Introduction

Among cardiovascular illnesses, acute coronary syndrome (ACS) events are associated with higher mortality and morbidity.1 Majority of the cardiovascular disease risk burden will be taken by the Indian subcontinent in the future.2 The mechanism of inflammation involved in ACS includes atherosclerotic plaque development, followed by development of plaque rupture and thrombosis.3

ACS events are not only due to the stenosis of coronary arterial system but also due to other pathophysiological mechanisms involved in the development of acute coronary events. In the development of acute coronary events, leukocytes play an important role through the processes of inflammation.4 Macrophages and T-cells, which are located in the atherosclerotic plaque core, get activated when endothelium is injured, and there is release of cytokines and procoagulants by these cells, which promote the thrombus formation. These mechanisms increase the risk of thrombogenicity and the development of ACS.5

Increased leukocyte (white blood cell [WBC]) count is helpful in predicting clinical outcome in patients with ACS.6 Mean platelet volume (MPV) is a marker of platelet activation is an inflammatory marker, which can be useful in assessing prognosis in patients with ACS.7 As a combination of both these markers (WBC and MPV), WBC count to MPV ratio (WMR) has been recently found as a novel noninvasive marker for predicting long-term outcomes in patients with ACS8. However, the use of this novel marker for assessing prognosis in persons with ACS in Indians is not yet studied. Therefore, in the present study, we are evaluating whether WMR can be useful as a marker of prognosis in Indian persons presenting with ACS.

Aims and Objectives

To detect usefulness of WMR for predicting short-term (30 days) major adverse cardiac events (MACE) in patients presenting with ACS, and also compare values and MACE events in males and females.

Materials and Methods

The present study was conducted in a tertiary care hospital from September 2020 to December 2020. In the present study, the sample size was 60 cases with ACS, which is based on the study by Adam et al, in which the sensitivity of WMR was 69% with mortality rate of 14%, and the minimum sample size required was 25 cases with ACS.9 Inclusion criteria include patients with ACS. ACS patients were identified by using the following criteria: non-ST-segment elevated myocardial infarction (NSTEMI) was diagnosed if persons had increased cardiac enzymes without detectable ST-segment elevation on the electrocardiogram (ECG). STEMI was diagnosed if person complained of typical angina which lasted for more than 20 minutes along with any one of the following features: ST-segment elevation of at least 1 mm in two or more contiguous leads, formation of new Q wave or left bundle branch block (LBBB) formation, and/or two times increase in the cardiac enzymes. Unstable angina (UA) is diagnosed if there is detectable ischemic changes on an ECG without cardiac enzymes elevation.10

A total of 60 patients presenting with ACS, who fulfilled the selection criterion, were studied. The clearance from the Institutional Ethical committee (IEC) was obtained prior to the initiation of the study. Eligible patients for the study were explained about the study and investigations to be conducted, and written informed consent was taken. All the necessary data including age and gender, clinical features, history of diabetes mellitus, hypertension, smoking, alcohol consumption, and tobacco chewing were taken from the eligible patients, and physical examination carried out to assess the vital parameters. Patients were also evaluated for Killip clinical examination classification and New York Heart Association (NYHA) classification.11 12

Inclusion Criteria

• All patients with clinical suspicion of ACS are included.

• 18 to 90 years age people are included.

• Both gender are included.

Exclusion Criteria

• Non-ACS patients, patients with malignancy history, inflammatory diseases, autoimmune disorders and infections, and those who are immunosuppressed.

Statistical Analysis

• Data has been collected, compiled using Microsoft Excel, and statistical analyzed with the help of SSPS v20. Results on continuous variables are presented as mean and standard deviation (SD). Results on categorical variables are presented as percentages. Chi-square test is used to find out the significance of study parameters on a categorical scale between two investigations. Receiver operating characteristic (ROC) curve analysis was conducted to determine prognostic accuracy of WMR in predicting MACE. Continuous variables are analyzed using independent t-tests for normal distribution; otherwise, the Mann–Whitney U-test is employed. All p-values are two-tailed, and p < 0.05 is considered statistically significant.

Results

In this study, a total of 60 patients with ACS were enrolled.

We observed a slightly greater number of males (n = 36, 60%) than females (n = 24, 40%) in the present study, as shown in Table 1.

Comorbidities of patients: Among 60, 36 (60%) had hypertension and 24 did not have hypertension, 21 (35%) were diabetic, 26 (43.3%) were alcoholics, 21(35%) were smokers, and 10 (16.67%) had hypothyroid, as shown in Table 2.

Diagnosis of patients: Out of 60 patients presenting with ACS, 9 had anterior wall myocardial infarction (AWMI), 8 presented with extensive anterior wall myocardial infarction (EAWMI), 4 presented with inferior wall myocardial infarction (IWMI), 1 with IWMI with complete heart block (CHB), 2 had EAWMI, 5 had inferior wall posterior wall myocardial infarction (IWPWMI), 1 had extensive inferior wall posterior wall myocardial infarction (EIWPWMI), 16 had NSTEMI, and 13 presented with UA, as shown in Table 3.

Out of 60 patients, 24 had single vessel disease (left anterior descending [LAD] 13, left circumflex [LCX] 2, right coronary artery [RCA] 9), 1 had left main, triple vessel disease, 9 had triple vessel disease, 26 had double vessel disease (LAD LCX 14, LAD RCA 6, LCX RCA 6) disease. Out of 60 patients 15 patients underwent PCI to LAD, 10 patients underwent PCI to RCA, 4 underwent PCI to LCX, 8 underwent coronary artery bypass graft (CABG) surgery, and 1 underwent multivessel PCI.

In present study, the ROC curve (as shown in Fig. 1 below) showed cutoff value of WMR as 1059 with area under curve (AUC) of 0.6 (95% CI 0.4–0.9). The area under ROC curve is maximum at 1059 value with better sensitivity.

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Fig. 1 Receiver operating characteristic (ROC) curve showing area under curve (AUC) for white blood cell count to mean platelet volume ratio (WMR) in predicting major adverse cardiac event (MACE).

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Fig. 1 Receiver operating characteristic (ROC) curve showing area under curve (AUC) for white blood cell count to mean platelet volume ratio (WMR) in predicting major adverse cardiac event (MACE).

MACE was noted in 12 patients and mortality was noted in 6 patients. MACE like recurrent myocardial infarction (REMI) occurred in 6 patients with high WMR (> 1059) and in 1 patient with low WMR (< 1059), arrhythmias occurred in 4 patients with high WMR (1059) and in 1 patient with low WMR (1059), and cardiogenic shock occurred in 8 patients with high WMR (1059).

WMR with a cutoff value of 1059 was significant and highly accurate in predicting MACE with sensitivity of 91.6%, specificity of 87.5%, positive predictive value (PPV) of 64.7%, negative predictive value (NPV) of 97.6%, and diagnostic accuracy of 88.3%.

Accuracy Of WMR in Predicting MACE (Overall)

MACE occurred in 12 patients; among them, 11 patients had WMR ratio > 1059 and 1 patient had low WMR ratio < 1059, with sensitivity of 91.6%, specificity of 87.5%, PPV of 64.7%, NPV of 97.6%, and diagnostic accuracy of 88.3% (Table 4).

Accuracy of WMR in Predicting MACE in Females

MACE occurred in 12 patients; among them, 6 patients were females. Among those 6 females, 5 patients had WMR ratio >1059 and 1 patient had low WMR ratio < 1059 with sensitivity of 83.3%, specificity of 94.4%, PPV of 83.33%, NPV of 94.44%, and diagnostic accuracy of 91.67% (Table 6).

Comparing WMR and MACE

About 20 MACE events occurred; among them, 18 events occurred in patients with WMR ratio > 1059 and 2 patients had low WMR ratio < 1059, with sensitivity of 90%, specificity of37.5%, PPV of 41.6%, NPV of 88.24%, and diagnostic accuracy of 55% (Table 7).

Major Adverse Cardiac Events

Overall, 20 MACE occurred in 12 patients. Out of them, 6 were males (10%) and 6 were females (10%). Hence, in the present study, MACE did not show any gender predilection ( and 1 0).

Comparison of Baseline Investigations with WMR (Table 11)

Comparison of Baseline Investigations with MACE (Table 12)

Discussion

WMR is a novel noninvasive marker, which is highly accurate in predicting MACE in patients presenting with ACS. Raised WMR with cutoff value of 1059 with AUC of 0.6 (95% CI 0.4–0.9), sensitivity of 91.6%, specificity of 87.5%, PPV of 64.7%, NPV of 97.6%, and diagnostic accuracy of 88.3% (p = 0.01).

MACE occurred in 12 patients; among them, 6 patients were females. Compared to males, females had less sensitivity to, high specificity to, and high diagnostic accuracy of WMR ratio in predicting MACE.

Overall, 20 MACE occurred in 12 patients. Out of them, 6 were males (10%) and 6 were females (10%). Hence, in the present study, MACE did not show any gender predilection.

Out of 60 patients presenting with ACS, 7 patients developed REMI (11.66%). Among them, 3 were males (5%) and 4 were females (6.66%). Compared to males, females had slight increase of incidence of REMI.

Out of 60 patients presenting with ACS, 5 patients developed arrhythmias (8.33%). Among them, 3 were males (5%) and 2 were females (3.3%). Compared to males, females had slight decrease of incidence of arrhythmias.

Out of 60 patients 8 patients developed cardiogenic shock. Among them, 4 were males (6.66%) and 4 were females (6.66%). Compared to males, females had equal incidence of cardiogenic shock.

Out of 60 patients, death occurred in 6 patients in the present study. Among them, 3 were males (5%) and 3 were females (5%). Males and females had similar death rates.

Out of 60 patients 6 patients died, and cause of death was cardiogenic shock in 5 and arrhythmia in 1 patient. Cause of death in males was cardiogenic shock, and in females, cause of death was cardiogenic shock and arrhythmia.

Along with WMR, higher WBC and higher neutrophil count were other predicators of MACE.

WMR is a ratio derived from WBC count to MPV ratio. In the present study, baseline MPV level in patients with MACE was 11.78± 1.449, and in patients without MACE, it was 10.82± 1.239.

In the present study, mean WBC count was found significantly high in patients with MACE (14669.16±2632.169) than those without MACE (9647.9116±1906.31) and the difference was significant (p < 0.0001). An increased WBC count is a prominent indicator of compromised microvascular reperfusion. Barron et al presented that acute MI patients with a leucocyte count in the highest quintile had a higher 30-day mortality rate than patients with a leucocyte count in the lower quintiles.15 In the present study, it was also found that increased WBC count was associated with MACE.

The present study demonstrated that raised WMR, that is with a cutoff value of 1059, holds greater predictive value for short-term MACE in patients presenting with ACS, yielding higher diagnostic accuracy (88.3%), sensitivity (91%), specificity (87.5%) with low PPV (64.7%) and high NPV (97.6%) as well as high positive likelihood ratio (7.33) and lower negative likelihood ratio (0.10) (p = 0.01). Recently, Adam et al reported sensitivity of 68.3% and specificity of 63.7% with slightly higher WMR cutoff values (1068.75, AUC = 0.734 95% CI: 0.656–0.812; p < 0.001), which is very much comparable with the present study.

The present study results show that WMR had a higher sensitivity to predict short-term outcomes; therefore, calculating WMR is not only sensitive but a faster and a more efficient marker.

Overall, the present study demonstrates that raised WMR (≥ 1059) is highly accurate in discriminating poor outcome, that is, MACE within 30 days of patients presenting with ACS.

However, these conclusions require careful interpretation due to potential limitations of this study

Limitations of this Study

The conclusions drawn from the present study were based on a single-centre study comprising a relatively smaller sample size, using a nonrandomized sampling technique. Furthermore, we did not measure other more specific proinflammatory markers, including P-selectin, high-sensitivity C-reactive protein (CRP), interleukins, selectin molecules, adhesion ligands and receptors, and markers of oxidative stress to show any comparison between WMR and such biomarkers. Further studies are required to validate these results and define the exact role of WMR in predicting short-term MACE.

Conclusion

In patients who presented with ACS, high WMR values were associated with worse short-term outcomes and independently predicted short-term MACE. Compared to males, females had less sensitivity, high specificity, and high diagnostic accuracy of WMR ratio in predicting MACE.