Oral Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Circulating Wnt antagonists and severe abdominal aortic calcification in elderly women: a cross-sectional study (#143)

Wilhelmina A Touw 1 , Thor Ueland 2 , Jens Bollerslev 3 , John T Schousboe 4 , Wai H Lim 5 6 , Germaine Wong 7 , Peter L Thompson 8 , Douglas P Kiel 9 , Richard Prince 5 10 , Fernando Rivadeneira 1 , Joshua Lewis 5 11
  1. Erasmus MC, Rotterdam, Netherlands
  2. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
  3. Endocrinology, Oslo University Hospital Rikshospitalet, Oslo, Norway
  4. Division of Health Policy and Management, University of Minnesota, Minneapolis, USA
  5. School of Medicine and Pharmacology, Sir Charles Gairdner Hospital Unit , University of Western Australia, Perth
  6. Renal Medicine, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
  7. Centre for Kidney Research, School of Public Health, School of Medicine, University of Sydney, Sydney, NSW, Australia
  8. Cardiology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
  9. Institute for Aging Research, Hebrew Senior Life, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
  10. Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital , Perth
  11. University of Sydney, Westmead, NSW, Australia

The Wnt/β-catenin signalling pathway is important for angiogenesis. The canonical Wnt/β-catenin signalling antagonist Dickkopf-1 (DKK1) is inversely associated with severe abdominal aortic calcification (AAC24 score >5) in men. However, studies of other Wnt antagonists and studies in elderly women remain limited. We therefore measured circulating Wnt antagonists that predominantly impact the canonical Wnt signalling (DKK1), non-canonical Wnt signalling (secreted frizzled related protein 3 [sFRP3]) and both Wnt signalling pathways (Wnt inhibitory factor 1 [WIF1]) to investigate their cross-sectional relationship with severe abdominal aortic calcification in 768 elderly women aged over 70 recruited from the Calcium Intake Fracture Outcome Study (CAIFOS) a 5-year prospective, randomised, controlled trial of oral calcium supplements to prevent osteoporotic fractures. Fasting blood samples were collected at baseline (1998) and stored at -80C until testing. Circulating Wnt-antagonists DKK1, sFRP3 and WIF1 concentrations were determined using enzyme immunoassay (EIA) provided by R&D Systems (Minneapolis, MN) with intra and inter assay coefficients of variation were <10% for all assays while abdominal aortic calcification 24 scores was calculated from lateral spine images captured during bone densitometry in 1998 or 1999. DKK1 but not sFRP3 or WIF1 (P>0.05) was associated with the presence of severe AAC in these elderly women. After adjusting for other risk factors including age, body mass index, smoking history, cardiovascular medications, history of diabetes or atherosclerotic vascular disease and estimated kidney function using creatinine and cystatin C women in the second lowest and lowest quartile of circulating DKK1 had increased odds of severe AAC compared to women in the highest quartile (multivariable-adjusted OR 1.83, 95%CI; 1.05-3.19, P=0.035 and OR 2.05, 95%CI; 1.18-3.56, P=0.011 respectively). This study of elderly women suggests that canonical Wnt/β-catenin signalling is an important inhibitor of vascular calcification independent of conventional cardiovascular risk factors and renal function in elderly women.