Lp(a) surges during COVID-19 hospitalisation and those with the biggest rise face a 3-fold higher risk of blood clots, a Dutch pilot study of 219 patients (Atherosclerosis 2022)

Original title: Lipoprotein(a), venous thromboembolism and COVID-19: A pilot study

Atherosclerosis · 21 December 2021 · 6

Nurmohamed NS, Collard D, Reeskamp LF, Kaiser Y, Kroon J, Tromp TR, Amsterdam UMC Covid-19 Biobank, van den Born BH, Coppens M, Vlaar APJ, Beudel M, van de Beek D et al.

In 219 patients hospitalised with COVID-19 (146 with serial measurements), Lp(a), interleukin-6 (IL-6) and C-reactive protein were measured over the first 21 days of admission. Lp(a) rose by a mean of 16.9 mg/dL during this period. Patients in the top tertile of Lp(a) increase had a venous thromboembolism (VTE) rate of 56.2%, compared with 18.4% in the lowest tertile (relative risk 3.06, 95% CI 1.61-5.81, P<0.001), an association that remained significant after adjusting for age, sex, IL-6 and CRP change, and number of measurements. Increases in IL-6 and CRP were not themselves associated with VTE, though the rise in Lp(a) correlated strongly with the rise in IL-6 (r=0.44, 95% CI 0.30-0.56, P<0.001). The findings suggest acute IL-6-driven increases in anti-fibrinolytic Lp(a) may tip hospitalised COVID-19 patients toward venous thromboembolism.

Original 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.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.