Effectiveness of ACE inhibition in patients with Marfan's syndrome on β-blockade

Ahimastos AA et al. (2007) Effect of perindopril on large artery stiffness and aortic root diameter in patients with Marfan syndrome: a randomized controlled trial. JAMA 298: 1539–1547

The standard treatment for the connective tissue disorder Marfan's syndrome (MFS) is β-blockade, aimed at reducing aortic wall stress. Angiotensin II type 1 and 2 receptors (AT₁ and AT₂) are implicated in the pathogenesis of MFS. Researchers have tested the efficacy of the angiotensin-converting-enzyme (ACE) inhibitor perindopril at reducing aortic stiffening and dilatation—two of the most serious complications of MFS—and found it to have additive benefit in patients receiving standard β-blocker therapy.

Over a period of 24 weeks, 10 patients with MFS received 8 mg perindopril daily, and 7 patients received placebo. Patients on perindopril had significantly reduced arterial stiffness (measured as increased systemic arterial compliance and reduced central and peripheral pulse wave velocities). Systolic and end-diastolic aortic diameters were significantly lower with the drug than with placebo. Perindopril reduced the mean arterial pressure, but the changes in stiffness and aortic diameters were still significant when this factor was included as a covariate in multivariate analyses.

The authors also studied the relationship between the aortic changes and plasma levels of matrix metalloproteinase (MMP) and transforming growth factor-β (TGF-β)—two factors that are partly responsible for the aortic degeneration in MFS. MMP-2, MMP-3 and TGF-β were reduced significantly with perindopril compared with placebo. The reductions in aortic stiffness and aortic root diameter with perindopril could, therefore, result from reduced AT₁ and AT₂ receptor signaling; reduced AT₁ leads to reduction in MMP-2, MMP-3 and TGF-β signaling, while reduced AT₂ could protect from cystic medial degeneration.