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

Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) Study Group, Scott T. Chiesa, M. Loredana Marcovecchio, Paul Benitez-Aguirre, Fergus J. Cameron, Maria E. Craig, Jennifer J. Couper, Elizabeth A. Davis, R. Neil Dalton, Denis Daneman, Kim C. Donaghue, Timothy W. Jones, Farid H. Mahmud, Sally M. Marshall, H. Andrew W. Neil, David B. Dunger, John E. Deanfield

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)1734-1743
Number of pages10
JournalHypertension
Volume76
Issue number6
DOIs
Publication statusPublished - 2020

Fingerprint Dive into the research topics of 'Vascular Effects of ACE (Angiotensin-Converting Enzyme) Inhibitors and Statins in Adolescents with Type 1 Diabetes'. Together they form a unique fingerprint.

Cite this