TY - JOUR
T1 - Lipoprotein(a), venous thromboembolism and COVID-19
T2 - A pilot study
AU - Nurmohamed, Nick S.
AU - Collard, Didier
AU - Reeskamp, Laurens F.
AU - Kaiser, Yannick
AU - Kroon, Jeffrey
AU - Tromp, Tycho R.
AU - van den Born, Bert-Jan H.
AU - Coppens, Michiel
AU - Vlaar, Alexander P. J.
AU - Beudel, Martijn
AU - van de Beek, Diederik
AU - van Es, Nick
AU - Moriarty, Patrick M.
AU - Amsterdam UMC Covid-19 Biobank
AU - Tsimikas, Sotirios
AU - Stroes, Erik S. G.
N1 - Funding Information: The Amsterdam UMC Covid-19 Biobank is funded by Corona Research Fund , Amsterdam UMC , and Dr C.J. Vaillant Fund, to D. van de Beek. Publisher Copyright: © 2021 The Author(s)
PY - 2022/1/1
Y1 - 2022/1/1
N2 - 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.
AB - 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.
KW - COVID-19
KW - IL-6
KW - Lipoprotein(a)
KW - VTE
UR - http://www.scopus.com/inward/record.url?scp=85122200658&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.atherosclerosis.2021.12.008
DO - https://doi.org/10.1016/j.atherosclerosis.2021.12.008
M3 - Article
C2 - 34995986
SN - 0021-9150
VL - 341
SP - 43
EP - 49
JO - Atherosclerosis
JF - Atherosclerosis
ER -