Intracoronary Imaging, Cholesterol Efflux, and Transcriptomes after Intensive Statin Treatment: The YELLOW II study

• Published in: Journal of the American College of Cardiology Vol. 69; no. 6; pp. 628 - 640
• Main Authors: Kini, Annapoorna S., MD, Vengrenyuk, Yuliya, PhD, Shameer, Khader, PhD, Maehara, Akiko, MD, Purushothaman, Meerarani, PhD, Yoshimura, Takahiro, MD, Matsumura, Mitsuaki, BS, Aquino, Melissa, MS, Haider, Nezam, PhD, Johnson, Kipp W., BS, Readhead, Ben, MBBS, Kidd, Brian A., PhD, Feig, Jonathan E., MD, PhD, Krishnan, Prakash, MD, Sweeny, Joseph, MD, Mahajan, Milind, PhD, Moreno, Pedro, MD, Mehran, Roxana, MD, Kovacic, Jason C., MD, PhD, Baber, Usman, MD, Dudley, Joel T., PhD, Narula, Jagat, MD, PhD, Sharma, Samin, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Limited 14.02.2017
• Subjects: Apolipoproteins; Cardiology; Cardiovascular; Cardiovascular disease; Coronary Artery Disease - blood; Coronary Artery Disease - diagnostic imaging; Coronary Artery Disease - therapy; Delta-5 Fatty Acid Desaturase; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Internal Medicine; Leukocytes, Mononuclear; Lipids; Low density lipoprotein; Male; Multimodal Imaging; Percutaneous Coronary Intervention; Plaque, Atherosclerotic - blood; Plaque, Atherosclerotic - diagnostic imaging; Plaque, Atherosclerotic - therapy; Prospective Studies; Rosuvastatin Calcium - therapeutic use; Statins; Studies; Tomography, Optical Coherence; Transcriptome; ABCA1; CEC; peripheral blood mononuclear cells; OCT; intravascular ultrasound; cholesterol efflux capacity; non-culprit lesion; optical coherence tomography; fibrous cap thickness; IVUS; minimal fibrous cap thickness; PBMC; ATP-binding cassette A1 transporter; FCT; NCL; plaque stability; high-dose statin; NIRS; near infrared spectroscopy; thin-cap fibroatheroma
• DOI: 10.1016/j.jacc.2016.10.029
• ISSN: 0735-1097

Abstract Background Despite the extensive evidence for the beneficial effects of statins on clinical outcomes, the mechanisms underlying these effects in remain elusive. Objectives To assess the changes in plaque morphology by intravascular imaging with a comprehensive evaluation of cholesterol efflux capacity (CEC) and peripheral blood mononuclear cells (PBMC) transcriptomics in patients receiving high-dose statin therapy. Methods In a prospective study, 85 patients with stable multivessel coronary artery disease underwent percutaneous coronary intervention for a culprit lesion followed by intracoronary multi-modality imaging including optical coherence tomography (OCT) of an obstructive non-culprit lesion (NCL). All subjects received 40 mg of rosuvastatin every day for 8-12 weeks, when the NCL was reimaged and intervention was performed. Blood samples were drawn at both times to assess cholesterol CEC and transcriptomic profile in PBMC. Results Baseline OCT minimal fibrous cap thickness (FCT) was 100.9 ± 41.7 μm and CEC 0.81 ± 0.14, which increased upon follow-up-FCT (108.6 ± 39.6 μm, P<0.001), CEC (0.84 ± 0.14, P=0.003). The prevalence of thin-cap fibroatheroma reduced from 20.0% to 7.1% (P=0.003). The changes in FCT were independently associated with the increase in CEC by multivariate analysis (β, 0.30; 95%CI, 0.07-0.54; P=0.01). Microarray analysis of PBMC detected 117 differentially expressed genes at follow-up compared to baseline including genes playing key role in cholesterol synthesis ( SQLE ), regulation of fatty acids unsaturation ( FADS1 ), cellular cholesterol uptake ( LDLR ), efflux ( ABCA1 , ABCG1 ) and inflammation ( DHCR24 ). Weighted coexpression network analysis revealed unique clusters of genes associated with favorable changes in FCT and CEC. Conclusions The study demonstrates an independent association between the thickening of the fibrous cap and improved CEC that may contribute to morphological changes suggesting plaque stabilization among patients on intensive statin therapy. Furthermore, the significant transcriptomic perturbations related to cholesterol synthesis, regulation of fatty acid unsaturation, cellular cholesterol uptake, efflux and inflammation may co-operate in determining the beneficial effects of statin on plaque stabilization.