Preoperative Full Blood Count Markers as a Predictor of Mortality and Morbidity Risk After Cardiac Surgery

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Heart, Lung and Circulation (2021) 30, 414–418
1443-9506/20/$36.00
https://doi.org/10.1016/j.hlc.2020.05.115
ORIGINAL ARTICLE
Preoperative Neutrophil and Lymphocyte
Ratio as a Predictor of Mortality and
Morbidity After Cardiac Surgery
Cheyaanthan Haran, MBChB
a,
*, Damian Gimpel, MBBS
b
,
Helen Clark, MSocSci, PhD
b
, David J. McCormack, FRCS(CTh)
a,b,c
a
Department of Surgery, Faculty of Medical & Health Sciences, The University of Auckland, Auckland, New Zealand
b
Waikato Cardiothoracic Unit, Waikato Hospital, Hamilton, New Zealand
c
Waikato Institute of Surgical Education and Research, Hamilton, New Zealand
Received 14 March 2020; accepted 18 May 2020; online published-ahead-of-print 6 July 2020
Background Inflammatory markers, such as neutrophils and lymphocytes, for risk stratification of postoperative
morbidity and mortality in patients with cardiovascular disease may provide benefit for patient selection
for cardiac surgery. This study aimed to investigate the association between preoperative neutrophil to
leucocyte ratio (NLR) after cardiac surgery.
Methods A retrospective study from September 2014 to November 2017 undergoing cardiac surgery at Waikato
Hospital was conducted. Preoperative haematological profiles, patient factors and primary and secondary
endpoints were obtained. The primary endpoint was 30-day new postoperative atrial fibrillation requiring
treatment, new neurological insult, readmission within 30 days and 30-day mortality. The secondary
endpoint was long-term all cause mortality.
Results Of the 1,694 patients included in the study, 21% (356/1,694) of patients had new atrial fibrillation (AF),
3.0% (51/1,694) strokes, 10.6% (180/1,694) readmissions and 2.8% (47/1,694) deaths within 30 days were
observed. Receiver operator curve (ROC) returned a cut-off value of NLR equal to or greater than 3.23 (high
NLR) to be associated with greatest mortality. Subsequently, a high NLR was compared to the endpoints.
High NLR was associated with higher postoperative (p,0.001) and discharge creatinine, longer ICU stay
(p=0.012), prolonged intubation and ventilation (p,0.001), new neurological status (p=0.002) and increased
risk of returning to theatre (p=0.009). After logistic regression, high NLR was associated with increased
mortality (OR 3.36, p=0.001).
Conclusions The interpretation and utilisation of readily available haematological markers can provide further risk
stratification data to the surgeon when considering the postoperative cardiac surgery risks.
Keywords Cardiac surgery Risk stratification Inflammatory markers Neutrophil Lymphocyte
Introduction
The use of inflammatory markers for risk stratification of
morbidity and mortality for patients with cardiovascular
disease may provide benefit for careful patient selection [1].
Inflammatory biomarkers, such as white cell count and
c-reactive protein, measure a patient’s response to
inflammation. White cell subtypes such as neutrophils and
lymphocytes may offer additional information for patient
outcomes after cardiac surgery [2].
Neutrophil lymphocyte ratio (NLR) as a biomarker is well
studied in the literature with outcome studies looking at risk
prediction, such as in chronic obstructive pulmonary disease
and atrial fibrillation [3,4]. In patients undergoing
*Corresponding author at: Wellington Regional Hospital, Riddiford Street, Wellington, New Zealand. Email: cheyaanthan.haran@ccdhb.org.nz
Ó2020 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ).
Published by Elsevier B.V. All rights reserved.

angiography or cardiac revascularisation, NLR is a predictor
of all-cause mortality and cardiovascular events [5].
Preoperative NLR is an independent predictor of saphenous
vein graft patency in patients after coronary artery
bypass graft (CABG) [6]. However, the relationship between
NLR and cardiac surgery patient outcomes is not well
understood.
The aim of this study was to investigate the association
between preoperative NLR and mortality and morbidity
outcomes after cardiac surgery. This study planned to add
new data from a New Zealand specific patient cohort to the
literature on the effect of NLR on cardiac surgery patient
outcomes. The benefit of understanding the association be-
tween NLR and patient outcomes allows for identification of
high-risk patients. This will help improve clinical decision
making in the preoperative setting to allow for better patient
selection.
Material and Methods
A retrospective study of records of patients who
underwent elective cardiac surgery from 29 September
2014 until 13 October 2017 at Waikato Hospital was
conducted. The records were collected from the Waikato
Cardiothoracic Surgery unit’s electronic database.
This resulted in a total of 1,792 records of which 98
patients had incomplete electronic records for analysis.
The total number of patients analysed was 1,694.
Long-term death data was received from the chronic
disease database which is updated monthly by the
associated government agency. This data was acquired
on 14 December 2017 and is the endpoint for long-term
mortality analysis.
Receiver operating characteristic (ROC) curves were used
in order to calculate the optimal NLR cut-off point for mor-
tality. Univariate analyses (Chi-square, Mann Whitney U)
were conducted to test for statistically significant differences
across baseline patient characteristics and postoperative
complications. Multivariate logistic regression were used to
assess the relationship between variables and mortality in
patients with a high NLR.
All statistical analyses were performed using IBM SPSS for
Windows Version 24.0 (IBM Corp., Armonk, NY, USA).
Results
Preoperative blood counts available for 1,694 patients were
included in the analysis. The mean age was 65.1 years with
male:female as 58:19. The optimal NLR cut-off for mortality
was equal to or greater than 3.23. Therefore, a low NLR was
deemed to be less than 3.23 and a high NLR was equal to or
greater than 3.23.
Dividing the 1,694 patients according to high and low
NLR, the baseline characteristics are illustrated in Table 1.
Differences are apparent in the following categories: age,
arrythmia, critical preoperative state, haemoglobin, obesity,
preoperative creatinine level, history of congestive heart
failure and requiring dialysis.
Direct univariate analysis of postoperative events/com-
plications showed patients who had a high NLR, compared
to that of low NLR, were more likely to have a higher
discharge creatinine (107.5 mmol/L6112.9, p,0.001), great-
est highest postoperative creatinine (123.8 mmol/L6116.0,
p,0.001), lower discharge haemoglobin (88.2 g/L631.0,
p=0.016), longer intensive care unit (ICU) stay (39.6
hours661.5, p=0.012), longer intubation period (p,0.001),
prolonged ventilation of greater than 24 hours (p,0.001),
observed new neurological status (p=0.002), increased
likelihood of returning to theatre (p=0.009). Finally, 30-day
mortality for the low NLR group was observed at 1.8%
(22/198 patients) and for the high NLR it was greater at 5%
(25/496 patients). The complete comparison of the
postoperative complications are recorded in Table 2.
Final predictors of outcome was calculated using multi-
variate regression analysis and this is outlined in Table 3.
Statistically significant results for predictors of mortality
included gender, of which being male (OR 1.87, 1.24–2.49),
low haemoglobin (OR 0.98, 0.96–1.00), history of congestive
heart failure (CHF) (OR 2.34, 1.12–4.91), and an elevated
NLR (OR 3.36, 1.63–6.91). Of the remaining primary end-
points investigated in this study, an elevated NLR did not
return an odds ratio that was statistically significant. For new
atrial arrythmia, there were no other predictors of outcome
that increased the risk. For new neurological status, age (OR
0.97, 0.95–1.00) and haemoglobin (OR 1.03, 1.01–1.06) were
predictors of outcome with statistically significant odds ra-
tios. Finally, for 30-day readmission after surgery, haemo-
globin (OR 0.99, 0.98–1.00) and obesity (OR 1.72, 1.19–2.49)
were statistically significant predictors of outcome.
Discussion
White cell ratio biomarkers, such as NLR, have recently
emerged as a potential aid to the clinician for risk
stratification of patients with atherosclerotic disease. This
present study suggests that an elevated NLR of 3.23 or
higher is associated with increased 30-day mortality and is
associated with a higher postoperative and discharge
creatinine, longer ICU stay, prolonged intubation and
ventilation, new neurological status and increased risk of
returning to theatre.
Our study confirms the current findings in the literature
for the association between NLR and postoperative mortality
after cardiac surgery. In a recent, large, retrospective review
of 3,027 patients, Silberman et al. found elevated levels of
NLR of 2.6 or higher to be an independent predictor of
operative mortality (HR 2.15, p,0.0001) and late mortality
(HR 1.19, p,0.0001) [7]. A recent meta-analysis by Tan et al.,
a pooled analysis of three studies including 3,108 patients,
suggested a raised preoperative NLR is associated with
increased all-cause mortality after cardiac and vascular op-
erations with a hazard ratio of 1.85, (CI 1.46–2.36, p,0.00001)
Preoperative NLR to Predict Mortality and Morbidity After Cardiac Surgery 415

[8]. The cut-off for cardiac surgery was greater than 3.3 and
greater than 5 for vascular surgery. Though an association is
inherent, the cut-off value for NLR varies widely between
studies. This may be reflected by the patient selection, patient
baseline characteristics and availability of clinical data of the
individual studies. Just like current risk stratification tools
used in cardiac surgery, such as the Society for Thoracic
Surgeons (STS), EuroScore and AUScore, the NLR may be
Table 1 Baseline patient characteristics.
Variables NLR,3.23 NLR≥3.23 P
Number of patients 1,198 496
Male 74.0% (886) 78.6% (390) 0.042
Age (yr) 64.1611.3 67.4610.5 ,0.001
Arrhythmia 18.0% (212) 25.4% (123) 0.001
Cerebrovascular disease 7.5% (89) 9.5% (46) 0.187
Critical preoperative state 4.0% (48) 10.8% (53) ,0.001
Diabetes 21.8% (257) 20.0% (97) 0.415
Ejection fraction (EF) 57.4612.9 57.1612.6 0.676
Family history of coronary artery disease 36.2% (423) 35.4% (169) 0.781
Haemoglobin (Hb, g/L) 138.0616.2 132.5618.4 ,0.001
Hypercholesterolaemia 64.3% (758) 63.2% (306) 0.680
Hypertension 70.8% (836) 74.6% (361) 0.132
Myocardial infarction (MI) 35.7% (421) 36.5% (176) 0.756
Obesity 33.7% (388) 26.4% (125) 0.004
Preoperative creatinine level (mmol/L) 93.5657.6 111.56108.1 0.001
Pulmonary hypertension 15.2% (179) 16.9% (82) 0.387
History of congestive heart failure (CHF) 14.3% (169) 20.3% (98) 0.003
Renal: Dialysis 0.7% (8) 2.7% (13) 0.001
Smoking history 58.1% (686) 56.6% (274) 0.580
Dyspnoea status 0.333
1 36.2% (425) 40.3% (195)
2 38.4% (451) 34.9% (169)
3 21.1% (248) 19.8% (96)
4 4.2% (49) 5.0% (24)
Number of diseased coronary systems 0.653
None 27.5% (329) 29.0% (144)
1 9.3% (111) 8.5% (42)
2 14.5% (173) 15.1% (75)
3 46.0% (551) 43.5% (216)
Table 2 Postoperative complications.
Variables NLR,3.23 NLR≥3.23 P
Discharge creatinine (mmol/L) 87.7654.2 107.56112.9 ,0.001
Discharge haemoglobin (g/L) 92.2629.1 88.2631.0 0.016
Highest postoperative creatinine (mmol/L) 103.4672.4 123.86116.0 ,0.001
Intercostal catheter loss 282.26219.5 302.46264.9 0.115
Intensive care unit stay (hr) 31.6648.5 39.6661.5 0.012
Postoperative stay (d) 7.064.0 8.1617.8 0.170
Prolonged intubation 7.8% (89) 13.9% (65) ,0.001
Prolonged ventilation greater than 24 hr 7.3% (84) 14.9% (71) ,0.001
New neurological status 2.3% (26) 5.3% (25) 0.002
Readmitted within 30 d from surgery 10.5% (119) 13.0% (61) 0.149
Return to theatre 7.6% (91) 11.6% (57) 0.009
Mortality within 30 d 1.8% (22) 5.0% (25) ,0.001
416 C. Haran et al.

region specific thus a different cut-off may be suggestive of
increased postoperative morbidity and mortality.
After logistic regression analysis, this present study did
not find an association between NLR and postoperative
atrial arrythmia, neurological status or increased read-
mission rates within 30 days of surgery. Other studies in the
medical literature also confirm that there is no association
between NLR and atrial fibrillation [9,10]. There is no current
literature looking at the association of NLR with
postoperative stroke or 30-day readmission. However, the
current literature suggests NLR may be associated with other
postoperative morbidity outcomes such as acute kidney
injury [11–13] and prolonged ICU and in hospital stay [2].
Given the lack of published data in the literature it is difficult
to compare the findings of the association of NLR with
postoperative morbidity in cardiac surgery.
The current universal marker of inflammation, specifically
used in all surgical specialities in New Zealand, is the c-
Table 3 Multivariate regression analysis of predictors of outcomes with high NLR≥3.23.
Variables Odds ratio 95% CI P
30-d mortality
Male 1.87 1.24–2.49 0.098
Age 0.99 0.98–1.00 0.427
Arrhythmia 1.14 1.01–1.27 0.771
Critical preoperative state 0.58 0.04–1.13 0.342
Hb 0.98 0.96–1.00 0.024
Obesity 1.91 1.26–2.56 0.148
Preoperative creatinine 1.00 1.00–1.00 0.659
History of congestive heart failure (CHF) 2.34 1.12–4.91 0.025
Elevated NLR (3.23) 3.36 1.63–6.91 0.001
New atrial arrhythmia
Male 0.93 0.85–1.00 0.668
Age 1.00 1.00–1.01 0.573
Arrhythmia 0.84 0.67–1.01 0.294
Critical preoperative state 1.39 1.06–1.73 0.286
Haemoglobin 1.01 1.00–1.01 0.274
Obesity 1.02 1.00–1.04 0.902
Preoperative creatinine 1.00 1.00–1.00 0.915
History of congestive heart failure (CHF) 1.25 1.03–1.47 0.266
Elevated NLR (NLR3.23) 0.90 0.80–1.01 0.502
Change in neurological status
Male 1.32 1.04–1.59 0.511
Age 0.97 0.95–1.00 0.044
Arrhythmia 0.91 0.83–1.00 0.825
Critical preoperative state 0.72 0.39–1.05 0.591
Haemoglobin 1.03 1.01–1.06 0.010
Obesity 1.80 1.21–2.38 0.132
Preoperative creatinine 1.001 1.00–1.002 0.816
History of congestive heart failure (CHF) 0.999 0.998–1.00 0.999
Elevated NLR (NLR3.23) 1.03 1.00–1.05 0.948
Readmitted 30-d from surgery
Male 0.79 0.56–1.02 0.316
Age 1.00 1.00–1.00 0.976
Arrhythmia 1.07 1.00–1.13 0.781
Critical preoperative state 0.87 0.73–1.01 0.693
Haemoglobin 0.99 0.98–1.00 0.017
Obesity 1.72 1.19–2.49 0.004
Preoperative creatinine 0.996 0.992–1.00 0.159
History of congestive heart failure (CHF) 1.21 1.02–1.40 0.463
Elevated NLR (NLR3.23) 0.83 0.64–1.02 0.343
Preoperative NLR to Predict Mortality and Morbidity After Cardiac Surgery 417

reactive protein (CRP). CRP is synthesised by the liver, and
often there is a time delay until the peak serum CRP con-
centration is achieved. This yields diagnostic challenges,
especially in early hospital presentations of inflammatory
conditions. The association between CRP and NLR in cardiac
surgery is lacking. However, given the time delay of CRP,
NLR may provide a clinical advantage if the peak serum
NLR concentration rises faster than that of CRP. In a recent
colorectal cancer open surgery study, at day 4 after colorectal
surgery, NLR and CRP were found to correlate accurately for
predicting anastomotic leak [14]. Further, CRP is an expen-
sive test, yet the complete or full blood count is compara-
tively cheaper where the ratio can be calculated from the
absolute neutrophil and lymphocyte count that is produced.
To effectively consider the use of NLR in cardiac surgery risk
stratification a thorough comprehensive analysis is required
in comparing the time course of NLR with other inflamma-
tory conditions such as CRP, interleukins and white cell
count, and a cost-benefit analysis is also required.
The present study includes a wide and diverse ethnic cohort
of patients, given the location of the Waikato Cardiothoracic
Department is set in Hamilton (New Zealand) with a
populous, unique indigenous community, Maori. Thus the
findings of this study will be hard to apply outside
New Zealand. Much of the current surgical literature reports
the association of NLR and coronary artery disease. Finally,
future analysis could investigate various cardiac surgery
procedures and whether there is an association of NLR on the
outcomes after a specific procedures, such as CABG, valve
repair or replacement, or open aortic interventions.
Conclusion
In conclusion, a high NLR (3.23) is suggestive to be asso-
ciated with increased 30-day mortality, higher postoperative
and discharge creatinine, longer ICU stay, prolonged intu-
bation and ventilation, new neurological status and
increased risk of returning to theatre. NLR may be a useful
prognostic biomarker for the surgeon to help assist and
guide perioperative risk assessment of patients undergoing
cardiac surgery.
Funding Sources
No funding sources to disclose.
Conflicts of Interest
No conflicts of interest.
References
[1] Newall N, Grayson AD, Oo AY, Palmer ND, Dihmis WC, Rashid A, et al.
Preoperative white blood cell count is independently associated with
higher perioperative cardiac enzyme release and increased 1-year
mortality after coronary artery bypass grafting. Ann Thorac Surg
2006;81(2):583–9.
[2] Giakoumidakis K, Fotos NV, Patelarou A, Theologou S, Argiriou M,
Chatziefstratiou AA, et al. Perioperative neutrophil to lymphocyte ratio
as a predictor of poor cardiac surgery patient outcomes. Pragmat Obs Res
2017;8:9–14.
[3] Acarturk Tuncay E, Karakurt Z, Aksoy E, Salturk C, Gungor S,
Ciftaslan N, et al. Eosinophilic and non-eosinophilic COPD patients with
chronic respiratory failure: neutrophil-to-lymphocyte ratio as an exacer-
bation marker. Int J Chron Obstruct Pulmon Dis 2017;12:3361–70.
[4] Fukuda Y, Okamoto M, Tomomori S, Matsumura H, Tokuyama T,
Nakano Y, et al. In paroxysmal atrial fibrillation patients, the neutrophil-
to-lymphocyte ratio is related to thrombogenesis and more closely asso-
ciated with left atrial appendage contraction than with the left atrial body
function. Intern Med 2018;57(5):633–40.
[5] Wang X, Zhang G, Jiang X, Zhu H, Lu Z, Xu L. Neutrophil to
lymphocyte ratio in relation to risk of all-cause mortality and
cardiovascular events among patients undergoing angiography or
cardiac revascularization: a meta-analysis of observational studies.
Atherosclerosis 2014;234(1):206–13.
[6] Tasoglu I, Turak O, Nazli Y, Ozcan F, Colak N, Sahin S, et al.
Preoperative neutrophil-lymphocyte ratio and saphenous vein graft
patency after coronary artery bypass grafting. Clin Appl Thromb Hemost
2014;20(8):819–24.
[7] 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.
[8] Tan TP, Arekapudi A, Metha J, Prasad A, Venkatraghavan L. Neutrophil-
lymphocyte ratio as predictor of mortality and morbidity in cardiovas-
cular surgery: a systematic review. ANZ J Surg 2015;85(6):414–9.
[9] Durukan AB, Gurbuz HA, Unal EU, Tavlasoglu M, Durukan E,
Salman N, et al. Role of neutrophil/lymphocyte ratio in assessing the risk
of postoperative atrial fibrillation. J Cardiovasc Surg 2014;55(2):287–93.
[10] Jacob KA, Buijsrogge MP, Frencken JF, Ten Berg MJ, Suyker WJ, van
Dijk D, et al. White blood cell count and new-onset atrial fibrillation after
cardiac surgery. Int J Cardiol 2017;228:971–6.
[11] Kim WH, Park JY, Ok SH, Shin IW, Sohn JT. Association between the
neutrophil/lymphocyte ratio and acute kidney injury after cardiovascu-
lar surgery: a retrospective observational study. Medicine 2015;
94(43):e1867.
[12] Koo CH, Eun Jung D, Park YS, Bae J, Cho YJ, Kim WH, et al. Neutrophil,
lymphocyte, and platelet counts and acute kidney injury after cardio-
vascular surgery. J Cardiothorac Vasc Anesth 2018;32(1):212–22.
[13] Parlar H, Saskin H. Are Pre and postoperative platelet to lymphocyt e ratio
and neutrophil to lymphocyte ratio associated with early postoperative
AKI following CABG? Braz J Cardiovasc Surg 2018;33(3):233–41.
[14] Mik M, Dziki L, Berut M, Trzcinski R, Dziki A. Neutrophil to lymphocyte
ratio and c-reactive protein as two predictive tools of anastomotic leak in
colorectal cancer open surgery. Dig Surg 2018;35(1):77–84.
418 C. Haran et al.