Predictive value of elevated neutrophil–lymphocyte ratio on cardiac mortality in patients with stable coronary artery disease

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Abstract

Background

An association between white blood cell count (WBC), severity of coronary artery disease (CAD) and survival has been described in patients with acute coronary syndrome. Our aim was to analyze the predictive ability for cardiac events of differential WBC, which is still not well characterized, against established risk factors in angiographically proven CAD patients.

Methods

We prospectively evaluated complete blood count, biomarkers of inflammation [(C-reactive protein (CRP) and serum iron (SI)], glucose/lipid metabolism [(fasting glucose (FG), total, high-density lipoprotein (HDL) and low-density lipoprotein cholesterol] and established risk factors in 422 consecutive ischemic patients with angiographically documented stable CAD. On a 3-year follow-up, cardiac death and non-fatal myocardial infarction (MI) were considered as end-points.

Results

At multivariate analysis neutrophil to lymphocyte ratio (N/L) emerged as independent predictor of cardiac death (HR 8.13; p = 0.02) together with CRP, left ventricular ejection fraction (LVEF), FG, HDL and SI. CRP, LVEF, and HDL showed an independent prognostic value for cardiac death and non-fatal MI. Event-free survival according to N/L tertiles was 99% for the first tertile (1.23 ± 0.26), 96.5% for the second (2.05 ± 0.29), and 88.8% for the third one (5.19 ± 3.81).

Conclusions

N/L is an independent predictor of cardiac mortality in stable CAD patients.

Introduction

Atherosclerosis is a complex multifactorial inflammatory disease the evolution of which is influenced by both inborn and acquired risk factors [1]. In coronary artery disease (CAD) inflammation plays a key role at all stages [2], [3]. Atherogenic lipoproteins, such as low density lipoproteins (LDL) modified by oxidation or glycation are involved in the pro-inflammatory reaction, whereas high density lipoproteins (HDL) exert anti-inflammatory and anti-atherogenic functions. Oxidized-LDL may enhance the inflammatory response by stimulating the replication of monocyte-derived macrophages and the entry of monocytes and lymphocytes within the atherosclerotic lesion. Here monocytes and macrophages produce a variety of cytokines which further enhance the inflammatory process [4], favoring destabilization of the atherosclerotic plaque and related cardiac events.

Different inflammatory biomarkers, such as C-reactive protein and leukocyte count, are used in clinical practice for cardiac risk stratification in stable CAD as well as in acute coronary syndromes [5], [6], [7], [8], [9], [10].

To date, relatively few studies have dealt with the association between a specific leukocyte subtype and the increase of cardiac and total mortality or occurrence of nonfatal myocardial infarction. One retrospective study of patients with chronic CAD showed that 5-year survival was significantly better for patients with normal, as compared to low, relative lymphocyte count (%L) [11]. Moreover, in patients with congestive heart failure %L emerged as a prognostic indicator of long-term mortality [12], [13]. Only three recent studies reported a relationship between elevation of neutrophil to lymphocyte ratio (N/L) and long-term mortality in patients with angiographically assessed CAD [14], [15] and undergoing surgical revascularization [16].

The aim of this study was to evaluate the predictive ability for cardiac events of differential WBC in chronic CAD patients, as compared to conventional risk factors and markers of inflammation.

Section snippets

Patients

Our study prospectively evaluated 422 consecutive adult patients with ascertained significant obstructive CAD at coronary angiography, hospitalized in our Institute between 1997 and 2000. Patients with hematologic disorders (WBC count < 3.5 × 109/L or > 25.0 × 109/L), infectious or inflammatory disease, severe liver or renal disease were excluded from the study. All patients gave informed consent and the study was approved by the Institutional Ethics Committee. Patients enrolled in the study

Results

Considering patients' withdrawal either at a first cardiac event, non-cardiac death, or a revascularization procedure, follow-up averaged 36 months. No patient died during hospitalization. 64% of patients (272) underwent percutaneous transluminal coronary angioplasty during the follow-up and 13% (55) coronary artery bypass grafting. There were 13 cardiac deaths – 10 male (M) and 3 female (F) patients – caused by acute myocardial infarction (n = 9), sudden death (n = 1), and congestive heart failure

Discussion

According to our study the value of N/L resulted predictive for cardiac death in patients with chronic CAD. This finding follows recent reports [14], [15], [16] on N/L predictive value for all-cause death in unstable and chronic CAD patients. Because most studies on the association of leukocytosis and cardiac risk in CAD patients have considered a total WBC only, there are few data on the usefulness of leukocyte subpopulations in predicting cardiac mortality and non-fatal myocardial infarction.

Conclusions

High N/L was associated with increased cardiac mortality in clinically stable patients with CAD together with other cardiac risk factors. Our findings suggest that a multimarker approach including differential WBC may be useful for cardiac risk stratification in CAD patients.

Acknowledgements

We thank Manuella Walker for the revision of English style.

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