Intracoronary Imaging, Cholesterol Efflux, and Transcriptomes After Intensive Statin Treatment: The YELLOW II Study

Area of Science:

• Cardiovascular Medicine
• Molecular Biology
• Pharmacology

Background:

• Statins are known to improve clinical outcomes, but their precise mechanisms of action remain unclear.
• Understanding these mechanisms is crucial for optimizing cardiovascular disease treatment.

Purpose of the Study:

• To investigate the effects of high-dose rosuvastatin on coronary plaque morphology and cholesterol efflux capacity (CEC).
• To analyze changes in peripheral blood mononuclear cell (PBMC) transcriptomics in response to statin therapy.

Main Methods:

• Prospective study of 85 patients with stable coronary artery disease receiving 40 mg rosuvastatin daily for 8-12 weeks.
• Intracoronary multimodality imaging (including OCT) to assess plaque morphology (fibrous cap thickness) before and after treatment.
• Blood samples analyzed for CEC and PBMC gene expression using microarrays.

Main Results:

• Significant increase in fibrous cap thickness (FCT) and CEC after statin therapy (p=0.003).
• Reduction in thin-cap fibroatheroma prevalence from 20.0% to 7.1% (p=0.003).
• FCT changes were independently associated with CEC increase (β: 0.30; p=0.01); 117 genes in PBMCs showed differential expression, including those involved in cholesterol metabolism and inflammation.

Conclusions:

• High-dose statin therapy is associated with plaque stabilization, evidenced by increased fibrous cap thickness and improved CEC.
• PBMC transcriptomic alterations provide insights into the molecular mechanisms underlying statin-mediated plaque stabilization.