{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T11:47:22Z","timestamp":1768564042649,"version":"3.49.0"},"posted":{"date-parts":[[2023,12,14]]},"group-title":"Cardiovascular Medicine","reference-count":29,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,12,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>The performance of high sensitivity troponin T (hs-cTnT), hs-cTnI, and N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) in patients with chronic kidney disease (CKD) is poorly understood.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We included adults with CKD (eGFR&lt;60 ml\/min\/1.73m\n                    <jats:sup>2<\/jats:sup>\n                    ) in the 1999-2004 NHANES. We calculated the 99\n                    <jats:sup>th<\/jats:sup>\n                    percentile of hs-cTnT, hs-cTnI (Abbott, Ortho, and Siemens assays), and NT-proBNP, measured the association between eGFR and cardiac biomarker concentration, and used Cox regression models to assess the relationship between cardiac biomarkers and CVD mortality.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Across 1,068 adults with CKD, the mean [SD] age was 71.9[12.7] years and 61.2% were female; 78.8% had elevated NT-proBNP and 42.6% had elevated hs-cTnT based on traditional clinical reference limits. The 99\n                    <jats:sup>th<\/jats:sup>\n                    percentile of hs-cTnT was 122 ng\/L (95% confidence interval (CI) 101-143), hs-cTnI\n                    <jats:sub>Abbott<\/jats:sub>\n                    was 69 ng\/L (95% CI 38-99), and NT-proBNP was 8952 pg\/mL (95% CI 7506-10,399). A 10 ml\/min decrease in eGFR was associated with greater increases in hs-cTnT and NT-proBNP than hs-cTnI (hs-cTnT: 27.5% increase (\u03b2=27.5, 95% CI 28.2-43.3)), NT-proBNP 46.0% increase (\u03b2=46.0, 95% CI 36.0-56.8), hs-cTnI\n                    <jats:sub>Siemens<\/jats:sub>\n                    17.9% (\u03b2=17.9, 95% CI 9.7-26.7). Each doubling of hs-cTnT, hs-cTnI, and NT-proBNP were associated with CVD mortality (hs-cTnT HR 1.62 [95% CI 1.32-1.98],\n                    <jats:italic>p<\/jats:italic>\n                    &lt;0.0001; hs-cTnI\n                    <jats:sub>Siemens<\/jats:sub>\n                    HR 1.40 [95% CI 1.26-1.55],\n                    <jats:italic>p<\/jats:italic>\n                    &lt;0.0001; NT-proBNP HR 1.29 [95% CI 1.19-1.41],\n                    <jats:italic>p<\/jats:italic>\n                    &lt;0.0001).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions and Relevance<\/jats:title>\n                  <jats:p>Community dwelling adults with CKD have elevated concentrations of cardiac biomarkers, above established reference ranges. Of the troponin assays, hs-cTnI concentration appears to be most stable across eGFR categories and is associated with CVD mortality.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Clinical Perspective<\/jats:title>\n                  <jats:sec>\n                    <jats:title>What is new?<\/jats:title>\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>This study investigated two important questions relevant to clinical practice. First, which cardiac biomarker (hs-cTnT or hs-cTnI) and which assay is least impacted eGFR in patients with CKD. Second, whether elevated levels of cardiac biomarkers in community-dwelling patients convey prognostic information in CKD in a more representative population.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Community dwelling adults with CKD have elevated concentrations of cardiac biomarkers, above established reference ranges. Of the troponin assays, hs-CTnI concentration appears to be most stable across the eGFR categories and is associated with CVD mortality in individuals with CKD.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>What are the clinical implications?<\/jats:title>\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>Community dwelling adults with CKD had elevated levels of cardiac biomarkers suggestive of subclinical myocardial injury, which were associated with increased risk of cardiovascular death.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>hs-cTnI was least affected by eGFR and retained prognostic significance, suggesting that it may be the superior assay for clinical use in CKD.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:sec>\n                <\/jats:sec>","DOI":"10.1101\/2023.12.12.23299886","type":"posted-content","created":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T18:30:19Z","timestamp":1702578619000},"source":"Crossref","is-referenced-by-count":3,"title":["Association of cardiac biomarkers, kidney function, and mortality among adults with chronic kidney disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7695-4674","authenticated-orcid":false,"given":"Sophie E.","family":"Claudel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sushrut S.","family":"Waikar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3534-9360","authenticated-orcid":false,"given":"Deepa M.","family":"Gopal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9497-6327","authenticated-orcid":false,"given":"Ashish","family":"Verma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023121808161808000_2023.12.12.23299886v1.1","doi-asserted-by":"crossref","unstructured":"Bansal N , Katz R , Seliger S , deFilippi C, Wettersten N , Zelnick LR , Berry JD , de Lemos JA , Christenson R , Killeen AA , Shlipak MG , Ix JH. Kidney Function Specific Reference Limits for N-terminal Pro Brain Natriuretic Peptide and High Sensitivity Troponin T: The Systolic Blood Pressure Intervention Trial. Kidney Med. 2022;4:100517.","DOI":"10.1016\/j.xkme.2022.100517"},{"key":"2023121808161808000_2023.12.12.23299886v1.2","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1053\/j.ajkd.2021.06.017","article-title":"Upper Reference Limits for High-Sensitivity Cardiac Troponin T and N-Terminal Fragment of the Prohormone Brain Natriuretic Peptide in Patients With CKD","volume":"79","year":"2022","journal-title":"American Journal of Kidney Diseases"},{"key":"2023121808161808000_2023.12.12.23299886v1.3","first-page":"387","article-title":"Universal Definition and Classification of Heart Failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology","volume":"27","year":"2021","journal-title":"Japanese Heart Failure Society and writing committee of the universal definition o. J Card Failure"},{"key":"2023121808161808000_2023.12.12.23299886v1.4","doi-asserted-by":"crossref","unstructured":"Havranek EP , Mujahid MS , Barr D a., Blair I V., Cohen MS , Cruz-Flores S , Davey-Smith G , Dennison- Himmelfarb CR , Lauer MS , Lockwood DW , Rosal M , Yancy CW . Social Determinants of Risk and Outcomes for Cardiovascular Disease. Circulation. 2015;CIR.0000000000000228.","DOI":"10.1161\/CIR.0000000000000228"},{"key":"2023121808161808000_2023.12.12.23299886v1.5","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.319811"},{"key":"2023121808161808000_2023.12.12.23299886v1.6","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1053\/j.ajkd.2020.09.021","article-title":"Change in Cardiac Biomarkers and Risk of Incident Heart Failure and Atrial Fibrillation in CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study","volume":"77","year":"2021","journal-title":"American Journal of Kidney Diseases"},{"key":"2023121808161808000_2023.12.12.23299886v1.7","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014010108"},{"key":"2023121808161808000_2023.12.12.23299886v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2020.08.028"},{"key":"2023121808161808000_2023.12.12.23299886v1.9","unstructured":"Centers for Disease Control and Prevention National Center for Health Statistics. NHANES Questionnaires, Datasets, and Related Documentation [Internet]. National Health and Nutrition Examination Survey. 2022;Available from: https:\/\/wwwn.cdc.gov\/nchs\/nhanes\/default.aspx"},{"key":"2023121808161808000_2023.12.12.23299886v1.10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMOA2102953\/SUPPL_FILE\/NEJMOA2102953_DISCLOSURES.PDF"},{"key":"2023121808161808000_2023.12.12.23299886v1.11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1114248"},{"key":"2023121808161808000_2023.12.12.23299886v1.12","first-page":"151","article-title":"Variance Estimation with Hot Deck Imputation: A Simulation Study of Three Methods","volume":"31","year":"2005","journal-title":"Statistics Canada [Internet"},{"key":"2023121808161808000_2023.12.12.23299886v1.13","doi-asserted-by":"crossref","unstructured":"Fang M , Wang D , Tang O , Mcevoy JW , Echouffo- JB , Christenson RH , Selvin E . Subclinical Cardiovascular Disease in US Adults With and Without Diabetes. J Am Heart Assoc. 2023;12.","DOI":"10.1161\/JAHA.122.029083"},{"key":"2023121808161808000_2023.12.12.23299886v1.14","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehad328"},{"key":"2023121808161808000_2023.12.12.23299886v1.15","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.cca.2020.01.027","article-title":"The 99th percentile upper reference limit for the 5th generation cardiac troponin T assay in the United States","volume":"504","year":"2020","journal-title":"Clinica Chimica Acta"},{"key":"2023121808161808000_2023.12.12.23299886v1.16","doi-asserted-by":"crossref","unstructured":"Govindarajulu US , Malloy EJ , Ganguli B , Spiegelman D , Eisen EA . The comparison of alternative smoothing methods for fitting non-linear exposure-response relationships with Cox models in a simulation study. International Journal of Biostatistics. 2009;5.","DOI":"10.2202\/1557-4679.1104"},{"key":"2023121808161808000_2023.12.12.23299886v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2015.01.008"},{"key":"2023121808161808000_2023.12.12.23299886v1.18","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1093\/clinchem\/45.7.1018","article-title":"Degradation of Cardiac Troponin I in Serum Complicates Comparisons of Cardiac Troponin I Assays","volume":"45","year":"1999","journal-title":"Clin Chem [Internet"},{"key":"2023121808161808000_2023.12.12.23299886v1.19","first-page":"1","article-title":"Comparisons of multiple troponin assays for detecting chronic myocardial injury in the general population: redundant or complementary?","volume":"00","year":"2023","journal-title":"Eur Heart J"},{"key":"2023121808161808000_2023.12.12.23299886v1.20","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehad328"},{"key":"2023121808161808000_2023.12.12.23299886v1.21","doi-asserted-by":"crossref","unstructured":"Kampmann J , Heaf J , Mogensen CB , Pedersen AK , Granh\u00f8j J , Mickley H , Kristensen F . Troponin Cut-Offs for Acute Myocardial Infarction in Patients with Impaired Renal Function\u2014A Systematic Review and Meta-Analysis. Diagnostics. 2022;12.","DOI":"10.3390\/diagnostics12020276"},{"key":"2023121808161808000_2023.12.12.23299886v1.22","doi-asserted-by":"crossref","unstructured":"Chesnaye NC , Szummer K , B\u00e1r\u00e1ny P , Heimb\u00fcrger O , Magin H , Almquist T , Uhlin F , Dekker FW , Wanner C , Jager KJ , Evans M , Cupisti A , Sagliocca A , Ferraro A , Musia\u0142a A , Mele A , Naticchia A , C\u00f2saro A , Woodman A , Ranghino A , Stucchi A , Jonsson A , Schneider A , Pignataro A , Schrander A , Torp A , McKeever A , Szymczak A , Blom AL , De Blasio A , Pani A , Tsalouichos A , Ullah A , McLaren B , van Dam B , Iwig B , Antonio B , Iorio BR Di , Rogland B , Perras B , Alessandra B , Harron C , Wallquist C , Siegert C , Barrett C , Gaillard C , Abaterusso C , Beerenhout C , O\u2019Toole C , Somma C , Marx C , Drechsler C , Summersgill C , Blaser C , D\u2019alessandro C , Emde C , Torino C , Zullo C , Pozzi C , Geddes C , Verburgh C , Janmaat C , Bergamo D , Ciurlino D , Motta D , Glowski D , McGlynn D , Vargas D , Krieter D , Russo D , Fuchs D , Sands D , Hoogeveen E , Irmler E , Dim\u00e9ny E , Favaro E , Platen E , Olczyk E , Hoorn E , Vigotti F , Caskey F , Ansali F , Conte F , Cianciotta F , Giacchino F , Cappellaio F , Pizzarelli F , Sundelin F , Greco G , Roy G , Porto G , Bigatti G , Marinangeli G , Cabiddu G , Hirst G , Fumagalli G , Caloro G , Piccoli G , et al. Association Between Renal Function and Troponin T Over Time in Stable Chronic Kidney Disease Patients. J Am Heart Assoc. 2019;8.","DOI":"10.1161\/JAHA.119.013091"},{"key":"2023121808161808000_2023.12.12.23299886v1.23","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1111\/j.1600-6143.2012.04317.x","article-title":"Cardiac troponin T before and after kidney transplantation: Determinants and implications for posttransplant survival","volume":"13","year":"2013","journal-title":"American Journal of Transplantation"},{"key":"2023121808161808000_2023.12.12.23299886v1.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2017.02.007"},{"key":"2023121808161808000_2023.12.12.23299886v1.25","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.029986"},{"key":"2023121808161808000_2023.12.12.23299886v1.26","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs163"},{"key":"2023121808161808000_2023.12.12.23299886v1.27","doi-asserted-by":"publisher","DOI":"10.1542\/peds.112.1.e70"},{"key":"2023121808161808000_2023.12.12.23299886v1.28","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.jacc.2021.11.023","article-title":"Association of Longitudinal High-Sensitivity Troponin T With Mortality in Patients With Chronic Kidney Disease","volume":"79","year":"2022","journal-title":"J Am Coll Cardiol"},{"key":"2023121808161808000_2023.12.12.23299886v1.29","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfn341"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.12.12.23299886","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:46:37Z","timestamp":1768506397000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2023.12.12.23299886"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,14]]},"references-count":29,"URL":"https:\/\/doi.org\/10.1101\/2023.12.12.23299886","relation":{},"subject":[],"published":{"date-parts":[[2023,12,14]]},"subtype":"preprint"}}