Blood levels of immune-related biomarkers and future risk for prefrailty/frailty: The prospective ATTICA sub-study 2002-2024

BACKGROUND: Given that low-grade inflammation is implicated in the pathophysiology of age-related frailty, we tested the hypothesis that individual blood biomarkers are associated with the risk of developing frailty in later life. METHODS: Participants of the ATTICA cohort aged ≥ 33 years in 2002 were assessed for age-related frailty in 2024. By multivariable logistic regression models, we tested the association of an array of baseline immune-related biomarkers, as well as of an aggregate score, namely ImmActScore, that combines IL-6, TNF-α and fibrinogen, on the odds of later-life frailty. RESULTS: Among 574 participants (mean baseline age 48 ± 8; 50% male), phenotypic FRAIL scale assessment categorized 6% as frail, 29% as prefrail, and 65% as robust. After adjustments for various socio-demographic and clinical characteristics, baseline fibrinogen (OR=1.004, 95%CI:1.000-1.007, p = 0.037) and ImmActScore (OR=1.239, 95%CI:1.007-1.525, p = 0.042) showed significant associations, suggesting that higher baseline levels are associated with increased odds for prefrailty/frailty in the very long-term. CONCLUSIONS: Fibrinogen and a composite score capturing immune activation status by combining IL-6, TNF-α and fibrinogen, were both associated with the odds of prefrailty/frailty after 22 years. Further studies are warranted to confirm whether assessing immune-related biomarkers in middle-age may help identify individuals with a higher likelihood of frailty.