Mount Sinai Researchers Find Improved Cholesterol Efflux Linked to Plaque Stabilization in Statin-Treated Patients
Researchers at the Mount Sinai Cardiac Catheterization Lab have found that patients treated with intensive statin therapy undergo changes in plaque morphology, specifically a thickening of the fibrous cap, that are associated with improved cholesterol transport and distinct genomic changes. The results of this study, titled YELLOW II (Reduction in Yellow Plaque by Aggressive Lipid-Lowering Therapy), were published October 29 in the Journal of the American College of Cardiology, simultaneously with presentation on October 31 in the Featured Science Session at TCT 2016 in Washington, DC.
“While previous studies including our own have shown that treatment with high-dose statins results in plaque stabilization, we wanted to explore the mechanistic basis of changes in plaque morphology, especially focusing on how is the fat removed from the plaque,” said lead investigator Annapoorna Kini, MD, Director of the Cardiac Catheterization Laboratory at Mount Sinai Heart. “Our results are promising and provide a wider snapshot of how high-dose statin therapy exerts its influence, and points to underlying changes in gene expression that result from treatment. We see many patients who develop blockages, despite taking their medications and improving their LDL cholesterol levels and blood chemistry. We’re optimistic this research will help lead to future answers.”
The study included 85 patients with stable multivessel coronary artery disease who underwent PCI for a culprit lesion. Patients also underwent multimodality imaging of an obstructive nonculprit lesion with optical coherence tomography (OCT), near-infrared spectroscopy, and intravascular ultrasound (IVUS). Cholesterol efflux capacity (CEC) was assessed. Following enrollment, patients were treated with high doses of rosuvastatin for 8-12 weeks and then follow-up imaging, CEC and genomic changes were reassessed.
In addition to markedly lower bad cholesterol, inflammation and improved cholesterol efflux, the researchers also evaluated gene expression in isolated samples of peripheral blood mononuclear cells before and after high-dose statin therapy. They identified 6 differentially expressed genes which were involved in cholesterol synthesis (SQLE), regulation of fatty acid unsaturation (FADS1), cellular cholesterol uptake (LDLR), cholesterol efflux (ABCA1, ABCG1), and inflammation (DHCR24).
“The transcriptomic research is an attempt to isolate specific genomic biomarkers that might one day be used to identify responders to statin therapy, without the need for invasive imaging,” said Joel Dudley, PhD, Associate Professor of Genetics and Genomic Sciences and Director of the Institute for Next Generation Healthcare at the Icahn School of Medicine at Mount Sinai.
Dr. Narula, the director of imaging services at Sinai added that “this study was a unique attempt at bring the best of clinical, intravascular imaging, cell biology and genomic studies together. This is the true example of the translational science as best as it gets.”
“This study was able to recruit 85 patients in a short time from a single center for this very involved research effort. It is a monumental feat and speaks high of Mount Sinai Catheterization laboratory which carries out the largest number of interventions in the country with the best safety data,” said study author Samin K. Sharma, MD, Director of Clinical and Interventional Cardiology at The Mount Sinai Hospital. “This study has now demonstrated that Sinai cath lab can deliver the quality research at the same level as it has done so for outstanding patient care.”
The YELLOW II trial was conducted with support from the Investigator-Sponsored Study Program of AstraZeneca, partial support from InfraReDx and Mount Sinai catheterization laboratory endowment funds.
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Mount Sinai Health System is one of the nation’s leading integrated academic health systems and one of the largest in the New York metropolitan area. Its comprehensive system includes seven hospitals, more than 400 outpatient practices, over 600 research and clinical laboratories, the Icahn School of Medicine at Mount Sinai, the Graduate School of Biomedical Sciences, and the Mount Sinai Phillips School of Nursing. Together, the Health System comprises approximately 48,000 employees, more than 9,000 physicians, and 8,600 nurses.
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