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Methods: UK Biobank data were analyzed; serum BCAAs (leucine, isoleucine, valine) were measured by nuclear magnetic resonance metabolic profiling, with RHD identified via inpatient records and death registries, using multivariable Cox regression and causal mediation. Results: 273,595 participants yielded 6,051 cases; higher total BCAAs correlated with increased RHD risk, with valine strongest, and immune markers significantly mediated effects. Conclusions: Serum BCAAs associate with elevated RHD risk, especially in adults \u003C65, and immune-modulatory pathways may be therapeutic targets, though causality needs experimental validation.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/serum-branched-chain-amino-acids-and-chronic-rheumatic-heart-diseases-evidence-from-a-population-based-prospective-study/457345/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/serum-branched-chain-amino-acids-and-chronic-rheumatic-heart-diseases-evidence-from-a-population-based-prospective-study/457345.png","ImageObject",300,407,{"name":92,"@type":93},"Stanley","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What was the primary objective of the study?","Question",{"text":112,"@type":113},"To evaluate the association between serum branched-chain amino acids (BCAAs) and chronic rheumatic heart disease risk, and to explore immune-marker mediated mechanisms.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were serum BCAAs and chronic RHD cases determined?",{"text":117,"@type":113},"Serum BCAAs (leucine, isoleucine, valine) were measured using nuclear magnetic resonance metabolic profiling, while chronic RHD was identified from hospital inpatient records and death registries.",{"name":119,"@type":110,"acceptedAnswer":120},"What did the study find about the relationship between BCAAs and RHD risk?",{"text":121,"@type":113},"An increase in total BCAAs was associated with higher RHD risk, and valine showed the strongest association among individual BCAAs; mediation analysis indicated immune markers significantly mediated the BCAA–RHD link.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},457345,1791151786,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},2336477405376,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Rev. Cardiovasc. Med. 2025; 26(12): 44157 [https://doi.org/10.31083/RCM44157](https://doi.org/10.31083/RCM44157)  \nOriginal Research  \nSerum Branched-Chain Amino Acids and Chronic Rheumatic Heart Diseases: Evidence From a Population-Based Prospective Study  \nLingling Xu 1 ,†, Zhixing Fan2 ,†, Bo Pang 1 , *  \n1Department of Hematology and Rheumatology, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, 430022 Wuhan, Hubei, China  \n2Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University, 443003 Yichang, Hubei, China  \n*Correspondence: [35479962@qq.com](35479962@qq.com) (Bo Pang)†These authors contributed equally.  \nAcademic Editor: Anindita Das  \nSubmitted: 23 June 2025 Revised: 16 September 2025 Accepted: 22 September 2025 Published: 23 December 2025  \nAbstract  \nBackground: 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 \u003C65 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 \u003C65 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.  \nKeywords: branched-chain amino acids; chronic rheumatic heart diseases; immune markers; therapeutic targets  \n1. Introduction  \nRheumatic heart disease (RHD) represents one of the most significant yet preventable cardiovascular conditions globally, continuing to impose a substantial burden on public health systems worldwide [1,2] . Despite being eminently preventable for over 70 years, RHD is the predominant cause of cardiovascular morbidity and early death among young people worldwide, with a particular impact on those in low-and middle-income countries [3,4] . Current epidemiological data reveal alarming statistics: an estimated 54.8 million cases of RHD existed globally in 2021, with South Asia alone accounting for 57.6% of global RHD-related deaths [3,5] . The disease demonstrates particularly high prevalence rates in endemic regions, with African populations showing rates of 18.41 per 1000 individuals [6] . This substantial disease burden translates into significant economic costs and prolonged disability, disproportionately affecting children and young adults in their most energetic years [7] . RHD primarily results from an autoimmune response triggered by group A β-hemolytic streptococca","cbCaidwBmps4u0oK","https://ap.wps.com/l/cbCaidwBmps4u0oK","pdf",964252,13,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Introduction\n## Rheumatic heart disease burden and pathogenesis\n## Branched-chain amino acids and cardiovascular relevance","[{\"question\":\"What was the primary objective of the study?\",\"answer\":\"To evaluate the association between serum branched-chain amino acids (BCAAs) and chronic rheumatic heart disease risk, and to explore immune-marker mediated mechanisms.\"},{\"question\":\"How were serum BCAAs and chronic RHD cases determined?\",\"answer\":\"Serum BCAAs (leucine, isoleucine, valine) were measured using nuclear magnetic resonance metabolic profiling, while chronic RHD was identified from hospital inpatient records and death registries.\"},{\"question\":\"What did the study find about the relationship between BCAAs and RHD risk?\",\"answer\":\"An increase in total BCAAs was associated with higher RHD risk, and valine showed the strongest association among individual BCAAs; mediation analysis indicated immune markers significantly mediated the BCAA–RHD link.\"}]","Serum Branched-Chain Amino Acids and Chronic Rheumatic Heart Diseases: Evidence From a Population-Based Prospective Study | PDF",1790748936,33]