{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T04:10:52Z","timestamp":1778299852225,"version":"3.51.4"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:p>\n                    Carfilzomib is highly effective in the treatment of multiple myeloma, but it has been associated with cardiovascular adverse events that impact patient outcomes. Our prior global metabolomic analyses indicated an association between hydrophilic bile acids and carfilzomib\u2010cardiotoxicity risk, although a causal relationship remained to be determined. Here, our objective was to validate the previously identified bile acids in an independent cohort and investigate whether these hydrophilic bile acids play a causal role in carfilzomib\u2010cardiotoxicity using Mendelian randomization. Using targeted metabolomics, we validated the association between glycoursodeoxycholic acid and carfilzomib\u2010cardiotoxicity in an independent cohort (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200961). We then performed two\u2010sample Mendelian randomization analyses, using metabolome\u2010wide association study results to provide the genetic instruments for bile acid levels as exposure and genome\u2010wide association study summary statistics from the UK Biobank (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009484,598) as the outcome data for cardiovascular adverse events. Causal inference was assessed with the inverse\u2010variance weighted method, followed by multiple sensitivity analyses. Higher glycoursodeoxycholic acid concentration (odds ratio\u2009=\u20090.34,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.032) was associated with lower cardiotoxicity risk after adjusting for hypertension and high levels of brain natriuretic peptides. Mendelian randomization analysis demonstrated a robust causal effect of glycoursodeoxycholic acid on cardiotoxicity risk (\u03b2\u2009=\u2009\u22120.00065,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20096.2\u2009\u00d7\u200910\n                    <jats:sup>\u22125<\/jats:sup>\n                    ). Gene enrichment analysis indicated pathways involving potassium channel regulation and thromboxane signaling to be implicated. This integrative metabolomic and genetic investigation supports a potential protective role of glycoursodeoxycholic acid in cardiovascular vulnerability and motivates larger, carfilzomib\u2010specific studies to evaluate its utility for risk stratification.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70222","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T06:22:36Z","timestamp":1770013356000},"page":"1494-1502","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Causal Effects of Hydrophilic Bile Acids on Carfilzomib\u2010Related Cardiovascular Events in Multiple Myeloma: A Mendelian Randomization Study"],"prefix":"10.1002","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4811-2322","authenticated-orcid":false,"given":"Samia","family":"Shabnaz","sequence":"first","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research, College of Pharmacy University of Florida  Gainesville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0281-3796","authenticated-orcid":false,"given":"Eric","family":"Farber\u2010Eger","sequence":"additional","affiliation":[{"name":"Vanderbilt Institute for Clinical and Translational Research Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Department of Medicine, Division of Cardiovascular Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6767-1093","authenticated-orcid":false,"given":"Marwa","family":"Tantawy","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research, College of Pharmacy University of Florida  Gainesville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neyousha","family":"Shahisavandi","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research, College of Pharmacy University of Florida  Gainesville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1623-009X","authenticated-orcid":false,"given":"Timothy J.","family":"Garrett","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, College of Medicine University of Florida  Gainesville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5568-4441","authenticated-orcid":false,"given":"Samuel M.","family":"Rubinstein","sequence":"additional","affiliation":[{"name":"Division of Hematology University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3719-2523","authenticated-orcid":false,"given":"Michael G.","family":"Fradley","sequence":"additional","affiliation":[{"name":"Cardio\u2010Oncology Center of Excellence, Division of Cardiology, Department of Medicine Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4713-7245","authenticated-orcid":false,"given":"Mohammed E.","family":"Alomar","sequence":"additional","affiliation":[{"name":"Cardio\u2010Oncology Program H. Lee Moffitt Cancer Center &amp; Research Institute  Tampa Florida USA"},{"name":"Division of Cardiovascular Sciences, Morsani College of Medicine University of South Florida  Tampa Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5421-3425","authenticated-orcid":false,"given":"Danny","family":"DeAvila","sequence":"additional","affiliation":[{"name":"Department of Malignant Hematology H. Lee Moffitt Cancer Center &amp; Research Institute  Tampa Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4178-8888","authenticated-orcid":false,"given":"Kenneth H","family":"Shain","sequence":"additional","affiliation":[{"name":"Department of Malignant Hematology H. Lee Moffitt Cancer Center &amp; Research Institute  Tampa Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2011-1475","authenticated-orcid":false,"given":"R. Frank","family":"Cornell","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9458-0154","authenticated-orcid":false,"given":"Daniel","family":"Lenihan","sequence":"additional","affiliation":[{"name":"Cape Cardiology Group Saint Francis Medical Center  Cape Girardeau Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7943-966X","authenticated-orcid":false,"given":"Qing","family":"Lu","sequence":"additional","affiliation":[{"name":"College of Public Health and Health Professions &amp; College of Medicine University of Florida  Gainesville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4141-1520","authenticated-orcid":false,"given":"Quinn S","family":"Wells","sequence":"additional","affiliation":[{"name":"Vanderbilt Institute for Clinical and Translational Research Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Department of Medicine, Division of Cardiovascular Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4538-4733","authenticated-orcid":false,"given":"Rachid C.","family":"Baz","sequence":"additional","affiliation":[{"name":"Department of Malignant Hematology H. 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