Association of circulating Wnt antagonists with severe abdominal aortic calcification in elderly women

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

    Research output: Contribution to journalArticle

    Abstract

    Context: There is great interest in the biology of vascular calcification. Wnt/b-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).
    Original languageEnglish
    Pages (from-to)26-38
    Number of pages13
    JournalJournal of the Endocrine Society
    Volume1
    Issue number1
    DOIs
    Publication statusPublished - 12 Jan 2017

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    Odds Ratio
    Wnt Proteins
    Vascular Calcification
    Outcome Assessment (Health Care)
    Independent Living
    Catenins
    Bone Density
    Spine
    Cross-Sectional Studies
    Calcium
    Population
    frizzled related protein-3

    Cite this

    Touw, Wilhelmina A. ; Ueland, Thor ; Bollerslev, Jens ; Schousboe, John T. ; Lim, Wai H. ; Wong, Germaine ; Thompson, Peter L. ; Kiel, Douglas P. ; Prince, Richard L. ; Rivadeneira, Fernando ; Lewis, Joshua R. / Association of circulating Wnt antagonists with severe abdominal aortic calcification in elderly women. In: Journal of the Endocrine Society. 2017 ; Vol. 1, No. 1. pp. 26-38.
    @article{39b3776fe50f4350bc6bfcd806fd14e6,
    title = "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/b-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{\%} confidenceinterval (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).",
    author = "Touw, {Wilhelmina A.} and Thor Ueland and Jens Bollerslev and Schousboe, {John T.} and Lim, {Wai H.} and Germaine Wong and Thompson, {Peter L.} and Kiel, {Douglas P.} and Prince, {Richard L.} and Fernando Rivadeneira and Lewis, {Joshua R.}",
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    Touw, WA, Ueland, T, Bollerslev, J, Schousboe, JT, Lim, WH, Wong, G, Thompson, PL, Kiel, DP, Prince, RL, Rivadeneira, F & Lewis, JR 2017, 'Association of circulating Wnt antagonists with severe abdominal aortic calcification in elderly women' Journal of the Endocrine Society, vol. 1, no. 1, pp. 26-38. https://doi.org/10.1210/js.2016-1040

    Association of circulating Wnt antagonists with severe abdominal aortic calcification in elderly women. / Touw, Wilhelmina A.; Ueland, Thor; Bollerslev, Jens; Schousboe, John T.; Lim, Wai H.; Wong, Germaine; Thompson, Peter L.; Kiel, Douglas P.; Prince, Richard L.; Rivadeneira, Fernando; Lewis, Joshua R.

    In: Journal of the Endocrine Society, Vol. 1, No. 1, 12.01.2017, p. 26-38.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Association of circulating Wnt antagonists with severe abdominal aortic calcification in elderly women

    AU - Touw, Wilhelmina A.

    AU - Ueland, Thor

    AU - Bollerslev, Jens

    AU - Schousboe, John T.

    AU - Lim, Wai H.

    AU - Wong, Germaine

    AU - Thompson, Peter L.

    AU - Kiel, Douglas P.

    AU - Prince, Richard L.

    AU - Rivadeneira, Fernando

    AU - Lewis, Joshua R.

    PY - 2017/1/12

    Y1 - 2017/1/12

    N2 - Context: There is great interest in the biology of vascular calcification. Wnt/b-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% confidenceinterval (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).

    AB - Context: There is great interest in the biology of vascular calcification. Wnt/b-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% confidenceinterval (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).

    U2 - 10.1210/js.2016-1040

    DO - 10.1210/js.2016-1040

    M3 - Article

    VL - 1

    SP - 26

    EP - 38

    JO - Journal of the Endocrine Society

    JF - Journal of the Endocrine Society

    SN - 2472-1972

    IS - 1

    ER -