{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T15:52:51Z","timestamp":1781970771722,"version":"3.54.5"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":169,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002429","name":"Amgen Inc.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002429","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011949","name":"Abbott Vascular Inc.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011949","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Calcified nodules (CNs) contribute to 3\u20135% of acute coronary syndromes (ACS). Identifying peri-calcific lipid-rich areas is challenging with conventional imaging but feasible using near-infrared spectroscopy (NIRS). This YELLOW III substudy investigated the impact of maximal lipid-lowering on CN morphology and lipid content over 26 weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Patients with stable CAD and lipid-rich, non-obstructive plaques (lipid arc &amp;gt;90\u00b0, FCT &amp;lt;120\u2005\u00b5m on OCT) received Evolocumab (140\u2005mg biweekly) plus maximally tolerated statins. Lesions were evaluated at baseline and 26 weeks using combined NIRS\u2013IVUS and OCT. Exploratory endpoints were the maximum 4\u2005mm lipid core burden index (LCBI) in segments containing CNs (maxLCBI4mm-CN) and morphological changes in CN. Linear mixed-effects models were used to evaluate temporal changes and group interactions. Peripheral blood mononuclear cell (PBMC) transcriptomics were analysed. Among 110 patients, 43 (39.1%) had CNs. A total of 73 paired CNs were analysed for morphology, of which 65 CNs were \u22654\u2005mm. CNs with lipid signal (CNLS) demonstrated a significant reduction in maxLCBI4mm-CN from 176.8 to 113.3 (\u03b2 = \u221263.51 \u00b1 17.63; P &amp;lt; 0.001), whereas no change was observed in dense CNs (P = 0.317). Morphological parameters remained largely unchanged in both groups. A modest increase in the surrounding calcium arc was observed in CNLS (P = 0.018), while depth showed a differential change between groups (pinteraction = 0.012). Transcriptomic analysis demonstrated baseline enrichment of neutrophil degranulation pathways in CN patients, which diminished at follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Intensive lipid-lowering significantly reduces peri-calcific lipid burden without measurable short-term changes in CN morphology. The clinical implications of LCBI reduction in CNs warrant further investigation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>Calcified nodules (CNs) are high-risk coronary features responsible for a significant portion of acute coronary syndromes, yet their response to intensive medical therapy remains poorly understood. This YELLOW III substudy utilized multi-modality intravascular imaging (NIRS\u2013IVUS and OCT) to investigate the impact of 26 weeks of Evolocumab and maximally tolerated statins on CN morphology. In 43 patients with identified CNs, intensive lipid-lowering therapy led to a significant reduction in the maxLCBI4mmCN. Morphological parameters of CNs remained largely unchanged except for a modest increase in the surrounding calcium arc. Simultaneously, PBMC transcriptomic analysis revealed a marked attenuation of the neutrophil degranulation pathway, which was highly enriched at baseline. While the therapy successfully reduced the systemic inflammatory profile, a transition towards coagulation-related pathways at follow-up suggests a shift in the residual risk profile. These findings provide a novel mechanistic basis for using PCSK9 inhibitors to stabilize calcium-related high-risk plaques. Collectively, the data demonstrate that aggressive lipid-lowering not only modifies plaque architecture but also shifts the systemic biological environment from an inflammatory to a more stable one.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ehjimp\/qyag092","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T11:39:43Z","timestamp":1781782783000},"source":"Crossref","is-referenced-by-count":0,"title":["Intra-coronary imaging and transcriptomics of calcified nodules before and after intensive lipid-lowering therapy: a YELLOW III substudy"],"prefix":"10.1093","volume":"4","author":[{"given":"Pruthvi C","family":"Revaiah","sequence":"first","affiliation":[{"name":"Division of Interventional Cardiology, Ichan School of Medicine at Mount Sinai and Fuster Heart Hospital at Mount Sinai , One Gustave L. Levy Place, Box 1030, New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuliya","family":"Vengrenyuk","sequence":"additional","affiliation":[{"name":"Division of Interventional Cardiology, Ichan School of Medicine at Mount Sinai and Fuster Heart Hospital at Mount Sinai , One Gustave L. Levy Place, Box 1030, New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JiaJia","family":"Liu","sequence":"additional","affiliation":[{"name":"University of Texas Health Sciences Center , Houston, TX ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Yasumura","sequence":"additional","affiliation":[{"name":"Division of Interventional Cardiology, Ichan School of Medicine at Mount Sinai and Fuster Heart Hospital at Mount Sinai , One Gustave L. Levy Place, Box 1030, New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vemuri Krishna","family":"Santosh","sequence":"additional","affiliation":[{"name":"Division of Interventional Cardiology, Ichan School of Medicine at Mount Sinai and Fuster Heart Hospital at Mount Sinai , One Gustave L. Levy Place, Box 1030, New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Karki","sequence":"additional","affiliation":[{"name":"Division of Interventional Cardiology, Ichan School of Medicine at Mount Sinai and Fuster Heart Hospital at Mount Sinai , One Gustave L. Levy Place, Box 1030, New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishani","family":"Bansal","sequence":"additional","affiliation":[{"name":"Division of Interventional Cardiology, Ichan School of Medicine at Mount Sinai and Fuster Heart Hospital at Mount Sinai , One Gustave L. Levy Place, Box 1030, New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5659-5873","authenticated-orcid":false,"given":"Amit","family":"Hooda","sequence":"additional","affiliation":[{"name":"Division of Interventional Cardiology, Ichan School of Medicine at Mount Sinai and Fuster Heart Hospital at Mount Sinai , One Gustave L. Levy Place, Box 1030, New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph K","family":"Sweeny","sequence":"additional","affiliation":[{"name":"Division of Interventional Cardiology, Ichan School of Medicine at Mount Sinai and Fuster Heart Hospital at Mount Sinai , One Gustave L. Levy Place, Box 1030, New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahil","family":"Khera","sequence":"additional","affiliation":[{"name":"Division of Interventional Cardiology, Ichan School of Medicine at Mount Sinai and Fuster Heart Hospital at Mount Sinai , One Gustave L. Levy Place, Box 1030, New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal","family":"Kapur","sequence":"additional","affiliation":[{"name":"Division of Interventional Cardiology, Ichan School of Medicine at Mount Sinai and Fuster Heart Hospital at Mount Sinai , One Gustave L. Levy Place, Box 1030, New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakash","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Division of Interventional Cardiology, Ichan School of Medicine at Mount Sinai and Fuster Heart Hospital at Mount Sinai , One Gustave L. Levy Place, Box 1030, New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro R","family":"Moreno","sequence":"additional","affiliation":[{"name":"Division of Interventional Cardiology, Ichan School of Medicine at Mount Sinai and Fuster Heart Hospital at Mount Sinai , One Gustave L. Levy Place, Box 1030, New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5546-262X","authenticated-orcid":false,"given":"Roxana","family":"Mehran","sequence":"additional","affiliation":[{"name":"Division of Interventional Cardiology, Ichan School of Medicine at Mount Sinai and Fuster Heart Hospital at Mount Sinai , One Gustave L. Levy Place, Box 1030, New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobo","family":"Zhou","sequence":"additional","affiliation":[{"name":"University of Texas Health Sciences Center , Houston, TX ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0280-3996","authenticated-orcid":false,"given":"Jagat","family":"Narula","sequence":"additional","affiliation":[{"name":"University of Texas Health Sciences Center , Houston, TX ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samin K","family":"Sharma","sequence":"additional","affiliation":[{"name":"Division of Interventional Cardiology, Ichan School of Medicine at Mount Sinai and Fuster Heart Hospital at Mount Sinai , One Gustave L. 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