Abstract
Background and aims
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.
Methods
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.
Results
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).
Conclusions
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.
【저자키워드】 COVID-19, IL-6, Lipoprotein(a), VTE, 【초록키워드】 Coronavirus disease 2019, Biomarker, Mortality, Sex, CRP, Venous Thromboembolism, Clinical outcome, adverse outcome, Patient, age, incidence, Admission, patients, COVID-19 patients, association, COVID-19 patient, C-reactive protein (CRP, Logistic regression analysis, 95% CI, acute phase, upregulation, Kaplan-Meier, Effect, lowest, Result, analyzed, significantly, investigated, remained, linear, increase, contribute, hospitalized patient, correlated, increase in, driven by, were measured, baseline, patients hospitalized, patients with COVID-19, pro-thrombotic, the cytokine storm, with COVID-19, 【제목키워드】 Venous Thromboembolism, pilot study,