{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T10:50:08Z","timestamp":1768474208602,"version":"3.49.0"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["HL134738"],"award-info":[{"award-number":["HL134738"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["HL169201"],"award-info":[{"award-number":["HL169201"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["HL168630"],"award-info":[{"award-number":["HL168630"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017618","name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["T32 DK112751"],"award-info":[{"award-number":["T32 DK112751"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015728","name":"Clinical Science Research and Development","doi-asserted-by":"publisher","award":["I01BX007087-06"],"award-info":[{"award-number":["I01BX007087-06"]}],"id":[{"id":"10.13039\/100015728","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UM1TR004403"],"award-info":[{"award-number":["UM1TR004403"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Prediabetes is a growing public health concern that increases the risk of major adverse cardiovascular events (MACE). Vascular dysfunction worsens with hyperglycemia and is associated with MACE in several high-risk populations. However, it is unknown whether vascular dysfunction contributes to MACE in prediabetes. We hypothesized that vascular dysfunction is associated with elevated risk of MACE in prediabetes.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We conducted an observational study of 5742 adults (age 54.9\u2009\u00b1\u200911.5 years, 54% female) in the Framingham Offspring and Generation III cohorts. Prediabetes was defined using the ADA criteria. Endothelial function was determined via brachial artery flow-mediated dilation (BA-FMD), aortic stiffness via carotid-femoral pulse wave velocity (cfPWV), and coronary artery calcium (CAC) score via computed tomography. Stepwise selection models evaluated BA-FMD, cfPWV, and CAC score by prediabetes status. The association of BA-FMD, cfPWV, and CAC score with time to MACE was assessed via Cox proportional hazards regression.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Individuals with prediabetes had lower BA-FMD and higher cfPWV and CAC score (p\u2009&lt;\u20090.001). In stepwise selection models, age, sex, smoking history, systolic blood pressure, triglycerides, high-density lipoprotein, low-density lipoprotein, and fasting glucose related to vascular dysfunction. After adjusting for traditional cardiovascular risk factors, BA-FMD (HR [95% CI], 0.93 [0.90,0.97]; p\u2009&lt;\u20090.001) and CAC score &gt;100 [HR [95% CI], 4.15 [2.24, 7.70]; p\u2009&lt;\u20090.001)] were associated with MACE in prediabetes while cfPWV was not (p\u2009=\u20090.051).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Vascular dysfunction measured by BA-FMD independently associates with MACE in prediabetes. Therapies that target vascular dysfunction may reduce CVD risk in prediabetes.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0324945","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T17:38:57Z","timestamp":1749145137000},"page":"e0324945","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Vascular dysfunction is associated with major adverse cardiovascular events in prediabetes: A cohort 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