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We investigated how three types of endotheliopathy biomarkers relate to pro\u2010 and anti\u2010inflammatory responses and clinical outcomes in intensive care unit (ICU) patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this secondary, explorative analysis of a prospective single\u2010centre cohort (<jats:italic>n<\/jats:italic>\u2009=\u2009459), we assessed associations between endotheliopathy biomarkers (syndecan\u20101, soluble thrombomodulin (sTM), platelet endothelial cell adhesion molecule\u20101 (PECAM\u20101)) and inflammatory biomarkers (pro\u2010inflammatory: IFN\u2010\u03d2, IL\u20101\u03b2, IL\u20102, IL\u20106, IL\u20108, IL\u201012p70, TNF\u2010\u03b1; anti\u2010inflammatory: IL\u20104, IL\u201010, IL\u201013) at ICU admission using linear regression. Associations with 30\u2010day clinical outcomes were analysed using linear and Cox regression. All models were adjusted for age, sex, septic shock, pre\u2010ICU surgery and chronic disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Higher levels of all three endotheliopathy biomarkers were associated with higher levels of inflammatory biomarkers. PECAM\u20101, however, showed no significant association with IFN\u2010\u03d2, IL\u20101\u03b2 and IL\u201012p70. IL\u20104 was excluded from linear regression due to &gt;\u200950% imputed values. Higher levels of all three endotheliopathy biomarkers were significantly associated with increased mean and maximum modified Sequential Organ Failure Assessment (mSOFA) scores over 30\u2009days, as well as with renal, hepatic, and coagulation failure, and 30\u2010day all\u2010cause mortality. Only sTM was significantly associated with cardiovascular failure; none were significantly associated with respiratory failure. Higher levels of sTM were associated with the highest levels of inflammatory biomarkers, the largest increases in mean and maximum mSOFA scores, and the highest hazard ratios for organ failure and 30\u2010day all\u2010cause mortality, compared with syndecan\u20101 and PECAM\u20101.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In this cohort of critically ill ICU patients, endotheliopathy was associated with (1) higher levels of pro\u2010 and anti\u2010inflammatory biomarkers at ICU admission and (2) MODS, single organ failure, and 30\u2010day all\u2010cause mortality. Among the three endotheliopathy biomarkers, sTM demonstrated the most consistent and strongest associations with both inflammatory biomarkers and clinical outcomes. These findings are exploratory and should be interpreted as hypothesis\u2010generating.<\/jats:p><\/jats:sec><jats:sec><jats:title>Editor's Comment<\/jats:title><jats:p>In this analysis of different biomarkers in a critically ill cohort, associations are demonstrated between markers related to endothelial stress, cytokines related to modulation of inflammation, and severity of illness scores.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aas.70117","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T05:31:08Z","timestamp":1757395868000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pro\u2010 and Anti\u2010Inflammatory Responses and Clinical Outcomes in Critically Ill Patients With Endotheliopathy: A Cohort 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