{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T03:17:28Z","timestamp":1789269448471,"version":"build-2803163510"},"reference-count":15,"publisher":"American Medical Association (AMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2024,6,1]]},"abstract":"<jats:sec><jats:title>Importance<\/jats:title><jats:p>High-dose trivalent compared with standard-dose quadrivalent influenza vaccine did not significantly reduce all-cause mortality or cardiopulmonary hospitalizations in patients with high-risk cardiovascular disease in the INVESTED trial. Whether humoral immune response to influenza vaccine is associated with clinical outcomes is unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To examine the antibody response to high-dose trivalent compared with standard-dose quadrivalent inactivated influenza vaccine and its associations with clinical outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This secondary analysis is a prespecified analysis of the immune response substudy of the randomized, double-blind, active-controlled INVESTED trial, which was conducted at 157 sites in the United States and Canada over 3 influenza seasons between September 2016 and January 2019. Antibody titers were determined by hemagglutination inhibition assays at randomization and 4 weeks during the 2017-2018 and 2018-2019 seasons. Eligibility criteria included recent acute myocardial infarction or heart failure hospitalization and at least 1 additional risk factor. Data were analyzed from February 2023 to June 2023.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Mean antibody titer change, seroprotection (antibody titer level \u22651:40) and seroconversion (\u22654-fold increase in titer) at 4 weeks, and the association between seroconversion status and the risk for adverse clinical outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interventions<\/jats:title><jats:p>High-dose trivalent or standard-dose quadrivalent inactivated influenza vaccine, with revaccination up to 3 seasons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Antibody data were available for 658 of 5260 randomized participants (12.5%; mean [SD] age, 66.2 [11.4] years; 507 male [77.1%], 151 female [22.9%]; 348 with heart failure [52.9%]). High-dose vaccine was associated with an increased magnitude in antibody titers for A\/H1N1, A\/H3N2, and B-type antigens compared with standard dose. More than 92% of all participants achieved seroprotection for each of the contained antigens, while seroconversion rates were higher in participants who received high-dose vaccine. Seroconversion for any antigen was not associated with the risk for cardiopulmonary hospitalizations or all-cause mortality (hazard ratio, 1.09; 95% CI, 0.79-1.53; <jats:italic>P<\/jats:italic>\u2009=\u2009.59), irrespective of randomized treatment (<jats:italic>P<\/jats:italic>\u2009=\u2009.38 for interaction).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Relevance<\/jats:title><jats:p>High-dose vaccine elicited a more robust humoral response in patients with heart failure or prior myocardial infarction enrolled in the INVESTED trial, with no association between seroconversion status and the risk for cardiopulmonary hospitalizations or all-cause mortality. Vaccination to prevent influenza remains critical in high-risk populations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT02787044\">NCT02787044<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamacardio.2024.0468","type":"journal-article","created":{"date-parts":[[2024,4,7]],"date-time":"2024-04-07T13:30:30Z","timestamp":1712496630000},"page":"574","source":"Crossref","is-referenced-by-count":16,"title":["Influenza Vaccine Immune Response in Patients With High-Risk Cardiovascular Disease"],"prefix":"10.1001","volume":"9","author":[{"given":"Alexander","family":"Peikert","sequence":"first","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"},{"name":"University Heart Center Graz, Department of Cardiology, Medical University of Graz, Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Claggett","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob A.","family":"Udell","sequence":"additional","affiliation":[{"name":"Peter Munk Cardiac Centre, University Health Network and Women\u2019s College Hospital, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Joseph","sequence":"additional","affiliation":[{"name":"Department of Medicine, VA Providence Healthcare System and Brown University, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila M.","family":"Hegde","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KyungMann","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Medical Informatics, University of Wisconsin\u2013Madison, Madison"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Medical Informatics, University of Wisconsin\u2013Madison, Madison"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Medical Informatics, University of Wisconsin\u2013Madison, Madison"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas C.","family":"Havighurst","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Medical Informatics, University of Wisconsin\u2013Madison, Madison"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Farkouh","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Health System, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak L.","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Mount Sinai Heart, Icahn School of Medicine at Mount Sinai Health System, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew C.","family":"Tattersall","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin\u2013Madison, Madison"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawton S.","family":"Cooper","sequence":"additional","affiliation":[{"name":"National Heart, Lung, and Blood Institute, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott 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