Intracoronary Imaging, Cholesterol Efflux, and Transcriptomics after Intensive Statin Treatment in Diabetes

Kipp W Johnson,Jagat Narula,Surbhi Chamaria,Aparna A Divaraniya,Annapoorna S Kini,Usman Baber,Yuliya Vengrenyuk,Roxana Mehran,Pedro Moreno,Khader Shameer,Joel T Dudley,Benjamin S Glicksberg,Li Li,Akiko Maehara,Samin K Sharma,Samit Bhatheja

doi:10.1038/s41598-017-07029-7

Abstract

Residual atherothrombotic risk remains higher in patients with versus without diabetes mellitus (DM) despite statin therapy. The underlying mechanisms are unclear. This is a retrospective post-hoc analysis of the YELLOW II trial, comparing patients with and without DM (non-DM) who received rosuvastatin 40 mg for 8–12 weeks and underwent intracoronary multimodality imaging of an obstructive nonculprit lesion, before and after therapy. In addition, blood samples were drawn to assess cholesterol efflux capacity (CEC) and changes in gene expression in peripheral blood mononuclear cells (PBMC). There was a significant reduction in low density lipoprotein-cholesterol (LDL-C), an increase in CEC and beneficial changes in plaque morphology including increase in fibrous cap thickness and decrease in the prevalence of thin cap fibro-atheroma by optical coherence tomography in DM and non-DM patients. While differential gene expression analysis did not demonstrate differences in PBMC transcriptome between the two groups on the single-gene level, weighted gene coexpression network analysis revealed two modules of coexpressed genes associated with DM, Collagen Module and Platelet Module, related to collagen catabolism and platelet function respectively. Bayesian network analysis revealed key driver genes within these modules. These transcriptomic findings might provide potential mechanisms responsible for the higher cardiovascular risk in DM patients.

Highlights

Designed to assess the changes in plaque morphology of an obstructive non culprit lesion (NCL) by optical coherence tomography (OCT), near-infrared spectroscopy (NIRS) and IVUS with a comprehensive evaluation of high density lipoprotein (HDL) functionality and peripheral blood mononuclear cells (PBMC) transcriptomics in patients receiving high-dose statin therapy. In this post-hoc analysis we studied the differences in response to statin therapy between diabetes mellitus (DM) and non-DM patients and whether the residual cardiovascular risk in patients with stable coronary artery disease (CAD) undergoing percutaneaous coronary intervention (PCI) and concomitant DM could be related to impaired statin-responsiveness
There was a significant decrease in low density lipoprotein-cholesterol (LDL-C) (P < 0.001) and total cholesterol levels (P < 0.001) in both groups with total cholesterol levels lower in DM group compared to non-DM patients at follow-up (P = 0.045)
DM group did not demonstrate a significant decrease in hs-C-reactive protein (CRP) levels at follow-up (P = 0.058) or increase in ApoA1 (P = 0.47) in contrast to the non-DM group, which had reduced high-sensitivity C-reactive protein (hs-CRP) levels at follow up (P = 0.001) and increased ApoA1 (P = 0.003)

Summary

Introduction

Designed to assess the changes in plaque morphology of an obstructive non culprit lesion (NCL) by optical coherence tomography (OCT), near-infrared spectroscopy (NIRS) and IVUS with a comprehensive evaluation of high density lipoprotein (HDL) functionality and peripheral blood mononuclear cells (PBMC) transcriptomics in patients receiving high-dose statin therapy. In this post-hoc analysis we studied the differences in response to statin therapy between DM and non-DM patients and whether the residual cardiovascular risk in patients with stable coronary artery disease (CAD) undergoing percutaneaous coronary intervention (PCI) and concomitant DM could be related to impaired statin-responsiveness

Methods

Results

Discussion

Conclusion