High neutrophil to lymphocyte ratio is associated with white matter hyperintensity in a healthy population

Highlights

• High neutrophil to lymphocyte ratio is associated with the burden of white matter hyperintensity in a healthy population

• It may provide clues to the inflammatory pathophysiology of white matter hyperintensity development

• Cerebral microbleeds, or silent brain infarcts did not seem to be related to NLR as white matter hyperintensity

Abstract

High neutrophil to lymphocyte ratio (NLR) is correlated with the occurrence, morbidity and mortality of cerebrovascular disease as a marker of systemic inflammation. However, its effect on cerebral white matter hyperintensity (WMH) is unclear. We investigated high NLR burden as a surrogate marker of WMH volume in a healthy population. Healthy subjects with voluntary health check-ups between January 2006 and December 2013, including brain MRI and laboratory examination, were collected. WMH volumes were rated quantitatively. A total of 2875 subjects were enrolled, and the mean volume of WMH was 2.63 ± 6.26 mL. In multivariate linear regression analysis, NLR [β = 0.191, 95% confidence interval (CI) = 0.104 to 0.279, P < 0.001] remained significant after adjusting for confounders. Age (β = 0.049, 95% CI = 0.045 to 0.054, P < 0.001), hypertension (β = 0.191, 95% CI = 0.101 to 0.281, P < 0.001), diabetes (β = 0.153, 95% CI = 0.045 to 0.261, P = 0.006), and extracranial atherosclerosis (β = 0.348, 95% CI = 0.007 to 0.688, P = 0.045) were also significant independently from NLR. Additionally, the high NLR group (NLR ≥ 1.52) was related to male sex, hypertension, diabetes, current smoking, extracranial atherosclerosis, silent brain infarct, and high WMH volumes. In conclusion, high NLR is associated with larger WMH volumes in a healthy population. Assessment of NLR may be helpful in detecting cerebral WMH burdens in high risk groups.

Introduction

Cerebral white matter hyperintensity (WMH) is a pathologic marker of tissue rarefaction, commonly found in the elderly, especially those with vascular risk factors or symptomatic cerebrovascular disease (CVD) [1]. It is a well-known prognostic marker of CVD [2], [3], [4], [5], [6]. However, its pathophysiologic mechanisms are still unclear. Only diffuse hypoperfusion and chronic endothelial dysfunction have been suggested as causes, however these appear inadequate to fully explain the association [7], [8], [9].

Inflammation has a key role in development of CVD [10], [11]. Focal inflammation which follows local arterial occlusion and systemic inflammation which is related to atherosclerosis formation have been known to be associated with the burden, morbidity, and even mortality of CVD [12], [13], [14], [15]. However, the impact of inflammation on WMH, which shares various risk factors and is thought to be closely related to CVD [16], remains unknown.

Neutrophil to lymphocyte ratio (NLR) is a simple marker of systemic inflammation [17], and is easily obtained from differential blood cell counts. Elevated NLR has been used as a predictor of poor prognoses in vascular disease; including cardiovascular disease, peripheral vascular disease, and CVD [10], [18], [19], [20], [21]. In this study, we evaluated the relationship between NLR levels and WMH volumes, thereby gaining clues as to mechanisms underlying pathophysiology of WMH.