Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Atherosclerosis. 2022 Jan;341:43-49. doi: 10.1016/j.atherosclerosis.2021.12.008. Epub 2021 Dec 21.
Thrombosis is a major driver of adverse outcome and mortality in patients with Coronavirus disease 2019 (COVID-19). Hypercoagulability may be related to the cytokine storm associated with COVID-19, which is mainly driven by interleukin (IL)-6. Plasma lipoprotein(a) [Lp(a)] levels increase following IL-6 upregulation and Lp(a) has anti-fibrinolytic properties. This study investigated whether Lp(a) elevation may contribute to the pro-thrombotic state hallmarking COVID-19 patients.
Lp(a), IL-6 and C-reactive protein (CRP) levels were measured in 219 hospitalized patients with COVID-19 and analyzed with linear mixed effects model. The baseline biomarkers and increases during admission were related to venous thromboembolism (VTE) incidence and clinical outcomes in a Kaplan-Meier and logistic regression analysis.
Lp(a) levels increased significantly by a mean of 16.9 mg/dl in patients with COVID-19 during the first 21 days after admission. Serial Lp(a) measurements were available in 146 patients. In the top tertile of Lp(a) increase, 56.2% of COVID-19 patients experienced a VTE event compared to 18.4% in the lowest tertile (RR 3.06, 95% CI 1.61-5.81; p < 0.001). This association remained significant after adjusting for age, sex, IL-6 and CRP increase and number of measurements. Increases in IL-6 and CRP were not associated with VTE. Increase in Lp(a) was strongly correlated with increase in IL-6 (r = 0.44, 95% CI 0.30-0.56, p < 0.001).
Increases in Lp(a) levels during the acute phase of COVID-19 were strongly associated with VTE incidence. The acute increase in anti-fibrinolytic Lp(a) may tilt the balance to VTE in patients hospitalized for COVID-19.
血栓形成是导致 2019 年冠状病毒病（COVID-19）患者不良结局和死亡的主要原因。高凝状态可能与 COVID-19 相关的细胞因子风暴有关，而细胞因子风暴主要由白细胞介素（IL）-6 驱动。IL-6 上调后，血浆脂蛋白（a）[Lp(a)]水平升高，而 Lp(a)具有抗纤维蛋白溶解的特性。本研究旨在探讨 Lp(a)升高是否有助于 COVID-19 患者的血栓形成状态。
在 219 例住院 COVID-19 患者中测量 Lp(a)、IL-6 和 C 反应蛋白（CRP）水平，并通过线性混合效应模型进行分析。通过 Kaplan-Meier 和逻辑回归分析，将基线生物标志物和住院期间的增加与静脉血栓栓塞（VTE）发生率和临床结局相关联。
COVID-19 患者入院后 21 天内 Lp(a)水平平均升高 16.9mg/dl。在 146 例患者中可进行 Lp(a)系列测量。在 Lp(a)增加的最高三分位中，56.2%的 COVID-19 患者发生 VTE 事件，而最低三分位中为 18.4%（RR 3.06，95%CI 1.61-5.81；p<0.001）。在调整年龄、性别、IL-6 和 CRP 增加以及测量次数后，这种相关性仍然显著。IL-6 和 CRP 的增加与 VTE 无关。Lp(a)的增加与 IL-6 的增加呈强相关（r=0.44，95%CI 0.30-0.56，p<0.001）。
COVID-19 急性期 Lp(a)水平的升高与 VTE 发生率密切相关。COVID-19 住院患者抗纤维蛋白溶解 Lp(a)的急性增加可能使 VTE 的平衡向血栓形成倾斜。
