Abstract

BackgroundPreviously, we have reported that daily glucose fluctuations could affect coronary plaque vulnerability, but the underlying mechanisms remained unclear. This study sought to investigate the impact of CD14++CD16+ monocytes on plaque vulnerability, as assessed by virtual histology intravascular ultrasound (VH-IVUS), as well as their relationship to fluctuating glucose levels in patients with asymptomatic coronary artery disease (CAD).MethodsFifty-one patients with asymptomatic CAD, who were undergoing lipid-lowering therapy and underwent VH-IVUS evaluation for angiographically mild to moderate lesions, were enrolled in the study. Standard VH-IVUS parameters, including the percentage volume of the necrotic core (%NC) within the plaque and the presence of a virtual histology thin-cap fibroatheroma (VH-TCFA), were then evaluated. Additionally, monocyte subsets were assessed by flow cytometry, and daily glucose fluctuations were analyzed by measuring the mean amplitude of glycemic excursion (MAGE).ResultsAmong 82 plaques from 22 diabetes mellitus (DM) patients and 29 non-DM patients, 15 VH-TCFAs were identified. CD14++CD16+ monocyte counts significantly correlated with both %NC and the presence of VH-TCFA (%NC: r = 0.339, p = 0.002; VH-TCFA: p = 0.003). Multivariate logistic regression analysis revealed that CD14++CD16+ monocyte counts were independently associated with VH-TCFA (odds ratio = 1.029, p = 0.004). Furthermore, CD14++CD16+ monocyte counts were significantly correlated with the MAGE score in the non-DM patients (r = 0.544, p = 0.005).ConclusionsCD14++CD16+ monocyte levels are associated with coronary plaque vulnerability and can serve as a biomarker for VH-TCFA in patients with CAD undergoing lipid-lowering therapy. In patients without DM, glucose fluctuations may alter the balance of monocyte subsets.Trial registration UMIN Registry number: UMIN000021228

Highlights

  • We have reported that daily glucose fluctuations could affect coronary plaque vulnerability, but the underlying mechanisms remained unclear

  • We investigated the impact of C­ D14++CD16+ monocytes on coronary plaque vulnerability and daily glucose fluctuations in patients with asymptomatic coronary artery disease (CAD), who were undergoing lipidlowering therapy

  • Four of the non-diabetes mellitus (DM) patients were excluded from blood glucose analysis because of a poor quality of the continuous glucose monitoring (CGM) data, and 22 DM and 25 nonDM patients were included in the final CGM data analysis

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Summary

Introduction

We have reported that daily glucose fluctuations could affect coronary plaque vulnerability, but the underlying mechanisms remained unclear. This study sought to investigate the impact of C­ D14++CD16+ monocytes on plaque vulnerability, as assessed by virtual histology intravascular ultrasound (VH-IVUS), as well as their relationship to fluctuating glucose levels in patients with asymptomatic coronary artery disease (CAD). Human monocytes can be divided into three subsets based on the CD14/ CD16 expression: classical C­D14++CD16− monocytes, intermediate ­CD14++CD16+ monocytes, and non-classical ­CD14+CD16+ monocytes [2]. Classical ­CD14++CD16− monocytes are phenotypically similar to ­Ly6Chigh/Gr-1+ mouse monocytes, with both groups expressing high levels of C–C chemokine receptor type 2 (CCR2), CD62L, and CD64 and low levels of CX3C chemokine receptor 1 (CX3CR1) [3]. Non-classical C­D14+CD16+ monocytes express low levels of CCR2 and high levels of CX3CR1 and resemble ­Ly6Clow/Gr-1− mouse monocytes. A large cohort study has reported that C­ D14++CD16+ monocytes independently predicted future cardiovascular events in subjects referred for elective coronary angiography (CAG) [1]

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