{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:38:09Z","timestamp":1789537089661,"version":"build-2803163510"},"reference-count":54,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T00:00:00Z","timestamp":1735171200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Adults with congenital heart disease (ACHD) can face a lifelong risk of premature cardiovascular events. Endothelial dysfunction and arterial stiffness may be some of the key mechanisms involved. Early identification of endothelial damage in ACHD could be crucial to mitigate the adverse events. This systematic review and meta\u2010analysis aims to investigate micro\u2010 and macroangiopathy in ACHD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We systematically searched four major electronic databases (PubMed, CENTRAL, Scopus and Web of Science), <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link> and grey literature according to PRISMA guidelines. We included studies evaluating endothelial function with any semi\u2010 or non\u2010invasive method in ACHD and healthy controls. Studies exploring arterial stiffness indices and carotid intima\u2010media thickness were also investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 31 studies (1118 ACHD, 794 controls) were included in this systematic review. Brachial artery endothelium\u2010dependent (assessed via flow\u2010mediated dilatation, FMD) and \u2010independent vasodilation (assessed via nitroglycerine\u2010mediated dilatation, NMD) were attenuated in ACHD versus controls (mean difference [MD] \u22122.5, 95% confidence intervals [CI] \u22123.7; \u22121.3 and MD \u22123.9, 95% CI \u22126.8; \u22121.0, respectively). ACHD also demonstrated impaired microvascular function, evaluated via peripheral arterial tonometry (PAT), with significantly lower reactive hyperemia index and PAT ratio compared to controls (MD \u2212.26, 95% CI \u2212.48; \u2212.04 and MD \u2212.4, 95% CI \u2212.5; \u2212.4, respectively). Regarding arterial stiffness, pooled analysis revealed non\u2010significant differences in pulse wave velocity between the study groups (standardized MD .2, 95% CI \u2212.2; .6). However, the augmentation index was significantly higher in ACHD (standardized MD 1.6, 95% CI .8; 2.4).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>ACHD exhibit impaired macro\u2010 and microvascular function and elevated arterial stiffness, factors that may be responsible for the increased adverse cardiovascular events in this population.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.14376","type":"journal-article","created":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T10:05:31Z","timestamp":1735207531000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Endothelial dysfunction in adults with congenital heart disease: A systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0182-8259","authenticated-orcid":false,"given":"Amalia","family":"Baroutidou","sequence":"first","affiliation":[{"name":"First 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