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

Abstract

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.

• Authors: Wilhelmina A Touw, Thor Ueland, Jens Bollerslev, John T Schousboe, Wai H Lim, Germaine Wong, Peter L Thompson, Douglas P Kiel, Richard L Prince, Fernando Rivadeneira, Joshua R Lewis
• Journal: Journal of the Endocrine Society (J Endocr Soc) Vol. 1 Issue 1 Pg. 26-38 (Jan 01 2017) ISSN: 2472-1972 [Print] United States
• PMID: 29264443 (Publication Type: Journal Article)