Relationship of neutrophil–lymphocyte ratio with arterial stiffness and coronary calcium score

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Abstract

Background

Emerging evidence suggests that the neutrophil/lymphocyte ratio (NLR) may be a useful marker of cardiovascular disease and a more powerful predictor than any other leukocyte subtypes. We determined whether NLR is related to atherosclerosis measured by brachial–ankle pulse wave velocity (baPWV) and coronary calcium score (CCS).

Methods

We examined the relationship of NLR with baPWV and CCS in 849 Korean adults in a health examination program. The odds ratios for a high baPWV or a high CCS were calculated using multivariate logistic regression analysis across NLR quartiles. A high baPWV was defined as > 1500 cm/s (> 75th percentile) and a high CCS was defined as over 100 (at least moderate atherosclerotic plaque burden).

Results

The ORs (95% CIs) for a high baPWV by NLR quartiles were 1.00, 0.76 (0.41–1.39), 1.08 (0.61–1.90), and 2.12 (1.18–3.83) after adjusting for confounding variables.

Similarly, positive associations between NLR and a high CCS were also observed after adjusting for the same co-variables.

Conclusion

A higher NLR was independently associated with arterial stiffness and CCS. Accordingly, a higher NLR may be a useful additional measure in assessing cardiovascular risks in clinical practice.

Introduction

Although the atherosclerotic pathogenesis remains unclear, an increasing body of evidence suggests that arterial inflammation may play a crucial role [1], [2]. Higher levels of inflammatory markers, such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and interleukin-6 (IL-6) have been significantly associated with cardiovascular disease (CVD) morbidity and mortality [1], [2]. White blood cell (WBC) count is one of the useful inflammatory biomarkers in clinical practice. Recently, WBC count has become a useful predictor of certain diseases as well as a marker of infection. A higher level of WBC count, even within normal range, has been associated with atherosclerotic CVD events [3]. WBCs are composed of five different types of immune cells. Each subtype of WBCs exerts its own effect in different manners. More recently, the neutrophil/lymphocyte ratio (NLR) has been also proposed as a useful biomarker to predict cardiovascular risk [4], [5], [6]. Epidemiologic evidence has shown that NLR could be a prognostic marker in acute coronary syndrome and a more powerful predictor than any other WBC subtypes [6], [7].

Various non-invasive markers of early arterial wall alteration such as arterial wall thickness and stiffness are now available. Pulse wave velocity (PWV) is a reliable indicator of vascular damage and atherosclerosis [8], [9]. Previous studies have shown that increased PWV is independently associated with CVD incidence and mortality [10], [11]. Moreover, the coronary calcium score (CCS), measured by multidetector computed tomography (MDCT), is a sensitive marker of coronary artery atherosclerosis and reflects the severity of coronary artery stenosis to some extent [12], [13]. Recent epidemiologic evidence suggests that the measurement of arterial stiffness and CCS could be additive to the Framingham risk score to help identify patients with cardiovascular risks [14], [15].

Until now, the association between NLR and subclinical atherosclerosis in the general population has been poorly understood. Thus, we examined whether NLR is related to atherosclerosis measured by baPWV and CCS in Korean adults in a health examination program.

Section snippets

Subjects

We retrospectively reviewed the medical records of 849 consecutive adults (540 men and 309 women) who voluntarily participated in a medical examination program at the Health Promotion Center in Gangnam Severance Hospital, Seoul, Korea, between October 2007 and November 2008. The inclusion criteria included subjects that were healthy, community-dwelling people.

Subjects meeting any of the following criteria were excluded (n = 45): any missing covariate information; age above 80 years to rule out

Results

Table 1 shows the general characteristics of the study population of 804 subjects with mean age 52.4 ± 9.2 y. The mean WBC count (x103 cells/μL) was 5.9±1.6 and the mean NLR was 2.1 ± 0.8. The mean baPWV was 1398.5 cm/s, and the geometric mean CCS was 36.6±6.1. Overall, hypertension was prevalent in 32.5% of the study population, and the proportion of diabetes was 9.0%.

The clinical and biochemical characteristics according to NLR quartiles are shown in Table 2. The percentage of current smokers and

Discussion

In this cross-sectional study, we found that the risk for high baPWV and CCS is significantly increased in the highest quartile of NLR. This effect remained after adjusting the presence of drugs that could modify vascular function parameters, such as blood pressure lowering drugs, anti-diabetic drugs, and lipid lowering drugs.

The reference value for baPWV is different according to age and blood pressure categories [16]. A baPWV > 1400 cm/s has been shown to be a useful predictor of cardiovascular

Acknowledgement

The authors would like to thank Mr. Tim Gitzen for his help in editing the manuscript.

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