Circulating Fibrinogen Gamma Chain as a Novel Biomarker for Chronic Heart Failure: Development and Validation of a Diagnostic Nomogram

Circulating Fibrinogen Gamma Chain as a Novel Biomarker for Chronic Heart Failure: Development and Validation of a Diagnostic Nomogram | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Circulating Fibrinogen Gamma Chain as a Novel Biomarker for Chronic Heart Failure: Development and Validation of a Diagnostic Nomogram Nanyuan Gu, Chao Yang, Longhuan Zeng, Yang Chen, Leifei Chen, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9205829/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background To evaluate the potential of serum fibrinogen gamma chain (FGG) as a biomarker for chronic heart failure (CHF) by investigating its expression levels and associations with clinical variables, and to develop and validate a diagnostic nomogram for the early detection of CHF. Methods This cross-sectional diagnostic study enrolled 386 inpatients from the Department of Cardiology between November 2023 and November 2024, including 209 patients with CHF and 177 controls. In addition, comprehensive clinical data, echocardiographic parameters, and laboratory indices were systematically collected. Serum FGG levels were quantified using a standardized enzyme-linked immunosorbent assay (ELISA). Key predictors were identified using multivariate logistic regression. An FGG-integrated nomogram was constructed using the rms package in R and rigorously validated for discriminative performance and clinical utility by receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA). Results Serum FGG levels were significantly elevated in the CHF group compared with the control group. FGG demonstrated high diagnostic accuracy for CHF, with an area under the curve (AUC) of 0.918 (95% confidence interval [CI]: 0.886–0.943). Notably, at the optimal cutoff value of 325.75 ng/mL, FGG yielded a sensitivity of 92.82% and a specificity of 83.05%. Importantly, multivariate analysis identified elevated FGG (≥ 325.75 ng/mL) as a strong independent predictor of CHF (adjusted odds ratio [OR] = 132.13, 95% CI: 37.02–471.59; P < 0.0001). The nomogram incorporating FGG, BNP, age, BMI, BUN, and homocysteine demonstrated excellent discriminative ability, achieving an AUC of 0.982 (95% CI: 0.963–0.993), and provided superior net clinical benefit according to DCA. Conclusion Serum FGG is an independent predictor of CHF. The FGG-based nomogram provides an effective, quantifiable tool for early identification of CHF by integrating this biomarker with routine clinical variables. chronic heart failure fibrinogen gamma chain nomogram Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 12 May, 2026 Reviews received at journal 04 May, 2026 Reviewers agreed at journal 29 Apr, 2026 Reviewers agreed at journal 28 Apr, 2026 Reviewers invited by journal 21 Apr, 2026 Editor invited by journal 27 Mar, 2026 Editor assigned by journal 25 Mar, 2026 Submission checks completed at journal 25 Mar, 2026 First submitted to journal 23 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9205829","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":631961651,"identity":"0a1bae33-0da1-40b9-b370-89b2ad385dcb","order_by":0,"name":"Nanyuan Gu","email":"","orcid":"","institution":"Hangzhou Geriatric Hospital","correspondingAuthor":false,"prefix":"","firstName":"Nanyuan","middleName":"","lastName":"Gu","suffix":""},{"id":631961652,"identity":"b5496c1b-19c0-43d1-8a00-264683a90add","order_by":1,"name":"Chao Yang","email":"","orcid":"","institution":"Hangzhou Geriatric 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02:40:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9205829/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9205829/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108492015,"identity":"b9f29b72-4f39-4b8d-9e7d-734b38ae185d","added_by":"auto","created_at":"2026-05-05 09:56:36","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":848690,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript2026324.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9205829/v1_covered_7994e872-8b93-4208-82e3-0787f02dabf6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Circulating Fibrinogen Gamma Chain as a Novel Biomarker for Chronic Heart Failure: Development and Validation of a Diagnostic Nomogram","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"chronic heart failure, fibrinogen gamma chain, nomogram","lastPublishedDoi":"10.21203/rs.3.rs-9205829/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9205829/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eTo evaluate the potential of serum fibrinogen gamma chain (FGG) as a biomarker for chronic heart failure (CHF) by investigating its expression levels and associations with clinical variables, and to develop and validate a diagnostic nomogram for the early detection of CHF.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis cross-sectional diagnostic study enrolled 386 inpatients from the Department of Cardiology between November 2023 and November 2024, including 209 patients with CHF and 177 controls. In addition, comprehensive clinical data, echocardiographic parameters, and laboratory indices were systematically collected. Serum FGG levels were quantified using a standardized enzyme-linked immunosorbent assay (ELISA). Key predictors were identified using multivariate logistic regression. An FGG-integrated nomogram was constructed using the rms package in R and rigorously validated for discriminative performance and clinical utility by receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eSerum FGG levels were significantly elevated in the CHF group compared with the control group. FGG demonstrated high diagnostic accuracy for CHF, with an area under the curve (AUC) of 0.918 (95% confidence interval [CI]: 0.886\u0026ndash;0.943). Notably, at the optimal cutoff value of 325.75 ng/mL, FGG yielded a sensitivity of 92.82% and a specificity of 83.05%. Importantly, multivariate analysis identified elevated FGG (\u0026ge;\u0026thinsp;325.75 ng/mL) as a strong independent predictor of CHF (adjusted odds ratio [OR]\u0026thinsp;=\u0026thinsp;132.13, 95% CI: 37.02\u0026ndash;471.59; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). The nomogram incorporating FGG, BNP, age, BMI, BUN, and homocysteine demonstrated excellent discriminative ability, achieving an AUC of 0.982 (95% CI: 0.963\u0026ndash;0.993), and provided superior net clinical benefit according to DCA.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eSerum FGG is an independent predictor of CHF. The FGG-based nomogram provides an effective, quantifiable tool for early identification of CHF by integrating this biomarker with routine clinical variables.\u003c/p\u003e","manuscriptTitle":"Circulating Fibrinogen Gamma Chain as a Novel Biomarker for Chronic Heart Failure: Development and Validation of a Diagnostic Nomogram","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-30 19:32:49","doi":"10.21203/rs.3.rs-9205829/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-12T11:42:40+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-05T01:46:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"218031374984939429606010124491728420031","date":"2026-04-29T18:16:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"259731102254443918444488338025568505099","date":"2026-04-28T22:19:25+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-21T14:44:57+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-27T11:46:46+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-25T06:21:42+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-25T06:21:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cardiovascular Disorders","date":"2026-03-24T02:31:18+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b4aca2fe-ee6e-413a-8397-172bab7e47c7","owner":[],"postedDate":"April 30th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-12T11:42:40+00:00","index":55,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-05T01:46:50+00:00","index":54,"fulltext":""},{"type":"reviewerAgreed","content":"218031374984939429606010124491728420031","date":"2026-04-29T18:16:05+00:00","index":51,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-30T19:32:49+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-30 19:32:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9205829","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9205829","identity":"rs-9205829","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}