{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:26:22Z","timestamp":1790015182429,"version":"4.0.1"},"reference-count":56,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T00:00:00Z","timestamp":1651017600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Effect\u2010size underestimation impedes biomarker identification. Long follow\u2010up time in prospective studies attenuates effect\u2010size estimates for transient biomarkers, while disease category\u2013specific biomarkers are affected by merging of categories. Venous thromboembolism (VTE) encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE).<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>(i) To re\u2010analyze untargeted proteomic data to identify biomarker candidates for future VTE that differ between DVT and PE and are attenuated by extended time between sampling and VTE. (ii) To perform targeted candidate validation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients\/Methods<\/jats:title><jats:p>A VTE case\u2010control discovery study and a nested case\u2010control validation study were derived from the general population surveyed in 1994\u201395. Plasma was obtained at study enrollment, and VTE events were registered until 2007. Untargeted proteomic data were re\u2010analyzed for candidate discovery. Lipopolysaccharide\u2010binding protein (LBP) was validated by enzyme\u2010linked immunosorbent assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Elevated LBP was discovered as a candidate DVT biomarker in women with less than 3 years between blood sampling and DVT. In the validation study, the odds ratio (OR) for DVT was 2.03 (95% confidence intervals [CI]: 1.53\u20132.74) per standard deviation (SD) increase in LBP for women with less than 3 years between blood sampling and DVT. Adjustment for age, body mass index, and C\u2010reactive protein attenuated the OR to 1.79 (95% CI: 1.25\u20132.62) per SD. In the validation study, we observed an OR for VTE of 0.47 (95% CI: 0.28\u20130.77) for men in the 25<jats:sup>th<\/jats:sup> to 50<jats:sup>th<\/jats:sup> percentiles when compared to the lowest quartile.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We discovered and validated increased LBP as a predictive biomarker for DVT in women. We found an increased VTE risk for men in the lowest quartile of LBP.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.13502","type":"journal-article","created":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T04:44:31Z","timestamp":1649997871000},"page":"523-535","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Plasma lipopolysaccharide\u2010binding protein is a biomarker for future venous thromboembolism: Results from discovery and validation studies"],"prefix":"10.1111","volume":"292","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1892-2735","authenticated-orcid":false,"given":"S\u00f8ren Beck","family":"Jensen","sequence":"first","affiliation":[{"name":"Research Institute of Internal Medicine Oslo University Hospital Rikshospitalet  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadezhda","family":"Latysheva","sequence":"additional","affiliation":[{"name":"K. G. Jebsen Thrombosis Research and Expertise Center Department of Clinical Medicine UiT\u2014The Arctic University of Norway  Troms\u00f8 Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Hindberg","sequence":"additional","affiliation":[{"name":"K. G. Jebsen Thrombosis Research and Expertise Center Department of Clinical Medicine UiT\u2014The Arctic University of Norway  Troms\u00f8 Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thor","family":"Ueland","sequence":"additional","affiliation":[{"name":"Research Institute of Internal Medicine Oslo University Hospital Rikshospitalet  Oslo Norway"},{"name":"K. G. Jebsen Thrombosis Research and Expertise Center Department of Clinical Medicine UiT\u2014The Arctic University of Norway  Troms\u00f8 Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,4,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2015.83"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-149-10-200811180-00004"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032274"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02476-4"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-02-407551"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)91013-2"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.006502"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.116.004311"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13329"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.004768"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12678"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-021-00813-w"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d813"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a010013"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14220"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-08-371831"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-0098"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902383"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyr049"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwq066"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M116.066019"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2015.07.044"},{"issue":"4","key":"e_1_2_10_24_1","first-page":"619","article-title":"Activation of innate immunity in patients with venous thrombosis: the Leiden Thrombophilia study","volume":"2","author":"Reitsma PH","year":"2004","journal-title":"JTH."},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1067\/mva.2002.121746"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.109.198473"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199704033361401"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(02)01345-1"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2010.034991"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2009.011866"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-017-0277-4"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12742"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.565"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13369"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.186957"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.145151"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0030334"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH11-09-0611"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)61963-2"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx145"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13098-018-0360-3"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-017-0545-3"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2017.12.034"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2013.07.004"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2011.06.001"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)37218-6"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200318921"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.10.6185"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-08-371831"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.3109\/1354750X.2012.654406"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2016.07.017"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/rth2.12100"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14699"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.314480"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-09860-4"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1714"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac502040v"}],"container-title":["Journal of Internal Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/joim.13502","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/joim.13502","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/joim.13502","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T23:09:03Z","timestamp":1692832143000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/joim.13502"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,27]]},"references-count":56,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,9]]}},"alternative-id":["10.1111\/joim.13502"],"URL":"https:\/\/doi.org\/10.1111\/joim.13502","archive":["Portico"],"relation":{},"ISSN":["0954-6820","1365-2796"],"issn-type":[{"value":"0954-6820","type":"print"},{"value":"1365-2796","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,27]]},"assertion":[{"value":"2022-04-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}