Inflammatory biomarkers and frailty transitions in older adults with cancer: Findings from a national cohort study.

person Weijiao Zhou Peking University, Beijing, China info_outline Weijiao Zhou, Junlan Pu, Youmin Cho

Authors person Weijiao Zhou Peking University, Beijing, China info_outline Weijiao Zhou, Junlan Pu, Youmin Cho Organizations Peking University, Beijing, China, Peking Unviersity, Beijing, China, Chungnam National University College of Nursing, Daejeon, South Korea Abstract Disclosures Research Funding No funding sources reported Background: Approximately 67% of cancer survivors were aged 65 or older in the U.S.; they face a heightened risk of frailty, as both cancer and anti-cancer treatment impose additional stressors on the older adults’ physiological reserves. Inflammatory biomarkers such as serum C-reactive protein (CRP) and Interleukin-6 (IL-6) levels were associated with frailty. However, the role of inflammatory biomarkers on the transitions of frailty states remains unclear. This study aimed to describe transitions between frailty states and death and quantify the predictive effect of inflammatory biomarkers on transitions. Methods: We used data from the National Health and Aging Trends Study (NHATS) from 2017 to 2022. A total of 1,219 older cancer survivors (>67 years) were included. Frailty was assessed annually using the Fried Frailty Phenotype (exhaustion, low physical activity, shrinking, low walking speed, and weakness) to categorize participants as “non-frail,”“pre-frail,” and “frail.” Inflammatory biomarkers were obtained via dried blood spots at baseline (2017). Plasma-equivalent values of CRP and IL-6 were used. Covariates included sex, age category, race, education level, marital status, obesity, and number of comorbidities. We defined four states that included three frailty states (non-frail, pre-frail, and frail) and an absorbing state of death. The multi-state Markov models were performed to capture possible transitions between frailty states and examine the effect of CRP and IL-6 on the five main transitions between states (non-frail to pre-frail, pre-frail to non-frail, pre-frail to frail, frail to pre-frail, frail to death). Results: At baseline, 25.27% were non-frail, 52.34% were pre-frail, and 22.40% were frail. During the follow-up time of 5 years, 1,396 transitions were observed, with 950 (68.05%) progressions (or to death) and 446 (31.95%) reversals. For participants who were non-frail, they were highly likely to develop pre-frailty (transition intensity=0.63). For participants with pre-frailty, progression to frailty was a little more likely than recovery to non-frailty (0.25 vs 0.21). Once entering the frail state, the likelihood of death outweighed that of recovery (0.30 vs 0.28). A higher level of CRP or IL-6 was associated with frailty progression (non-frail to pre-frail and frail to death), while a lower level of CRP or IL-6 was associated with recovery of frailty (pre-frail to non-frail and frail to pre-frail). Conclusions: This study is the first to investigate the longitudinal relationship between inflammatory biomarkers and frailty transitions in older cancer survivors using a nationally representative survey dataset. Our findings outlined potential transitions between frailty states and death, highlighting the role of elevated serum CRP and IL-6 levels on the increased risk of frailty progression and reduced risk of frailty recovery over 5 years.