Abstract Background Transthyretin (TTR), a hepatically synthesized protein involved in the transport of thyroxine and retinol-binding protein, has emerged as a potential biomarker in cardiovascular (CV) disease. Evidence suggests that serum TTR levels may have prognostic significance for CV outcomes. However, the existing data are fragmented, necessitating a comprehensive synthesis to clarify its clinical relevance. Objective This meta-analysis sought to evaluate the prognostic utility of serum TTR levels in predicting CV events across diverse patient populations. Methods A systematic literature search was conducted across major electronic databases up to February 2025. Studies reporting hazard ratios (HRs) or risk estimates for the association between serum TTR levels and outcomes of interest (CV events) were included. Pooled HRs with 95% confidence intervals (CIs) were calculated using random-effects models. Results A total of 16 studies involving 76,118 participants were included in the analysis. Low serum TTR levels were significantly associated with an increased risk of CV events (HR=1.48 with 1.26 to 1.70, 95% CI, p 0.001). Analyses across various populations, including those with heart failure, chronic kidney disease, elderly individuals and patients with aTTR amyloidosis, provided similar results. Conclusions Serum TTR is a predictor of CV events, across different populations, underscoring its potential use as a biomarker of in clinical practice, even in populations without overt aTTR amyloidosis, suggesting a potential early effect on the cardiovascular system.
Koilakou et al. (2025) studied this question.