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

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

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.

Keywords: Blood cell count; Coronary heart disease; Neutrophil to lymphocyte ratio; Perioperative care; Platelet to lymphocyte ratio.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Differential blood count. Prior to non-cardiac surgery, differential blood counts were performed in the 38 included patients. a-f After adjustment for multiple comparisons (p = 0.05/8 = 0.006), no difference in subpopulations could be detected between patients who suffered MACCE and patients who did not. g, h Patients with MACCE had a higher PLR (309 [206; 380] vs. 160 [132; 203], p = 0.001), as well as higher NLR (4.9 [3.5; 8.1] vs. 2.6 [2.2; 3.4], p = 0.001) prior to surgery. MACCE: major adverse cardiovascular and cerebrovascular events, PLR: Platelet to Lymphocyte Ratio, NLR: Neutrophil to Lymphocyte Ratio
Fig. 2
Fig. 2
Receiver operating characteristics analysis of NLR and PLR. a, b) Receiver operating characteristics curve analyses were performed to evaluate discriminatory power of PLR and NLR for MACCE. Based on the maximized Youden Index, the optimal cut-off of PLR > 204.4 and NLR > 3.1 were calculated. Test characteristics based on Woolf Chi-square analyses are displayed. PLR: Platelet to Lymphocyte Ratio, NLR: Neutrophil to Lymphocyte Ratio, MACCE: major adverse cardiovascular and cerebrovascular events, AUC: Area under the curve, CI: confidence interval, PPV: positive predictive value, NPV: negative predictive value, OR: odds ratio
Fig. 3
Fig. 3
Odds ratios for MACCE and secondary outcomes. Woolf Chi-square analyses were performed to assess odds ratios. a A preoperative PLR of > 204.4 was associated with an increased risk of 30-day MACCE (OR 7; 95% CI [1.2; 44.7], p = 0.034. b A preoperative NLR > 3.1 was associated with an increased risk of 30-day MACCE (OR 36; 95% CI [1.8; 686.6], p = 0.001). In this population, no significant association was found for any of the secondary endpoints. PLR: Platelet to Lymphocyte Ratio, MACCE: major adverse cardiovascular and cerebrovascular events, MI: myocardial infarction, MINS: myocardial injury after non-cardiac surgery, AKI: acute kidney injury, OR: odds ratio, NLR: Neutrophil to Lymphocyte Ratio
Fig. 4
Fig. 4
NET reclassification improvement analysis for NLR or PLR in addition to hs- cTnT or NT-proBNP for perioperative cardiovascular risk stratification. Reclassification tables are shown for patients with MACCE and patients without MACCE. yes: at risk, no: not at risk; Correctly reclassified patients: blue, incorrectly reclassified patients: red. a, b The combination of hs-cTnT or NT-proBNP with PLR > 204.4 did not show reclassification improvement (hs-cTnT: NRItotal = 0.01, p = 0.984; NT-proBNP: NRItotal = 0.07 p = 0.762). c The addition of NLR > 3.1 to hs-cTnT led to an overall improvement by seven correctly reclassified patients in the no MACCE group (NRItotal = 0.23, p = 0.008). d The addition of NLR > 3.1 to NT-proBNP led to the correct reclassification of eight patients in the no MACCE group and overall classification improvement (NRItotal = 0.26, p = 0.005). PLR: Platelet to Lymphocyte Ratio, NLR: Neutrophil to Lymphocyte Ratio, MACCE: major adverse cardiovascular and cerebrovascular events

References

    1. 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.
    1. 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.
    1. 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):405–411.
    1. 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):213–217.
    1. Balta S, Ozturk C. The platelet-lymphocyte ratio: a simple, inexpensive and rapid prognostic marker for cardiovascular events. Platelets. 2015;26(7):680–681.
    1. 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):463–470.
    1. 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):233–241.
    1. Chen D, Xiao D, Guo J, Chahan B, Wang Z. Neutrophil-lymphocyte count ratio as a diagnostic marker for acute kidney injury: a systematic review and meta-analysis. Clin Exp Nephrol. 2019. 10.1007/s10157-019-01800-y.
    1. 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):414–419.
    1. 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):581–586.
    1. 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):180–187.
    1. 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):243–247.
    1. 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):741–748.
    1. 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.
    1. 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.
    1. 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.
    1. 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. 10.1213/ANE.0000000000003738.
    1. Scholz AS, Handke J, Gillmann HJ, Zhang Q, Dehne S, Janssen H, et al. Frontline science: low regulatory T cells predict perioperative major adverse cardiovascular and cerebrovascular events after noncardiac surgery. J Leukoc Biol. 2019. 10.1002/JLB.5HI1018-392RR.
    1. 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.
    1. 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):564–578.
    1. 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):642–650.
    1. 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):792–798.
    1. Swirski FK, Nahrendorf M. Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure. Science. 2013;339(6116):161–166.
    1. 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):326–334.
    1. 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):80–82.
    1. 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.
    1. 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):1638–1643.
    1. 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):470–476.
    1. 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):227–231.
    1. 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):157–162.
    1. 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;138:158–164.
    1. 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;266:31–37.
    1. 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.
    1. 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.
    1. 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.
    1. Giede-Jeppe A, Madzar D, Sembill JA, Sprugel MI, Atay S, Hoelter P, et al. Increased neutrophil-to-lymphocyte ratio is associated with unfavorable functional outcome in acute ischemic stroke. Neurocrit Care. 2019. 10.1007/s12028-019-00859-5.
    1. 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):517–573.

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