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. 2025 Jun;35(6):103905.
doi: 10.1016/j.numecd.2025.103905. Epub 2025 Feb 5.

Serum klotho concentration, vitamin D concentration and cardiovascular diseases risk: Evidence from the NHANES database 2007-2016

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Serum klotho concentration, vitamin D concentration and cardiovascular diseases risk: Evidence from the NHANES database 2007-2016

Rong Chen et al. Nutr Metab Cardiovasc Dis. 2025 Jun.

Abstract

Background and aim: Epidemiologic studies have shown that serum vitamin D (VD) deficiency is associated with an increased risk of cardiovascular diseases (CVDs) and CVDs-mortality. Klotho is a well-recognized anti-aging protein. However, it is limited understanding the role of Klotho on the association of serum VD and CVDs risk. This study aimed to explore the role of serum Klotho on the association between serum VD and CVDs risk.

Methods and results: Totally 12,634 subjects were included from NHANES (2007-2016), of whom 1365 (10.80 %) had CVDs. Subjects were divided into serum VD deficient group sufficient group with the cutoff value of 50 nmol/L. Serum Klotho concentrations were detected by ELISA kit. Weighted univariate and multivariate were utilized to explore the association of serum Klotho, serum VD and CVDs risk, with odds ratios (ORs) and 95 % confidence intervals (CIs). Subjects with deficient serum VD had a 56 % increase in CVDs risk (OR = 1.56, 95%CI: 1.21-2.00); subjects with deficient serum VD and low serum Klotho have the highest CVDs risk (OR = 1.58, 95%CI: 1.19-2.11). We further found the association of low serum VD and CVDs risk was only observed in low serum Klotho concentration (OR = 1.74, 95%CI: 1.27-2.39), these results suggested serum Klotho concentration play a moderating effect on the association of serum VD concentration and CVDs risk. The results of subgroup analyses suggested these moderating effects were more prominent in subjects with overweight/obese (OR = 1.85, 9 %%CI: 1.25-2.72), and with the history of hypertension (OR = 1.87, 9 %%CI: 1.32-2.65) and dyslipidemia (OR = 1.81, 95%CI: 1.32-2.49).

Conclusions: Low serum VD was associated with high CVDs risk and high serum Klotho may play a moderating effect on the association between serum VD and CVDs risk.

Keywords: Cardiovascular diseases risk; Cross-sectional study; NHANES database; Serum klotho; Serum vitamin D.

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