Impact of CD14++CD16+ monocytes on plaque vulnerability in diabetic and non-diabetic patients with asymptomatic coronary artery disease: a cross-sectional study

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: UMIN000021228Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-017-0577-8) contains supplementary material, which is available to authorized users.

Comparison of Intravascular Ultrasound Virtual Histology Parameters in Diabetes versus Non-Diabetes with Acute Coronary Syndrome

“…The fibro-fatty percentage was significantly lower with a corresponding higher necrotic core in the DM group. This relative variation in plaque composition is strongly associated with blood glucose fluctuations, as described previously by Yoshida et al [16].…”

“…The changes in high-sensitivity C-reactive protein (hs-CRP) correlate with the increase in necrotic core and dense calcium percentage, along with the decrease in fibrous tissue in diabetic patients [15]. Studies have shown the association of a higher necrotic core in DM patients and greater glucose fluctuations [16]. IVUS studies have reported a 16–66% incidence of plaque rupture, TCFA being a precursor, in patients with ACS [17-19].…”

Plaque volume and plaque risk profile in diabetic vs. non-diabetic patients undergoing lipid-lowering therapy: a study based on 3D intravascular ultrasound and virtual histology

“…Additional differences between the DM and non-DM patients included a higher glucose variability in DM patients leading to an increase of plaque burden and lipid content and a decrease of fibrous tissue in their atherosclerotic plaques [ 43 ]. Yoshida et al [ 44 ] described an increase of necrotic core in plaque with DM patients with higher glucose fluctuations. We found a notable correlation of both baseline and follow-up glycemia with plaque burden in the DM patients.…”

Reduced coronary collateralization in type 2 diabetic patients with chronic total occlusion

“…These coronary lesion characteristics favor plaque instability and degradation, and predict future major adverse cardiac events independent of myocardial ischemia [ 15 ]. Previous studies have revealed that glucose fluctuations provoke oxidative stress that leads to endothelial cell dysfunction, progression of coronary atherosclerosis, and plaque vulnerability [ 16 , 17 ]. These results suggest that there may be a symbiotic relationship between vulnerable plaque and T2DM.…”