Skip to main content
Top
Published in: Immunity & Ageing 1/2014

Open Access 01-12-2014 | Hypothesis

Age-related limitations of interleukin-6 in predicting early mortality in acute ST-elevation myocardial infarction

Authors: Dominika Kanikowska, Małgorzata Pyda, Katarzyna Korybalska, Stefan Grajek, Maciej Lesiak, Andrzej Bręborowicz, Janusz Witowski

Published in: Immunity & Ageing | Issue 1/2014

Login to get access

Abstract

Interleukin-6 (IL-6) is an inflammatory cytokine whose levels increase significantly during myocardial infarction (MI).
It has been hypothesised that the concentrations of IL-6 at admission may be useful in prognosticating long-term outcomes. It is unclear, however, whether IL-6 could improve the prognosis of early mortality in MI.
We have compared serum IL-6 levels and analysed the disease course in 158 patients with ST-elevation MI (STEMI) who either survived (n = 148) or died (n = 10) within 30 days following the admission. Patients were treated in a single university centre with primary percutaneous coronary intervention (PCI).
The non-survivors (6.3%) displayed most of typical risk factors for poor outcome. In addition they had significantly higher concentrations of IL-6 at hospital admission (median values 8.5 vs. 2.0 pg/ml; p = 0.038). However, they were also significantly older than the survivors (median values 72 vs. 57 years; p = 0.0001). IL-6 levels are known to increase with age and we could confirm a significant correlation between patients’ calendar age and circulating IL-6 (p = 0.009). Regression analysis revealed that IL-6 concentrations were significantly affected by patients’ age but they did not independently relate to patients’ outcome.
Such results indicate that circulating IL-6 at admission may be of limited value in predicting early mortality in STEMI. It is important to recognize that, because of the small group of patients who died (N = 10), the results must be interpreted with caution. Therefore, we stress that these results should be viewed as preliminary and further validated in a larger set of patients.
Appendix
Available only for authorised users
Literature
1.
go back to reference Mihara M, Hashizume M, Yoshida H, Suzuki M, Shiina M: IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci (Lond). 2012, 122: 143-159. 10.1042/CS20110340.CrossRef Mihara M, Hashizume M, Yoshida H, Suzuki M, Shiina M: IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci (Lond). 2012, 122: 143-159. 10.1042/CS20110340.CrossRef
2.
go back to reference Rincon M: Interleukin-6: from an inflammatory marker to a target for inflammatory diseases. Trends Immunol. 2012, 33: 571-577. 10.1016/j.it.2012.07.003.CrossRefPubMed Rincon M: Interleukin-6: from an inflammatory marker to a target for inflammatory diseases. Trends Immunol. 2012, 33: 571-577. 10.1016/j.it.2012.07.003.CrossRefPubMed
3.
go back to reference Hartman J, Frishman WH: Inflammation and atherosclerosis: a review of the role of interleukin-6 in the development of atherosclerosis and the potential for targeted drug therapy. Cardiol Rev. 2014, 22 (3): 147-51. 10.1097/CRD.0000000000000021.CrossRefPubMed Hartman J, Frishman WH: Inflammation and atherosclerosis: a review of the role of interleukin-6 in the development of atherosclerosis and the potential for targeted drug therapy. Cardiol Rev. 2014, 22 (3): 147-51. 10.1097/CRD.0000000000000021.CrossRefPubMed
4.
go back to reference Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S: The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta. 2011, 1813: 878-888. 10.1016/j.bbamcr.2011.01.034.CrossRefPubMed Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S: The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta. 2011, 1813: 878-888. 10.1016/j.bbamcr.2011.01.034.CrossRefPubMed
5.
go back to reference Danesh J, Kaptoge S, Mann AG, Sarwar N, Wood A, Angleman SB, Wensley F, Higgins JP, Lennon L, Eiriksdottir G, Rumley A, Whincup PH, Lowe GD, Gudnason V: Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review.PLoS Med 2008, 5:e78., Danesh J, Kaptoge S, Mann AG, Sarwar N, Wood A, Angleman SB, Wensley F, Higgins JP, Lennon L, Eiriksdottir G, Rumley A, Whincup PH, Lowe GD, Gudnason V: Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review.PLoS Med 2008, 5:e78.,
6.
go back to reference Hingorani AD, Casas JP: The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis. Lancet. 2012, 379: 1214-1224. 10.1016/S0140-6736(12)60110-X.CrossRef Hingorani AD, Casas JP: The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis. Lancet. 2012, 379: 1214-1224. 10.1016/S0140-6736(12)60110-X.CrossRef
7.
go back to reference Garcia-Salas JM, Tello-Montoliu A, Manzano-Fernandez S, Casas-Pina T, Lopez-Cuenca A, Perez-Berbel P, Puche-Morenilla C, Martínez-Hernández P, Valdés M, Marín F: Interleukin-6 as a predictor of cardiovascular events in troponin-negative non-ST elevation acute coronary syndrome patients. Int J Clin Pract. 2014, 68: 294-303. 10.1111/ijcp.12245.CrossRefPubMed Garcia-Salas JM, Tello-Montoliu A, Manzano-Fernandez S, Casas-Pina T, Lopez-Cuenca A, Perez-Berbel P, Puche-Morenilla C, Martínez-Hernández P, Valdés M, Marín F: Interleukin-6 as a predictor of cardiovascular events in troponin-negative non-ST elevation acute coronary syndrome patients. Int J Clin Pract. 2014, 68: 294-303. 10.1111/ijcp.12245.CrossRefPubMed
8.
go back to reference Su D, Li Z, Li X, Chen Y, Zhang Y, Ding D, Deng X, Xia M, Qiu J, Ling W: Association between serum interleukin-6 concentration and mortality in patients with coronary artery disease.Mediators Inflamm 2013, 2013:726178., Su D, Li Z, Li X, Chen Y, Zhang Y, Ding D, Deng X, Xia M, Qiu J, Ling W: Association between serum interleukin-6 concentration and mortality in patients with coronary artery disease.Mediators Inflamm 2013, 2013:726178.,
9.
go back to reference Zamani P, Schwartz GG, Olsson AG, Rifai N, Bao W, Libby P, Ganz P, Kinlay S, Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators: Inflammatory biomarkers, death, and recurrent nonfatal coronary events after an acute coronary syndrome in the MIRACL study.J Am Heart Assoc 2013, 2:e003103., Zamani P, Schwartz GG, Olsson AG, Rifai N, Bao W, Libby P, Ganz P, Kinlay S, Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators: Inflammatory biomarkers, death, and recurrent nonfatal coronary events after an acute coronary syndrome in the MIRACL study.J Am Heart Assoc 2013, 2:e003103.,
10.
go back to reference Hartford M, Wiklund O, Mattsson HL, Persson A, Karlsson T, Herlitz J, Caidahl K: C-reactive protein, interleukin-6, secretory phospholipase A2 group IIA and intercellular adhesion molecule-1 in the prediction of late outcome events after acute coronary syndromes. J Intern Med. 2007, 262: 526-536. 10.1111/j.1365-2796.2007.01862.x.CrossRefPubMed Hartford M, Wiklund O, Mattsson HL, Persson A, Karlsson T, Herlitz J, Caidahl K: C-reactive protein, interleukin-6, secretory phospholipase A2 group IIA and intercellular adhesion molecule-1 in the prediction of late outcome events after acute coronary syndromes. J Intern Med. 2007, 262: 526-536. 10.1111/j.1365-2796.2007.01862.x.CrossRefPubMed
11.
go back to reference Kavsak PA, Ko DT, Newman AM, Palomaki GE, Lustig V, Macrae AR, Jaffe AS: “Upstream markers” provide for early identification of patients at high risk for myocardial necrosis and adverse outcomes. Clin Chim Acta. 2008, 387: 133-138. 10.1016/j.cca.2007.09.023.PubMedCentralCrossRefPubMed Kavsak PA, Ko DT, Newman AM, Palomaki GE, Lustig V, Macrae AR, Jaffe AS: “Upstream markers” provide for early identification of patients at high risk for myocardial necrosis and adverse outcomes. Clin Chim Acta. 2008, 387: 133-138. 10.1016/j.cca.2007.09.023.PubMedCentralCrossRefPubMed
12.
go back to reference Bennermo M, Nordin M, Lundman P, Boqvist S, Held C, Samnegard A, Ericsson CG, Silveira A, Hamsten A, Nastase MM, Tornvall P: Genetic and environmental influences on the plasma interleukin-6 concentration in patients with a recent myocardial infarction: a case–control study. J Interferon Cytokine Res. 2011, 31: 259-264. 10.1089/jir.2010.0036.CrossRefPubMed Bennermo M, Nordin M, Lundman P, Boqvist S, Held C, Samnegard A, Ericsson CG, Silveira A, Hamsten A, Nastase MM, Tornvall P: Genetic and environmental influences on the plasma interleukin-6 concentration in patients with a recent myocardial infarction: a case–control study. J Interferon Cytokine Res. 2011, 31: 259-264. 10.1089/jir.2010.0036.CrossRefPubMed
13.
go back to reference Kazmierczak E, Grajek S, Kowal J, Chmara E, Grygier M, Pyda M, Bogdanski P, Cieslewicz A, Jablecka A: Prognostic usefulness of IL-6 and VEGF for the occurrence of changes in coronary arteries of patients with stable angina and implanted stents. Eur Rev Med Pharmacol Sci. 2014, 18 (15): 2169-2175.PubMed Kazmierczak E, Grajek S, Kowal J, Chmara E, Grygier M, Pyda M, Bogdanski P, Cieslewicz A, Jablecka A: Prognostic usefulness of IL-6 and VEGF for the occurrence of changes in coronary arteries of patients with stable angina and implanted stents. Eur Rev Med Pharmacol Sci. 2014, 18 (15): 2169-2175.PubMed
14.
go back to reference Geppert A, Dorninger A, Delle-Karth G, Zorn G, Heinz G, Huber K: Plasma concentrations of interleukin-6, organ failure, vasopressor support, and successful coronary revascularization in predicting 30-day mortality of patients with cardiogenic shock complicating acute myocardial infarction. Crit Care Med. 2006, 34: 2035-2042. 10.1097/01.CCM.0000228919.33620.D9.CrossRefPubMed Geppert A, Dorninger A, Delle-Karth G, Zorn G, Heinz G, Huber K: Plasma concentrations of interleukin-6, organ failure, vasopressor support, and successful coronary revascularization in predicting 30-day mortality of patients with cardiogenic shock complicating acute myocardial infarction. Crit Care Med. 2006, 34: 2035-2042. 10.1097/01.CCM.0000228919.33620.D9.CrossRefPubMed
15.
go back to reference Prondzinsky R, Unverzagt S, Lemm H, Wegener NA, Schlitt A, Heinroth KM, Dietz S, Buerke U, Kellner P, Loppnow H, Fiedler MG, Thiery J, Werdan K, Buerke M: Interleukin-6, −7, −8 and −10 predict outcome in acute myocardial infarction complicated by cardiogenic shock. Clin Res Cardiol. 2012, 101: 375-384. 10.1007/s00392-011-0403-3.CrossRefPubMed Prondzinsky R, Unverzagt S, Lemm H, Wegener NA, Schlitt A, Heinroth KM, Dietz S, Buerke U, Kellner P, Loppnow H, Fiedler MG, Thiery J, Werdan K, Buerke M: Interleukin-6, −7, −8 and −10 predict outcome in acute myocardial infarction complicated by cardiogenic shock. Clin Res Cardiol. 2012, 101: 375-384. 10.1007/s00392-011-0403-3.CrossRefPubMed
16.
go back to reference Shanmugasundaram M, Alpert JS: Acute coronary syndrome in the elderly. Clin Cardiol. 2009, 32: 608-613. 10.1002/clc.20623.CrossRefPubMed Shanmugasundaram M, Alpert JS: Acute coronary syndrome in the elderly. Clin Cardiol. 2009, 32: 608-613. 10.1002/clc.20623.CrossRefPubMed
17.
go back to reference De Luca G, Suryapranata H, van ‘t-Hof AW, de Boer MJ, Hoorntje JC, Dambrink JH: Prognostic assessment of patients with acute myocardial infarction treated with primary angioplasty: implications for early discharge. Circulation. 2004, 109: 2737-2743. 10.1161/01.CIR.0000131765.73959.87.CrossRefPubMed De Luca G, Suryapranata H, van ‘t-Hof AW, de Boer MJ, Hoorntje JC, Dambrink JH: Prognostic assessment of patients with acute myocardial infarction treated with primary angioplasty: implications for early discharge. Circulation. 2004, 109: 2737-2743. 10.1161/01.CIR.0000131765.73959.87.CrossRefPubMed
18.
go back to reference Ferrucci L, Corsi A, Lauretani F, Bandinelli S, Bartali B, Taub DD, Guralnik JM, Longo DL: The origins of age-related proinflammatory state. Blood. 2005, 105: 2294-2299. 10.1182/blood-2004-07-2599.CrossRefPubMed Ferrucci L, Corsi A, Lauretani F, Bandinelli S, Bartali B, Taub DD, Guralnik JM, Longo DL: The origins of age-related proinflammatory state. Blood. 2005, 105: 2294-2299. 10.1182/blood-2004-07-2599.CrossRefPubMed
19.
go back to reference Miles EA, Rees D, Banerjee T, Cazzola R, Lewis S, Wood R, Oates R, Tallant A, Cestaro B, Yaqoob P, Wahle KW, Calder PC: Age-related increases in circulating inflammatory markers in men are independent of BMI, blood pressure and blood lipid concentrations. Atherosclerosis. 2008, 196: 298-305. 10.1016/j.atherosclerosis.2006.11.002.CrossRefPubMed Miles EA, Rees D, Banerjee T, Cazzola R, Lewis S, Wood R, Oates R, Tallant A, Cestaro B, Yaqoob P, Wahle KW, Calder PC: Age-related increases in circulating inflammatory markers in men are independent of BMI, blood pressure and blood lipid concentrations. Atherosclerosis. 2008, 196: 298-305. 10.1016/j.atherosclerosis.2006.11.002.CrossRefPubMed
20.
go back to reference Giugliano RP, Braunwald E: The year in acute coronary syndrome. J Am Coll Cardiol. 2014, 263: 201-214. 10.1016/j.jacc.2013.10.041.CrossRef Giugliano RP, Braunwald E: The year in acute coronary syndrome. J Am Coll Cardiol. 2014, 263: 201-214. 10.1016/j.jacc.2013.10.041.CrossRef
21.
go back to reference Nash SD, Cruickshanks KJ, Klein R, Klein BE, Nieto FJ, Chappell R, Schubert CR, Tsai MY: Long-term variability of inflammatory markers and associated factors in a population-based cohort. J Am Geriatr Soc. 2013, 61: 1269-1276. 10.1111/jgs.12382.PubMedCentralCrossRefPubMed Nash SD, Cruickshanks KJ, Klein R, Klein BE, Nieto FJ, Chappell R, Schubert CR, Tsai MY: Long-term variability of inflammatory markers and associated factors in a population-based cohort. J Am Geriatr Soc. 2013, 61: 1269-1276. 10.1111/jgs.12382.PubMedCentralCrossRefPubMed
22.
go back to reference Zhu S, Patel KV, Bandinelli S, Ferrucci L, Guralnik JM: Predictors of interleukin-6 elevation in older adults. J Am Geriatr Soc. 2009, 57: 1672-1677. 10.1111/j.1532-5415.2009.02426.x.PubMedCentralCrossRefPubMed Zhu S, Patel KV, Bandinelli S, Ferrucci L, Guralnik JM: Predictors of interleukin-6 elevation in older adults. J Am Geriatr Soc. 2009, 57: 1672-1677. 10.1111/j.1532-5415.2009.02426.x.PubMedCentralCrossRefPubMed
23.
go back to reference Rodondi N, Marques-Vidal P, Butler J, Sutton-Tyrrell K, Cornuz J, Satterfield S, Harris T, Bauer DC, Ferrucci L, Vittinghoff E, Newman AB: Markers of atherosclerosis and inflammation for prediction of coronary heart disease in older adults. Am J Epidemiol. 2010, 171: 540-549. 10.1093/aje/kwp428.PubMedCentralCrossRefPubMed Rodondi N, Marques-Vidal P, Butler J, Sutton-Tyrrell K, Cornuz J, Satterfield S, Harris T, Bauer DC, Ferrucci L, Vittinghoff E, Newman AB: Markers of atherosclerosis and inflammation for prediction of coronary heart disease in older adults. Am J Epidemiol. 2010, 171: 540-549. 10.1093/aje/kwp428.PubMedCentralCrossRefPubMed
24.
go back to reference Greque GV, Serrano CV Jr, Strunz CM, Soeiro A, Santos M, Pivateli F, Jacob JL, Pesaro AE, Nicolau J, Kalil-Filho R: Preprocedural statin therapy, inflammation and myocardial injury in low-risk stable coronary artery disease patients submitted to coronary stent implantation.Catheter Cardiovasc Interv 2013. Apr 16. [Epub ahead of print]., Greque GV, Serrano CV Jr, Strunz CM, Soeiro A, Santos M, Pivateli F, Jacob JL, Pesaro AE, Nicolau J, Kalil-Filho R: Preprocedural statin therapy, inflammation and myocardial injury in low-risk stable coronary artery disease patients submitted to coronary stent implantation.Catheter Cardiovasc Interv 2013. Apr 16. [Epub ahead of print].,
25.
go back to reference Korybalska K, Kawka E, Breborowicz A, Witowski J: Atorvastatin does not impair endothelial cell wound healing in an in vitro model of vascular injury. J Physiol Pharmacol. 2012, 63: 389-395.PubMed Korybalska K, Kawka E, Breborowicz A, Witowski J: Atorvastatin does not impair endothelial cell wound healing in an in vitro model of vascular injury. J Physiol Pharmacol. 2012, 63: 389-395.PubMed
26.
go back to reference Sipahi I, Akay MH, Dagdelen S, Blitz A, Alhan C: Coronary artery bypass grafting vs percutaneous coronary intervention and long-term mortality and morbidity in multivessel disease: meta-analysis of randomized clinical trials of the arterial grafting and stenting era. JAMA Intern Med. 2014, 174 (2): 223-230. 10.1001/jamainternmed.2013.12844.CrossRefPubMed Sipahi I, Akay MH, Dagdelen S, Blitz A, Alhan C: Coronary artery bypass grafting vs percutaneous coronary intervention and long-term mortality and morbidity in multivessel disease: meta-analysis of randomized clinical trials of the arterial grafting and stenting era. JAMA Intern Med. 2014, 174 (2): 223-230. 10.1001/jamainternmed.2013.12844.CrossRefPubMed
Metadata
Title
Age-related limitations of interleukin-6 in predicting early mortality in acute ST-elevation myocardial infarction
Authors
Dominika Kanikowska
Małgorzata Pyda
Katarzyna Korybalska
Stefan Grajek
Maciej Lesiak
Andrzej Bręborowicz
Janusz Witowski
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Immunity & Ageing / Issue 1/2014
Electronic ISSN: 1742-4933
DOI
https://doi.org/10.1186/s12979-014-0023-7

Other articles of this Issue 1/2014

Immunity & Ageing 1/2014 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine