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Growth differentiation factor 15 in a community-based sample: age-dependent reference limits and prognostic impact.

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Growth differentiation factor 15 (GDF-15) levels increase with age in healthy adults. Age-dependent GDF-15 reference values are independently predictive of all-cause mortality, aiding clinical risk stratification.

Keywords:
All-cause mortalityGDF-15protein biomarkersreference valuessurvival analysis

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Area of Science:

  • Biomarkers
  • Gerontology
  • Cardiovascular Disease

Background:

  • Limited data exists on Growth Differentiation Factor 15 (GDF-15) in healthy populations.
  • Current GDF-15 cutoffs do not account for age-related variations.
  • GDF-15 prognostic impact in healthy individuals requires further investigation.

Purpose of the Study:

  • To establish age-dependent reference values for GDF-15 in apparently healthy older adults.
  • To assess the prognostic significance of these age-dependent GDF-15 values concerning all-cause mortality.

Main Methods:

  • Utilized generalized additive models for location scale and shape (GAMLSS) to model GDF-15 in 268 healthy older adults.
  • Developed age-dependent centile curves for GDF-15.
  • Employed Cox proportional hazards models to analyze the association between GDF-15 centiles and all-cause mortality.

Main Results:

  • Observed a clear age-dependent increase in GDF-15 levels among healthy participants.
  • A three-fold difference in GDF-15 was noted between the 5th and 95th centiles across ages.
  • Higher GDF-15 centiles significantly predicted all-cause mortality, with a hazard ratio of 3.04 for those at or above the 95th centile.

Conclusions:

  • Age-adjusted GDF-15 centile values derived from healthy older adults are significant independent predictors of mortality.
  • These age-dependent GDF-15 reference values offer a valuable tool for clinical risk stratification.
  • Further research can refine GDF-15's role in predicting mortality in diverse populations.