Association of circulating sclerostin with vascular calcification in Afro-Caribbean men

Abstract

Objective Sclerostin, a Wingless (Wnt) pathway antagonist, is an established regulator of bone mineralization in humans but its potential importance in the regulation of vascular calcification is less clear. Therefore, our objective was to assess the relationship of serum sclerostin levels with coronary and aortic artery calcification (CAC and AAC, respectively) in Afro-Caribbean men on the island of Tobago. Methods Serum sclerostin levels and computed tomography of CAC and AAC were measured in 191 men (age mean(SD): 62.9(8.0)years) recruited without regard to health status. Multivariable logistic regression models were used to assess the cross-sectional association of sclerostin with prevalent arterial calcification. Results Mean(SD) sclerostin was 45.2 pmol/L (15.6 pmol/L). After adjusting for risk factors including age, physical and lifestyle characteristics, comorbidities, lipoproteins and kidney function, 1 SD greater sclerostin level was associated with a 1.61-times (95%CI 1.02–2.53) greater odds of having CAC. Sclerostin was not associated with AAC in any model. Conclusions This is the first study to show that, among Afro-Caribbean men, greater serum sclerostin concentrations were associated with prevalence and extent of CAC. Further studies are needed to better define the role of the Wnt signaling pathway in arterial calcification in humans.

Serum sclerostin values are associated with abdominal aortic calcification and predict cardiovascular events in patients with chronic kidney disease stages 3–5D

“…However, whether it promotes or inhibits vascular calcification is unclear. To our knowledge, although Register et al found a positive association with aortic calcification and carotid plaques in type 2 diabetes, this contradicts the findings of another study that demonstrated a lack of correlation between sclerostin level and abdominal artery calcification in Afro‐Caribbean men, as assessed by CT‐derived measurements of calcification . In this study, we found a positive association between serum sclerostin and AAC and valve calcification.…”

“…Previous studies have described contradictory relationships between sclerostin and vascular calcification, with three studies showing a positive correlation with coronary artery calcification and one study reporting an inverse association with AAC . However, Kuipers recently reported a lack of association between sclerostin and AAC . These results are inconsistent, and do not describe the role of AAC in CKD patients.…”

“…Sclerostin is upregulated in calcified vascular smooth muscle cells and aortic valve, but its effect on vascular calcification is unclear. Previous studies have described contradictory relationships between sclerostin and vascular calcification, with three studies showing a positive correlation with coronary artery calcification and one study reporting an inverse association with AAC . However, Kuipers recently reported a lack of association between sclerostin and AAC .…”

Sclerostin: Intracellular mechanisms of action and its role in the pathogenesis of skeletal and vascular disorders

“…52 Recently, Kuipers et al showed that increases by 1 standard deviation of sclerostin levels are associated with a 1.61-times (95% CI 1.02-2.53) greater risk of having coronary artery calcification. 53 and estradiol levels were associated with the response to bisphosphonate therapy in women with postmenopausal osteoporosis. Also, sclerostin concentrations were associated with the index of resistance to compression (IRC) in the fractal analysis of the distal radius, a parameter of bone microstructure.…”

Fatores dietéticos associados à calcificação vascular em pacientes com doença renal crônica em tratamento conservador

“…Ao passo que estudos epidemiológicos demonstraram uma associação direta entre a esclerostina circulante e calcificação (125)(126)(127)(128), outros estudos também descreveram uma relação inversa entre ambos (129)(130)(131). Há duas principais possibilidades para esses achados.…”