02440nas a2200181 4500008004100000245015400041210006900195260001600264520180100280100001802081700001802099700002002117700002102137700002002158700002002178700002402198856003602222 2024 eng d00aAssociations of Serum GDF-15 Levels with Physical Performance, Mobility Disability, Cognition, Cardiovascular Disease, and Mortality in Older Adults.0 aAssociations of Serum GDF15 Levels with Physical Performance Mob c2024 Aug 083 a

BACKGROUND: Growth differentiation factor 15 (GDF-15) is a member of the TGFβ superfamily secreted by many cell types and found at higher blood concentrations as chronological age increases (1). Given the emergence of GDF-15 as a key protein associated with aging, it is important to understand the multitude of conditions with which circulating GDF-15 is associated.

METHODS: We pooled data from 1,174 randomly selected Health ABC Study (Health ABC) participants and 1,503 Cardiovascular Health Study (CHS) participants to evaluate the risk of various conditions and age-related outcomes across levels of GDF-15. The primary outcomes were (1) risk of mobility disability and falls; (2) impaired cognitive function; (3) and increased risk of cardiovascular disease and total mortality.

RESULTS: The pooled study cohort had a mean age of 75.4 +/-4.4 years. Using a Bonferroni-corrected threshold, our analyses show that high levels of GDF-15 were associated with a higher risk of severe mobility disability (HR: 2.13 [1.64, 2.77]), coronary heart disease (HR: 1.47 [1.17, 1.83]), atherosclerotic cardiovascular disease (HR: 1.56 [1.22, 1.98]), heart failure (HR: 2.09 [1.66, 2.64]), and mortality (HR: 1.81 [1.53, 2.15]) when comparing the highest and lowest quartiles. For CHS participants, analysis of extreme quartiles in fully adjusted models revealed a 3.5-fold higher risk of dementia (HR: 3.50 [1.97, 6.22]).

CONCLUSIONS: GDF-15 is associated with several age-related outcomes and diseases, including mobility disability, impaired physical and cognitive performance, dementia, cardiovascular disease, and mortality. Each of these findings demonstrates the importance of GDF-15 as a potential biomarker for many aging-related conditions.

1 aWebber, Katey1 aPatel, Sheena1 aKizer, Jorge, R1 aEastell, Richard1 aPsaty, Bruce, M1 aNewman, Anne, B1 aCummings, Steven, R uhttps://chs-nhlbi.org/node/9748