Activated GDF11/8 subforms predict cardiovascular events and mortality in humans.

Nature communications
Authors
Abstract

Circulating Growth Differentiation Factors 11 and 8 (GDF11/8) exist in both latent and active forms, and it is unclear if specific forms can predict disease outcomes. Our data suggest that a dual-specific aptamer selectively binds GDF11/8 after prodomain activation. In 11,609 patients at risk for future cardiovascular events, low dual-specific aptamer-detected GDF11/8 levels strongly predicted adverse outcomes, including cardiovascular events (HR = 0.43, p = 9.1 × 10⁻⁶³) and all-cause mortality (HR = 0.33, p = 4.8 × 10⁻⁴⁰). Use of selective aptamers suggested that results observed with the dual-specific aptamer for cardiovascular and mortality risk replicated with a GDF8 aptamer although with a smaller effect size. In a second cohort of 4110 individuals (ARIC), low dual-specific aptamer-detected GDF11/8 levels also predicted increased 8 year dementia risk (HR = 0.66, p = 0.00148). Our findings reveal that activation of GDF11/8 may be a factor in future aging-related cardiovascular and cognitive decline.

Year of Publication
2025
Journal
Nature communications
Volume
16
Issue
1
Pages
6534
Date Published
07/2025
ISSN
2041-1723
DOI
10.1038/s41467-025-61815-w
PubMed ID
40664633
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