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Elevated Plasma GDF-15 Levels Are Associated with Aging, Multimorbidity, and Tobacco Exposure in People with HIV

Fecha de publicación: Fecha Ahead of Print:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Lopez-Lopez, A.
  • Alonso-Domínguez, J.
  • Martínez-Barros, I.
  • Pérez-González, A.
  • Ocampo, A.
  • Morano, L.
  • Calderón-Cruz, B.
  • Martínez-López de Castro, N.
  • Bisbal Pardo, O.
  • Pérez-Olmeda, M.
  • Sánchez-Villegas, J.
  • Asensi, V.
  • Rodríguez-Rosado Martinez-Echevarría, R.
  • Poveda, E.

Grupos

Abstract

Introduction: Aging in people with HIV (PWH) is accompanied by an increased burden of multimorbidity and persistent inflammation. Identifying biomarkers that reflect comorbidity risk can help improve long-term care. This study evaluated the association of multimorbidity with GDF-15, sICAM-1, sVCAM-1, and sP-selectin in PWH. Methods: A cross-sectional study was performed in two cohorts of adults receiving antiretroviral therapy: a discovery cohort (n = 74) and a validation cohort (Spanish CoRIS network) (n = 150). Median age was 53 years in both cohorts (IQR 44–60 and 45–58), and women represented 19 (25.7%) and 75 (50.0%), respectively. Multimorbidity was defined as = 2 comorbidities, including but not limited to cardiovascular, metabolic, renal, and non-AIDS-defining cancers. Plasma GDF-15, sICAM-1, sVCAM-1, and sP-selectin were quantified by multiplex immunoassay. Associations with log-transformed GDF-15 were assessed using multivariable linear regression including age-multimorbidity ordinal categories, tobacco smoking, and CD4+ nadir. Results: Multimorbidity prevalence was 48.6% (36) in the hospital cohort and 54.7% (82) in CoRIS. In both cohorts, participants with multimorbidity had significantly higher GDF-15 levels (hospital: 771.5 vs. 390.0 pg/ml; CoRIS: 485.2 vs. 360.1 pg/ml; both p < 0.001). In the hospital cohort, smoking and age-multimorbidity were independently associated with elevated GDF-15, with 26.1% and 16.0% increases per category, respectively (p < 0.05). These associations were confirmed in CoRIS, with 5.44% and 19.0% increases (p < 0.01). CD4+ nadir showed no significant association with GDF-15. No significant associations were observed between multimorbidity and sICAM-1, sVCAM-1, or sP-selectin (all p > 0.05). Conclusions: Elevated GDF-15 was consistently associated with multimorbidity in PWH, primarily driven by aging and tobacco smoking. GDF-15 appears to reflect a broader state of multisystem physiological stress than traditional endothelial activation markers, supporting its utility as a biomarker to identify PWH at higher risk of age-related comorbidities and to monitor the impact of modifiable risk factors in clinical care. © The Author(s) 2026.

Datos de la publicación

ISSN/ISSNe:
2193-8229, 2193-6382

Infectious Diseases and Therapy  SPRINGER LONDON LTD

Tipo:
Article
Páginas:
715-731
PubMed:
41563586
Enlace a otro recurso:
www.scopus.com
Factor de Impacto:
1,141 SCImago ℠
Cuartil:
Q2 SCImago ℠

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Keywords

  • Aging; Biomarkers; GDF-15; HIV; Multimorbidity

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