Endothelial dysfunction in adults with congenital heart disease: A systematic review and meta‐analysis

Abstract Background 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‐analysis aims to investigate micro‐ and macroangiopathy in ACHD. Methods We systematically searched four major electronic databases (PubMed, CENTRAL, Scopus and Web of Science), ClinicalTrials.gov and grey literature according to PRISMA guidelines. We included studies evaluating endothelial function with any semi‐ or non‐invasive method in ACHD and healthy controls. Studies exploring arterial stiffness indices and carotid intima‐media thickness were also investigated. Results In total, 31 studies (1118 ACHD, 794 controls) were included in this systematic review. Brachial artery endothelium‐dependent (assessed via flow‐mediated dilatation, FMD) and ‐independent vasodilation (assessed via nitroglycerine‐mediated dilatation, NMD) were attenuated in ACHD versus controls (mean difference [MD] −2.5, 95% confidence intervals [CI] −3.7; −1.3 and MD −3.9, 95% CI −6.8; −1.0, 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 −.26, 95% CI −.48; −.04 and MD −.4, 95% CI −.5; −.4, respectively). Regarding arterial stiffness, pooled analysis revealed non‐significant differences in pulse wave velocity between the study groups (standardized MD .2, 95% CI −.2; .6). However, the augmentation index was significantly higher in ACHD (standardized MD 1.6, 95% CI .8; 2.4). Conclusions ACHD exhibit impaired macro‐ and microvascular function and elevated arterial stiffness, factors that may be responsible for the increased adverse cardiovascular events in this population.