Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev and Gentofte, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev and Gentofte, Denmark.
Atherosclerosis. 2022 Sep;357:33-40. doi: 10.1016/j.atherosclerosis.2022.07.015. Epub 2022 Aug 2.
High levels of lipoprotein(a) could worsen the outcome of COVID-19 due to prothrombotic and proinflammatory properties of lipoprotein(a). We tested the hypotheses that during COVID-19 hospitalization i) increased thrombotic activity and inflammation are associated with lipoprotein(a) levels, and ii) lipoprotein(a) levels are associated with rate of hospital death and discharge.
We studied 211 patients admitted to Copenhagen University Hospital in 2020 with COVID-19, that is, prior to any vaccination. Thrombotic activity was marked by elevated D-dimer while inflammation was marked by elevated interleukin-6, C-reactive protein, and procalcitonin. Patients were followed until death (N = 36) or discharge (N = 175).
A 2-fold higher D-dimer was associated with 14% (95%CI: 8.1-20%) higher lipoprotein(a). Conversely, 2-fold higher interleukin-6, C-reactive protein, and procalcitonin were associated with respectively 4.3% (0.62-7.8%), 5.7% (0.15-5.2%), and 8.7% (5.2-12%) lower lipoprotein(a). For hospital death, the multivariable adjusted hazard ratio per 2-fold higher lipoprotein(a) was 1.26 (95%CI:0.91-1.73). Corresponding hazard ratios per 2-fold higher biomarker were 0.93 (0.75-1.16) for D-dimer, 1.42 (1.17-1.73) for interleukin-6, 1.44 (0.95-2.17) for C-reactive protein, and 1.44 (1.20-1.73) for procalcitonin. For hospital discharge, the multivariable adjusted hazard ratio per 2-fold higher lipoprotein(a) was 0.91 (95%CI:0.79-1.06). Corresponding hazard ratios per 2-fold higher biomarker were 0.86 (0.75-0.98) for D-dimer, 0.84 (0.76-0.92) for interleukin-6, 0.80 (0.71-0.90) for C-reactive protein, and 0.76 (0.67-0.88) for procalcitonin.
In COVID-19 patients, thrombotic activity marked by elevated D-dimer was associated with higher lipoprotein(a) while elevated inflammatory biomarkers of interleukin-6, C-reactive protein, and procalcitonin were associated with lower lipoprotein(a); however, elevated lipoprotein(a) was not associated with rate of hospital death or discharge.
载脂蛋白(a)水平升高可能会使 COVID-19 患者的预后恶化,这是由于载脂蛋白(a)具有促血栓形成和促炎作用。我们检验了以下假设,即在 COVID-19 住院期间:i)升高的血栓形成活性和炎症与载脂蛋白(a)水平相关,ii)载脂蛋白(a)水平与住院死亡和出院率相关。
我们研究了 2020 年在哥本哈根大学医院因 COVID-19 入院的 211 例患者,这些患者在接种疫苗之前。血栓形成活性以升高的 D-二聚体为标志,而炎症则以升高的白细胞介素-6、C 反应蛋白和降钙素原为标志。患者随访至死亡(n=36)或出院(n=175)。
D-二聚体升高 2 倍与载脂蛋白(a)升高 14%(95%CI:8.1-20%)相关。相反,白细胞介素-6、C 反应蛋白和降钙素原升高 2 倍与载脂蛋白(a)降低分别为 4.3%(0.62-7.8%)、5.7%(0.15-5.2%)和 8.7%(5.2-12%)相关。对于医院死亡,每升高 2 倍载脂蛋白(a)的多变量调整后的危险比为 1.26(95%CI:0.91-1.73)。相应的危险比每升高 2 倍生物标志物分别为 D-二聚体 0.93(0.75-1.16)、白细胞介素-6 1.42(1.17-1.73)、C 反应蛋白 1.44(0.95-2.17)和降钙素原 1.44(1.20-1.73)。对于医院出院,每升高 2 倍载脂蛋白(a)的多变量调整后的危险比为 0.91(95%CI:0.79-1.06)。相应的危险比每升高 2 倍生物标志物分别为 D-二聚体 0.86(0.75-0.98)、白细胞介素-6 0.84(0.76-0.92)、C 反应蛋白 0.80(0.71-0.90)和降钙素原 0.76(0.67-0.88)。
在 COVID-19 患者中,以 D-二聚体升高为标志的血栓形成活性与载脂蛋白(a)升高相关,而升高的白细胞介素-6、C 反应蛋白和降钙素原炎症生物标志物与载脂蛋白(a)降低相关;然而,载脂蛋白(a)的升高与医院死亡率或出院率无关。