Association of lower serum sclerostin levels with elevated risk for increased arterial stiffness: The JPOS Cohort Study

J Clin Endocrinol Metab. 2024 Nov 12:dgae795. doi: 10.1210/clinem/dgae795. Online ahead of print.

Abstract

Objectives: Studies on the relationship between serum sclerostin, a Wnt/β-catenin pathway inhibitor, and atherosclerosis have yielded inconsistent results. We aim to longitudinally investigate the relationship between serum sclerostin levels and the risk of increased arterial stiffness in Japanese community-dwelling women.

Methods: Of 1044 women aged ≥50 years whose brachial-ankle pulse wave velocity (baPWV) value was available in a baseline survey in 2011-2012, we excluded 374 whose baPWVs were ≥1800 cm/s, set as the cutoff for increased arterial stiffness, and eight with missing data. Of the remaining 662 women, we included in the analysis 556 followed in the 4- to 5-year follow-up study. The coefficient of variation of the sclerostin measurement was 3.45%. We obtained odds ratios (ORs) for sclerostin at baseline categorized by tertiles, with the high tertile as reference for increased arterial stiffness.

Results: Ninety-four women showed increased arterial stiffness during a mean follow-up of 4.0 years. The increased arterial stiffness rates in the low, medium, and high tertiles were 22.2%, 16.1%, and 12.4%, respectively (trend test p = 0.013). The ORs for the medium and low tertiles for increased arterial stiffness were 1.58 (p = 0.205) and 2.16 (p = 0.027), respectively, after adjusting for age and baseline baPWV. After further adjustment for baseline BMI, hypertension, hyperlipidemia, diabetes mellitus, eGFR, and BMC at whole body, the ORs for the medium and low tertiles were 1.65 (p = 0.181) and 2.50 (p = 0.014), respectively.

Conclusion: Lower serum sclerostin levels were associated with elevated risks for increased arterial stiffness in Japanese community-dwelling women.

Keywords: Sclerostin; arterial stiffness; cohort study; community-dwelling women; longitudinal analysis.