The predictive value of Atherogenic index of plasma and Clonal Hematopoiesis of Indeterminate Potential among Patients with STEMI---from a prospective cohort study

The predictive value of Atherogenic index of plasma and Clonal Hematopoiesis of Indeterminate Potential among Patients with STEMI---from a prospective cohort study | 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 The predictive value of Atherogenic index of plasma and Clonal Hematopoiesis of Indeterminate Potential among Patients with STEMI---from a prospective cohort study Xiaoxiao Zhao, Jiannan Li, Runzhen Chen, Yu Tan, Nan Li, Linghan Xue, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6685829/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 13 Aug, 2025 Read the published version in Cardiovascular Diabetology → Version 1 posted 9 You are reading this latest preprint version Abstract Acute coronary syndrome (ACS) remains a leading global cause of mortality despite advances in revascularization therapies. This prospective cohort study investigated the synergistic prognostic impact of clonal hematopoiesis of indeterminate potential (CHIP) and atherogenic index of plasma (AIP) in 1,396 ACS patients undergoing primary percutaneous coronary intervention at Fuwai Hospital (2017–2020). Using deep targeted sequencing (42 genes, median depth 14,219×), we identified CHIP mutations (VAF ≥ 2%) in 14.5% of participants, with DNMT3A (23.7%), TET2 (2.8%), and ASXL1 (1.9%) being most prevalent. High-AIP patients were younger (57.7 vs 63.1 years), had elevated hs-CRP (7.0 vs 6.0 mg/L), and higher smoking rates, suggesting accelerated atherosclerosis. Multivariable Cox regression revealed that in patients with AIP ≥ median, CHIP carriers exhibited significantly higher all-cause mortality (adjusted HR 2.22, 95% CI 1.24–3.98; p = 0.007), particularly for TET2 mutations (HR 6.37, CI 95%: 2.92–13.93; p<0.001) and TET2/ASXL1 co-mutations (HR 4.31, CI 95%: 2.13–8.74 ; p<0.001). Notably, DNMT3A frameshift variants showed non-significant mortality trends (HR 2.18, CI 95%: 0.65–7.38). Kaplan-Meier analyses confirmed the mortality risk stratification by AIP-CHIP interaction (log-rank p = 0.006), while no association emerged in low-AIP patients. These findings establish AIP as a critical modifier of CHIP-related cardiovascular risk, potentially through enhanced inflammatory pathways in younger ACS populations. The study highlights the clinical utility of combining lipid-based (AIP) and genetic (CHIP) biomarkers for precision prognostication, though validation in larger cohorts and mechanistic investigations of the AIP-CHIP interplay are warranted to guide targeted therapies. AIP clonal hematopoiesis of indeterminate potential ST-segment elevation myocardial infarction mortality Full Text Additional Declarations No competing interests reported. Supplementary Files supplement20250517.docx Cite Share Download PDF Status: Published Journal Publication published 13 Aug, 2025 Read the published version in Cardiovascular Diabetology → Version 1 posted Editorial decision: Revision requested 26 Jun, 2025 Reviews received at journal 26 Jun, 2025 Reviewers agreed at journal 05 Jun, 2025 Reviews received at journal 05 Jun, 2025 Reviewers agreed at journal 20 May, 2025 Reviewers invited by journal 20 May, 2025 Editor assigned by journal 17 May, 2025 Submission checks completed at journal 17 May, 2025 First submitted to journal 17 May, 2025 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. 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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-6685829","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":459615056,"identity":"7b094145-6ad8-4568-aedc-c2ac7e23c1e0","order_by":0,"name":"Xiaoxiao Zhao","email":"","orcid":"","institution":"Chinese Academy of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Xiaoxiao","middleName":"","lastName":"Zhao","suffix":""},{"id":459615057,"identity":"c5e08302-2d32-426e-929e-db48240d2fc9","order_by":1,"name":"Jiannan Li","email":"","orcid":"","institution":"Chinese Academy of Medical 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study","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"cardiovascular-diabetology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cvdb","sideBox":"Learn more about [Cardiovascular Diabetology](http://cardiab.biomedcentral.com/)","snPcode":"12933","submissionUrl":"https://submission.nature.com/new-submission/12933/3","title":"Cardiovascular Diabetology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"AIP, clonal hematopoiesis of indeterminate potential, ST-segment elevation myocardial infarction, mortality","lastPublishedDoi":"10.21203/rs.3.rs-6685829/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6685829/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAcute coronary syndrome (ACS) remains a leading global cause of mortality despite advances in revascularization therapies. This prospective cohort study investigated the synergistic prognostic impact of clonal hematopoiesis of indeterminate potential (CHIP) and atherogenic index of plasma (AIP) in 1,396 ACS patients undergoing primary percutaneous coronary intervention at Fuwai Hospital (2017\u0026ndash;2020). Using deep targeted sequencing (42 genes, median depth 14,219\u0026times;), we identified CHIP mutations (VAF\u0026thinsp;\u0026ge;\u0026thinsp;2%) in 14.5% of participants, with DNMT3A (23.7%), TET2 (2.8%), and ASXL1 (1.9%) being most prevalent. High-AIP patients were younger (57.7 vs 63.1 years), had elevated hs-CRP (7.0 vs 6.0 mg/L), and higher smoking rates, suggesting accelerated atherosclerosis. Multivariable Cox regression revealed that in patients with AIP\u0026thinsp;\u0026ge;\u0026thinsp;median, CHIP carriers exhibited significantly higher all-cause mortality (adjusted HR 2.22, 95% CI 1.24\u0026ndash;3.98; p\u0026thinsp;=\u0026thinsp;0.007), particularly for TET2 mutations (HR 6.37, CI 95%: 2.92\u0026ndash;13.93; p\u0026lt;0.001) and TET2/ASXL1 co-mutations (HR 4.31, CI 95%: 2.13\u0026ndash;8.74 ; p\u0026lt;0.001). Notably, DNMT3A frameshift variants showed non-significant mortality trends (HR 2.18, CI 95%: 0.65\u0026ndash;7.38). Kaplan-Meier analyses confirmed the mortality risk stratification by AIP-CHIP interaction (log-rank p\u0026thinsp;=\u0026thinsp;0.006), while no association emerged in low-AIP patients. These findings establish AIP as a critical modifier of CHIP-related cardiovascular risk, potentially through enhanced inflammatory pathways in younger ACS populations. The study highlights the clinical utility of combining lipid-based (AIP) and genetic (CHIP) biomarkers for precision prognostication, though validation in larger cohorts and mechanistic investigations of the AIP-CHIP interplay are warranted to guide targeted therapies.\u003c/p\u003e","manuscriptTitle":"The predictive value of Atherogenic index of plasma and Clonal Hematopoiesis of Indeterminate Potential among Patients with STEMI---from a prospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-22 10:02:25","doi":"10.21203/rs.3.rs-6685829/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-06-26T15:58:29+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-26T15:44:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"270244992602099023489414522516894531217","date":"2025-06-05T15:37:42+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-05T14:31:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"336920270782493304837253446881442743666","date":"2025-05-20T17:55:40+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-20T14:24:01+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-17T15:40:21+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-17T14:05:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"Cardiovascular Diabetology","date":"2025-05-17T08:52:37+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"cardiovascular-diabetology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cvdb","sideBox":"Learn more about [Cardiovascular Diabetology](http://cardiab.biomedcentral.com/)","snPcode":"12933","submissionUrl":"https://submission.nature.com/new-submission/12933/3","title":"Cardiovascular Diabetology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"06be8847-7b6f-491a-b647-fed4ea781da6","owner":[],"postedDate":"May 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-08-18T16:01:52+00:00","versionOfRecord":{"articleIdentity":"rs-6685829","link":"https://doi.org/10.1186/s12933-025-02877-4","journal":{"identity":"cardiovascular-diabetology","isVorOnly":false,"title":"Cardiovascular Diabetology"},"publishedOn":"2025-08-13 15:56:52","publishedOnDateReadable":"August 13th, 2025"},"versionCreatedAt":"2025-05-22 10:02:25","video":"","vorDoi":"10.1186/s12933-025-02877-4","vorDoiUrl":"https://doi.org/10.1186/s12933-025-02877-4","workflowStages":[]},"version":"v1","identity":"rs-6685829","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6685829","identity":"rs-6685829","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}