Higher levels of circulating desphospho-uncarboxylated matrix Gla protein over time are associated with worse survival: the prospective Maastricht Intensive Care COVID cohort
Abstract Background Extra-hepatic vitamin K-status, measured by dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP), maintains vascular health, with high levels reflecting poor vitamin K status. The occurrence of extra-hepatic vitamin K deficiency throughout the disease of COVID-19 and pos...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-12-01
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| Series: | Journal of Intensive Care |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40560-023-00712-0 |
| _version_ | 1797377110683156480 |
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| author | Mark M. G. Mulder Joep Schellens Jan-Willem E. M. Sels Frank van Rosmalen Anne-Marije Hulshof Femke de Vries Ruud Segers Casper Mihl Walther N. K. A. van Mook Aalt Bast Henri M. H. Spronk Yvonne M. C. Henskens Iwan C. C. van der Horst Hugo ten Cate Leon J. Schurgers Marjolein Drent Bas C. T. van Bussel |
| author_facet | Mark M. G. Mulder Joep Schellens Jan-Willem E. M. Sels Frank van Rosmalen Anne-Marije Hulshof Femke de Vries Ruud Segers Casper Mihl Walther N. K. A. van Mook Aalt Bast Henri M. H. Spronk Yvonne M. C. Henskens Iwan C. C. van der Horst Hugo ten Cate Leon J. Schurgers Marjolein Drent Bas C. T. van Bussel |
| author_sort | Mark M. G. Mulder |
| collection | DOAJ |
| description | Abstract Background Extra-hepatic vitamin K-status, measured by dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP), maintains vascular health, with high levels reflecting poor vitamin K status. The occurrence of extra-hepatic vitamin K deficiency throughout the disease of COVID-19 and possible associations with pulmonary embolism (PE), and mortality in intensive care unit (ICU) patients has not been studied. The aim of this study was to investigated the association between dp-ucMGP, at endotracheal intubation (ETI) and both ICU and six months mortality. Furthermore, we studied the associations between serially measured dp-ucMGP and both PE and mortality. Methods We included 112 ICU patients with confirmed COVID-19. Over the course of 4 weeks after ETI, dp-ucMGP was measured serially. All patients underwent computed tomography pulmonary angiography (CTPA) to rule out PE. Results were adjusted for patient characteristics, disease severity scores, inflammation, renal function, history of coumarin use, and coronary artery calcification (CAC) scores. Results Per 100 pmol/L dp-ucMGP, at ETI, the odds ratio (OR) was 1.056 (95% CI: 0.977 to 1.141, p = 0.172) for ICU mortality and 1.059 (95% CI: 0.976 to 1.059, p = 0.170) for six months mortality. After adjustments for age, gender, and APACHE II score, the mean difference in plasma dp-ucMGP over time of ICU admission was 167 pmol/L (95% CI: 4 to 332, p = 0.047). After additional adjustments for c-reactive protein, creatinine, and history of coumarin use, the difference was 199 pmol/L (95% CI: 50 to 346, p = 0.010). After additional adjustment for CAC score the difference was 213 pmol/L (95% CI: 3 to 422, p = 0.051) higher in ICU non-survivors compared to the ICU survivors. The regression slope, indicating changes over time, did not differ. Moreover, dp-ucMGP was not associated with PE. Conclusion ICU mortality in COVID-19 patients was associated with higher dp-ucMGP levels over 4 weeks, independent of age, gender, and APACHE II score, and not explained by inflammation, renal function, history of coumarin use, and CAC score. No association with PE was observed. At ETI, higher levels of dp-ucMGP were associated with higher OR for both ICU and six month mortality in crude and adjusted modes, although not statistically significantly. |
| first_indexed | 2024-03-08T19:49:15Z |
| format | Article |
| id | doaj.art-5350234c011e4986b380f9e8c03db898 |
| institution | Directory Open Access Journal |
| issn | 2052-0492 |
| language | English |
| last_indexed | 2024-03-08T19:49:15Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Intensive Care |
| spelling | doaj.art-5350234c011e4986b380f9e8c03db8982023-12-24T12:10:54ZengBMCJournal of Intensive Care2052-04922023-12-0111111210.1186/s40560-023-00712-0Higher levels of circulating desphospho-uncarboxylated matrix Gla protein over time are associated with worse survival: the prospective Maastricht Intensive Care COVID cohortMark M. G. Mulder0Joep Schellens1Jan-Willem E. M. Sels2Frank van Rosmalen3Anne-Marije Hulshof4Femke de Vries5Ruud Segers6Casper Mihl7Walther N. K. A. van Mook8Aalt Bast9Henri M. H. Spronk10Yvonne M. C. Henskens11Iwan C. C. van der Horst12Hugo ten Cate13Leon J. Schurgers14Marjolein Drent15Bas C. T. van Bussel16Department of Intensive Care Medicine, Maastricht University Medical Centre+Department of Intensive Care Medicine, Maastricht University Medical Centre+Department of Intensive Care Medicine, Maastricht University Medical Centre+Department of Intensive Care Medicine, Maastricht University Medical Centre+Central Diagnostic Laboratory, Maastricht University Medical Centre+Central Diagnostic Laboratory, Maastricht University Medical Centre+Department of Intensive Care Medicine, Maastricht University Medical Centre+Department of Radiology and Nuclear Medicine, Maastricht University Medical Centre+Department of Intensive Care Medicine, Maastricht University Medical Centre+Department of Pharmacology and Toxicology, Maastricht UniversityDepartment of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht UniversityCentral Diagnostic Laboratory, Maastricht University Medical Centre+Department of Intensive Care Medicine, Maastricht University Medical Centre+Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht UniversityDepartment of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht UniversityDepartment of Pharmacology and Toxicology, Maastricht UniversityDepartment of Intensive Care Medicine, Maastricht University Medical Centre+Abstract Background Extra-hepatic vitamin K-status, measured by dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP), maintains vascular health, with high levels reflecting poor vitamin K status. The occurrence of extra-hepatic vitamin K deficiency throughout the disease of COVID-19 and possible associations with pulmonary embolism (PE), and mortality in intensive care unit (ICU) patients has not been studied. The aim of this study was to investigated the association between dp-ucMGP, at endotracheal intubation (ETI) and both ICU and six months mortality. Furthermore, we studied the associations between serially measured dp-ucMGP and both PE and mortality. Methods We included 112 ICU patients with confirmed COVID-19. Over the course of 4 weeks after ETI, dp-ucMGP was measured serially. All patients underwent computed tomography pulmonary angiography (CTPA) to rule out PE. Results were adjusted for patient characteristics, disease severity scores, inflammation, renal function, history of coumarin use, and coronary artery calcification (CAC) scores. Results Per 100 pmol/L dp-ucMGP, at ETI, the odds ratio (OR) was 1.056 (95% CI: 0.977 to 1.141, p = 0.172) for ICU mortality and 1.059 (95% CI: 0.976 to 1.059, p = 0.170) for six months mortality. After adjustments for age, gender, and APACHE II score, the mean difference in plasma dp-ucMGP over time of ICU admission was 167 pmol/L (95% CI: 4 to 332, p = 0.047). After additional adjustments for c-reactive protein, creatinine, and history of coumarin use, the difference was 199 pmol/L (95% CI: 50 to 346, p = 0.010). After additional adjustment for CAC score the difference was 213 pmol/L (95% CI: 3 to 422, p = 0.051) higher in ICU non-survivors compared to the ICU survivors. The regression slope, indicating changes over time, did not differ. Moreover, dp-ucMGP was not associated with PE. Conclusion ICU mortality in COVID-19 patients was associated with higher dp-ucMGP levels over 4 weeks, independent of age, gender, and APACHE II score, and not explained by inflammation, renal function, history of coumarin use, and CAC score. No association with PE was observed. At ETI, higher levels of dp-ucMGP were associated with higher OR for both ICU and six month mortality in crude and adjusted modes, although not statistically significantly.https://doi.org/10.1186/s40560-023-00712-0Vitamin K deficiencyMatrix Gla proteinCOVID-19Intensive carePulmonary embolism |
| spellingShingle | Mark M. G. Mulder Joep Schellens Jan-Willem E. M. Sels Frank van Rosmalen Anne-Marije Hulshof Femke de Vries Ruud Segers Casper Mihl Walther N. K. A. van Mook Aalt Bast Henri M. H. Spronk Yvonne M. C. Henskens Iwan C. C. van der Horst Hugo ten Cate Leon J. Schurgers Marjolein Drent Bas C. T. van Bussel Higher levels of circulating desphospho-uncarboxylated matrix Gla protein over time are associated with worse survival: the prospective Maastricht Intensive Care COVID cohort Journal of Intensive Care Vitamin K deficiency Matrix Gla protein COVID-19 Intensive care Pulmonary embolism |
| title | Higher levels of circulating desphospho-uncarboxylated matrix Gla protein over time are associated with worse survival: the prospective Maastricht Intensive Care COVID cohort |
| title_full | Higher levels of circulating desphospho-uncarboxylated matrix Gla protein over time are associated with worse survival: the prospective Maastricht Intensive Care COVID cohort |
| title_fullStr | Higher levels of circulating desphospho-uncarboxylated matrix Gla protein over time are associated with worse survival: the prospective Maastricht Intensive Care COVID cohort |
| title_full_unstemmed | Higher levels of circulating desphospho-uncarboxylated matrix Gla protein over time are associated with worse survival: the prospective Maastricht Intensive Care COVID cohort |
| title_short | Higher levels of circulating desphospho-uncarboxylated matrix Gla protein over time are associated with worse survival: the prospective Maastricht Intensive Care COVID cohort |
| title_sort | higher levels of circulating desphospho uncarboxylated matrix gla protein over time are associated with worse survival the prospective maastricht intensive care covid cohort |
| topic | Vitamin K deficiency Matrix Gla protein COVID-19 Intensive care Pulmonary embolism |
| url | https://doi.org/10.1186/s40560-023-00712-0 |
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