Plasma Klotho concentration is associated with the presence, burden and progression of cerebral small vessel disease in patients with acute ischaemic stroke

Ho Geol Woo, Yoonkyung Chang, Dong Ryeol Ryu, Tae Jin Song

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17 Scopus citations

Abstract

Klotho is a soluble or membrane-bound anti-aging protein, whose protective actions are important for a prudential function of many organs. Because Klotho and cerebral small vessel disease (SVD) are associated with ageing process and endothelial dysfunction, it is possible that Klotho has an association with cerebral SVD. We aimed to investigate the association of plasma Klotho concentration with the presence, burden and progression of cerebral SVD. We prospectively enrolled 262 patients with first-ever acute cerebral infarction, performed brain MRI and collected their blood samples within 24 hours of admission. An enzyme-linked immunosorbent assay was used for evaluating plasma Klotho concentration. We estimated the total SVD score of each patient after determining the presence and burden of high-grade white matter hyperintensities (HWMHs), cerebral microbleeds (CMBs), high-grade perivascular spaces (HPVSs) and asymptomatic lacunar infarctions (ALIs). Univariate and multivariate analyses were conducted to investigate association of Klotho with cerebral SVD and the total SVD score. Of the 262 patients, 152 (58.0%) were men. The mean age of these patients was 64.7 years. The mean ± standard deviation of plasma Klotho concentration was 329.8 ± 194.1 pg/mL. In multivariate analysis, plasma Klotho concentration was negatively associated with the presence of HWMHs [Odds ratio (OR): 0.13, p = 0.047], HPVSs (OR: 0.22, p = 0.024) and ALIs (OR: 0.53, p = 0.021) but not associated with the presence of CMBs (OR: 0.39, p = 0.404). Plasma Klotho concentration was also negatively related to the total SVD score (unstandardized coefficients beta: −0.895, standard error = 0.317, p = 0.005, R2 = 0.239). Furthermore, plasma Klotho concentration was negatively related to the presence (OR: 0.75, 95% CI: 0.59–0.96, p = 0.025) and severity of cerebral SVD progression (OR: 0.72, 95% CI: 0.56–0.92, p = 0.009). In conclusion, plasma Klotho concentration was negatively associated with the presence, burden and progression of cerebral SVD.

Original languageEnglish
Article numbere0220796
JournalPLoS ONE
Volume14
Issue number8
DOIs
StatePublished - 1 Aug 2019

Bibliographical note

Funding Information:
This project was supported by grant from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (2018R1D1A1B07040959 to T-JS). This work was supported by the Ewha Womans University Research Grant of 2018 to T-JS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2019 Woo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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