Angiotensin Receptor Blockers Are Associated with Reduced Fibrosis and Interleukin-6 Expression in Calcific Aortic Valve Disease

Abstract

Background: Calcific aortic valve disease (CAVD) is a chronic disorder characterized by the mineralization of the aortic valve and involving fibrosis. Objectives: In this work we sought to determine if the fibrotic component of the remodeling process of CAVD was related to the use of angiotensin-converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARBs). Methods: In 477 patients with CAVD, the aortic valve was examined by histology. A semiquantitative score of fibrosis was generated and associations with clinical/cardiometabolic variables examined. In a subset of 103 patients the aortic valve was available to study the infiltration by inflammatory cells and expression of interleukin-6 (IL-6) by quantitative real-time PCR. Results: The fibrosis score of the aortic valve was independently related to the hemodynamic severity of CAVD measured by echocardiography. The fibrotic score of the aortic valve was also related to the expression of IL-6. The use of ARBs but not of ACEi was associated with a lower fibrosis score of the aortic valve even after correction for covariates. In addition, patients under ARBs had lower aortic valve inflammation and expression of IL-6. Conclusions: These findings suggest that ARBs may alter the fibrotic process of the aortic valve in CAVD, possibly by lowering tissue inflammation.

Fibrotic Aortic Valve Stenosis in Hypercholesterolemic/Hypertensive Mice

“…Côté et al found at least 25-fold variability in valve collagen among patients with severe aortic stenosis, and also found that about 20% of explanted valves demonstrated minimal valve collagen. 23 This new finding, taken together with studies in CAVS mice, demonstrates that mechanisms leading to severe aortic stenosis can be diverse in mice, as is the case in humans.…”

Effect of age and aortic valve anatomy on calcification and haemodynamic severity of aortic stenosis

“…Hence, it is likely that compared with TAV, fibrosis is accentuated in BAV and alter valve haemodynamics significantly. In this regard, in 477 surgically explanted stenotic aortic valves, Côté et al 31 identified that BAV anatomy was independently associated with higher fibrosis score. In a small-size study, Ferda et al found a significant correlation between AVC and haemodynamic severity of AS but they did not find significant differences in AVC between BAV and TAV patients.…”

Innate and Adaptive Immunity in Calcific Aortic Valve Disease

“…Moreover, immunohistological analyses revealed in stenotic aortic valves that angiotensin II was present in the vicinity of mineralized nodules and colocalized with TNF- α and IL-6 [ 55 ]. Patients under a therapy with angiotensin receptor blockers (ARBs) have a lower level of transcript encoding for IL-6 in their aortic valves [ 56 ]. Moreover, a retrospective study showed that ARBs are associated with a slower progression rate of aortic stenosis [ 57 ].…”