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Vascular Effects of ACE (Angiotensin-Converting Enzyme) Inhibitors and Statins in Adolescents With Type 1 Diabetes

Chiesa, ST; Marcovecchio, ML; Benitez-Aguirre, P; Cameron, FJ; Craig, ME; Couper, JJ; Davis, EA; ... Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDI, .; + view all (2020) Vascular Effects of ACE (Angiotensin-Converting Enzyme) Inhibitors and Statins in Adolescents With Type 1 Diabetes. Hypertension , 76 (6) pp. 1734-1743. 10.1161/HYPERTENSIONAHA.120.15721. Green open access

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Abstract

An increased albumin-creatinine ratio within the normal range can identify adolescents at higher risk of developing adverse cardio-renal outcomes as they progress into adulthood. Utilizing a parallel randomized controlled trial and observational cohort study, we characterized the progression of vascular phenotypes throughout this important period and investigated the effect of ACE (angiotensin-converting enzyme) inhibitors and statins in high-risk adolescents. Endothelial function (flow-mediated dilation and reactive hyperemia index) and arterial stiffness (carotid-femoral pulse wave velocity) were assessed in 158 high-risk participants recruited to a randomized, double-blind placebo-controlled 2×2 factorial trial (randomized, placebo-controlled trial) of ACE inhibitors and/or statins in adolescents with type 1 diabetes (AdDIT [Adolescent Type 1 Diabetes cardio-renal Intervention Trial]). Identical measures were also assessed in 215 lower-risk individuals recruited to a parallel observational study. In the randomized, placebo-controlled trial, high-risk patients randomized to ACE inhibitors had improved flow-mediated dilation after 2 to 4 years of follow-up (mean [95% CI]: 6.6% [6.0-7.2] versus 5.3% [4.7-5.9]; P=0.005), whereas no effect was observed following statin use (6.2% [5.5-6.8] versus 5.8% [5.1-6.4]; P=0.358). In the observational study, patients classed as high-risk based on albumin-creatinine ratio showed evidence of endothelial dysfunction at the end of follow-up (flow-mediated dilation=4.8% [3.8-5.9] versus 6.3% [5.8-6.7] for high-risk versus low-risk groups; P=0.015). Neither reactive hyperemia index nor pulse wave velocity were affected by either treatment (P>0.05 for both), but both were found to increase over the duration of follow-up (0.07 [0.03-0.12]; P=0.001 and 0.5 m/s [0.4-0.6]; P<0.001 for reactive hyperemia index and pulse wave velocity, respectively). ACE inhibitors improve endothelial function in high-risk adolescents as they transition through puberty. The longer-term protective effects of this intervention at this early age remain to be determined. Registration- URL: https://www.clinicaltrials.gov; Unique identifier NCT01581476.

Type: Article
Title: Vascular Effects of ACE (Angiotensin-Converting Enzyme) Inhibitors and Statins in Adolescents With Type 1 Diabetes
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1161/HYPERTENSIONAHA.120.15721
Publisher version: https://doi.org/10.1161/HYPERTENSIONAHA.120.15721
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: adolescent, arteries, diabetes, type 1, puberty, vascular diseases
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Clinical Science
URI: https://discovery.ucl.ac.uk/id/eprint/10115303
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