Associations between CT-determined visceral fat burden, hepatic steatosis, circulating white blood cell counts and neutrophil-to-lymphocyte ratio.

Kuo-Tzu Sung,Ta-Chuan Hung,Tung-Hsin Wu,Chris T Longenecker,Chuan-Chuan Liu,Richard Kuo,Chung-Lieh Hung,Shun-Chuan Chang,Hung-I Yeh,Hiram G Bezerra,Chun-Ho Yun,David A Zidar,Jing-Yi Sun,Ricardo C Cury,Charles Jia-Yin Hou,Anna Halama

doi:10.1371/journal.pone.0207284

Abstract

Visceral adiposity is associated with cardiovascular disease, an association that may be mediated in part by inflammation. We hypothesized that regional measures of visceral adiposity would associate with commonly obtained clinical measures of immune status. We consecutively studied 3,291 subjects (mean age, 49.8±9.8 years) who underwent an annual cardiovascular risk survey. Peri-cardial (PCF) and thoracic peri-aortic adipose tissue (TAT) volumes were determined by dedicated computed tomography (CT) software (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). Hepatic steatosis was assessed by abdominal ultrasonography. We explored cross-sectional associations between visceral fat measures and high-sensitivity C-reactive protein (hs-CRP), leukocyte counts, and the neutrophil-to-lymphocyte ration (NLR). Among 3,291 study participants, we observed positive linear associations between PCF and TAT, higher degree of hepatic steatosis and hs-CRP, various leukocyte counts, either total and its differential counts, and NLR (all trend p<0.001). Multi-variate linear and logistic regression models showed independent associations between PCF/TAT (ß-Coef: 0.14/0.16, both p<0.05) and total WBC counts, with only TAT further demonstrated significant relations with neutrophil counts and NLR (both p<0.05) and independently identified abnormally high WBC and NLR (Odds ratio: 1.18 & 1.21, both p<0.05). C-statistics showed significant incremental model prediction for abnormally high WBC and NLR (both ΔAUROC<0.05) when TAT was superimposed on traditional cardiovascular risks and biochemical information. Greater visceral adiposity burden and hepatic steatosis may be associated with higher circulating leukocyte counts and markers for atherosclerosis, with more pronounced influences for peri-aortic adiposity. Our data suggested the differential biological impacts for region-specific visceral adiposity.

Highlights

Excessive adipose tissue is associated with a chronic inflammatory status that leads to a variety of metabolic disorders including dyslipidemia, hypertension, and type 2 diabetes with regionspecific properties [1]
Higher quintile of Pericardial fat (PCF) and thoracic peri-aortic adipose tissue (TAT) volume was associated with more advanced age, higher systolic/diastolic blood pressures, increased body height and weight, greater body mass index (BMI), higher fasting glucose, higher glycosylated hemoglobin level (HbA1c), and unfavorable lipid profiles including higher total cholesterol, higher low-density lipoprotein (LDL), lower level of high-density lipoprotein (HDL), and lower estimated glomerular filtration rate
In the final model 4, addition of TAT—but not PCF—statistically significantly increased the C-statistic for both total white blood cell count (WBC) count and neutrophil-to-lymphocyte ratio (NLR) (Fig 5A-5D). In this large cohort of subjects who underwent a cardiovascular health survey in Taiwan, we demonstrate that 3 measures of visceral adiposity—PCF, TAT and hepatic steatosis—are associated with circulating WBC counts and the systemic inflammatory marker high-sensitivity C-reactive protein (hs-CRP)

Summary

Introduction

Excessive adipose tissue is associated with a chronic inflammatory status that leads to a variety of metabolic disorders including dyslipidemia, hypertension, and type 2 diabetes with regionspecific properties [1]. Over-production of various pro-inflammatory paracrines and mediators by visceral adipose tissue leads to obesity-related systemic inflammation and insulin resistance [3, 4]. Fatty liver disease—characterized by excessive fatty infiltration of liver tissue— is an increasingly recognized cause of chronic liver disease worldwide, and is highly associated with central obesity, local hepatic inflammation, insulin resistance and increased systemic oxidative stress [5, 6]. The local inflammatory milieu of visceral adipose tissue is characterized by monocyte/macrophage infiltration and a diversity of lymphocyte subtypes [7, 8]. The neutrophil-to-lymphocyte ratio (NLR) has been proposed as a risk marker for adverse inflammatory status in metabolic syndrome, several cardiovascular disorders and cancer [11]

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