Role of Preoperative Inflammatory Blood Cell Indexes as a Postoperative Risk Predictor Among Patients Undergoing On‐Pump Cardiac Surgery

Alagha S., Miniksar Ö.H., Polat M.N., Kara M., Şenaylı Y.

Shvartz V., Sokolskaya M., Ispiryan A., Basieva M., Kazanova P., Shvartz E., Talibova S., Petrosyan A., Kanametov T., Donakanyan S., Bockeria L., Golukhova E.

Introduction. The pathogenesis of aortic stenosis includes the processes of chronic inflammation, calcification, lipid metabolism disorders, and congenital structural changes. The goal of our study was to determine the predictive value of novel biomarkers of systemic inflammation and some hematological indices based on the numbers of leukocytes and their subtypes in the development of early hospital medical conditions after mechanical aortic valve replacement in patients with aortic stenosis. Materials and methods. This was a cohort study involving 363 patients who underwent surgical intervention for aortic valve pathology between 2014 and 2020. The following markers of systemic inflammation and hematological indices were studied: SIRI (Systemic Inflammation Response Index), SII (Systemic Inflammation Index), AISI (Aggregate Index of Systemic Inflammation), NLR (Neutrophil/Lymphocyte Ratio), PLR (Platelet/Lymphocyte Ratio), and MLR (Monocyte/Lymphocyte Ratio). Associations of the levels of these biomarkers and indices with the development of in-hospital death, acute kidney injury, postoperative atrial fibrillation, stroke/acute cerebrovascular accident, and bleeding were calculated. Results. According to an ROC analysis, an SIRI > 1.5 (p < 0.001), an SII > 718 (p = 0.002), an AISI > 593 (p < 0.001), an NLR > 2.48 (p < 0.001), a PLR > 132 (p = 0.004), and an MLR > 0.332 (p < 0.001) were statistically significantly associated with in-hospital death. Additionally, an SIRI > 1.5 (p < 0.001), an NLR > 2.8 (p < 0.001), and an MLR > 0.392 (p < 0.001) were associated with bleeding in the postoperative period. In a univariate logistic regression, SIRI, SII, AISI, and NLR were statistically significant independent factors associated with in-hospital death. In a multivariate logistic regression model, SIRI was the most powerful marker of systemic inflammation. Conclusion. SIRI, SII, AISI, and NLR as novel biomarkers of systemic inflammation were associated with in-hospital mortality. Of all markers and indices of systemic inflammation in our study, SIRI was the strongest predictor of a poor outcome in the multivariate regression model.

Shri I., Magoon R., Kashav R., Dey S., Walian A., Kohli J.

Ghobadi H., Mohammadshahi J., Javaheri N., Fouladi N., Mirzazadeh Y., Aslani M.R.

BackgroundSystemic inflammation indices, including neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), platelet/lymphocyte ratio (PLR), derived neutrophil/lymphocyte ratio (dNLR), neutrophil/lymphocyte*platelet ratio (NLPR), aggregate index of systemic inflammation (AISI), systemic inflammation response index (SIR-I), and systemic inflammation index (SII) are well-expressed inflammatory indices that have been used to predict the severity and mortality of various inflammatory diseases. This study aimed to investigate the role of systemic inflammatory markers in predicting mortality in non-elderly and elderly COVID-19 patients.MethodsIn a retrospective study, laboratory parameters were examined for 1,792 COVID-19 patients (elderly = 710 and non-elderly = 1,082). The ability of inflammatory markers to distinguish the severity of COVID-19 was determined by receiver operating characteristic (ROC) analysis, and survival probability was determined by the mean of Kaplan–Meier curves, with the endpoint being death.ResultsIn the non-survivor non-elderly and elderly patients, the parameters PLR, MLR, dNLR, NLPR, AISI, SIR-I, and SII were significantly higher than in the surviving patients. WBC count (HR = 4.668, 95% CI = 1.624 to 13.413, P &lt; 0.01), neutrophil count (HR = 6.395, 95% CI = 2.070 to 19.760, P &lt; 0.01), dNLR (HR = 0.390, 95% CI = 0.182 to 0.835, P &lt; 0.05), and SII (HR = 10.725, 95% CI = 1.076 to 106.826, P &lt; 0.05) were significantly associated with survival. On the other hand, in elderly patients, it was found that WBC count (HR = 4.076, 95% CI = 2.176 to 7.637, P &lt; 0.001) and neutrophil count (HR = 2.412, 95% CI = 1.252 to 4.647, P &lt; 0.01) were significantly associated with survival.ConclusionWBC count and neutrophil count in non-elderly and elderly patients, were reliable predictors of mortality.

Su X., Wang J., Lu X.

Objective To analyze the relationship between monocyte-to-lymphocyte ratio (MLR) and postoperative delirium (POD). Methods This cohort study was conducted in the Medical Information Mart for Intensive Care-III (MIMIC-III) version 1.4 database. MLR was measured according to the complete blood count. ICD-9 was used to measure postoperative delirium. Multivariable logistic regression was utilized to examine the relationship between MLR and POD. Results Three thousand eight hundred sixty-eight patients who had received cardiac surgery were retrospectively enrolled, including 2171 males and 1697 females, with a mean age of 63.9 ± 16.2 years. The univariate analysis suggested that high MLR (as a continuous variable) as associated with a 21% higher risk of POD (O R: 1.12, 95% CI, 1.02, 1.43, p = 0.0259), After adjustments for other confounding factors, gender, age, race, temperature, SBP, DBP, MAP, respiratory rate, SOFA, peripheral vascular disease, AG, psychoses, drug, and alcohol addiction, the results showed that high MLR (as a continuous variable) independently served as a risk factor for POD (OR: 1.21; 95% CI: 1.01–1.44; p = 0.0378). MLR was assessed as quintile and tertiles, high MLR was an independent risk factor for POD. In the subgroup analysis, there were no differences in MLR for patients with POD in pre-specified subgroups. Conclusions Monocyte-to-lymphocyte ratio was a risk factor for POD. More research is necessary to thoroughly examine the function of MLR in POD.

Urbanowicz T., Michalak M., Olasińska-Wiśniewska A., Rodzki M., Witkowska A., Gąsecka A., Buczkowski P., Perek B., Jemielity M.

Background: Several perioperative inflammatory markers are postulated to be significant factors for long-term survival after off-pump coronary artery bypass surgery (OPCAB). Hematological parameters, whether single or combined as indices, provide higher predictive values. Methods: The study group comprised 538 consecutive patients (125 (23%) females and 413 (77%) males) with a mean age of 65 ± 9 years, who underwent OPCAB with a mean follow-up time of 4.7 ± 1.7 years. This single-center retrospective analysis included perioperative inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR), systemic inflammatory response index (SIRI), aggregate index of systemic inflammation (AISI), and systemic inflammatory index (SII). Results: Multivariable analysis identified levels of neutrophils above 4.3 × 109/L (HR 13.44, 95% CI 1.05–3.68, p = 0.037), values of SIRI above 5.4 (HR 0.29, 95% CI 0.09–0.92, p = 0.036) and values of NLR above 3.5 (HR 2.21, 95% CI 1.48–3.32, p < 0.001) as being significant predictors of long-term mortality. The multifactorial models revealed the possibility of strong prediction by combining preoperative factors (COPD, stroke, PAD, and preoperative PLR) and postoperative neutrophil counts (p = 0.0136) or NLR (p = 0.0136) or SIRI (p = 0.0136). Conclusions: Among the postoperative inflammatory indices, the levels of neutrophils, NLR, and SIRI are the most prominent markers for long-term survival after off-pump coronary artery bypass surgery, when combined with preoperative characteristics.

Urbanowicz T., Michalak M., Olasińska-Wiśniewska A., Witkowska A., Rodzki M., Błażejowska E., Gąsecka A., Perek B., Jemielity M.

Background and objective: Coronary artery disease is one of the leading causes of deaths nowadays and the trends in diagnosis and revascularization are still in plateau despite well-known factors. Simple whole blood count parameters may be used to measure inflammatory reactions that are involved in processes of atherosclerosis progression. The aim of our study was to analyse the association between simply available hematologic indices and long-term mortality following off-pump coronary artery bypass grafting (OPCAB). Material and Methods: The study group comprised 129 consecutive patients (16 females and 113 males, mean age 66 ± 6 years) who underwent surgical revascularization with off-pump technique between January 2014 and September 2019. The mean follow-up was 4.7 +/−1.9 years. A receiver operating characteristics curve was applied to estimate demographical and perioperative parameters including MLR for mortality. Results: Cox regression analysis revealed chronic pulmonary obstructive disease (HR = 2.86, 95%CI 1.05–7.78), MLR (HR = 3.81, 95%CI 1.45–10.06) and right coronary artery blood flow (HR = 1.06, 95%CI 1.00–1.10) as significant factors predicting increased mortality risk. In the presented model, the MLR > 1.44 on 1st postoperative day was a significant predictor of late mortality after the OPCAB procedure (HR = 3.82, 95%CI 1.45–10.06). Conclusions: Pronounced inflammatory reaction after off-pump surgery measured by MLR > 1.44 can be regarded as a worse long-term prognostic factor.

Dey S., Kashav R., Kohli J.K., Magoon R., ItiShri, Walian A., Grover V.

Objectives To investigate the role of preoperative hematologic indices (neutrophil-lymphocyte ratio [NLR], platelet-lymphocyte ratio [PLR], systemic immune-inflammation index [SII; neutrophil × platelet/lymphocyte) in predicting short-term outcomes after off-pump coronary artery bypass grafting (OPCABG). Design A single-center, retrospective, risk-prediction study. Setting A tertiary cardiac center. Participants 1,007 patients undergoing elective OPCABG. Interventions No specific intervention. Measurements and Main Results Two hundred five patients out of 1,007 (20.4%) manifested poor postoperative outcome (defined by ≥1 of: major adverse cardiac and cardiovascular events, duration of mechanical ventilation (DO-MV) >24 hours, new-onset renal failure, sepsis, and death). On univariate analysis, age, diabetes mellitus (DM), European System for Cardiac Operative Risk Evaluation II (EuroSCORE II), left-main disease, recent myocardial infarction, poor left ventricular ejection fraction, hemoglobin, NLR, PLR, and SII significantly predicted poor outcome. However, DM, EuroSCORE II, and SII emerged as independent predictors on multivariate analysis (odds ratio 0.136; 0.035-0.521, 3.377; 95% confidence interval 2.373-4.806, 1.01, 1.003-1.016). The SII cutoff of 878.06 × 103/mm3 predicted poor outcome with 97.6% sensitivity, 91%, specificity, and area under the curve 0.984. There was a significant positive correlation between the SII values and DO-MV and length of intensive care unit stay (R = 0.676; 0.527, p < 0.001). The incidence of complications, such as atrial fibrillation, intra-aortic balloon pump requirement, vasoactive-ionotropic score >20 for >6 hours, and other infections, was also significantly higher in patients with SII ≥878.06 × 103/mm3. Conclusions SII constitutes a parsimonious and reproducible parameter demonstrating the potential of delineating the patients vulnerable to poor outcomes after OPCABG given the combined contribution of pro-inflammatory and pro-thrombotic corpuscular lines in computing the novel index.

Bauer A., Korten I., Juchem G., Kiesewetter I., Kilger E., Heyn J.

Despite modern advances in intensive care medicine and surgical techniques, mortality rates in cardiac surgical patients are still about 3%. Considerable efforts were made to predict morbidity and mortality after cardiac surgery. In this study, we analysed the predictive properties of EuroScore and IL-6 for mortality in ICU, prolonged postoperative mechanical ventilation, and prolonged stay in ICU. We enrolled 2972 patients undergoing cardiac surgery. The patients either underwent aortic valve surgery (AV), mitral valve surgery (MV), coronary artery bypass grafting (CABG), and combined operations of aortic valve and coronary artery bypass grafting (AV + CABG) or of mitral and tricuspid valve (MV + TV). Different laboratory and clinical parameters were analysed. EuroScore as well as IL-6 were associated with increased mortality after cardiac surgery. Furthermore, a higher EuroScore and elevated levels of IL-6 were predictors for prolonged mechanical ventilation and a longer stay in ICU. Especially, highly significant elevated IL-6 levels and an increased EuroScore showed a strong association. Statistics suggested superiority when both parameters were combined in a single model. Our results suggest that EuroScore and IL-6 are helpful in predicting the course in ICU after cardiac surgery, and therefore, the use of intensive care resources. Especially, the combination of highly elevated levels of IL-6 and EuroScore may prove to be excellent predictors for an unfortunate postoperative course in ICU.

Li Y., Zou Z., Zhang Y., Zhu B., Ning Y., Shen B., Wang C., Luo Z., Xu J., Ding X.

In this study, we applied a composite index of neutrophil-lymphocyte * platelet ratio (NLPR), and explore the significance of the dynamics of perioperative NLPR in predicting cardiac surgery-associated acute kidney injury (CSA-AKI).During July 1st and December 31th 2019, participants were prospectively derived from the 'Zhongshan Cardiovascular Surgery Cohort'. NLPR was determined using neutrophil counts, lymphocyte and platelet count at the two-time points. Dose-response relationship analyses were applied to delineate the non-linear odds ratio (OR) of CSA-AKI in different NLPR levels. Then NLPRs were integrated into the generalized estimating equation (GEE) to predict the risk of AKI.Of 2449 patients receiving cardiovascular surgery, 838 (34.2%) cases developed CSA-AKI with stage 1 (n = 658, 26.9%), stage 2-3 (n = 180, 7.3%). Compared with non-AKI patients, both preoperative and postoperative NLPR were higher in AKI patients (1.1[0.8, 1.8] vs. 0.9[0.7,1.4], p < 0.001; 12.4[7.5, 20.0] vs. 10.1[6.4,16.7], p < 0.001). Such an effect was a 'J'-shaped relationship: CSA-AKI's risk was relatively flat until 1.0 of preoperative NLPR and increased rapidly afterward, with an odds ratio of 1.13 (1.06-1.19) per 1 unit. Similarly, patients whose postoperative NLPR value >11.0 were more likely to develop AKI with an OR of 1.02. Integrating the dynamic NLPRs into the GEE model, we found that the AUC was 0.806(95% CI 0.793-0.819), which was significantly higher than the AUC without NLPR (0.799, p < 0.001).Dynamics of perioperative NPLR is a promising marker for predicting acute kidney injury. It will facilitate AKI risk management and allow clinicians to intervene early so as to reverse renal damage.

Aydınlı B., Demir A., Güçlü Ç.Y., Bölükbaşı D., Ünal E.U., Koçulu R., Selçuk G.

The present study was to investigate if five values that are part of the hemogram analysis routinely checked before heart surgeries can be used as a high-quality, quick, low-cost, and easy-to-use outcome predictor. This investigation was a retrospective, observational, cross-sectional study. Univariate and multivariate logistic regression was used to identify independent predictors for combined adverse events. We enrolled 1500 consecutive patients who underwent elective, on-pump, open-heart surgery from 2011 to 2014. Preoperative hemogram evaluation, red cell distribution width (RDW), mean platelet volume (MPV), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) were recorded. We classified combined adverse events (CAE) as (1) myocardial infarction, (2) cardiac reoperation, (3) prolonged mechanical ventilation, (4) prolonged hospital stay, (5) rehospitalization, or (6) mortality. It was found that several parameters obtained as part of the hemogram, namely RDW, MPV, PLR, and NLR, can predict, individually or in combinations, the outcomes in open-heart surgery patients. It was found that the prediction success of NLR (4.8 fold) was higher compared to RDW (1.8 fold) and MPV (1.5 fold). When the prediction success of the combined parameters was investigated, the NLR–RDW (4.7 fold) pair was found higher in the prediction of CAE occurrence. The predictive success of the triple combination of NLR–MPV–RDW (5.5 fold) was higher than other combinations. The triple combination of parameters obtained as part of the hemogram, NLR–RDW–MPV, indicated a much more predictive power than two parameters coupled. This combination of three parameters, NLR–RDW–MPV, is to be considered as a sensitive, high-quality, low-cost outcome prediction marker for cardiac surgery patients that is less time consuming and easy to use.

Şaşkın H., Düzyol Ç., Özcan K.S., Aksoy R., Idiz M.

<strong>Objective:</strong> To investigate the association of platelet to lymphocyte ratio to mortality and morbidity after coronary artery bypass grafting operation.<br /><strong>Methods:</strong> We evaluated records of 916 patients who underwent coronary artery bypass grafting operation between January 2009 and May 2014 retrospectively. Patients were grouped as Group 1 (n = 604) if the platelet to lymphocyte ratio was above 142 and Group 2 (n = 312) if platelet to lymphocyte ratio was below 142.<br /><strong>Results:</strong> The number of patients who developed a neurologic event during the hospital stay and in the first postoperative month was 7 (1.2%) in Group 1 and 12 (3.8%) in Group 2 for which the difference was statistically significant (P = .007). Early term mortality occurred in 3 patients (0.5%) in Group 1 and in 10 patients (3.2%) in Group 2 for which the difference was statistically highly significant (P = .001). In univariate and multivariate regression analysis, the preoperative platelet to lymphocyte ratio was determined as an independent risk factor for occurrence of atrial fibrillation in the early postoperative period, reoperation for sternum dehiscence, occurrence of a neurologic event, prolonged stay in the hospital and mortality.<br /><strong>Conclusion:</strong> In this study, elevated levels of platelet to lymphocyte ratio were associated with mortality and morbidity after coronary artery bypass grafting operation.

Wang X., Zhang G., Jiang X., Zhu H., Lu Z., Xu L.

AbstractObjective The aim of this study was to investigate whether neutrophil to lymphocyte ratio (NLR) was an independent predictor for all-cause mortality or cardiovascular events in patients undergoing angiography or cardiac revascularization with observational studies by meta-analysis. Methods Pubmed and Embase were searched without language restrictions for cohort studies published prior to November 2013. Citations were independently screened by 2 authors, and those meeting the inclusion criteria defined a priori were retained. Data on authors, year of publication, location, target participant, comparison of NLR, outcome assessment, number of event and sample size, duration and statistical adjustments were abstracted. Results Eight studies were identified that reported on all-cause mortality and five studies were identified that reported on cardiovascular events. The pooled relative risk (RR) of all-cause mortality was 2.33 (95% CI 1.88–2.88) and the RR of cardiovascular events was 1.89 (95% CI 1.42, 2.52) comparing the highest with the lowest category of NLR. Conclusions The meta-analysis indicates that NLR is a predictor of all-cause mortality and cardiovascular events. Further well-designed trials are warranted to confirm this association.

Nashef S.A., Roques F., Sharples L.D., Nilsson J., Smith C., Goldstone A.R., Lockowandt U.

To update the European System for Cardiac Operative Risk Evaluation (EuroSCORE) risk model.A dedicated website collected prospective risk and outcome data on 22,381 consecutive patients undergoing major cardiac surgery in 154 hospitals in 43 countries over a 12-week period (May-July 2010). Completeness and accuracy were validated during data collection using mandatory field entry, error and range checks and after data collection using summary feedback confirmation by responsible officers and multiple logic checks. Information was obtained on existing EuroSCORE risk factors and additional factors proven to influence risk from research conducted since the original model. The primary outcome was mortality at the base hospital. Secondary outcomes were mortality at 30 and 90 days. The data set was divided into a developmental subset for logistic regression modelling and a validation subset for model testing. A logistic risk model (EuroSCORE II) was then constructed and tested.Compared with the original 1995 EuroSCORE database (in brackets), the mean age was up at 64.7 (62.5) with 31% females (28%). More patients had New York Heart Association class IV, extracardiac arteriopathy, renal and pulmonary dysfunction. Overall mortality was 3.9% (4.6%). When applied to the current data, the old risk models overpredicted mortality (actual: 3.9%; additive predicted: 5.8%; logistic predicted: 7.57%). EuroSCORE II was well calibrated on testing in the validation data subset of 5553 patients (actual mortality: 4.18%; predicted: 3.95%). Very good discrimination was maintained with an area under the receiver operating characteristic curve of 0.8095.Cardiac surgical mortality has significantly reduced in the last 15 years despite older and sicker patients. EuroSCORE II is better calibrated than the original model yet preserves powerful discrimination. It is proposed for the future assessment of cardiac surgical risk.

Gibson P.H., Croal B.L., Cuthbertson B.H., Small G.R., Ifezulike A.I., Gibson G., Jeffrey R.R., Buchan K.G., El-Shafei H., Hillis G.S.

An elevated preoperative white blood cell count has been associated with a worse outcome after coronary artery bypass grafting (CABG). Leukocyte subtypes, and particularly the neutrophil-lymphocyte (N/L) ratio, may however, convey superior prognostic information. We hypothesized that the N/L ratio would predict the outcome of patients undergoing surgical revascularization.Baseline clinical details were obtained prospectively in 1938 patients undergoing CABG. The differential leukocyte was measured before surgery, and patients were followed-up 3.6 years later. The primary end point was all-cause mortality.The preoperative N/L ratio was a powerful univariable predictor of mortality (hazard ratio [HR] 1.13 per unit, P < .001). In a backward conditional model, including all study variables, it remained a strong predictor (HR 1.09 per unit, P = .004). In a further model, including the European system for cardiac operative risk evaluation, the N/L ratio remained an independent predictor (HR 1.08 per unit, P = .008). Likewise, it was an independent predictor of cardiovascular mortality and predicted death in the subgroup of patients with a normal white blood cell count. This excess hazard was concentrated in patients with an N/L ratio in the upper quartile (>3.36).An elevated N/L ratio is associated with a poorer survival after CABG. This prognostic utility is independent of other recognized risk factors.