Circulating Growth Differentiation Factors 11 and 8, Their Antagonists Follistatin and Follistatin-Like-3, and Risk of Heart Failure in Elders

Year: 2023

Type: article

Abstract: BACKGROUND: Heterochronic parabiosis has identified growth differentiation factor (GDF)-11 as a potential means of cardiac rejuvenation, but findings have been inconsistent. A major barrier has been lack of assay specificity for GDF-11 and its homolog GDF-8. METHODS: We tested the hypothesis that GDF-11 and GDF-8, and their major antagonists follistatin and follistatin-like (FSTL)-3, are associated with incident heart failure (HF) and its subtypes in elders. Based on validation experiments, we used liquid chromatography-tandem mass spectrometry to measure total serum GDF-11 and GDF-8, along with follistatin and FSTL-3 by immunoassay, in 2 longitudinal cohorts of older adults. RESULTS: In 2 599 participants (age 75.2 ± 4.3) followed for 10.8 ± 5.6 years, 721 HF events occurred. After adjustment, neither GDF-11 (HR per doubling: 0.93 [0.67, 1.30]) nor GDF-8 (HR: 1.02 per doubling [0.83, 1.27]) was associated with incident HF or its subtypes. Positive associations with HF were detected for follistatin (HR: 1.15 [1.00, 1.32]) and FLST-3 (HR: 1.38 [1.03, 1.85]), and with HF with preserved ejection fraction for FSTL-3 (HR: 1.77 [1.03, 3.02]). (All HRs per doubling of biomarker.) FSTL-3 associations with HF appeared stronger at higher follistatin levels and vice versa, and also for men, Blacks, and lower kidney function. CONCLUSIONS: Among older adults, serum follistatin and FSTL-3, but not GDF-11 or GDF-8, were associated with incident HF. These findings do not support the concept that low serum levels of total GDF-11 or GDF-8 contribute to HF late in life, but do implicate transforming growth factor-β superfamily pathways as potential therapeutic targets.

Source: The Journals of Gerontology Series A

DOI: 10.1093/gerona/glad206

Authors: Jorge R Kizer, Sheena Patel, Peter Ganz, Anne B Newman, Shalender Bhasin, Se-Jin Lee, Peggy M Cawthon, Nathan K LeBrasseur, Sanjiv J Shah, Bruce M Psaty, Russell P Tracy, Steven R Cummings

Institutions: San Francisco VA Medical Center, University of California, San Francisco, San Francisco VA Health Care System, California Pacific Medical Center, San Francisco General Hospital, University of Pittsburgh, Brigham and Women's Hospital, Harvard University, University of Connecticut, Jackson Laboratory, Mayo Clinic, Northwestern University, University of Washington, University of Vermont

Language: English

Topic: GDF15 and Related Biomarkers

Subfield: Rheumatology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Nursing Research, National Institute of Neurological Disorders and Stroke

OpenAlex ID: W4386169486