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A transcriptomic model to predict increase in fibrous cap thickness in response to high-dose statin treatment: Validation by serial intracoronary OCT imaging

BACKGROUND: Fibrous cap thickness (FCT), best measured by intravascular optical coherence tomography (OCT), is the most important determinant of plaque rupture in the coronary arteries. Statin treatment increases FCT and thus reduces the likelihood of acute coronary events. However, substantial stat...

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Autores principales: Johnson, Kipp W., Glicksberg, Benjamin S., Shameer, Khader, Vengrenyuk, Yuliya, Krittanawong, Chayakrit, Russak, Adam J., Sharma, Samin K., Narula, Jagat N., Dudley, Joel T., Kini, Annapoorna S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607084/
https://www.ncbi.nlm.nih.gov/pubmed/31126891
http://dx.doi.org/10.1016/j.ebiom.2019.05.007
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author Johnson, Kipp W.
Glicksberg, Benjamin S.
Shameer, Khader
Vengrenyuk, Yuliya
Krittanawong, Chayakrit
Russak, Adam J.
Sharma, Samin K.
Narula, Jagat N.
Dudley, Joel T.
Kini, Annapoorna S.
author_facet Johnson, Kipp W.
Glicksberg, Benjamin S.
Shameer, Khader
Vengrenyuk, Yuliya
Krittanawong, Chayakrit
Russak, Adam J.
Sharma, Samin K.
Narula, Jagat N.
Dudley, Joel T.
Kini, Annapoorna S.
author_sort Johnson, Kipp W.
collection PubMed
description BACKGROUND: Fibrous cap thickness (FCT), best measured by intravascular optical coherence tomography (OCT), is the most important determinant of plaque rupture in the coronary arteries. Statin treatment increases FCT and thus reduces the likelihood of acute coronary events. However, substantial statin-related FCT increase occurs in only a subset of patients. Currently, there are no methods to predict which patients will benefit. We use transcriptomic data from a clinical trial of rosuvastatin to predict if a patient's FCT will increase in response to statin therapy. METHODS: FCT was measured using OCT in 69 patients at (1) baseline and (2) after 8–10 weeks of 40  mg rosuvastatin. Peripheral blood mononuclear cells were assayed via microarray. We constructed machine learning models with baseline gene expression data to predict change in FCT. Finally, we ascertained the biological functions of the most predictive transcriptomic markers. FINDINGS: Machine learning models were able to predict FCT responders using baseline gene expression with high fidelity (Classification AUC = 0.969 and 0.972). The first model (elastic net) using 73 genes had an accuracy of 92.8%, sensitivity of 94.1%, and specificity of 91.4%. The second model (KTSP) using 18 genes has an accuracy of 95.7%, sensitivity of 94.3%, and specificity of 97.1%. We found 58 enriched gene ontology terms, including many involved with immune cell function and cholesterol biometabolism. INTERPRETATION: In this pilot study, transcriptomic models could predict if FCT increased following 8–10 weeks of rosuvastatin. These findings may have significance for therapy selection and could supplement invasive imaging modalities.
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spelling pubmed-66070842019-07-15 A transcriptomic model to predict increase in fibrous cap thickness in response to high-dose statin treatment: Validation by serial intracoronary OCT imaging Johnson, Kipp W. Glicksberg, Benjamin S. Shameer, Khader Vengrenyuk, Yuliya Krittanawong, Chayakrit Russak, Adam J. Sharma, Samin K. Narula, Jagat N. Dudley, Joel T. Kini, Annapoorna S. EBioMedicine Research paper BACKGROUND: Fibrous cap thickness (FCT), best measured by intravascular optical coherence tomography (OCT), is the most important determinant of plaque rupture in the coronary arteries. Statin treatment increases FCT and thus reduces the likelihood of acute coronary events. However, substantial statin-related FCT increase occurs in only a subset of patients. Currently, there are no methods to predict which patients will benefit. We use transcriptomic data from a clinical trial of rosuvastatin to predict if a patient's FCT will increase in response to statin therapy. METHODS: FCT was measured using OCT in 69 patients at (1) baseline and (2) after 8–10 weeks of 40  mg rosuvastatin. Peripheral blood mononuclear cells were assayed via microarray. We constructed machine learning models with baseline gene expression data to predict change in FCT. Finally, we ascertained the biological functions of the most predictive transcriptomic markers. FINDINGS: Machine learning models were able to predict FCT responders using baseline gene expression with high fidelity (Classification AUC = 0.969 and 0.972). The first model (elastic net) using 73 genes had an accuracy of 92.8%, sensitivity of 94.1%, and specificity of 91.4%. The second model (KTSP) using 18 genes has an accuracy of 95.7%, sensitivity of 94.3%, and specificity of 97.1%. We found 58 enriched gene ontology terms, including many involved with immune cell function and cholesterol biometabolism. INTERPRETATION: In this pilot study, transcriptomic models could predict if FCT increased following 8–10 weeks of rosuvastatin. These findings may have significance for therapy selection and could supplement invasive imaging modalities. Elsevier 2019-05-22 /pmc/articles/PMC6607084/ /pubmed/31126891 http://dx.doi.org/10.1016/j.ebiom.2019.05.007 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research paper
Johnson, Kipp W.
Glicksberg, Benjamin S.
Shameer, Khader
Vengrenyuk, Yuliya
Krittanawong, Chayakrit
Russak, Adam J.
Sharma, Samin K.
Narula, Jagat N.
Dudley, Joel T.
Kini, Annapoorna S.
A transcriptomic model to predict increase in fibrous cap thickness in response to high-dose statin treatment: Validation by serial intracoronary OCT imaging
title A transcriptomic model to predict increase in fibrous cap thickness in response to high-dose statin treatment: Validation by serial intracoronary OCT imaging
title_full A transcriptomic model to predict increase in fibrous cap thickness in response to high-dose statin treatment: Validation by serial intracoronary OCT imaging
title_fullStr A transcriptomic model to predict increase in fibrous cap thickness in response to high-dose statin treatment: Validation by serial intracoronary OCT imaging
title_full_unstemmed A transcriptomic model to predict increase in fibrous cap thickness in response to high-dose statin treatment: Validation by serial intracoronary OCT imaging
title_short A transcriptomic model to predict increase in fibrous cap thickness in response to high-dose statin treatment: Validation by serial intracoronary OCT imaging
title_sort transcriptomic model to predict increase in fibrous cap thickness in response to high-dose statin treatment: validation by serial intracoronary oct imaging
topic Research paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607084/
https://www.ncbi.nlm.nih.gov/pubmed/31126891
http://dx.doi.org/10.1016/j.ebiom.2019.05.007
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