperative anxiety and postoperative complications: a prospective cohort study. J Int Med Res. 2021 Feb;49(2):300060520977417. https://doi.org/10.1177/0300060520977417 DOI: https://doi.org/10.1177/0300060520977417
  23. Płotek W, Pielok J, Cybulski M, Samborska R. Emotional processes in patients undergoing coronary artery bypass graft surgeries with extracorporeal circulation in view of selected indicators of the inflammatory condition. Med Sci Monit. 2015 Jan;21:105–17. https://doi.org/10.12659/MSM.892372 DOI: https://doi.org/10.12659/MSM.892372
  24. Goldberg D. The heterogeneity of “major depression”. World Psychiatry. 2011 Oct;10(3):226–8. https://doi.org/10.1002/j.2051-5545.2011.tb00061.x DOI: https://doi.org/10.1002/j.2051-5545.2011.tb00061.x
  25. de Miranda Azevedo R, Roest AM, Hoen PW, de Jonge P. Cognitive/affective and somatic/affective symptoms of depression in patients with heart disease and their association with cardiovascular prognosis: a meta-analysis. Psychol Med. 2014 Oct;44(13):2689–703. https://doi.org/10.1017/S0033291714000063 DOI: https://doi.org/10.1017/S0033291714000063
  26. Borde D, Gandhe U, Hargave N, Pandey K, Khullar V. The application of European system for cardiac operative risk evaluation II (EuroSCORE II) and Society of Thoracic Surgeons (STS) risk-score for risk stratification in Indian patients undergoing cardiac surgery. Ann Card Anaesth. 2013;16(3):163–6. https://doi.org/10.4103/0971-9784.114234 DOI: https://doi.org/10.4103/0971-9784.114234
  27. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606–13. https://doi.org/10.1046/j.1525-1497.2001.016009606.x DOI: https://doi.org/10.1046/j.1525-1497.2001.016009606.x
  28. Spitzer RL, Kroenke K, Williams JB, Löwe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006 May;166(10):1092–7. https://doi.org/10.1001/archinte.166.10.1092 DOI: https://doi.org/10.1001/archinte.166.10.1092
  29. Stenman M, Sartipy U. Depression Screening in Cardiac Surgery Patients. Heart Lung Circ. 2019 Jun;28(6):953–8. https://doi.org/10.1016/j.hlc.2018.04.298 DOI: https://doi.org/10.1016/j.hlc.2018.04.298
  30. Kroenke K, Spitzer RL, Williams JB, Löwe B. The Patient Health Questionnaire Somatic, Anxiety, and Depressive Symptom Scales: a systematic review. Gen Hosp Psychiatry. 2010;32(4):345–59. https://doi.org/10.1016/j.genhosppsych.2010.03.006 DOI: https://doi.org/10.1016/j.genhosppsych.2010.03.006
  31. Tully PJ, Turnbull DA, Horowitz JD, Beltrame JF, Baune BT, Sauer-Zavala S, et al. Transdiagnostic Cognitive-Behavioral Therapy for Depression and Anxiety Disorders in Cardiovascular Disease Patients: Results From the CHAMPS Pilot-Feasibility Trial. Front Psychiatry. 2022 Apr;13:741039. https://doi.org/10.3389/fpsyt.2022.741039 DOI: https://doi.org/10.3389/fpsyt.2022.741039
  32. Sakia RM. The Box-Cox transformation technique: a review. Statistician. 1992;41(2):169–78. https://doi.org/10.2307/2348250 DOI: https://doi.org/10.2307/2348250
  33. Hemmerich W. Box-Cox Powertransformation berechnen. 2016. Available from: https://statistikguru.de/rechner/box-cox.html
  34. Tully PJ, Winefield HR, Baker RA, Turnbull DA, de Jonge P. Confirmatory factor analysis of the Beck Depression Inventory-II and the association with cardiac morbidity and mortality after coronary revascularization. J Health Psychol. 2011 May;16(4):584–95. https://doi.org/10.1177/1359105310383604 DOI: https://doi.org/10.1177/1359105310383604
  35. Guo P. Preoperative education interventions to reduce anxiety and improve recovery among cardiac surgery patients: a review of randomised controlled trials. J Clin Nurs. 2015 Jan;24(1-2):34–46. https://doi.org/10.1111/jocn.12618 DOI: https://doi.org/10.1111/jocn.12618
  36. Marsland AL, Walsh C, Lockwood K, John-Henderson NA. The effects of acute psychological stress on circulating and stimulated inflammatory markers: A systematic review and meta-analysis. Brain Behav Immun. 2017 Aug;64:208–19. https://doi.org/10.1016/j.bbi.2017.01.011 DOI: https://doi.org/10.1016/j.bbi.2017.01.011
  37. Galvis D, Zavala E, Walker JJ, Upton T, Lightman SL, Angelini GD, et al. Modelling the dynamic interaction of systemic inflammation and the hypothalamic-pituitary-adrenal (HPA) axis during and after cardiac surgery. J R Soc Interface. 2022 Apr;19(189):20210925. https://doi.org/10.1098/rsif.2021.0925 DOI: https://doi.org/10.1098/rsif.2021.0925
  38. von Känel R, Kudielka BM, Preckel D, Hanebuth D, Fischer JE. Delayed response and lack of habituation in plasma interleukin-6 to acute mental stress in men. Brain Behav Immun. 2006 Jan;20(1):40–8. https://doi.org/10.1016/j.bbi.2005.03.013 DOI: https://doi.org/10.1016/j.bbi.2005.03.013
  39. Julija Gecaite-Stonciene J, Hughes BM, Kazukauskiene N, Bunevicius A, Burkauskas J, Neverauskas J, et al. Cortisol Response to Psychosocial Stress in Coronary Artery Disease Patients: The Role of Mental Distress, Fatigue and Quality of Life. Sci Rep 2022 (preprint under review). doi: https://doi.org/10.21203/rs.3.rs-1519480/v1 DOI: https://doi.org/10.21203/rs.3.rs-1519480/v1
  40. Nikkheslat N, Zunszain PA, Horowitz MA, Barbosa IG, Parker JA, Myint AM, et al. Insufficient glucocorticoid signaling and elevated inflammation in coronary heart disease patients with comorbid depression. Brain Behav Immun. 2015 Aug;48:8–18. https://doi.org/10.1016/j.bbi.2015.02.002 DOI: https://doi.org/10.1016/j.bbi.2015.02.002
  41. Frasure-Smith N, Lespérance F, Irwin MR, Talajic M, Pollock BG. The relationships among heart rate variability, inflammatory markers and depression in coronary heart disease patients. Brain Behav Immun. 2009 Nov;23(8):1140–7. https://doi.org/10.1016/j.bbi.2009.07.005 DOI: https://doi.org/10.1016/j.bbi.2009.07.005

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