TY - JOUR
T1 - Intracoronary Imaging, Cholesterol Efflux, and Transcriptomes After Intensive Statin Treatment
T2 - The YELLOW II Study
AU - Kini, Annapoorna S.
AU - Vengrenyuk, Yuliya
AU - Shameer, Khader
AU - Maehara, Akiko
AU - Purushothaman, Meerarani
AU - Yoshimura, Takahiro
AU - Matsumura, Mitsuaki
AU - Aquino, Melissa
AU - Haider, Nezam
AU - Johnson, Kipp W.
AU - Readhead, Ben
AU - Kidd, Brian A.
AU - Feig, Jonathan E.
AU - Krishnan, Prakash
AU - Sweeny, Joseph
AU - Milind, Mahajan
AU - Moreno, Pedro
AU - Mehran, Roxana
AU - Kovacic, Jason C.
AU - Baber, Usman
AU - Dudley, Joel T.
AU - Narula, Jagat
AU - Sharma, Samin
N1 - Publisher Copyright:
© 2017 American College of Cardiology Foundation
PY - 2017/2/14
Y1 - 2017/2/14
N2 - Background Despite extensive evidence demonstrating the beneficial effects of statins on clinical outcomes, the mechanisms underlying these effects remain elusive. Objectives 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.
AB - Background Despite extensive evidence demonstrating the beneficial effects of statins on clinical outcomes, the mechanisms underlying these effects remain elusive. Objectives 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.
KW - fibrous cap thickness
KW - high-dose statin
KW - optical coherence tomography
KW - plaque stability
KW - thin-cap fibroatheroma
UR - http://www.scopus.com/inward/record.url?scp=85011589679&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85011589679&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2016.10.029
DO - 10.1016/j.jacc.2016.10.029
M3 - Article
C2 - 27989886
AN - SCOPUS:85011589679
SN - 0735-1097
VL - 69
SP - 628
EP - 640
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 6
ER -