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Serum Branched-Chain Amino Acids and Chronic Rheumatic Heart Diseases: Evidence From a Population-Based Prospective
Lingling Xu1, Zhixing Fan2, Bo Pang1
1Department of Hematology and Rheumatology, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, 430022 Wuhan, Hubei, China.
Insights
Higher serum branched-chain amino acids (BCAAs) are linked to an increased risk of rheumatic heart disease (RHD), particularly in younger adults. Immune markers significantly mediate this association, suggesting potential therapeutic targets for RHD prevention.
Area of Science:
- Cardiovascular Disease Epidemiology
- Metabolomics
- Immunology
Background:
- Rheumatic heart disease (RHD) poses a significant global health burden.
- Understanding the risk factors and underlying mechanisms of RHD is crucial for effective prevention and management.
Purpose of the Study:
- To investigate the association between serum branched-chain amino acids (BCAAs) and the risk of developing chronic RHD.
- To explore the role of immune markers as potential mediators in the relationship between BCAAs and RHD.
Main Methods:
- Prospective cohort study utilizing UK Biobank data.
- Serum BCAAs measured via nuclear magnetic resonance metabolic profiling.
- RHD cases identified through hospital records and death registries; Cox regression and causal mediation analyses performed.
Main Results:
- Increased serum BCAAs associated with higher RHD risk (HR=1.048 per SD increase).
- Valine showed the strongest association; risk elevation more pronounced in individuals <65 years.
- Immune markers significantly mediated the BCAA-RHD link, with lymphocyte-to-C-reactive protein ratio explaining 30.8% of the effect.
Conclusions:
- Serum BCAAs may serve as a biomarker for RHD risk, especially in younger populations.
- Immunomodulatory pathways are implicated in RHD pathogenesis, offering potential therapeutic targets.
- Findings contribute to understanding RHD etiology and may aid in risk stratification and prevention strategies.
Background:
This study aimed to systematically investigate the association between serum branched-chain amino acids (BCAAs) and the risk of chronic rheumatic heart disease (RHD), as well as to explore potential mediating mechanisms through immune markers.
Methods:
The data utilized in this prospective cohort study were derived from the UK Biobank. Serum BCAAs (leucine, isoleucine, and valine) were measured using metabolic profiling of nuclear magnetic resonance data. Chronic RHD cases were identified through hospital inpatient records and death registries. Multivariable Cox regression models were used to analyze the association between BCAAs and RHD risk. Causal mediation analysis was employed to investigate the mediated role of immune markers.
Results:
A total of 273,595 participants were included, with 6051 (2.21%) participants developing chronic RHD. Each one-unit standard deviation increase in total BCAAs was associated with a 4.8% increased risk of RHD (hazard ratio (HR) = 1.048, 95% confidence interval (CI): 1.023-1.074). Among individual BCAAs, valine exhibited the strongest association (HR = 1.061, 95% CI: 1.035-1.088). Subgroup analyses revealed significantly stronger associations in participants aged <65 years compared to those aged ≥65 years (p for interaction = 0.032). Mediation analysis demonstrated that immune markers significantly mediated the BCAA-RHD association, with lymphocyte-to-C-reactive protein ratio accounting for 30.8% of the total effect.
Conclusions:
Observational data suggest serum BCAAs correlate with increased RHD risk, especially in individuals aged <65 years; however, causation requires experimental verification. Immune markers significantly mediate the BCAA-RHD association, indicating that immunomodulatory pathways may be potential therapeutic targets. These findings provide novel insights into RHD pathogenesis and may inform risk stratification and prevention strategies.
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