Growth differentiation factor 15 (GDF-15) as a biomarker of cardiovascular risk in chronic musculoskeletal pain (2024)

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Rocío León-González, MD, MSc

Department of Preventive Medicine and Public Health, School of Medicine

, Universidad Autónoma de Madrid,

Spain

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,

Rosario Ortolá, MD, PhD

Department of Preventive Medicine and Public Health, School of Medicine

, Universidad Autónoma de Madrid,

Spain

CIBER of Epidemiology and Public Health (CIBERESP)

, Madrid,

Spain

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Adrián Carballo-Casla, PhD

CIBER of Epidemiology and Public Health (CIBERESP)

, Madrid,

Spain

Aging Research Center, Department of Neurobiology, Care Sciences and Society Karolinska Institutet & Stockholm University

, Stockholm,

Sweden

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Mercedes Sotos-Prieto, PhD

Department of Preventive Medicine and Public Health, School of Medicine

, Universidad Autónoma de Madrid,

Spain

Department of Environmental Health and Nutrition, Harvard T.H. Chan School of Public Health. Boston

, MA,

USA

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Antonio Buño-Soto, MD, PhD

Department of Laboratory Medicine, La Paz University Hospital-IdiPaz

, Madrid,

Spain

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Isabel Rodríguez-Sánchez, MD, PhD

Geriatrics Department, Hospital Clínico San Carlos

, Madrid,

Spain

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Roberto Pastor-Barriuso, PhD

CIBER of Epidemiology and Public Health (CIBERESP)

, Madrid,

Spain

National Center for Epidemiology, Carlos III Health Institute

, Madrid,

Spain

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Fernando Rodríguez-Artalejo, MD, PhD

Department of Preventive Medicine and Public Health, School of Medicine

, Universidad Autónoma de Madrid,

Spain

IMDEA Food Institute. CEI UAM+CSIC

, Madrid,

Spain

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Esther García-Esquinas, MD, PhD

CIBER of Epidemiology and Public Health (CIBERESP)

, Madrid,

Spain

National Center for Epidemiology, Carlos III Health Institute

, Madrid,

Spain

Correspondence to: Esther García-Esquinas, MD, PhD, Telephone number: +917447650, ORCID: 0000-0002-8688-5174, email: egarciag@isciii.es, National Center for Epidemiology, Carlos III Health Institute, C/Melchor Fernández de Almagro, 28029, Madrid, Spain

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The Journals of Gerontology: Series A, glae163, https://doi.org/10.1093/gerona/glae163

Published:

08 July 2024

Article history

Received:

21 December 2023

Published:

08 July 2024

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    Rocío León-González, Rosario Ortolá, Adrián Carballo-Casla, Mercedes Sotos-Prieto, Antonio Buño-Soto, Isabel Rodríguez-Sánchez, Roberto Pastor-Barriuso, Fernando Rodríguez-Artalejo, Esther García-Esquinas, Growth differentiation factor 15 (GDF-15) as a biomarker of cardiovascular risk in chronic musculoskeletal pain, The Journals of Gerontology: Series A, 2024;, glae163, https://doi.org/10.1093/gerona/glae163

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Abstract

Background

It is unknown whether growth differentiation factor 15 (GDF-15) is associated with chronic musculoskeletal pain (CMP) and whether or not its association with incident cardiovascular disease (CVD) changes according to CMP status.

Methods

1,957 randomly-selected adults aged ≥65 years without prior CVD were followed up between 2015-2023. CMP was classified according to its intensity, frequency, and interference with daily activities. The association between GDF-15 levels and CMP was assessed using linear models with progressive inclusion of potential confounders, whereas the association between GDF-15 and CVD risk was evaluated with Cox-proportional hazard models with similar adjustment and interaction terms between GDF-15 and CMP. The incremental predictive performance of GDF-15 over standard predictors was evaluated using discrimination and risk reclassification metrics.

Results

GDF-15 concentrations were 6.90% (95%CI:2.56;11.25) higher in individuals with CMP, and up to 8.89% (4.07;15.71) and 15.79% (8.43;23.16) higher in those with ≥3 CMP locations and interfering pain. These increased levels were influenced by a higher prevalence of cardiometabolic risk factors, functional impairments, depressive symptoms, and greater levels of inflammation in individuals with CMP. In fully-adjusted models, a two-fold increase in GDF-15 was associated with a with a 1.49 increased risk (95%CI: 1.08; 2.05) of a CVD event in individuals with CMP, but not among those without CMP [1.02 (0.77; 1.35)]; p-interaction 0.041. Adding GDF-15 to models including the Framingham Risk Score improved predictive performance among individuals with CMP.

Conclusions

We provide evidence that GDF-15 could serve as a biomarker to assess CMP, as well as to predict CVD incidence in individuals with CMP.

Biomarkers, pain, cardiovascular disease (CVD)

Growth differentiation factor 15 (GDF-15) as a biomarker of cardiovascular risk in chronic musculoskeletal pain (5) Accepted manuscripts

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© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.

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