{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T02:20:12Z","timestamp":1782872412499,"version":"3.54.5"},"reference-count":39,"publisher":"BMJ","issue":"1","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Open Heart"],"accepted":{"date-parts":[[2019,4,14]]},"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Cardiac biomarkers hold promise for follow-up and management of aortic valve stenosis (AVS). When interpreting serial biomarker measurements of patients with AVS, it can be challenging to distinguish \u2018real changes\u2019 from \u2018random fluctuation\u2019. Hence, robust estimation of the biological variation of these biomarkers is essential. In the present study we assessed biological variation of B-type natriuretic peptide (BNP), N-terminus pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin-T and high-sensitivity troponin-I (hs-TnT and hs-TnI), and ST2 in subjects with stable AVS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Serial blood sampling was performed in 25 subjects with moderate AVS\u2014confirmed by echocardiography\u2014and all free from acute cardiovascular events in the past 6 months. Blood samples were taken on seven standardised occasions during 1 year. Analytical variation (CV<jats:sub>A<\/jats:sub>), within-subject biological variation (CV<jats:sub>I<\/jats:sub>), between-subject biological variation (CV<jats:sub>G<\/jats:sub>), index of individuality (II) and reference change values were calculated for all cardiac biomarkers.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>CV<jats:sub>I<\/jats:sub> was highest for BNP (62.0%, 95% CI 52.5 to 75.4) and lowest for hs-TnI (9.2%, 95% CI 2.8 to 13.8). CV<jats:sub>G<\/jats:sub> exceeded the CV<jats:sub>I<\/jats:sub> for all biomarkers except BNP, and ranged from 19.8% (95% CI 13.8 to 33.4) for ST2 to 57.2% (95% CI 40.4 to 97.3) for hs-TnT. NT-proBNP, hs-TnT and ST2 revealed CV<jats:sub>A<\/jats:sub> &lt;5%, while BNP and hs-TnI showed a higher CV<jats:sub>A<\/jats:sub> (19.7 and 14.9, respectively). All biomarkers except BNP showed marked individuality, with II ranging from 0.21 to 0.67 (BNP 1.34).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This study provides the first biological variation estimates of cardiac biomarkers in patients with stable AVS. These estimates allow a more evidence-based interpretation of biomarker changes in the follow-up and management of patients with AVS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>\n                     <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT02510482\">NCT02510482<\/jats:ext-link>\n                  <\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/openhrt-2019-001040","type":"journal-article","created":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T08:25:38Z","timestamp":1557390338000},"page":"e001040","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["Biological variation of cardiac markers in patients with aortic valve stenosis"],"prefix":"10.1136","volume":"6","clinical-trial-number":[{"clinical-trial-number":"nct02510482","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6687-1330","authenticated-orcid":false,"given":"Frederique E C M","family":"Peeters","sequence":"first","affiliation":[{"name":"Cardiology, Maastricht University Medical Center+ and CARIM, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bas L J H","family":"Kietselaer","sequence":"additional","affiliation":[{"name":"Cardiology, Zuyderland Medisch Centrum Heerlen, Heerlen, Limburg, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Hilderink","sequence":"additional","affiliation":[{"name":"Clinical Chemistry, Maastricht University Medical Center+ and CARIM, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noreen","family":"van der Linden","sequence":"additional","affiliation":[{"name":"Clinical Chemistry, Maastricht University Medical Center+ and CARIM, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijke","family":"Niens","sequence":"additional","affiliation":[{"name":"Clinical Chemistry, Laurentius Ziekenhuis, Roermond, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry J G M","family":"Crijns","sequence":"additional","affiliation":[{"name":"Cardiology, Maastricht University Medical Center+ and CARIM, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J R","family":"Meex","sequence":"additional","affiliation":[{"name":"Clinical Chemistry, Maastricht University Medical Center+ and CARIM, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2019,5,8]]},"reference":[{"key":"2025081710174244000_6.1.e001040.1","doi-asserted-by":"crossref","unstructured":"Toutouzas K , Stathogiannis K , Latsios G , et al . 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