Skip to main content
Top
Published in: BMC Cardiovascular Disorders 1/2020

Open Access 01-12-2020 | Coronary Heart Disease | Research article

Preoperative neutrophil to lymphocyte ratio and platelet to lymphocyte ratio are associated with major adverse cardiovascular and cerebrovascular events in coronary heart disease patients undergoing non-cardiac surgery

Authors: Jan Larmann, Jessica Handke, Anna S. Scholz, Sarah Dehne, Christoph Arens, Hans-Jörg Gillmann, Florian Uhle, Johann Motsch, Markus A. Weigand, Henrike Janssen

Published in: BMC Cardiovascular Disorders | Issue 1/2020

Login to get access

Abstract

Background

Preoperative risk prediction in patients at elevated cardiovascular risk shows limited accuracy. Platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) indicate systemic inflammation. Both have been investigated for outcome prediction in the field of oncology and cardiovascular medicine, as well as risk prediction of adverse cardiovascular events in non-surgical patients at increased cardiovascular risk.

Methods

For this post-hoc analysis, we included all 38 coronary heart disease patients from the Leukocytes and Cardiovascular Perioperative Events cohort-1 study scheduled for elective non-cardiac surgery. We evaluated preoperative differential blood counts for association with major adverse cardiovascular and cerebrovascular events (MACCE) defined as the composite endpoint of death, myocardial ischemia, myocardial infarction, myocardial injury after non-cardiac surgery, or embolic or thrombotic stroke within 30 days after surgery. We used Youden’s index to calculate cut-off values for PLR and NLR. Additive risk-predictive values were assessed using receiver operating characteristic curve and net reclassification (NRI) improvement analyses.

Results

Patients with the composite endpoint MACCE had higher PLR and NLR (309 [206; 380] vs. 160 [132; 203], p = 0.001; 4.9 [3.5; 8.1] vs. 2.6 [2.2; 3.4]), p = 0.001). Calculated cut-offs for PLR > 204.4 and NLR > 3.1 were associated with increased risk of 30-day MACCE (OR 7, 95% CI [1.2; 44.7], p = 0.034; OR 36, 95% CI [1.8; 686.6], p = 0.001). Furthermore, NLR improved risk prediction in coronary heart disease patients undergoing non-cardiac surgery when combined with hs-cTnT or NT-proBNP (NRI total = 0.23, p = 0.008, NRI total = 0.26, p = 0.005).

Conclusions

Both PLR and NLR were associated with perioperative cardiovascular adverse events in coronary heart disease patients. NLR proved to be of additional value for preoperative risk stratification. Both PLR and NLR could be used as inexpensive and broadly available tools for perioperative risk assessment.

Trial registration

NCT02874508, August 22, 2016.
Literature
1.
go back to reference Templeton AJ, McNamara MG, Seruga B, Vera-Badillo FE, Aneja P, Ocana A, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106(6):dju124.PubMedCrossRef Templeton AJ, McNamara MG, Seruga B, Vera-Badillo FE, Aneja P, Ocana A, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106(6):dju124.PubMedCrossRef
2.
go back to reference Li B, Zhou P, Liu Y, Wei H, Yang X, Chen T, et al. Platelet-to-lymphocyte ratio in advanced Cancer: review and meta-analysis. Clin Chim Acta. 2018;483:48–56.PubMedCrossRef Li B, Zhou P, Liu Y, Wei H, Yang X, Chen T, et al. Platelet-to-lymphocyte ratio in advanced Cancer: review and meta-analysis. Clin Chim Acta. 2018;483:48–56.PubMedCrossRef
3.
go back to reference Balta S, Celik T, Mikhailidis DP, Ozturk C, Demirkol S, Aparci M, et al. The relation between atherosclerosis and the neutrophil-lymphocyte ratio. Clin Appl Thromb Hemost. 2016;22(5):405–11.PubMedCrossRef Balta S, Celik T, Mikhailidis DP, Ozturk C, Demirkol S, Aparci M, et al. The relation between atherosclerosis and the neutrophil-lymphocyte ratio. Clin Appl Thromb Hemost. 2016;22(5):405–11.PubMedCrossRef
4.
go back to reference Kalay N, Dogdu O, Koc F, Yarlioglues M, Ardic I, Akpek M, et al. Hematologic parameters and angiographic progression of coronary atherosclerosis. Angiology. 2012;63(3):213–7.PubMedCrossRef Kalay N, Dogdu O, Koc F, Yarlioglues M, Ardic I, Akpek M, et al. Hematologic parameters and angiographic progression of coronary atherosclerosis. Angiology. 2012;63(3):213–7.PubMedCrossRef
5.
go back to reference Balta S, Ozturk C. The platelet-lymphocyte ratio: a simple, inexpensive and rapid prognostic marker for cardiovascular events. Platelets. 2015;26(7):680–1.PubMedCrossRef Balta S, Ozturk C. The platelet-lymphocyte ratio: a simple, inexpensive and rapid prognostic marker for cardiovascular events. Platelets. 2015;26(7):680–1.PubMedCrossRef
6.
go back to reference Fest J, Ruiter TR, Groot Koerkamp B, Rizopoulos D, Ikram MA, van Eijck CHJ, et al. The neutrophil-to-lymphocyte ratio is associated with mortality in the general population: the Rotterdam study. Eur J Epidemiol. 2019;34(5):463–70.PubMedCrossRef Fest J, Ruiter TR, Groot Koerkamp B, Rizopoulos D, Ikram MA, van Eijck CHJ, et al. The neutrophil-to-lymphocyte ratio is associated with mortality in the general population: the Rotterdam study. Eur J Epidemiol. 2019;34(5):463–70.PubMedCrossRef
7.
go back to reference Parlar H, Saskin H. Are pre and postoperative platelet to lymphocyte ratio and neutrophil to lymphocyte ratio associated with early postoperative AKI following CABG? Braz J Cardiovasc Surg. 2018;33(3):233–41.PubMedPubMedCentralCrossRef Parlar H, Saskin H. Are pre and postoperative platelet to lymphocyte ratio and neutrophil to lymphocyte ratio associated with early postoperative AKI following CABG? Braz J Cardiovasc Surg. 2018;33(3):233–41.PubMedPubMedCentralCrossRef
9.
go back to reference Tan TP, Arekapudi A, Metha J, Prasad A, Venkatraghavan L. Neutrophil-lymphocyte ratio as predictor of mortality and morbidity in cardiovascular surgery: a systematic review. ANZ J Surg. 2015;85(6):414–9.PubMedCrossRef Tan TP, Arekapudi A, Metha J, Prasad A, Venkatraghavan L. Neutrophil-lymphocyte ratio as predictor of mortality and morbidity in cardiovascular surgery: a systematic review. ANZ J Surg. 2015;85(6):414–9.PubMedCrossRef
10.
go back to reference Silberman S, Abu-Yunis U, Tauber R, Shavit L, Grenader T, Fink D, et al. Neutrophil-lymphocyte ratio: prognostic impact in heart surgery. Early outcomes and late survival. Ann Thorac Surg. 2018;105(2):581–6.PubMedCrossRef Silberman S, Abu-Yunis U, Tauber R, Shavit L, Grenader T, Fink D, et al. Neutrophil-lymphocyte ratio: prognostic impact in heart surgery. Early outcomes and late survival. Ann Thorac Surg. 2018;105(2):581–6.PubMedCrossRef
11.
go back to reference Ackland GL, Abbott TEF, Cain D, Edwards MR, Sultan P, Karmali SN, et al. Preoperative systemic inflammation and perioperative myocardial injury: prospective observational multicentre cohort study of patients undergoing non-cardiac surgery. Br J Anaesth. 2019;122(2):180–7.PubMedCrossRef Ackland GL, Abbott TEF, Cain D, Edwards MR, Sultan P, Karmali SN, et al. Preoperative systemic inflammation and perioperative myocardial injury: prospective observational multicentre cohort study of patients undergoing non-cardiac surgery. Br J Anaesth. 2019;122(2):180–7.PubMedCrossRef
12.
go back to reference Durmus G, Belen E, Can MM. Increased neutrophil to lymphocyte ratio predicts myocardial injury in patients undergoing non-cardiac surgery. Heart Lung. 2018;47(3):243–7.PubMedCrossRef Durmus G, Belen E, Can MM. Increased neutrophil to lymphocyte ratio predicts myocardial injury in patients undergoing non-cardiac surgery. Heart Lung. 2018;47(3):243–7.PubMedCrossRef
13.
go back to reference Bonaventura A, Liberale L, Carbone F, Vecchie A, Bonomi A, Scopinaro N, et al. Baseline neutrophil-to-lymphocyte ratio is associated with long-term T2D remission after metabolic surgery. Acta Diabetol. 2019;56(7):741–8.PubMedCrossRef Bonaventura A, Liberale L, Carbone F, Vecchie A, Bonomi A, Scopinaro N, et al. Baseline neutrophil-to-lymphocyte ratio is associated with long-term T2D remission after metabolic surgery. Acta Diabetol. 2019;56(7):741–8.PubMedCrossRef
14.
go back to reference Lareyre F, Carboni J, Chikande J, Massiot N, Voury-Pons A, Umbdenstock E, et al. Association of Platelet to lymphocyte ratio and risk of 30-day postoperative complications in patients undergoing abdominal aortic surgical repair. Vasc Endovasc Surg. 2019;53(1):5–11.CrossRef Lareyre F, Carboni J, Chikande J, Massiot N, Voury-Pons A, Umbdenstock E, et al. Association of Platelet to lymphocyte ratio and risk of 30-day postoperative complications in patients undergoing abdominal aortic surgical repair. Vasc Endovasc Surg. 2019;53(1):5–11.CrossRef
15.
go back to reference Ford MK, Beattie WS, Wijeysundera DN. Systematic review: prediction of perioperative cardiac complications and mortality by the revised cardiac risk index. Ann Intern Med. 2010;152(1):26–35.PubMedCrossRef Ford MK, Beattie WS, Wijeysundera DN. Systematic review: prediction of perioperative cardiac complications and mortality by the revised cardiac risk index. Ann Intern Med. 2010;152(1):26–35.PubMedCrossRef
16.
go back to reference Janssen H, Felgner L, Kummer L, Gillmann HJ, Schrimpf C, Rustum S, et al. Sequential surgical procedures in vascular surgery patients are associated with perioperative adverse cardiac events. Front Cardiovasc Med. 2020;7:13.PubMedPubMedCentralCrossRef Janssen H, Felgner L, Kummer L, Gillmann HJ, Schrimpf C, Rustum S, et al. Sequential surgical procedures in vascular surgery patients are associated with perioperative adverse cardiac events. Front Cardiovasc Med. 2020;7:13.PubMedPubMedCentralCrossRef
17.
go back to reference Handke J, Scholz AS, Gillmann HJ, Janssen H, Dehne S, Arens C, et al. Elevated presepsin is associated with perioperative major adverse cardiovascular and cerebrovascular complications in elevated-risk patients undergoing noncardiac surgery: the leukocytes and cardiovascular perioperative events study. Anesth Analg. 2018. https://doi.org/10.1213/ANE.0000000000003738. Handke J, Scholz AS, Gillmann HJ, Janssen H, Dehne S, Arens C, et al. Elevated presepsin is associated with perioperative major adverse cardiovascular and cerebrovascular complications in elevated-risk patients undergoing noncardiac surgery: the leukocytes and cardiovascular perioperative events study. Anesth Analg. 2018. https://​doi.​org/​10.​1213/​ANE.​0000000000003738​.
18.
19.
go back to reference Duceppe E, Parlow J, MacDonald P, Lyons K, McMullen M, Srinathan S, et al. Canadian cardiovascular society guidelines on perioperative cardiac risk assessment and management for patients who undergo noncardiac surgery. Can J Cardiol. 2017;33(1):17–32.PubMedCrossRef Duceppe E, Parlow J, MacDonald P, Lyons K, McMullen M, Srinathan S, et al. Canadian cardiovascular society guidelines on perioperative cardiac risk assessment and management for patients who undergo noncardiac surgery. Can J Cardiol. 2017;33(1):17–32.PubMedCrossRef
20.
go back to reference Botto F, Alonso-Coello P, Chan MT, Villar JC, Xavier D, Srinathan S, et al. Myocardial injury after noncardiac surgery: a large, international, prospective cohort study establishing diagnostic criteria, characteristics, predictors, and 30-day outcomes. Anesthesiology. 2014;120(3):564–78.PubMedCrossRef Botto F, Alonso-Coello P, Chan MT, Villar JC, Xavier D, Srinathan S, et al. Myocardial injury after noncardiac surgery: a large, international, prospective cohort study establishing diagnostic criteria, characteristics, predictors, and 30-day outcomes. Anesthesiology. 2014;120(3):564–78.PubMedCrossRef
21.
go back to reference Giannitsis E, Becker M, Kurz K, Hess G, Zdunek D, Katus HA. High-sensitivity cardiac troponin T for early prediction of evolving non-ST-segment elevation myocardial infarction in patients with suspected acute coronary syndrome and negative troponin results on admission. Clin Chem. 2010;56(4):642–50.PubMedCrossRef Giannitsis E, Becker M, Kurz K, Hess G, Zdunek D, Katus HA. High-sensitivity cardiac troponin T for early prediction of evolving non-ST-segment elevation myocardial infarction in patients with suspected acute coronary syndrome and negative troponin results on admission. Clin Chem. 2010;56(4):642–50.PubMedCrossRef
22.
go back to reference Alcock RF, Kouzios D, Naoum C, Hillis GS, Brieger DB. Perioperative myocardial necrosis in patients at high cardiovascular risk undergoing elective non-cardiac surgery. Heart. 2012;98(10):792–8.PubMedCrossRef Alcock RF, Kouzios D, Naoum C, Hillis GS, Brieger DB. Perioperative myocardial necrosis in patients at high cardiovascular risk undergoing elective non-cardiac surgery. Heart. 2012;98(10):792–8.PubMedCrossRef
23.
24.
go back to reference Azab B, Shah N, Akerman M, McGinn JT Jr. Value of platelet/lymphocyte ratio as a predictor of all-cause mortality after non-ST-elevation myocardial infarction. J Thromb Thrombolysis. 2012;34(3):326–34.PubMedCrossRef Azab B, Shah N, Akerman M, McGinn JT Jr. Value of platelet/lymphocyte ratio as a predictor of all-cause mortality after non-ST-elevation myocardial infarction. J Thromb Thrombolysis. 2012;34(3):326–34.PubMedCrossRef
25.
go back to reference Bonaventura A, Carbone F, Liberale L, Mach F, Roth A, Burger F, et al. Platelet-to-lymphocyte ratio at the time of carotid endarterectomy is associated with acute coronary syndrome occurrence. J Cardiovasc Med (Hagerstown). 2020;21(1):80–2.CrossRef Bonaventura A, Carbone F, Liberale L, Mach F, Roth A, Burger F, et al. Platelet-to-lymphocyte ratio at the time of carotid endarterectomy is associated with acute coronary syndrome occurrence. J Cardiovasc Med (Hagerstown). 2020;21(1):80–2.CrossRef
26.
go back to reference Lareyre F, Carboni J, Chikande J, Massiot N, Voury-Pons A, Umbdenstock E, et al. Association of Platelet to lymphocyte ratio and risk of 30-day postoperative complications in patients undergoing abdominal aortic surgical repair. Vasc Endovascular Surg. 2019;53(1):5–11. Lareyre F, Carboni J, Chikande J, Massiot N, Voury-Pons A, Umbdenstock E, et al. Association of Platelet to lymphocyte ratio and risk of 30-day postoperative complications in patients undergoing abdominal aortic surgical repair. Vasc Endovascular Surg. 2019;53(1):5–11.
27.
go back to reference Horne BD, Anderson JL, John JM, Weaver A, Bair TL, Jensen KR, et al. Which white blood cell subtypes predict increased cardiovascular risk? J Am Coll Cardiol. 2005;45(10):1638–43.PubMedCrossRef Horne BD, Anderson JL, John JM, Weaver A, Bair TL, Jensen KR, et al. Which white blood cell subtypes predict increased cardiovascular risk? J Am Coll Cardiol. 2005;45(10):1638–43.PubMedCrossRef
28.
go back to reference Azab B, Zaher M, Weiserbs KF, Torbey E, Lacossiere K, Gaddam S, et al. Usefulness of neutrophil to lymphocyte ratio in predicting short- and long-term mortality after non-ST-elevation myocardial infarction. Am J Cardiol. 2010;106(4):470–6.PubMedCrossRef Azab B, Zaher M, Weiserbs KF, Torbey E, Lacossiere K, Gaddam S, et al. Usefulness of neutrophil to lymphocyte ratio in predicting short- and long-term mortality after non-ST-elevation myocardial infarction. Am J Cardiol. 2010;106(4):470–6.PubMedCrossRef
29.
go back to reference Bhutta H, Agha R, Wong J, Tang TY, Wilson YG, Walsh SR. Neutrophil-lymphocyte ratio predicts medium-term survival following elective major vascular surgery: a cross-sectional study. Vasc Endovasc Surg. 2011;45(3):227–31.CrossRef Bhutta H, Agha R, Wong J, Tang TY, Wilson YG, Walsh SR. Neutrophil-lymphocyte ratio predicts medium-term survival following elective major vascular surgery: a cross-sectional study. Vasc Endovasc Surg. 2011;45(3):227–31.CrossRef
30.
go back to reference Vaughan-Shaw PG, Rees JR, King AT. Neutrophil lymphocyte ratio in outcome prediction after emergency abdominal surgery in the elderly. Int J Surg. 2012;10(3):157–62.PubMedCrossRef Vaughan-Shaw PG, Rees JR, King AT. Neutrophil lymphocyte ratio in outcome prediction after emergency abdominal surgery in the elderly. Int J Surg. 2012;10(3):157–62.PubMedCrossRef
31.
go back to reference Groot HE, van Blokland IV, Lipsic E, Karper JC, van der Harst P. Leukocyte profiles across the cardiovascular disease continuum: a population-based cohort study. J Mol Cell Cardiol. 2019;138:158–64.PubMedCrossRef Groot HE, van Blokland IV, Lipsic E, Karper JC, van der Harst P. Leukocyte profiles across the cardiovascular disease continuum: a population-based cohort study. J Mol Cell Cardiol. 2019;138:158–64.PubMedCrossRef
32.
go back to reference Dentali F, Nigro O, Squizzato A, Gianni M, Zuretti F, Grandi AM, et al. Impact of neutrophils to lymphocytes ratio on major clinical outcomes in patients with acute coronary syndromes: a systematic review and meta-analysis of the literature. Int J Cardiol. 2018;266:31–7.PubMedCrossRef Dentali F, Nigro O, Squizzato A, Gianni M, Zuretti F, Grandi AM, et al. Impact of neutrophils to lymphocytes ratio on major clinical outcomes in patients with acute coronary syndromes: a systematic review and meta-analysis of the literature. Int J Cardiol. 2018;266:31–7.PubMedCrossRef
33.
go back to reference Zhang S, Diao J, Qi C, Jin J, Li L, Gao X, et al. Predictive value of neutrophil to lymphocyte ratio in patients with acute ST segment elevation myocardial infarction after percutaneous coronary intervention: a meta-analysis. BMC Cardiovasc Disord. 2018;18(1):75.PubMedPubMedCentralCrossRef Zhang S, Diao J, Qi C, Jin J, Li L, Gao X, et al. Predictive value of neutrophil to lymphocyte ratio in patients with acute ST segment elevation myocardial infarction after percutaneous coronary intervention: a meta-analysis. BMC Cardiovasc Disord. 2018;18(1):75.PubMedPubMedCentralCrossRef
34.
go back to reference Song SY, Zhao XX, Rajah G, Hua C, Kang RJ, Han YP, et al. Clinical significance of baseline neutrophil-to-lymphocyte ratio in patients with ischemic stroke or hemorrhagic stroke: an updated meta-analysis. Front Neurol. 2019;10:1032.PubMedPubMedCentralCrossRef Song SY, Zhao XX, Rajah G, Hua C, Kang RJ, Han YP, et al. Clinical significance of baseline neutrophil-to-lymphocyte ratio in patients with ischemic stroke or hemorrhagic stroke: an updated meta-analysis. Front Neurol. 2019;10:1032.PubMedPubMedCentralCrossRef
35.
go back to reference Wang L, Song Q, Wang C, Wu S, Deng L, Li Y, et al. Neutrophil to lymphocyte ratio predicts poor outcomes after acute ischemic stroke: a cohort study and systematic review. J Neurol Sci. 2019;406:116445.PubMedCrossRef Wang L, Song Q, Wang C, Wu S, Deng L, Li Y, et al. Neutrophil to lymphocyte ratio predicts poor outcomes after acute ischemic stroke: a cohort study and systematic review. J Neurol Sci. 2019;406:116445.PubMedCrossRef
37.
go back to reference Kristensen SD, Knuuti J, Saraste A, Anker S, Botker HE, De Hert S, et al. 2014 ESC/ESA guidelines on non-cardiac surgery: cardiovascular assessment and management: the joint task force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA). Eur J Anaesthesiol. 2014;31(10):517–73.PubMedCrossRef Kristensen SD, Knuuti J, Saraste A, Anker S, Botker HE, De Hert S, et al. 2014 ESC/ESA guidelines on non-cardiac surgery: cardiovascular assessment and management: the joint task force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA). Eur J Anaesthesiol. 2014;31(10):517–73.PubMedCrossRef
Metadata
Title
Preoperative neutrophil to lymphocyte ratio and platelet to lymphocyte ratio are associated with major adverse cardiovascular and cerebrovascular events in coronary heart disease patients undergoing non-cardiac surgery
Authors
Jan Larmann
Jessica Handke
Anna S. Scholz
Sarah Dehne
Christoph Arens
Hans-Jörg Gillmann
Florian Uhle
Johann Motsch
Markus A. Weigand
Henrike Janssen
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2020
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-020-01500-6

Other articles of this Issue 1/2020

BMC Cardiovascular Disorders 1/2020 Go to the issue