Identification of inflammatory phenotypes of heart failure using systemic inflammation response index (SIRI): A cross-sectional analysis of NHANES 2021-2023

Associations of heart failure and its comorbidities with systemic inflammation response index (SIRI): A cross-sectional, population-based analysis of NHANES 2021-2023 | 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 Associations of heart failure and its comorbidities with systemic inflammation response index (SIRI): A cross-sectional, population-based analysis of NHANES 2021-2023 Naval Asija This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6751874/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract Background Systemic inflammation plays a crucial role in heart failure (HF) and its comorbidities, yet inflammatory markers associated with HF with comorbidities remain inadequately characterized. Objective To identify the associations of systemic inflammation response index (SIRI) with HF with comorbid states, including anemia, cancer, coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), diabetes mellitus (DM), hyperlipidemia, hypertension, obesity, and stroke. Method Single- and dual-comorbid states of HF were obtained from the National Health and Nutrition Examination Survey (NHANES) 2021–2023. Prevalence rates and odds ratios of single and dual-comorbid states of HF were calculated for participants with SIRI below and above the median value. Receiver Operating Curve (ROC) analyses were performed to estimate the area under the ROC curve (AUC). Results This study analyzed 7,582 NHANES participants; the median SIRI was 0.94. All comorbid states showed significantly higher prevalence rates and odds ratios for the participants with SIRI above 0.94. In the ROC analysis, all comorbid states showed significant associations with SIRI, including strong associations for HF plus stroke plus cancer (AUC = 0.833; 95% CI = 0.742–0.925), HF plus stroke plus DM (AUC = 0.808; 95% CI = 0.743–0.873), and HF plus stroke plus CAD (AUC = 0.791; 95%CI = 0.707–0.875). Conclusion SIRI is associated with HF with comorbidities. HF comorbid states with strong associations with SIRI include cardiovascular-kidney-metabolic syndrome and cancer. Cardiac & Cardiovascular Systems Inflammation heart failure diagnosis Figures Figure 1 Full Text Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-6751874","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":463622272,"identity":"50bac460-54c6-47df-a5cb-e379cd9be432","order_by":0,"name":"Naval Asija","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA50lEQVRIiWNgGAWjYLCCBwwMPIwNzAeATAkZ4rQkgLWwJYC08BCtBQh4DMAkQdXm7GcMPyTU1Mkwt5/5/OpGjQUPA/vhoxvwabHsyTGWSDh2mIexJ3ebdc4xoMN40tJu4NNicCAtQSKB7QDQL7nbjHPYgFokeMzwazn/LPlHwr86Hsb+N8+Mc/4Ro+VG8jGJxDZmHsYZOcyPc9uI0vL4mEViH9AvM56ZMef2SfCwEfTL+cTmGx++1dkb9ic//pzzrU6On/3wMbxa4MCwgYFNAsRgI0o5CMgzMDB/IFr1KBgFo2AUjCgAANL0SAc6z46cAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0003-2395-7334","institution":"Independent Researcher, Delhi, India","correspondingAuthor":true,"prefix":"","firstName":"Naval","middleName":"","lastName":"Asija","suffix":""}],"badges":[],"createdAt":"2025-05-26 14:41:00","currentVersionCode":2,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-6751874/v2","doiUrl":"https://doi.org/10.21203/rs.3.rs-6751874/v2","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":95135464,"identity":"5ea5491e-5075-42d9-9648-1adb8b43d68f","added_by":"auto","created_at":"2025-11-04 16:09:16","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":258506,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptSIRIHFRevised.docx","url":"https://assets-eu.researchsquare.com/files/rs-6751874/v2/2439e05d1efd19425284a3e5.docx"},{"id":95224775,"identity":"8efcf420-654c-4437-8e5c-f1c2a5850079","added_by":"auto","created_at":"2025-11-05 16:24:16","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":342,"visible":true,"origin":"","legend":"","description":"","filename":"rs6751874.json","url":"https://assets-eu.researchsquare.com/files/rs-6751874/v2/7fab001e7a8330c2e481faed.json"},{"id":95135462,"identity":"22f4a9ee-7e64-4e30-bd11-000975acbe76","added_by":"auto","created_at":"2025-11-04 16:09:16","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":136847,"visible":true,"origin":"","legend":"","description":"","filename":"rs67518741enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-6751874/v2/85be6cad52ff911f3d23a796.xml"},{"id":95135463,"identity":"6d598107-f139-4d95-b608-bbedafc3cbe8","added_by":"auto","created_at":"2025-11-04 16:09:16","extension":"xml","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":135826,"visible":true,"origin":"","legend":"","description":"","filename":"rs67518741structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-6751874/v2/2b5489f366a93398469c7c10.xml"},{"id":95135460,"identity":"ec81d7bc-c44c-48a0-8a8a-0b47cee5f8cc","added_by":"auto","created_at":"2025-11-04 16:09:16","extension":"html","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":137915,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-6751874/v2/72680d5bbe7322638f64f7d2.html"},{"id":95135459,"identity":"1bf0a4e8-1e70-43db-8584-242bd0a78d38","added_by":"auto","created_at":"2025-11-04 16:09:16","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":351057,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStudy criteria and participant flow\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6751874/v2/296e1718e554ff19ab34a554.png"},{"id":95230245,"identity":"d517d9e7-d1f9-4aa9-8d4c-9b8eb5c97684","added_by":"auto","created_at":"2025-11-05 16:37:03","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":519932,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptSIRIHFRevised.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6751874/v2_covered_b516f92e-6aec-4819-a14d-2579ad4ee5ca.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eAssociations of heart failure and its comorbidities with systemic inflammation response index (SIRI): A cross-sectional, population-based analysis of NHANES 2021-2023\u003c/strong\u003e\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Independent Researcher","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Inflammation, heart failure, diagnosis","lastPublishedDoi":"10.21203/rs.3.rs-6751874/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6751874/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eSystemic inflammation plays a crucial role in heart failure (HF) and its comorbidities, yet inflammatory markers associated with HF with comorbidities remain inadequately characterized.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eTo identify the associations of systemic inflammation response index (SIRI) with HF with comorbid states, including anemia, cancer, coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), diabetes mellitus (DM), hyperlipidemia, hypertension, obesity, and stroke.\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e\u003cp\u003eSingle- and dual-comorbid states of HF were obtained from the National Health and Nutrition Examination Survey (NHANES) 2021\u0026ndash;2023. Prevalence rates and odds ratios of single and dual-comorbid states of HF were calculated for participants with SIRI below and above the median value. Receiver Operating Curve (ROC) analyses were performed to estimate the area under the ROC curve (AUC).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThis study analyzed 7,582 NHANES participants; the median SIRI was 0.94. All comorbid states showed significantly higher prevalence rates and odds ratios for the participants with SIRI above 0.94. In the ROC analysis, all comorbid states showed significant associations with SIRI, including strong associations for HF plus stroke plus cancer (AUC\u0026thinsp;=\u0026thinsp;0.833; 95% CI\u0026thinsp;=\u0026thinsp;0.742\u0026ndash;0.925), HF plus stroke plus DM (AUC\u0026thinsp;=\u0026thinsp;0.808; 95% CI\u0026thinsp;=\u0026thinsp;0.743\u0026ndash;0.873), and HF plus stroke plus CAD (AUC\u0026thinsp;=\u0026thinsp;0.791; 95%CI\u0026thinsp;=\u0026thinsp;0.707\u0026ndash;0.875).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eSIRI is associated with HF with comorbidities. HF comorbid states with strong associations with SIRI include cardiovascular-kidney-metabolic syndrome and cancer.\u003c/p\u003e","manuscriptTitle":"Associations of heart failure and its comorbidities with systemic inflammation response index (SIRI): A cross-sectional, population-based analysis of NHANES 2021-2023","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2025-11-04 16:09:11","doi":"10.21203/rs.3.rs-6751874/v2","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2025-05-29 11:58:43","doi":"10.21203/rs.3.rs-6751874/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"de34552f-425c-4413-96d4-0172229e572c","owner":[],"postedDate":"November 4th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":56635796,"name":"Cardiac \u0026 Cardiovascular Systems"}],"tags":[],"updatedAt":"2025-05-29T11:58:43+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-04 16:09:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v2","identity":"rs-6751874","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6751874","identity":"rs-6751874","version":["v2"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}