Association of Circulating Wnt Antagonists With Severe Abdominal Aortic Calcification in Elderly Women

Context 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.