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.

Association Between Abdominal Aortic Calcification, Bone Mineral Density, and Fracture in Older Women

“…Therefore, occlusion of these arteries may result in ischemia in the lumbar spine, which can lead to degeneration and asymptomatic vertebral fractures . Furthermore, local and systemic osteochondrogenic factors can be released by calcified atherosclerotic lesions, which can affect regional and systemic bone homeostasis …”

“…(9) Furthermore, local and systemic osteochondrogenic factors can be released by calcified atherosclerotic lesions, which can affect regional and systemic bone homeostasis. (10,11) In this article, we explore the hypothesis that the presence and severity of AAC is related to bone structure, prevalent fractures, and incident fractures using the same population in which we previously identified an association between AAC and CVD. (6) To do this, we used lateral spine imaging undertaken at the time of bone density testing.…”

Lifelong genetically lowered sclerostin and risk of cardiovascular disease

“…Our genetic data provide strong evidence in support of target-mediated adverse effects of sclerostin inhibition on coronary events. Sclerostin exerts its effects on bone as an inhibitor of the Wnt-signaling pathway (a pathway also previously linked to vascular calcification [50][51][52] ) by binding to the Wnt co-receptor low density lipoprotein receptor-related protein (LRP) 5 and 6. 53 Protein-coding mutations in both LRP5 and LRP6 have been linked to alterations in BMD and cardiometabolic risk profiles, including insulin resistance, dyslipidemia, hypertension and CHD, 54,55 which supports our findings of altered cardiometabolic disease in carriers of SOST variants.…”

Cruciferous vegetable intake is inversely associated with extensive abdominal aortic calcification in elderly women: a cross-sectional study

“…More than 99•5 % of the images were of sufficient quality to assess AAC (6) . AAC scores were then re-categorised as not extensive (AAC scores 0-5) and extensive (AAC scores 6-24), as previously used investigating the aetiology of AAC (6,21,22) .…”