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J Endocr Soc. 2017 Jan 12;1(1):26-38. doi: 10.1210/js.2016-1040. eCollection 2017 Jan 1.

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

Author information

1
Erasmus University, Rotterdam 3015GE, The Netherlands.
2
University of Western Australia School of Medicine and Pharmacology.
3
Research Institute of Internal Medicine and.
4
Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Rikshospitalet, N-0514 Oslo, Norway.
5
University of Oslo, N-0315 Oslo, Norway.
6
Park Nicollet Osteoporosis Center and HealthPartners Institute, Minneapolis, Minnesota 55416.
7
Division of Health Policy and Management, University of Minnesota, Minneapolis, Minnesota 55455.
8
Department of Renal Medicine.
9
Centre for Kidney Research, Children's Hospital at Westmead, School of Public Health, Sydney Medical School, The University of Sydney, Sydney, 2145 Australia.
10
Department of Cardiology, and.
11
Institute for Aging Research, Hebrew Senior Life, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02131; and.
12
Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Perth, 6009 Australia.
13
Department of Internal Medicine, Erasmus Medical Center, Rotterdam 3015GE, The Netherlands.

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.

KEYWORDS:

Dickkopf-1; Wnt inhibitory factor 1; elderly women; secreted frizzled related protein 3; severe abdominal aortic calcification

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