Skip to main content

Advertisement

SpringerLink
Log in

Association between interleukin-6 and the risk of cardiac events measured by coronary computed tomography angiography

  • Original Paper
  • Published:
The International Journal of Cardiovascular Imaging Aims and scope Submit manuscript

Abstract

Interleukin-6 (IL-6) has been found to be a predictor of heart attack. We aimed to investigate the relationship of risk factor IL-6 with extent and severity of the coronary artery disease (CAD) evaluated using coronary computed tomography angiography (CCTA). A total of 303 participants without history of CAD undergoing CCTA were enrolled. Using the model of risk-adjusted Cox proportional-hazards, the association of IL-6 level with major adverse cardiac events (MACE) was detected. The participants were assigned into three study groups based on serum IL-6 level. Compared with those in the lowest tertile, patients with highest IL-6 level displayed higher atherosclerotic burden such as plaque extent defined as prevalence of obstructive CAD and segments with any plaque. After a median 3.0 year follow-up period, we also found that patients with highest IL-6 level experienced higher MACE risk and all-cause death compared with those from the lowest tertile. Among participants without CAD history who underwent CCTA, patients with high level of IL-6 had increased burden of atherosclerosis and higher MACE risk compared to participants of low level of IL-6.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Sprague AH, Khalil RA (2009) Inflammatory cytokines in vascular dysfunction and vascular disease. Biochem Pharmacol 78:539–552. doi:10.1016/j.bcp.2009.04.029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH (1997) Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 336:973–979. doi:10.1056/NEJM199704033361401

    Article  CAS  PubMed  Google Scholar 

  3. Li Y, Takemura G, Okada H, Miyata S, Maruyama R, Li L, Higuchi M, Minatoguchi S, Fujiwara T, Fujiwara H (2006) Reduction of inflammatory cytokine expression and oxidative damage by erythropoietin in chronic heart failure. Cardiovasc Res 71:684–694. doi:10.1016/j.cardiores.2006.06.003

    Article  CAS  PubMed  Google Scholar 

  4. Groot HE, Hartman MH, Gu YL, de Smet BJ, van den Heuvel AF, Lipsic E, van der Harst P (2015) Soluble interleukin 6 receptor levels are associated with reduced myocardial reperfusion after percutaneous coronary intervention for acute myocardial infarction. Cytokine 73:207–212. doi:10.1016/j.cyto.2015.02.004

    Article  CAS  PubMed  Google Scholar 

  5. Mendoza CE, Rosado MF, Bernal L (2001) The role of interleukin-6 in cases of cardiac myxoma. Clinical features, immunologic abnormalities, and a possible role in recurrence. Tex Heart Inst J 28:3–7

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Lee JK, Bettencourt R, Brenner D, Le TA, Barrett-Connor E, Loomba R (2012) Association between serum interleukin-6 concentrations and mortality in older adults: the Rancho Bernardo study. PLoS ONE 7:e34218. doi:10.1371/journal.pone.0034218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Penninx BW, Kritchevsky SB, Yaffe K, Newman AB, Simonsick EM, Rubin S, Ferrucci L, Harris T, Pahor M (2003) Inflammatory markers and depressed mood in older persons: results from the health, aging and body composition study. Biol Psychiatry 54:566–572

    Article  CAS  PubMed  Google Scholar 

  8. Interleukin-6 Receptor Mendelian Randomisation Analysis, Swerdlow DI, Holmes MV, Kuchenbaecker KB, Engmann JE, Shah T, Sofat R, Guo Y, Chung C, Peasey A, Pfister R, Mooijaart SP, Ireland HA, Leusink M, Langenberg C, Li KW, Palmen J, Howard P, Cooper JA, Drenos F, Hardy J, Nalls MA, Li YR, Lowe G, Stewart M, Bielinski SJ, Peto J, Timpson NJ, Gallacher J, Dunlop M, Houlston R, Tomlinson I, Tzoulaki I, Luan J, Boer JM, Forouhi NG, Onland-Moret NC, van der Schouw YT, Schnabel RB, Hubacek JA, Kubinova R, Baceviciene M, Tamosiunas A, Pajak A, Topor-Madry R, Malyutina S, Baldassarre D, Sennblad B, Tremoli E, de Faire U, Ferrucci L, Bandenelli S, Tanaka T, Meschia JF, Singleton A, Navis G, Mateo Leach I, Bakker SJ, Gansevoort RT, Ford I, Epstein SE, Burnett MS, Devaney JM, Jukema JW, Westendorp RG, Jan de Borst G, van der Graaf Y, de Jong PA, Mailand-van der Zee AH, Klungel OH, de Boer A, Doevendans PA, Stephens JW, Eaton CB, Robinson JG, Manson JE, Fowkes FG, Frayling TM, Price JF, Whincup PH, Morris RW, Lawlor DA, Smith GD, Ben-Shlomo Y, Redline S, Lange LA, Kumari M, Wareham NJ, Verschuren WM, Benjamin EJ, Whittaker JC, Hamsten A, Dudbridge F, Delaney JA, Wong A, Kuh D, Hardy R, Castillo BA, Connolly JJ, van der Harst P, Brunner EJ, Marmot MG, Wassel CL, Humphries SE, Talmud PJ, Kivimaki M, Asselbergs FW, Voevoda M, Bobak M, Pikhart H, Wilson JG, Hakonarson H, Reiner AP, Keating BJ, Sattar N, Hingorani AD, Casas JP (2012) The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis. Lancet 379:1214–1224. doi:10.1016/S0140-6736(12)60110-X

    Article  Google Scholar 

  9. Collaboration IRGCERF, Sarwar N, Butterworth AS, Freitag DF, Gregson J, Willeit P, Gorman DN, Gao P, Saleheen D, Rendon A, Nelson CP, Braund PS, Hall AS, Chasman DI, Tybjaerg-Hansen A, Chambers JC, Benjamin EJ, Franks PW, Clarke R, Wilde AA, Trip MD, Steri M, Witteman JC, Qi L, van der Schoot CE, de Faire U, Erdmann J, Stringham HM, Koenig W, Rader DJ, Melzer D, Reich D, Psaty BM, Kleber ME, Panagiotakos DB, Willeit J, Wennberg P, Woodward M, Adamovic S, Rimm EB, Meade TW, Gillum RF, Shaffer JA, Hofman A, Onat A, Sundstrom J, Wassertheil-Smoller S, Mellstrom D, Gallacher J, Cushman M, Tracy RP, Kauhanen J, Karlsson M, Salonen JT, Wilhelmsen L, Amouyel P, Cantin B, Best LG, Ben-Shlomo Y, Manson JE, Davey-Smith G, de Bakker PI, O’Donnell CJ, Wilson JF, Wilson AG, Assimes TL, Jansson JO, Ohlsson C, Tivesten A, Ljunggren O, Reilly MP, Hamsten A, Ingelsson E, Cambien F, Hung J, Thomas GN, Boehnke M, Schunkert H, Asselbergs FW, Kastelein JJ, Gudnason V, Salomaa V, Harris TB, Kooner JS, Allin KH, Nordestgaard BG, Hopewell JC, Goodall AH, Ridker PM, Holm H, Watkins H, Ouwehand WH, Samani NJ, Kaptoge S, Di Angelantonio E, Harari O, Danesh J (2012) Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies. Lancet 379:1205–1213. doi:10.1016/S0140-6736(11)61931-4

    Article  Google Scholar 

  10. Gigante B, Strawbridge RJ, Velasquez IM, Golabkesh Z, Silveira A, Goel A, Baldassarre D, Veglia F, Tremoli E, Clarke R, Watkins H, Hamsten A, Humphries SE, de Faire U (2015) Analysis of the role of interleukin 6 receptor haplotypes in the regulation of circulating levels of inflammatory biomarkers and risk of coronary heart disease. PLoS ONE 10:e0119980. doi:10.1371/journal.pone.0119980

    Article  PubMed  PubMed Central  Google Scholar 

  11. Forster O, Ansari AA, Sliwa K (2006) Current issues in the diagnosis and management of peripartum cardiomyopathy. Womens Health 2:587–596. doi:10.2217/17455057.2.4.587

    Google Scholar 

  12. Gitsioudis G, Katus HA, Korosoglou G (2014) Assessment of coronary artery disease using coronary computed tomography angiography and biochemical markers. World J Cardiol 6:663–670. doi:10.4330/wjc.v6.i7.663

    Article  PubMed  PubMed Central  Google Scholar 

  13. Staniak HL, Bittencourt MS, Pickett C, Cahill M, Kassop D, Slim A, Blankstein R, Hulten E (2014) Coronary CT angiography for acute chest pain in the emergency department. J Cardiovasc Comput Tomogr 8:359–367. doi:10.1016/j.jcct.2014.08.001

    Article  PubMed  Google Scholar 

  14. Min JK, Shaw LJ, Devereux RB, Okin PM, Weinsaft JW, Russo DJ, Lippolis NJ, Berman DS, Callister TQ (2007) Prognostic value of multidetector coronary computed tomographic angiography for prediction of all-cause mortality. J Am Coll Cardiol 50:1161–1170. doi:10.1016/j.jacc.2007.03.067

    Article  PubMed  Google Scholar 

  15. Cesari M, Penninx BW, Newman AB, Kritchevsky SB, Nicklas BJ, Sutton-Tyrrell K, Tracy RP, Rubin SM, Harris TB, Pahor M (2003) Inflammatory markers and cardiovascular disease (the health, aging and body composition [health abc] study). Am J Cardiol 92:522–528

    Article  CAS  PubMed  Google Scholar 

  16. Goto K, Shiode N, Shirota K, Fukuda Y, Kitamura F, Tominaga K, Kato Y (2008) Impact of impaired renal function and diabetes on long-term prognosis in patients undergoing primary angioplasty for acute coronary syndrome. Intern Med 47:907–913

    Article  PubMed  Google Scholar 

  17. Staniak HL, Bittencourt MS, de Souza Santos I, Sharovsky R, Sabbag C, Goulart AC, Lotufo PA, Bensenor IM (2014) Association between psoriasis and coronary calcium score. Atherosclerosis 237:847–852. doi:10.1016/j.atherosclerosis.2014.11.004

    Article  CAS  PubMed  Google Scholar 

  18. Staniak HL, Salgado Filho W, Miname MH, Bensenor IM, Lotufo PA, Sharovsky R, Rochitte CE, Bittencourt MS, Santos RD (2014) Association between postprandial triglycerides and coronary artery disease detected by coronary computed tomography angiography. Atherosclerosis 233:381–386. doi:10.1016/j.atherosclerosis.2013.12.036

    Article  CAS  PubMed  Google Scholar 

  19. Sarojini A, Sai Ravi Shanker A, Anitha M (2013) Inflammatory markers-serum level of c-reactive protein, tumor necrotic factor-alpha, and interleukin-6 as predictors of outcome for peripartum cardiomyopathy. J Obstet Gynaecol India 63:234–239. doi:10.1007/s13224-013-0428-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhou J, Chen X, Ye H, Peng P, Ba Y, Yang X, Huang X, Lu Y, Jiang X, Lian J, Duan S (2014) An association study between genetic polymorphism in the interleukin-6 receptor gene and coronary heart disease. Biomed Res Int. doi:10.1155/2014/504727

    Google Scholar 

  21. Clarke MC, Figg N, Maguire JJ, Davenport AP, Goddard M, Littlewood TD, Bennett MR (2006) Apoptosis of vascular smooth muscle cells induces features of plaque vulnerability in atherosclerosis. Nat Med 12:1075–1080. doi:10.1038/nm1459

    Article  CAS  PubMed  Google Scholar 

  22. Patterson CC, Smith AE, Yarnell JW, Rumley A, Ben-Shlomo Y, Lowe GD (2010) The associations of interleukin-6 (IL-6) and downstream inflammatory markers with risk of cardiovascular disease: the caerphilly study. Atherosclerosis 209:551–557. doi:10.1016/j.atherosclerosis.2009.09.030

    Article  CAS  PubMed  Google Scholar 

  23. Rao M, Guo D, Perianayagam MC, Tighiouart H, Jaber BL, Pereira BJ, Balakrishnan VS (2005) Plasma interleukin-6 predicts cardiovascular mortality in hemodialysis patients. Am J Kidney Dis 45:324–333

    Article  CAS  PubMed  Google Scholar 

  24. Tuomisto K, Jousilahti P, Sundvall J, Pajunen P, Salomaa V (2006) C-reactive protein, interleukin-6 and tumor necrosis factor alpha as predictors of incident coronary and cardiovascular events and total mortality. A population-based, prospective study. Thromb Haemost 95:511–518. doi:10.1160/TH05-08-0571

    CAS  PubMed  Google Scholar 

  25. Arai Y, Takayama M, Gondo Y, Inagaki H, Yamamura K, Nakazawa S, Kojima T, Ebihara Y, Shimizu K, Masui Y, Kitagawa K, Takebayashi T, Hirose N (2008) Adipose endocrine function, insulin-like growth factor-1 axis, and exceptional survival beyond 100 years of age. J Gerontol A 63:1209–1218

    Article  Google Scholar 

  26. Haugen E, Gan LM, Isic A, Skommevik T, Fu M (2008) Increased interleukin-6 but not tumour necrosis factor-alpha predicts mortality in the population of elderly heart failure patients. Exp Clin Cardiol 13:19–24

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Zuo HP, Guo YY, Che L, Wu XZ (2016) Hypomethylation of interleukin-6 promoter is associated with the risk of coronary heart disease. Arq Bras Cardiol 107:131–136. doi:10.5935/abc.20160124

    PubMed  PubMed Central  Google Scholar 

  28. Haugen E, Tang MS, Isic A, Andersson B, Fu M (2008) TNFalpha antagonist upregulates interleukin-6 in rats with hypertensive heart failure. Int J Cardiol 130:64–68. doi:10.1016/j.ijcard.2007.08.047

    Article  PubMed  Google Scholar 

  29. Smart NA, Larsen AI, Le Maitre JP, Ferraz AS (2011) Effect of exercise training on interleukin-6, tumour necrosis factor alpha and functional capacity in heart failure. Cardiol Res Pract. doi:10.4061/2011/532620

    PubMed  PubMed Central  Google Scholar 

  30. Panichi V, Maggiore U, Taccola D, Migliori M, Rizza GM, Consani C, Bertini A, Sposini S, Perez-Garcia R, Rindi P, Palla R, Tetta C (2004) Interleukin-6 is a stronger predictor of total and cardiovascular mortality than C-reactive protein in haemodialysis patients. Nephrol Dial Transplant 19:1154–1160. doi:10.1093/ndt/gfh052

    Article  CAS  PubMed  Google Scholar 

  31. Li Y, Takemura G, Okada H, Miyata S, Esaki M, Maruyama R, Kanamori H, Li L, Ogino A, Misao Y, Khai NC, Mikami A, Minatoguchi S, Fujiwara T, Fujiwara H (2006) Treatment with granulocyte colony-stimulating factor ameliorates chronic heart failure. Lab Invest 86:32–44. doi:10.1038/labinvest.3700367

    Article  CAS  PubMed  Google Scholar 

  32. Ritschel VN, Seljeflot I, Arnesen H, Halvorsen S, Weiss T, Eritsland J, Andersen GO (2014) IL-6 signalling in patients with acute ST-elevation myocardial infarction. Results Immunol 4:8–13. doi:10.1016/j.rinim.2013.11.002

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Imaging Center, The Second Hospital of Shandong University, No. 247 Beiyuandajie, Jinan, 250033, Shandong, China

    Lei Zhao & Yuhai Yang

  2. Department of Nuclear Medicine, Changle People’s Hospital, No. 278 Liminjie, Weifang, 262499, Shandong, China

    Xilin Wang

Authors
  1. Lei Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xilin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuhai Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yuhai Yang.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, L., Wang, X. & Yang, Y. Association between interleukin-6 and the risk of cardiac events measured by coronary computed tomography angiography. Int J Cardiovasc Imaging 33, 1237–1244 (2017). https://doi.org/10.1007/s10554-017-1098-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10554-017-1098-y

Keywords

Search

Navigation