Combining white blood cell count and thrombosis for predicting in-hospital outcomes after acute myocardial infraction.

INTRODUCTION: Admission white blood cell (WBC) count and thrombosis in myocardial infarction (TIMI) risk score have been associated with adverse outcomes after acute myocardial infarction (AMI). This study investigated the joint effect of WBC count and TIMI risk score on predicting in-hospital outcomes in patients with AMI.
MATERIALS AND METHODS: WBC count and TIMI risk score were measured at the time of hospital admission in 70 patients with AMI. Echocardiogram was done on prior to discharge by a cardiologist and ejection fraction (EF) was determined according to the Simpson formula. Patients were stratified into tertiles (low and high) based on WBC count and TIMI risk score.
RESULTS: Patients with a high WBC count had a 5.0-fold increase in-hospital congestive heart failure and 2.2 increases in mortality compared with those with a low WBC count. Patients with a high TIMI risk score had a 10-fold increase in congestive heart failure presentation and mortality compared with those with a low TIMI risk score. When a combination of different strata for each variable was analyzed, a stepwise increase in mortality was seen. There were a few number of patients with a high WBC count and low TIMI risk score or with a low WBC count and high TIMI risk score. These patients had an intermediate risk, whereas those with a high WBC count and TIMI risk score had the highest risk.
CONCLUSION: These findings suggested that a simple combination of WBC count and TIMI risk score might provide further information for predicting outcomes in patients with AMI.

INTRODUCTION

The goal of risk stratification after acute ST elevation myocardial infarction (STEMI) is to identify patients whose outcomes can be improved by predicting complications.[1] Risk stratification should be a dynamic process throughout the patient's hospitalization.[1] Currently, risk stratification after myocardial infarction has largely focused on stratification after the patient leave the hospital. Although the evaluation prior to discharge remains an important component of risk stratification, the emphasis must also be placed on early and continual risk assessment done using simple bedside observations to prevent in-hospital mortality and morbidity. The reason for this is: Early identification of high-risk patients allows rapid triage for cardiac catheterization, thus, reducing both inpatient stays and overall cost. (Our center does not have catheterization lab and would require at least 2 hours of transfer time. Therefore, low-risk patients can be considered for shorter stays in the coronary care units, be subjected to fewer diagnostic evaluations, as well as earlier hospital discharge. white blood cell (WBC) count and thrombosis in myocardial infarction (TIMI) risk score are inexpensive risk markers that are routinely assessed at the time of hospital admission in clinical practice. Numerous studies have demonstrated that a high WBC count is associated with a large infarct, impaired left ventricular (LV) function and mortality after acute myocardial infarction (AMI).[2-9] The potential deleterious roles of the WBC count in promoting blood coagulation, mediating microvascular no-reflow, and causing myocyte dysfunction have been reported.[4] Inflammation associated with AMI is frequently marked by a peripheral leukocytosis and relative neutrophilia.[5] TIMI risk score provides independent prognostic information but is not currently used routinely in the assessment of patients with acute coronary syndromes.[5] The objective of this study was to examine the association between hospital admissions; peripheral total leukocyte count and TIMI risk score and presentation of heart failure and in-hospital mortality of patients.

MATERIALS AND METHODS

Informed consent was obtained from all patients. This study was approved by the ethics committees at two participating hospitals that lack interventional capabilities. As such, thrombolytic therapy was performed on all these patients except if the patient has had a contraindication to thrombolytics, then, angioplasty will be preferred modality. This cross-sectional study was carried out on 105 patients from January 15, 2008 to June 31, 2009 with a diagnosis of STEMI who were admitted to our two coronary care units located, in the two university hospitals, but 70 patients was qualified. Acute STEMI was defined by a combination of two of three characteristics i.e., chest pain consistent with ongoing myocardial ischemia that persisted ≥30 minutes, electrocardiographic changes and positive troponin ≥1. Electrocardiography on admission showed ST-segment elevation in all patients. The following criteria were used to define ST-segment elevation: new or presumed-new ST elevation at the J-point in two or more contiguous leads that is greater than or equal to 0.2 mV (2 mm) in leads V1 through V6 or greater than or equal to 0.1 mV (1 mm) in the other leads.[8] Serum troponin of all patients was measured. Mean time to admission was 4.7±6.8 hours. Patient were excluded if there were concomitant infections, inflammatory diseases, malignant diseases, hypoglycemia, corticosteroid consumption, any contraindication for thrombolytic therapy, as well as any other indications where primary PCI would have been preferred. These patients were not given any other drug that could affect the WBC count (for example, β-blocker). Fifteen patients received ASA previously. Five patients had consumed ACE-I prior to admission. (These are not exclusion criteria.) A blood sample was drawn for leukocyte count and blood sugar and troponin, on admission and repeated for troponin12 hours later. Total WBC, neutrophils count, lymphocytes count, and monocytes count were determined using an automated blood cell analyzer (Sysmex XE-2100) before thrombolytic therapy. All samples were analyzed by a central core laboratory. Total leukocyte was categorized as low if the TBC is less than 10000/ml or high if the TBS is 10000/ml or more. Echocardiogram was obtained prior to discharge by the cardiologist and the LV ejection fraction (LVEF), and cardiac volumes were determined according to Simpson formula. Congestive heart failure was defined as an EF less than 50% on echocardiogram.

Statistics

Statistical analysis was performed with χ2 test for categorical variables. The t-test and analysis of variance were used for continuous variables. The nominal regression model was used to obtain odds ratios (OR) and 95% confidence intervals (CI) for in-hospital mortality. In this model, WBC count was used as continuous variables. Differences were considered statistically significant at P<0.05.

RESULTS

The mean age of all patients was 56.8±12.3 years. There were five deaths (3.5%) during the hospitalization 4(80%) of them had TIMI risk score≥4 and 3 (60%) WBC count≥10000/ml. In-hospital mortality was more likely to be higher in patients whose WBC count was >10,000 (11% in high vs. 5% in low, OR=2.2, 95% CI,1.8-3.1, P=0.01. All patients had a troponin of ≥1. Predischarge LVEFs were 56±12% in the low WBC group, and 52±13% in the high count, (P=0.001) [Tables 1 and 2].

Table 1

Study characteristics of the patients with the admitting diagnosis of STEMI

Table 2

Factors prevalence in admitted patients according to their TIMI score

A higher TIMI risk score was also associated with higher in-hospital mortality (20% in TIMI ≥ 4 vs. 2% in TIMI <4, OR=10, 95% CI, 9.1-11, P=0.001). Patients with lower TIMI were younger and more likely to be current smokers but less likely to be hypertensive. Patients with a high WBC count had a 5.0-fold increase in-hospital congestive heart failure compared with those with a low WBC count. Patients with a high TIMI risk score had a 10-fold increase in congestive heart failure presentation compared with those with a low TIMI risk score. Predischarge LVEFs were 56±13% in the low TIMI, and 52±12% in the high TIMI (P≤0.001).

In group with TIMI<4, 91% had EF ≥50%, while in patients with TIMI≥4; 92% had EF below 50% (P=0.0001, χ2 =36; [Table 3])

Table 3

Association between ejection fraction and TIMI in admitted patients

If WBC≥10000 cells/ml: EF<50% in 80% and in 20% EF ≥50% (P=0.02).

IF WBC<10000 cells/ml: EF ≥50% in 87% and in 13% EF<50% (P<0.05, χ2 =33.1) [Table 4].

Table 4

Association between WBC and ejection fraction in admitted patients

Table 5 weighs other variables together. In univariate analysis, (OR 1.12 per 1000/mm increase, 95% CI 1.09-1.11, P<0.001) WBC count was associated with in-hospital mortality. Multivariate analysis showed that WBC count and TIMI risk score were independent predictors for in-hospital mortality.

Table 5

Comparison of two groups of variables

Influence of diabetes mellitus on in-hospital outcomes was also investigated. There was no significant difference in in-hospital mortality between diabetic and nondiabetic patients (6% vs. 7%, P=0.5). When we combined WBC count and TIMI risk score [Table 6], for predicting in-hospital outcomes, yielded a sensitivity of 86% and a specificity of 95% for identification of heart failure and a sensitivity of 100% and a specificity of 73% for prediction of mortality.

Table 6

Mortality and CHF combining WBC and TIMI score

DISCUSSION

This study showed that a high WBC count (as defined ≥10,000) and TIMI risk score ≥ 4) were strong predictors for in-hospital mortality after AMI. LV function decreased in a stepwise manner as WBC count and TIMI risk score increased. A TIMI risk score ≥4 yielded a sensitivity of 80% and a specificity of 95% for identification of heart failure and a sensitivity of 80% and a specificity of 72% for prediction of mortality.

Leukocytosis ≥10000/ml yielded a sensitivity of 82% and a specificity of 85% for identification of heart failure and a sensitivity of 60% and a specificity of 58% for prediction of mortality. These findings suggested that a combination of WBC count and TIMI risk score provide further information for predicting outcomes of patients with AMI. TIMI risk scores due to its simplicity, cost-effectiveness and wide availability are a potential risk stratification tool in AMI and emphasis must also be placed on its usage.

Several studies have demonstrated that in ST-segment elevation AMI a high WBC count was associated with short-term mortality and heart failure.[89] Several experimental studies have suggested that inflammation and WBC count may directly contribute to a larger infarct.[10] Evid[ence suggests that leukocytes may play an active role in the modulation of platelet function and vice versa. Myocardial ischemia causes release of chemotactic factors, migration of neutrophils, peroxidation of lipids and depletion of free radical scavengers. The invading neutrophils may injure the myocardial vasculature and sarcolemma by generating oxygen-free radicals.[1] All these can result to myocardial dysfunction. Nonetheless, it remains unclear as to whether a high WBC count results in a larger infarct or it is merely a consequence. Based on recent clinical studies, a high WBC count is not a simple reflection of a larger infarct before reperfusion therapy.[1011]

Limitations

Small numbers of patients in this study.

Serial leukocyte counts were not recorded; therefore, we cannot analyze the effect of peak counts on outcomes.

CONCLUSIONS

Despite the use of modern reperfusion therapies, STEMI patients with higher WBC count and TIMI risk scores are high-risk and strongly increased in-hospital mortality rates when compared with patients without these characteristics. These findings suggested that a combination of WBC count and TIMI risk scores provide further information for predicting in-hospital outcomes of patients with AMI. This study focused on STEMI that would be the importance of it as opposed to other studies which focused on the whole spectrum of ACS.