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CLINICAL RESEARCH: CONGENITAL HEART DISEASE

Effects of Ramipril on Endothelial Function and the Expression of Proinflammatory Cytokines and Adhesion Molecules in Young Normotensive Subjects With Successfully Repaired Coarctation of Aorta

A Randomized Cross-Over Study

First Cardiology Department, Athens University Medical School, Hippokration Hospital, Athens, Greece.

Manuscript received August 6, 2007; revised manuscript received October 16, 2007, accepted October 22, 2007.

^_* Reprint requests and correspondence: Prof. Dimitris Tousoulis, First Cardiology Department, Athens University Medical School, Hippokration Hospital, Vasilissis Sofias 114, Postal Code 153 44, Athens, Greece. (Email: tousouli{at}med.uoa.gr).

Objectives: The purpose of this study was to evaluate the effect of ramipril on endothelial function and inflammatory process in a group of normotensive subjects with successfully repaired coarctation of the aorta (SCR).

Background: Subjects with SCR experience higher long-term cardiovascular risk as a result of the relapse of arterial hypertension or owing to nonreversible structural changes in the pre-coarctation arterial tree. These subjects experience endothelial dysfunction in the right forearm and appear to have elevated levels of proatherogenic inflammatory markers, even in the absence of arterial hypertension.

Methods: Twenty young individuals age 27.3 ± 2.4 years old with SCR 13.9 ± 2.2 years previously, received ramipril 5 mg/day for 4 weeks in a randomized, cross-over, controlled trial. Endothelial function was evaluated in the right forearm by gauge-strain plethysmography, and serum levels of interleukin (IL)-1b, IL-6, soluble CD40 ligand (sCD40L), and soluble vascular cell adhesion molecule (sVCAM)-1 were determined by enzyme-linked immunosorbent assay.

Results: Ramipril improved endothelial function (p < 0.001) and decreased the expression of proinflammatory cytokine IL-6 (p < 0.05) and sCD40L (p < 0.01). Furthermore, ramipril decreased serum levels of sVCAM-1 (p < 0.01) but failed to affect serum levels of C-reactive protein. These effects were independent of blood pressure lowering.

Conclusions: Ramipril reversed the impaired endothelial function and decreased the expression of proinflammatory cytokine IL-6, sCD40L, and adhesion molecules in normotensive subjects with SCR. These findings imply that ramipril treatment may have antiatherogenic effects in subjects with SCR, even in the absence of arterial hypertension.

Abbreviations and Acronyms   ACEI = angiotensin-converting enzyme inhibitor(s)   FBF = forearm blood blow   IL = interleukin   NO = nitric oxide   RH = reactive hyperemia   sCD40L = soluble CD40 ligand   SCR = successful repair of coarctation of the aorta   sVCAM = soluble vascular cell adhesion molecule