{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T08:08:51Z","timestamp":1783930131825,"version":"3.55.0"},"reference-count":30,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:00:00Z","timestamp":1783728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["JP24K02714"],"award-info":[{"award-number":["JP24K02714"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Branched-chain amino acids (BCAAs) may play a protective role in the progression of heart failure; however, controversial results also exist. This study investigates the association between fasting serum BCAA levels and plasma NT-proBNP concentrations in individuals with fragmented QRS (fQRS) on ECGs within the HOZUGAWA health-checkup cohort in Japan, offering insights into cardiac health. Methods: This analysis included 252 participants who attended health check-ups. Fasting blood samples were analyzed using a standardized laboratory test. Unitless internal-standard-normalized relative peak-area ratios of BCAAs and selected amino-acid-related organic acids were measured and log-transformed for analysis. Results: NT-proBNP levels did not differ significantly between individuals with and without fQRS. Among those with fQRS, higher levels of BCAAs and 2-hydroxybutyric acid (2-HB) were associated with lower NT-proBNP levels: leucine (r = \u22120.38, p = 0.0001), while valine (r = \u22120.28, p = 0.0053) and isoleucine (r = \u22120.21, p = 0.041); 2-HB (r = \u22120.21, p = 0.039). After adjustment for age, sex, BMI, and estimated glomerular filtration rate (eGFR) (n = 252), leucine remained inversely associated with NT-proBNP in individuals with fQRS (r = \u22120.28, p = 0.0072) and positively associated in those without fQRS (r = 0.23, p = 0.0048). fQRS showed an interaction with leucine levels regarding NT-proBNP levels. Conclusions: Associations between relative leucine abundance and NT-proBNP levels varied by fQRS status, with significant inverse associations observed only among participants with fQRS, suggesting that lower relative BCAA abundance may be associated with markers of cardiac dysfunction and that leucine-related metabolic signatures may be linked to NT-proBNP levels in individuals with fQRS. Additional longitudinal and mechanistic studies are necessary to confirm these findings, particularly in individuals with cardiac fibrosis. Further research is warranted to explore therapeutic implications.<\/jats:p>","DOI":"10.3390\/nu18142271","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T07:28:27Z","timestamp":1783927707000},"page":"2271","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association Between Serum Leucine and NT-proBNP Levels in Relation to Fragmented QRS: A Multiomic Analysis of the HOZUGAWA Cohort"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6805-6428","authenticated-orcid":false,"given":"Kunimasa","family":"Yagi","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku 920-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1707-970X","authenticated-orcid":false,"given":"Hiroshi","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8651-4445","authenticated-orcid":false,"given":"Masahide","family":"Hamaguchi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3263-9469","authenticated-orcid":false,"given":"Noriyuki","family":"Kitagawa","sequence":"additional","affiliation":[{"name":"Department of Diabetology, Kameoka Municipal Hospital, Kyoto 621-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8794-0550","authenticated-orcid":false,"given":"Yoshitaka","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, Matsushita Memorial Hospital, Moriguchi 570-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Origasa","sequence":"additional","affiliation":[{"name":"Data Science and AI Innovation Research Promotion Center, Institute of Statistical Mathematics, Shiga University, Hikone 525-0034,  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0903-1797","authenticated-orcid":false,"given":"Michiaki","family":"Fukui","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.jchf.2018.03.006","article-title":"Temporal trends in the incidence of and mortality associated with heart failure with preserved and reduced ejection fraction","volume":"6","author":"Tsao","year":"2018","journal-title":"JACC Heart Fail."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1161\/CIRCRESAHA.121.318172","article-title":"Epidemiology of heart failure: A contemporary perspective","volume":"128","author":"Roger","year":"2021","journal-title":"Circ. 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