Treatment with high-dose statins results in plaque
stabilization, suggests previous study. 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.
of this study, titled YELLOW II (Reduction in Yellow Plaque by
Aggressive Lipid-Lowering Therapy), were published in the
Journal of the American College of Cardiology
‘Patients treated with intensive statin therapy undergo plaque stabilization associated with improved cholesterol transport and distinct transcriptomic perturbations.’
"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, Director of the
Cardiac Catheterization Laboratory at Mount Sinai Heart.
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 eight to 12 weeks and
then follow-up imaging, CEC and genomic changes were reassessed.
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 six 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).
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, 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, 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."