Circulating Biomarkers as Predictors of Improvement in Physical Function in Hospitalized Older Adults With Geriatric Syndromes: Findings From the REHAB-HF Trial

BACKGROUND: Biomarkers in heart failure (HF) provide mechanistic and prognostic insights, but their role in predicting treatment response is less understood. We evaluated whether multiple baseline biomarker profiles from the REHAB-HF trial (Rehabilitation Therapy in Older Acute Heart Failure Patients) could stratify functional improvement following a 12-week physical rehabilitation intervention (RI). METHODS: Participants ≥60 years hospitalized with heart failure were randomized to a 12-week outpatient RI or attention control. Functional outcomes included changes in the short physical performance battery and 6-minute walk distance. Blood collected at baseline and 12 weeks was analyzed for cardiac (cTnI and cTnT, NT-proBNP [N-terminal pro-brain natriuretic peptide]), renal (creatinine), and inflammatory (CRP [C-reactive protein]) biomarkers. Associations between baseline biomarker levels and 12-week functional gains by treatment group were evaluated using adjusted linear regression models and machine learning–based decision trees. RESULTS: Baseline biomarker data were available for 242 of 349 participants (69%). Using linear regression, higher cTnI and T were associated with greater 12-week gains in the short physical performance battery and 6-minute walk distance, respectively, among RI participants versus attention control (interaction P =0.040 and 0.032). In the decision tree, analyses combining all biomarkers, CRP emerged as the primary biomarker for both outcomes. Among participants with CRP ≥9.9 mg/L, RI was associated with a +2.4 point (95% CI, 1.8–3.1) greater increase in the short physical performance battery and a +79 m (95% CI, 50–109) greater increase in 6-minute walk distance compared with attention control. In contrast, for those with CRP <9.9 mg/L, the differential benefit of the RI was limited (+0.8 in short physical performance battery [95% CI, 0.1–1.6]; +30 m in 6-minute walk distance [95% CI, –1.0 to 61]). The biomarker levels (except for creatinine) decreased by 12 weeks posthospitalization, but with no differences based on treatment assignment. CONCLUSIONS: Higher inflammation, measured by CRP, may identify older adults recently hospitalized for heart failure with the greatest functional benefit from a physical RI. Biomarker profiling may predict the benefits of this treatment. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02196038.