The relationship between red blood cell distribution width-albumin ratio (RAR) and prognosis in acute coronary syndrome

Abstract

AimWe investigated the association of red blood cell distribution width-albumin ratio (RAR) with prognosis and clinical risk scores in patients with acute coronary syndrome (ACS).MethodsA total of 245 patients with ACS were retrospectively evaluated. RAR levels were obtained by dividing RDW by albumin. RAR was divided into two groups based on the cut-off value, with low and high RAR. All parameters were statistically compared between these groups. The correlation of RAR with risk scores was also evaluated.ResultsReceiver operating characteristic (ROC) analysis revealed that albumin and RAR exhibited the highest values in mortality prediction (Area Under Curve [AUC]: 0.961, 0.951 respectively). The RAR exhibited a significant positive correlation with the troponin I, TIMI (thrombolysis in myocardial infarction), and HEART (history, EKG, age, risk factors, and troponin) risk scores (p<0.05 for all).ConclusionRAR levels on admission may be a more powerful predictor of mortality than RDW, TIMI and HEART risk scores in patients with ACS. High RAR levels can readily identify those at high risk in these patients and can also predict adverse outcomes. In the prognostic risk classification of ACS patients, the RAR has high sensitivity and specificity with a cut-off value of 0.403.

Keywords

Introduction

Acute coronary syndrome (ACS), which is one of the most common causes of admission to the intensive care unit (ICU), is a condition with a high mortality and morbidity rate. Therefore, it is of great importance to be able to identify high-risk patients and to be able to make an accurate prognosis in order to be able to provide the most appropriate treatment. A number of clinical risk scores have been developed for the purpose of risk stratification in patients suspected of ACS. These include HEART (history, ECG, age, risk factors, and troponin), TIMI (thrombolysis in myocardial infarction), and others.¹ Moreover, due to their rapid and comprehensive advantages, haematological parameters remain indispensable in the prognostic evaluation of ACS.²
It is well established that inflammation plays a significant role in the prognosis of coronary artery disease (CAD). Haematological markers have been demonstrated to be valuable indicators of both inflammation and the prognosis of CAD.³ Red blood cell distribution width (RDW), a haematological parameter, has been suggested to be associated with poor prognosis in ACS.⁴ Serum albumin, an important protein in the circulatory system, is an indicator of nutritional and inflammatory status. Serum albumin has been shown to be a predictor of adverse outcomes in individuals with ACS.⁵ It has been reported that the ratio of RDW to albumin (RAR), which is calculated by dividing RDW by albumin, may serve as a potential marker for predicting mortality in ACS.^2,6-7-8 To date, no study has investigated the relationship between clinical risk scores and RAR in patients with ACS. Therefore, the objective of our study was to investigate the association of RAR with prognosis and clinical risk scores in this patient population.

Materials and Methods

Study Design and Patient PopulationA retrospective evaluation was conducted between September 1, 2023, and April 1, 2024, of patients admitted to the emergency department (ED) of a training and research hospital who were diagnosed with ACS based on complaints, history, electrocardiography (ECG), and laboratory investigations and underwent coronary angiography (CAG). The study included patients aged 18 years or older, of either gender, for whom all clinical and laboratory data were available in the hospital registry system and whose diagnosis of ACS was confirmed according to current guidelines.⁹ To ascertain the severity of the lesions, the TIMI and HEART scores of patients presenting with unstable angina pectoris (USAP)/non-ST-elevation myocardial infarction (NSTEMI) at the time of admission to the ED and the SYNTAX risk scores of all patients following CAG were calculated.^10-11-12 The following variables were obtained from the hospital registry system: age, gender, background, routine blood tests, type of ACS (ST-elevation myocardial infarction [STEMI], NSTEMI, USAP), need for inotropic support and/or mechanical ventilation (MV) in the ICU, length of ICU stay (LOS-ICU), total length of hospital stay (LOHS), and outcomes (discharge/death). Mortality evaluation was based on in-hospital mortality.
Patients under the age of 18, patients undergoing acute thrombolytic therapy, pregnant women, patients with a history of acute or chronic hematologic disease, cancers, active infection, immunosuppressive patients, and patients for whom information could not be obtained from the electronic registry system were excluded from the study. RAR levels were obtained from the ratio of RDW to albumin.² According to the RAR cut-off value, they were divided into two groups as low and high RAR. A statistical comparison was conducted between the two groups for all parameters. Variables that may be associated with mortality were subjected to receiver operating characteristic (ROC) analysis. The correlation of RAR with TIMI, HEART, and SYNTAX risk scores was also evaluated.Hematologic and Biochemical AnalysisThe RDW, albumin, and troponin I values were determined in blood samples obtained at the time of admission to the ED. The hematologic markers were quantified using the Mindray auto hematology analyser BC-6800 (Shenzhen, China). The biochemical parameters were analysed using the Mindray chemistry analyser BS-2000M (Shenzhen, China).Ethical ApprovalThis study was approved by The Necmettin Erbakan University Faculty of Medicine Local Ethics Committee (Date: 03.05.2024, Decision No: 2024(4935) ID:19215).Statistical AnalysisStatistical analyses in the study were performed using SPSS 27.0 (IBM Inc, Chicago, IL, USA) program. Kolmogrov-Smirnov test, histogram analysis, skewness/kurtosis data and Q-Q plots were used to evaluate the assumptions of normal distribution. Qualitative parameters were expressed as frequency and percentage (%). Descriptive statistics of scale data were expressed as interquartile range (IQR) (median [minimum–maximum]) or mean ± standard deviation according to the distribution pattern. Relationships between the two groups were evaluated with independent t test or Mann-Whitney U test. Relationships between nominal parameters were detailed with either chi-square analysis or Fisher’s exact tests. ROC analysis was performed to reveal the predictive values. In the entire study, the type-I error rate was taken as 5% (α=0.05) and p<0.05 was accepted as the significant limit.

Results

Table 1 presents the characteristics of the patients according to RAR groups. Of the total 245 patients, 206 were in the low RAR (≤0.403) group and 39 were in the high RAR (>0.403) group. A comparison of the high and low RAR groups in terms of gender, STEMI, NSTEMI, UAP, SYNTAX score, LOHS, and LOS-ICU revealed no significant differences (p>0.05 for all). The results demonstrated that age, RDW, troponin, TIMI score, HEART score, the need for vasopressor and MV support, and in-hospital mortality rate were significantly higher in the high RAR group (p<0.05 for all). Furthermore, albumin levels were found to be significantly lower in the high RAR group (p<0.001). Table 2 presents the results of ROC analyses of the parameters used in mortality prediction. Among all parameters, the SYNTAX score was not found to be statistically significant (p>0.05). Among the blood parameters, albumin and RAR exhibited the highest predictive value, with an area under the curve (AUC) of 0.961 and 0.951, respectively. Among the risk scores, the TIMI and HEART scores exhibited the highest and lowest AUC values, respectively (AUC: 0.775, 0.688, respectively). The correlation relationship between the parameters is presented in Table 3. Consequently, there was a moderately significant positive correlation between RDW and the TIMI and HEART risk scores. Albumin was found to be negatively correlated with troponin I, TIMI, HEART risk score, and LOHS. The RAR exhibited a mildly significant positive correlation with the troponin I, TIMI, and HEART risk score (p<0.05 for all).

Discussion

ACS involves complex pathophysiologic mechanisms of systemic/local inflammatory, immunologic and thrombotic systems involved in the formation and progression of atherosclerosis. The study of inflammation-based markers has emerged as a significant topic in this context. In recent years, hematologic parameters have been utilized for this purpose.³ RDW is a marker reflecting changes in the volume and function of RBCs. Physiologically, erythrocytes supply oxygen to tissue cells and secrete mediators for cardiovascular regulation. Therefore, changes in RBC have a predisposing effect on cardiovascular disease. Consequently, an increase in RDW is associated with pathophysiological processes associated with oxygen deficiency and inflammation.² One study demonstrated that RDW levels were elevated in the dying patient group compared to the surviving group.⁶ In another study, elevated RDW levels were associated with an increased risk of mortality in patients with ACS.⁷ In our study, the optimal RDW cut-off value was determined to be 14.85, with an AUC of 0.797, which accurately predicted mortality with 72.7% sensitivity and 85.8% specificity.
Albumin, which can reflect nutritional status and is an important protein in the regulation of osmotic pressure, is also known to have anti-inflammatory, antiaggregant and antioxidant effects.² For many years, albumin levels have been an indicator of morbidity and mortality in many diseases, including cardiovascular diseases.^8,13 A meta-analysis of 21667 ACS patients revealed that those with low serum albumin levels exhibited an elevated risk of all-cause mortality (odds ratio [OR] 2.15; 95% confidence interval [CI] 1.68-2.75).⁵ Jian L. et al. observed a reduction in albumin levels in deceased patients compared to survivors.⁶ In our study, albumin showed that it can be a useful parameter with a high AUC value in predicting mortality. Atherosclerotic lesions can be defined as an inflammatory disease characterized by a number of specific cellular and molecular responses.⁸
RAR, a novel biomarker, may provide far superior information compared to RDW and albumin to predict the prognosis of various inflammatory diseases. In recent years, RAR has also been extensively studied in predicting mortality in ACS.^2,6 In a study of 2594 patients with ACS, RAR was significantly higher in non-surviving patients than in survivors. Higher RAR values were associated with longer hospital and LOS-ICU and higher MV utilization rates.⁶ Another study found that ACS patients with a RAR cut-off ≥4 exhibited a 122% increase in 3-year mortality. Moreover, RAR demonstrated superior inflammatory response outcomes in comparison to both markers.² In their study, Li H. et al. demonstrated that the performance of RAR in predicting 90-day mortality in these patients was high, and that disease severity increased as RAR increased.⁷ Weng Y. et al. observed that the predictive power of RAR was higher than that of RDW and albumin, with AUC values of 0.699, 0.672, and 0.643, respectively. Moreover, RAR demonstrated a robust correlation with the Gensini score or troponin I.⁸
The results of our study indicated that the TIMI risk scores, the need for MV with vasopressor support, and the mortality rates were higher in the high RAR group. The optimal RAR cut-off value was determined to be 0.403, with AUC of 0.951, a sensitivity of 87.9%, and a specificity of 95.3%. According to ROC analysis, the mortality prediction power of RAR was found to be superior to that of RDW, troponin I, TIMI, and HEART scores. Therefore, we believe that RAR, which is cheap and accessible, can be used as a prognostic marker in these patients.

Limitations

The study is subject to several limitations. Primarily, the possibility of bias cannot be excluded, given that this study is a retrospective analysis with a small number of patients. Second, the data for this study were obtained from patients admitted to the ICU, which limits the generalizability of the results to all patients with ACS. Third, only the RAR levels at admission were considered, and the dynamic changes of RAR could not be tracked. Fourth, unexamined confounding factors may have influenced our results. Further and multicenter studies are necessary to confirm the results of this study. Despite these limitations, our study was significant in terms of the association between RAR and the prognosis of ACS.

Conclusion

RAR levels on admission may be a more powerful predictor of mortality than RDW, TIMI and HEART risk scores in patients with ACS. Moreover, the correlation between RAR and clinical risk scores enables the identification of those at high risk in patients with ACS, as well as the prediction of adverse outcomes. In the prognostic risk classification of ACS patients, the RAR has high sensitivity and specificity with a cut-off value of 0.403.

References

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