Low creatinine to cystatin C ratio is associated with lower muscle volumes and poorer gait speeds in the longitudinal Integrated Women's Health Program cohort

Darren Yuen Zhang Tan; Beverly Wen Xin Wong; Liang Shen; Ling-Jun Li; Eu-Leong Yong

doi:10.1097/GME.0000000000002524

Low creatinine to cystatin C ratio is associated with lower muscle volumes and poorer gait speeds in the longitudinal Integrated Women's Health Program cohort

Menopause. 2025 Mar 18. doi: 10.1097/GME.0000000000002524. Online ahead of print.

Authors

Darren Yuen Zhang Tan¹, Beverly Wen Xin Wong¹, Liang Shen², Ling-Jun Li, Eu-Leong Yong¹

Affiliations

¹ From the Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
² Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

PMID: 40100924
DOI: 10.1097/GME.0000000000002524

Abstract

Objective: Little is known about the longitudinal associations between creatinine-cystatin C ratios (CCR) with muscle volume and function during the menopausal transition. We investigated the longitudinal relationship of baseline CCR, with muscle volumes measured by magnetic resonance imaging (MRI), and objectively measured muscle strength and physical performance after 6.6-year follow-up.

Methods: Participants from the Integrated Women's Health Programme (IWHP) cohort (n = 891, baseline mean age 56.2 ± 6.0) who attended both baseline and follow-up visits underwent objectively measured muscle strength and physical performance assessments and MRI. Creatinine to cystatin C ratio was calculated as (creatinine [mg/dL] / cystatin C [mg/L]) and low CCR were those in the lowest tertile (CCR < 8.16). Multivariable regression analyses were used to determine the associations of baseline CCR with muscle volumes and function 6.6 years later.

Results: Baseline low CCR was associated with lower MRI-measured muscle volumes and poorer physical function 6.6 years later. Compared to high CCR group, mean fat-free thigh muscle volume of the low CCR group was 0.350 L lower (95% CI, 0.183-0.518) after adjustment for covariates. Similarly, the low CCR group was associated with 0.029 m/s slower (95% CI, 0.006-0.053) slower mean usual gait and 0.049 m/s slower (95% CI, 0.020-0.078) mean narrow gait speeds. CCR was not associated with handgrip strength and repeated chair stands and one-leg stand tests.

Conclusion: Low CCR at baseline was associated with lower fat-free muscle volumes and poorer gait speeds 6.6 years later. The potential of CCR as a predictive biomarker for adverse events related to sarcopenia in midlife women merits further investigation.