Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2026 Jan;30(1):100715.
doi: 10.1016/j.jnha.2025.100715. Epub 2025 Nov 8.

Association between Accelerometer-derived Physical Activity-related Metabolic Signature and Stroke: A Cohort Study from UK Biobank

Bowen Tan  1 , Hewanmeng Geng  2 , Zeyu Hao  1 , Zhirong Li  2 , Chengxiang Hu  2 , Tian Yu  3 , Pengyu Wang  1 , Yuanhao Chen  1 , Zhongping Feng  4 , Lina Jin  5 , Baofeng Xu  6 , Rui Liu  7
Affiliations

Association between Accelerometer-derived Physical Activity-related Metabolic Signature and Stroke: A Cohort Study from UK Biobank

Bowen Tan et al. J Nutr Health Aging. 2026 Jan.

Abstract

Background: Accelerometer-derived physical activity is associated with reduced stroke risk. The biological pathways underpinning this relationship, however, are not yet understood. Herein, we aim to identify metabolic signatures associated with accelerometer-measured PA and investigate their relationships with reduced stroke incidence.

Method: Utilizing UK Biobank accelerometer data, we derived physical activity into total physical activity (TPA), moderate-to-vigorous physical activity (MVPA), and light physical activity (LPA) and linked them to 249 NMR-quantified plasma metabolites. The metabolomic signatures (TPA-/MVPA-/LPA-metabolomic signatures) were developed through internal validation followed by elastic-net regression modeling. Cox proportional hazards models evaluated activity-stroke associations (adjusted for sociodemographic/genetic factors), followed by mediation analysis to quantify metabolomic signature effects.

Results: Through UK Biobank study (N = 29445; 14.1-year follow-up with 513 stroke events), we identified 195 TPA, 173 MVPA, and 164 LPA metabolite associations (FDR < 0.05), with 107, 92, and 15 validated, respectively. Elastic net-derived physical activity-metabolomic signatures (TPA-/MVPA-metabolomic signatures) correlated with physical activity intensities (r = 0.20-0.30, P < 0.001) and were associated with reduced stroke risk: TPA-metabolomic signatures (HR = 0.61, 95% CI: 0.44-0.87); MVPA-metabolomic signatures (HR = 0.50, 95%CI: 0.29-0.88). Mediation analyses showed TPA-metabolomic signatures and MVPA-metabolomic signatures explained 12.2% and 8.5% of physical activity-stroke associations (P < 0.001), implicating specific lipoprotein subclasses and lipids as key mediators.

Conclusion: TPA-metabolomic signatures and MVPA-metabolomic signatures, particularly the 11 key metabolites included, significantly mediate the association between accelerometer-derived physical activity and stroke risk.

Keywords: Accelerometer-derived physical activity; Metabolomics; Stroke; UK Biobank.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest The author declares no conflict of interest.

Figures

None
Graphical abstract
Fig. 1
Fig. 1
Flowchart of the individual selection.
Fig. 2
Fig. 2
(A) Heatmap of metabolite associations with accelerometer-derived physical activity (TPA, MVPA, LPA). (B) The weights of the metabolites selected in the PA‐MetS.
Fig. 3
Fig. 3
Estimated proportion of the association between Accelerometer-derived Physical Activity and all-cause stroke mediated by physical activity-related metabolic signature. Models were adjusted for Physical activity and Metabolic signature age, sex, ethnicity, townsend deprivation index, diet pattern, BMI, polygenic risk score for stroke, history of CVD, history of Hypertension. IE, the estimate of the indirect effect; DE, the estimate of the direct effect; Proportion of mediation = IE/DE.
See this image and copyright information in PMC

References

    1. Ferrari A.J., Santomauro D.F., Aali A., Abate Y.H., Abbafati C., Abbastabar H., et al. Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2024;403(10440):2133–2161. doi: 10.1016/S0140-6736(24)00757-8. - DOI - PMC - PubMed
    1. Bushnell C., Kernan W.N., Sharrief A.Z., Chaturvedi S., Cole J.W., Cornwell W.K., et al. 2024 Guideline for the primary prevention of stroke: a guideline from the American Heart Association/American Stroke Association. Stroke. 2024;55(12):e344–424. doi: 10.1161/STR.0000000000000475. - DOI - PubMed
    1. Martin S.S., Aday A.W., Allen N.B., Almarzooq Z.I., Anderson C.A.M., Arora P., et al. 2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association. Circulation. 2025;151(8):e1096. doi: 10.1161/CIR.0000000000001303. - DOI - PubMed
    1. Cao Z., Zhang J., Lu Z., Chen H., Min J., Hou Y., et al. Physical activity, mental activity, and risk of incident stroke: a prospective cohort study. Stroke. 2024;55(5) doi: 10.1161/STROKEAHA.123.044322. - DOI
    1. Garcia L., Pearce M., Abbas A., Mok A., Strain T., Ali S., et al. Non-occupational physical activity and risk of cardiovascular disease, cancer and mortality outcomes: a dose–response meta-analysis of large prospective studies. Br J Sports Med. 2023;57(15):979–989. doi: 10.1136/bjsports-2022-105669. - DOI - PMC - PubMed