title: Intracoronary Imaging, Cholesterol Efflux, and Transcriptomes After Intensive Statin Treatment: The YELLOW II Study.
abstract: BACKGROUND
  Despite extensive evidence demonstrating the beneficial effects of statins on clinical outcomes, the mechanisms underlying these effects remain elusive.
  
  
  OBJECTIVE
  This study assessed changes in plaque morphology using intravascular imaging, with a comprehensive evaluation of cholesterol efflux capacity (CEC) and peripheral blood mononuclear cell (PBMC) transcriptomics in patients receiving high-dose statin therapy.
  
  
  METHODS
  In a prospective study, 85 patients with stable coronary artery disease underwent percutaneous coronary intervention for a culprit lesion, followed by intracoronary multimodality imaging, including optical coherence tomography (OCT) of an obstructive nonculprit lesion. All subjects received 40 mg of rosuvastatin daily for 8 to 12 weeks, when the nonculprit lesion was reimaged and intervention performed. Blood samples were drawn at both times to assess CEC and transcriptomic profile in PBMC.
  
  
  RESULTS
  Baseline OCT minimal fibrous cap thickness (FCT) was 100.9 ± 41.7 μm, which increased to 108.6 ± 39.6 μm at follow-up, and baseline CEC was 0.81 ± 0.14, which increased at follow-up to 0.84 ± 0.14 (p = 0.003). Thin-cap fibroatheroma prevalence decreased from 20.0% to 7.1% (p = 0.003). Changes in FCT were independently associated with CEC increase by multivariate analysis (β: 0.30; p = 0.01). PBMC microarray analysis detected 117 genes that were differentially expressed at follow-up compared to baseline, including genes playing key roles in cholesterol synthesis (SQLE), regulation of fatty acids unsaturation (FADS1), cellular cholesterol uptake (LDLR), efflux (ABCA1 and ABCG1), and inflammation (DHCR24). Weighted coexpression network analysis revealed unique clusters of genes associated with favorable FCT and CEC changes.
  
  
  CONCLUSIONS
  The study demonstrated an independent association between fibrous cap thickening and improved CEC that may contribute to morphological changes suggesting plaque stabilization among patients taking intensive statin therapy. Furthermore, the significant perturbations in PBMC transcriptome may help determine the beneficial effects of statin on plaque stabilization. (Reduction in Coronary Yellow Plaque, Lipids and Vascular Inflammation by Aggressive Lipid Lowering [YELLOW II]; NCT01837823).
authors.affiliation: Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: annapoorna.kini@mountsinai.org.
authors.forename: Annapoorna S
authors.initials: AS
authors.lastname: Kini
authors.affiliation: Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Vengrenyuk
authors.affiliation: Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Khader
authors.initials: K
authors.lastname: Shameer
authors.affiliation: Division of Cardiology, Columbia University Medical Center and Cardiovascular Research Foundation, New York, New York.
authors.forename: Akiko
authors.initials: A
authors.lastname: Maehara
authors.affiliation: Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Meerarani
authors.initials: M
authors.lastname: Purushothaman
authors.affiliation: Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yoshimura
authors.affiliation: Division of Cardiology, Columbia University Medical Center and Cardiovascular Research Foundation, New York, New York.
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Matsumura
authors.affiliation: Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Melissa
authors.initials: M
authors.lastname: Aquino
authors.affiliation: Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Nezam
authors.initials: N
authors.lastname: Haider
authors.affiliation: Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Kipp W
authors.initials: KW
authors.lastname: Johnson
authors.affiliation: Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Ben
authors.initials: B
authors.lastname: Readhead
authors.affiliation: Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Kidd
authors.affiliation: Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Feig
authors.affiliation: Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Prakash
authors.initials: P
authors.lastname: Krishnan
authors.affiliation: Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Joseph
authors.initials: J
authors.lastname: Sweeny
authors.affiliation: Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Mahajan
authors.initials: M
authors.lastname: Milind
authors.affiliation: Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Pedro
authors.initials: P
authors.lastname: Moreno
authors.affiliation: Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.affiliation: Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Kovacic
authors.affiliation: Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Usman
authors.initials: U
authors.lastname: Baber
authors.affiliation: Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Joel T
authors.initials: JT
authors.lastname: Dudley
authors.affiliation: Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Jagat
authors.initials: J
authors.lastname: Narula
authors.affiliation: Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Samin
authors.initials: S
authors.lastname: Sharma
mesh_terms: D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging* / Q000628:therapy*; D000090943:Delta-5 Fatty Acid Desaturase; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear; D008297:Male; D064847:Multimodal Imaging; D062645:Percutaneous Coronary Intervention; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000000981:diagnostic imaging* / Q000628:therapy*; D011446:Prospective Studies; D000068718:Rosuvastatin Calcium / Q000627:therapeutic use; D041623:Tomography, Optical Coherence; D059467:Transcriptome
chemical_list: D000090943:Delta-5 Fatty Acid Desaturase; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000068718:Rosuvastatin Calcium; C000716847:FADS1 protein, human
keywords: fibrous cap thickness; high-dose statin; optical coherence tomography; plaque stability; thin-cap fibroatheroma