Abstract 10871: Serum Dickkopf-1 Signaling and Calcium Deposition in the Aortic Valve Are Significantly Related to the Presence of Concomitant Coronary Atherosclerosis in Patients with Symptomatic Calcified Aortic Stenosis
Background: The osteoprotegerin (OPG) / RANKL / RANK axis and Dickkopf-1 (Dkk-1) signaling have been linked to the development of atherosclerosis and might be part of the causal pathway in the regulation of valvular calcification in CAS.
Aim: This study aimed to assess serum RANKL/OPG ratios, serum Dkk-1 and deposition of calcium in the aortic valve in relation to the presence of concomitant coronary atherosclerosis in patients with symptomatic CAS.
Methods: OPG, RANKL and Dkk-1 were measured in 213 patients who were undergoing cardiac catheterization due to symptomatic CAS. Quantities of the studied compounds were compared between patients without (Group A) and with (Group B) concomitant coronary atherosclerosis. CT derived Agatston score and aortic valve calcium mass were assessed by using 256-slice CT.
Results: The presence of coronary atherosclerosis was related to significantly (p=0.007) higher OPG and to significantly (p=0.004) lower Dkk-1 in comparison to the presence of normal coronary arteries in patients with CAS. RANKL/OPG ratios (mean (95% C.I.)) were 20.04 (16.58; 24.23) in Group A and 12.69 (9.96; 16.17) in Group B, respectively, p=0.018. After adjustment for variables that significantly influenced levels of OPG and RANKL, the difference in RANKL/OPG ratio between Group A and Group B was no longer significant. Multivariable regression underscored the significance of the difference in Dkk-1 in relation to the presence of coronary atherosclerosis (p=0.016). Patients in group A had significantly higher Dkk-1, significantly higher deposition of calcium in the aortic valve and were symptomatic at a significantly younger age (p < 0.001) compared with patients in group B: Agatston score (mean (95% C.I.)) 4069.9 (3211.8;5134.5) and 2413.5 (1821.3;3198.1), p=0.007; and calcium mass 1032.5 (778.8; 1369.0) and 543.3 (387.3;736.9), p=0.004.
Conclusion: Circulating Dkk-1 signaling and deposition of calcium in the aortic valve differ significantly in relation to the presence of concomitant coronary atherosclerosis in patients with symptomatic CAS. A positive association was found between serum Dkk-1 signaling and calcium load in the aortic valve in patients with symptomatic CAS and angiographically normal coronary arteries.
- © 2012 by American Heart Association, Inc.