Touw, Wilhelmina A.Ueland, ThorBollerslev, JensSchousboe, John T.Lim, Wai H.Wong, GermaineThompson, Peter L.Kiel, DouglasPrince, Richard L.Rivadeneira, FernandoLewis, Joshua R.2018-01-182017Touw, W. A., T. Ueland, J. Bollerslev, J. T. Schousboe, W. H. Lim, G. Wong, P. L. Thompson, et al. 2017. “Association of Circulating Wnt Antagonists With Severe Abdominal Aortic Calcification in Elderly Women.” Journal of the Endocrine Society 1 (1): 26-38. doi:10.1210/js.2016-1040. http://dx.doi.org/10.1210/js.2016-1040.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34651750Context: There is great interest in the biology of vascular calcification. Wnt/β-catenin signaling is an important mediator of mineralization and may play a role in vascular calcification. Objective: We assessed the association between circulating Wnt antagonists and abdominal aortic calcification (AAC) severity in elderly women. Design: This was a cross-sectional analysis of the Calcium Intake Fracture Outcome Study. Setting: The participants were recruited from the community-dwelling elderly population. Participants: We examined 768 women aged over 70 years. Interventions: We collected blood samples, and lateral spine images captured during bone density assessment were used to score AAC with a validated 24-point scale. Main Outcome Measures: We tested the hypothesis that low Wnt antagonist levels of Dickkopf-1 (DKK1), secreted frizzled related protein 3 (sFRP3), and Wnt inhibitory factor 1 (WIF1) are associated with severe AAC (AAC24 score > 5). Results: Severe AAC was present in 146 women (19%). Lower levels of DKK1, but not WIF1 and sFRP3, were associated with higher odds of severe AAC. Per standard deviation decrease in DKK1 was associated with increased multivariable-adjusted odds ratio (OR) of severe AAC [OR, 1.26; 95% confidence interval (CI), 1.04 to 1.52; P = 0.017]. In quartile analyses, the lowest and second-lowest quartiles of DKK1 had increased multivariable-adjusted odds of severe AAC vs the highest quartile (OR, 2.05; 95% CI, 1.18 to 3.56; P = 0.011 and OR, 1.83; 95% CI, 1.05 to 3.19; P = 0.035). Conclusions: In elderly women, DKK1, but not sFRP3 or WIF1, is associated with severe AAC. This study supports the concept that Wnt/β-catenin signaling is an important regulator of vascular mineral metabolism and is independent of other risk factors.en-USLipids and CardiovascularDickkopf-1severe abdominal aortic calcificationsecreted frizzled related protein 3Wnt inhibitory factor 1elderly womenJournal Article2018-01-1810.1210/js.2016-1040