The association between systemic in flammatory indices and prognosis inacute coronary syndrome

Authors

Abstract

AimThis study investigated the prognosis in patients with acute coronary syndrome (ACS) and the relationship with systemic inflammatory indices such as neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), systemic immune inflammation index (SII), systemic inflammatory response index (SIRI), prognostic nutritional index (PNI).
MethodsA total of 215 patients diagnosed with ACS between 01.09.2023 and 01.03.2024 were evaluated retrospectively. Patients were divided into two groups as survivors and non-survivors. NLR, PLR, SII, SIRI and PNI levels were statistically compared between these two groups. Variables that may be associated with mortality were subjected to receiver operating characteristic (ROC) analysis.
ResultsNLR, PLR, SII and SIRI were significantly higher, whereas PNI was lower in the non-surviving group (p<0.05 for all). According to ROC analysis, SII had the highest and PLR the lowest predictive power of the inflammation indices (Area Under Curve [AUC] : 0.919 and 0.827, respectively).
ConclusionNLR, PLR, SII, SIRI and PNI levels may predict risk stratification and prognosis in patients with ACS.

Keywords

Introduction

Acute coronary syndrome (ACS), classified as unstable angina (UAP), non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI), is a leading cause of death worldwide. Modern antithrombotic therapy, secondary prevention and percutaneous coronary intervention (PCI) have reduced mortality from cardiac causes; however, these patients require continuous follow-up to assess and improve their prognosis.¹ In recent years, the use of early risk classification methods and biomarkers to predict the prognosis of patients with ACS has been recommended.²
Patient assessment using diagnostic tools such as history, physical examination, electrocardiogram (ECG) and cardiac biomarkers are the traditional methods used to differentiate low-risk from high-risk patients; however, none of these methods can reliably exclude ACS. Therefore, several clinical risk scores (e.g., HEART [history, ECG, age, risk factors and troponin], Thrombolysis in Myocardial Infarction [TIMI], The Global Registry of Acute Coronary Events [GRACE], etc.) have been developed to evaluate suspected patients.² In addition, although new biomarkers measured from peripheral blood can be used for this purpose, there is still a need for a cheap and easily accessible ideal indicator that can predict clinical outcomes.³
Atherosclerosis is defined as a continuous, dynamic and inflammatory process in blood vessels. Inflammation and thrombosis have been recognised as an important part of the ischaemia-reperfusion injury in patients with ACS.⁴ Indices related to prothrombotic status and inflammation, such as the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR), which are complete blood count (CBC) markers, may indicate the severity and prognosis of patients with ACS.⁵ In recent years, it has been reported that the systemic immune inflammation index (SII) and the systemic inflammation response index (SIRI), which consist of three routine blood markers, can be used for risk classification and prediction of adverse events in cardiovascular disease.⁶ Previous studies have shown that low serum albumin levels are associated with poor outcomes and prognosis in ACS. Therefore, it has been highlighted that albumin may be a better acute phase reactant than CBC parameters because it reflects both nutritional status and inflammatory response.⁷ The prognostic nutritional index (PNI) calculated from albumin and total lymphocytes was found to be independently associated with all-cause mortality in critically ill patients with ACS.¹
Therefore, in our study, we investigated the relationship between these indices and prognosis in patients with ACS.

Materials and Methods

Study Design and Patient PopulationBetween 01.09.2023 and 01.03.2024, patients who presented to the emergency department (ED) of a training and research hospital, who were diagnosed with ACS based on complaints, history, ECG, and laboratory investigations and underwent coronary angiography (CAG) were evaluated retrospectively. Patients older than 18 years of age, male or female, whose clinical and laboratory information could be accessed from the hospital registration system and whose diagnosis of ACS was confirmed according to current guidelines were included in the study.⁸
To determine lesion severity, TIMI and HEART scores of patients with UAP/NSTEMI at the time of presentation to the ED and SYNTAX risk scores of all patients after CAG were calculated.^9,10,11 Age, gender, history, routine blood tests, type of ACS (STEMI, NSTEMI, UAP), need for vasopressor support and/or mechanical ventilation (MV) in the intensive care unit (ICU), length of ICU stay (LOICUS), length of hospital stay (LOHS) and outcomes (discharge/mortality) were obtained through the hospital registry system and patient epicrises. Mortality evaluation was based on in-hospital mortality.
Patients under 18 years of age, patients receiving acute thrombolytic therapy, pregnant women, patients with a history of acute/chronic haematological diseases, cancers, presence of active infection, immunosuppressive patients and patients whose information could not be accessed from the electronic registry system were excluded from the study. NLR: neutrophil/lymphocyte count, PLR: platelet/lymphocyte count, SII: neutrophil × platelet/lymphocyte count, SIRI: neutrophil × monocyte/lymphocyte count and PNI: 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count (mm³).^1,5,12 Patients were divided into two groups as survivors and non-survivors. All parameters including NLR, PLR, SII, SIRI and PNI levels were statistically compared between these two groups. Variables that may be associated with mortality were subjected to receiver operating characteristic (ROC) analysis. The correlation of inflammatory indices with TIMI, HEART and SYNTAX risk scores was also evaluated.
Haematological and Biochemical AnalysisNeutrophil, monocyte, lymphocyte, platelet, albumin and Troponin I values were measured in blood samples taken at the time of admission to the ED. CBC markers were determined using Mindray auto haematology analyzer BC-6800 (Shenzhen, China). Mindray chemistry analyzer BS-2000M device was used for biochemical parameters (Shenzhen, China).
Ethical ApprovalThis study was approved by The Necmettin Erbakan University Faculty of Medicine Local Ethics Committee (Date: 05.04.2024, Decision No: 2024(4883)(ID:18697)).
Statistical AnalysisNumerical parameters were expressed as median (min-max) or mean ± SD, and categorical variables were expressed as frequency and percentage (%). Kolmogorov-Smirnov test, histogram analyses and skewness/kurtosis data were used to evaluate the conformity of the numerical variables to normal distribution. Levene’s test was used to analyse the intergroup homogeneity of the numerical parameters. For the comparison of two independent groups, independent t-test was used for the parameters showing normal distribution characteristics and Mann-Whitney U test was used for parameters that did not show normal distribution characteristics. Variables that may be associated with mortality were detailed by ROC analysis and diagnostic/predictive data were revealed. Correlation relationships were analysed by Spearman’s two-way correlation analysis. In our study, type-I error (alpha) was taken as 0.05 (5%), p<0.05 was accepted as significant and SPSS 21.0 (IBM Inc, Chicago, IL, USA) programme was used.

Results

A comparison of demographic, clinical and laboratory findings between the surviving and non-surviving patient groups is shown in Table 1. Out of a total of 215 patients, 191 patients survived and 24 patients died. When the surviving and non-surviving patients were compared in terms of gender, platelets, SYNTAX score, LOHS and LOICUS, no significant difference was detected (p>0.05 for all).
Age, neutrophils, monocytes, troponin, NLR, PLR, SII, SIRI, TIMI score, HEART score, the proportion of patients requiring MV support and vasopressors were significantly higher in the non-surviving group (p<0.05 for all). In addition, lymphocyte, albumin, PNI, STEMI, NSTEMI, USAP rates and EF values were significantly lower in the non-survival group (p<0.05 for all).
ROC analyses of blood parameters, inflammatory indices and risk scores in predicting mortality are shown in Table 2. Among all parameters, platelets and SYNTAX scores were not statistically significant (p>0.05 for all). Among the blood parameters, neutrophils had the highest and monocytes had the lowest predictive value (AUC: 0.950, 0.719, respectively). Among risk scores, TIMI and HEART had the highest and lowest AUC values (AUC: 0.813, 0.719, respectively). Among the inflammation indices, SII and PLR had the highest and lowest predictive power, respectively (AUC: 0.919, 0.827, respectively).
The correlation analysis of the inflammatory indices with the risk scores is shown in Table 3. According to this analysis, NLR, PLR, SII and SIRI had a weak positive correlation and PNI a weak negative correlation with the TIMI risk score. Only PNI had a slightly significant negative correlation with the HEART score. Only SIRI had a slightly significant positive correlation with the SYNTAX score. In addition, SIRI had a positive and slightly significant correlation with LOICUS (p<0.05 for all).

Discussion

Coronary artery disease (CAD) is a complex disease involving multiple pathways including inflammation, oxidative stress, myocardial injury, apoptosis, neurohormonal activation and haemodynamic stress. Biomarkers reflecting these pathways may aid in the diagnosis, management and prognosis of CAD and its complications.¹³ Different components of the CBC are currently being investigated to determine the severity and prognosis of CAD. Neutrophils, platelets and monocytes have been associated with inflammation, atherosclerosis and the incidence of adverse cardiac events.⁵ Lymphocyte-based indices of inflammation are readily available in clinical practice.⁶ Indices such as NLR and PLR may have high values in predicting the prognosis of various cardiovascular diseases. Karaca G et al. associated high NLR values with a higher risk of adverse outcomes in hospitalised STEMI patients.¹³ The NLR ratio has been shown to reflect the systemic inflammatory response process that often accompanies myocardial ischaemia and irreversible cardiac damage.¹⁴ In another study, NLR and PLR were significantly correlated with SYNTAX score and GENSINI score. In logistic regression analyses, only NLR was an independent predictor of CAD.¹⁵ Li Q et al. suggested that PLR has limited prognostic value in ACS patients and should be used together with other indices to predict cardiovascular outcomes.⁶ In our study, NLR and PLR were found to be significantly higher in the non-surviving patient group. However, NLR had a higher predictive power than PLR in predicting mortality (AUC: 0.913, 0.827, respectively). Therefore, NLR may have a stronger ability to predict systemic inflammatory response and mortality than PLR when assessing high-risk patients.
SII and SIRI, which can simultaneously reflect the body’s inflammatory and immune status, are novel prognostic markers that have recently been investigated for cardiovascular mortality. It is thought that SII and SIRI may have a higher predictive power for cardiovascular disease outcomes than NLR and PLR due to their interactions between three different blood cells.¹⁶ In a study of 5602 patients with CAD, higher SII levels were found in the ACS group compared to the non-ACS group, which is thought to reflect the severity of inflammation.³ In another study of STEMI patients, NLR and SII were found to be useful in predicting the risk of non-reflow after primary PCI.¹¹ Li et al. found that compared with other markers of systemic inflammation (NLR, PLR, MLR and SII), SIRI was more predictive of future major adverse cardiovascular events (MACE) in patients with CAD.⁶ Chen Y et al. also showed that both SII and SIRI were associated with the risk of all-cause mortality in elderly patients with ACS.¹² In our study, both SII and SIRI showed high AUC values for predicting mortality, which is consistent with the literature. In addition, SIRI appears to be a useful index for predicting poor outcomes due to its significant correlation with TIMI, SYNTAX risk scores and LOICUS.
Malnutrition is common in ACS patients and is strongly associated with cardiovascular events.⁷ Albumin levels, which have been used for many years to monitor the nutritional status of patients, are an indicator of increased morbidity and mortality in many diseases.¹⁷ In recent years, PNI, another marker that can indicate inflammation and nutritional status, may also be used as a prognostic marker in patients with ACS.⁷ Huang Y et al. found that ACS patients with low PNI had longer LOICUS and higher risk of in-hospital mortality compared to patients with high PNI levels.¹ Koçaş BB et al. also reported that PNI was an independent predictor of MACE and all-cause mortality in patients with ACS. In addition, it has been highlighted that PNI has the ability to discriminate patients at risk better than other inflammatory indices.⁷ In our study, PNI was significantly lower in non-survivors than in survivors. PNI was significantly correlated with both TIMI and HEART risk scores and predicted mortality better than these two risk scores. Therefore, PNI alone may be a useful marker for risk stratification of these patients.

Limitations

The study has several limitations. It is a retrospective and single-center study with a relatively small sample size and therefore cannot be generalized. Second, unmeasured confounders and short follow-up of patients may have affected the results. Therefore, larger prospective studies with longer follow-up periods are needed to confirm the findings. Third, the inflammatory indices investigated in our study were calculated only from CBC parameters at admission and their changes at different times may provide additional prognostic information.

Conclusion

NLR, PLR, SII, SIRI and PNI levels are inflammatory markers that prognosis in patients with ACS. Additionally, NLR, PLR, SII and SIRI had a positive correlation and PNI a negative correlation with the TIMI risk score. For this reason, these markers can early predict risk stratification and assist physicians in the management of ACS.

Declarations

References

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About This Article

Received:

April 3, 2024

Accepted:

May 20, 2024

Published Online:

June 5, 2024

Printed:

July 1, 2024