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

Posted on December 19, 2016




Despite the extensive evidence for the beneficial effects of statins on clinical outcomes, the mechanisms underlying these effects in remain elusive.


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.


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.


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.


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.