PDF(Pubmed)
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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：肝外维生素K状态，通过去磷酸化非羧化基质Gla蛋白（dp-ucMGP）测量，保持血管健康，高水平反映出维生素K状态差。在整个COVID-19疾病中肝外维生素K缺乏症的发生以及与肺栓塞（PE）的可能关联，重症监护病房（ICU）患者的死亡率尚未研究。这项研究的目的是调查dp-ucMGP之间的关联，在气管插管（ETI）和ICU和六个月死亡率。此外，我们研究了连续测量的dp-ucMGP与PE和死亡率之间的关联.
方法：我们纳入了112例确诊为COVID-19的ICU患者。在ETI后的4周内，连续测量dp-ucMGP。所有患者均行CT肺动脉造影（CTPA）以排除PE。结果根据患者特征进行了调整，疾病严重程度评分，炎症,肾功能,香豆素使用的历史，冠状动脉钙化（CAC）评分。
结果：每100pmol/Ldp-ucMGP，在ETI,ICU死亡率的比值比(OR)为1.056(95%CI:0.977~1.141,p=0.172),6个月死亡率的比值比为1.059(95%CI:0.976~1.059,p=0.170).经过年龄调整后，性别,和APACHEII得分,随着ICU入院时间的推移,血浆dp-ucMGP的平均差异为167pmol/L(95%CI:4~332,p=0.047).在对C反应蛋白进行额外调整后，肌酐,以及香豆素使用的历史，差异为199pmol/L（95％CI：50至346，p=0.010）。在对CAC评分进行额外调整后，与ICU幸存者相比，ICU非幸存者的差异高213pmol/L（95％CI：3至422，p=0.051）。回归斜率，指示随时间的变化，没有区别。此外，dp-ucMGP与PE无关。
结论：COVID-19患者的ICU死亡率与4周内较高的dp-ucMGP水平相关，独立于年龄,性别,和APACHEII得分,不能用炎症来解释，肾功能,香豆素使用的历史，和CAC得分。未观察到与PE的关联。在ETI,较高的dp-ucMGP水平与ICU和6个月死亡率的较高OR相关，虽然没有统计学意义。
方法：我们纳入了112例确诊为COVID-19的ICU患者。在ETI后的4周内，连续测量dp-ucMGP。所有患者均行CT肺动脉造影（CTPA）以排除PE。结果根据患者特征进行了调整，疾病严重程度评分，炎症,肾功能,香豆素使用的历史，冠状动脉钙化（CAC）评分。
结果：每100pmol/Ldp-ucMGP，在ETI,ICU死亡率的比值比(OR)为1.056(95%CI:0.977~1.141,p=0.172),6个月死亡率的比值比为1.059(95%CI:0.976~1.059,p=0.170).经过年龄调整后，性别,和APACHEII得分,随着ICU入院时间的推移,血浆dp-ucMGP的平均差异为167pmol/L(95%CI:4~332,p=0.047).在对C反应蛋白进行额外调整后，肌酐,以及香豆素使用的历史，差异为199pmol/L（95％CI：50至346，p=0.010）。在对CAC评分进行额外调整后，与ICU幸存者相比，ICU非幸存者的差异高213pmol/L（95％CI：3至422，p=0.051）。回归斜率，指示随时间的变化，没有区别。此外，dp-ucMGP与PE无关。
结论：COVID-19患者的ICU死亡率与4周内较高的dp-ucMGP水平相关，独立于年龄,性别,和APACHEII得分,不能用炎症来解释，肾功能,香豆素使用的历史，和CAC得分。未观察到与PE的关联。在ETI,较高的dp-ucMGP水平与ICU和6个月死亡率的较高OR相关，虽然没有统计学意义。
