Increased Serum Sclerostin Level Is a Risk Factor for Peripheral Artery Disease in Patients with Hypertension.

Background and

Objectives

Sclerostin and dickkopf-1 (DKK1), which are Wnt inhibitors, are involved in vascular calcification and atherosclerosis. Atherosclerotic peripheral artery disease (PAD) is highly prevalent, particularly in patients with hypertension. This study aimed to explore the association between serum concentrations of Wnt pathway inhibitors and PAD in patients with hypertension. Materials and

Methods

This cross-sectional trial recruited 92 patients with hypertension. PAD was defined as an ankle-brachial index < 0.9. The levels of sclerostin, DKK1, C-reactive protein (CRP), and other biochemical markers were assessed using fasting blood samples. Univariate and multivariate logistic regression and receiver operating characteristic curve analyses were conducted.

Results

Patients with PAD (15.2%) had significantly higher serum sclerostin (p < 0.001) and CRP (p = 0.001) levels than those without PAD. However, the two groups did not significantly differ in terms of the DKK1 levels. Based on the multivariate analysis, sclerostin was an independent predictor of PAD (odds ratio: 1.054 per 1 pmol/L increase, 95% confidence interval: 1.019-1.090, p = 0.002) after adjusting for body mass index, fasting glucose levels, diabetes, smoking, and CRP levels. Sclerostin had a strong discriminatory power for diagnosing PAD according to the receiver operating characteristic curve analysis (area under the curve: 0.806, p < 0.001), with the best cutoff value of 71.5 pmol/L (sensitivity: 71.4%, specificity: 78.2%). Further, sclerostin was negatively associated with the ankle-brachial index, renal function, and dyslipidemia markers.

Conclusions

Serum sclerostin levels are independently related to an increased risk for PAD in patients with hypertension. Therefore, it can be a potential biomarker for risk stratification and early diagnosis.