tetano
Editor, Senior Moderator
Atherosclerosis
. 2021 Dec 21;341:43-49.
doi: 10.1016/j.atherosclerosis.2021.12.008. Online ahead of print.
Lipoprotein(a), venous thromboembolism and COVID-19: A pilot study
Nick S Nurmohamed[SUP] 1 [/SUP], Didier Collard[SUP] 2 [/SUP], Laurens F Reeskamp[SUP] 2 [/SUP], Yannick Kaiser[SUP] 2 [/SUP], Jeffrey Kroon[SUP] 3 [/SUP], Tycho R Tromp[SUP] 2 [/SUP], Amsterdam UMC Covid-19 Biobank; Bert-Jan H van den Born[SUP] 2 [/SUP], Michiel Coppens[SUP] 2 [/SUP], Alexander P J Vlaar[SUP] 4 [/SUP], Martijn Beudel[SUP] 5 [/SUP], Diederik van de Beek[SUP] 5 [/SUP], Nick van Es[SUP] 2 [/SUP], Patrick M Moriarty[SUP] 6 [/SUP], Sotirios Tsimikas[SUP] 7 [/SUP], Erik S G Stroes[SUP] 8 [/SUP]
Affiliations
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.
Keywords: COVID-19; IL-6; Lipoprotein(a); VTE.
. 2021 Dec 21;341:43-49.
doi: 10.1016/j.atherosclerosis.2021.12.008. Online ahead of print.
Lipoprotein(a), venous thromboembolism and COVID-19: A pilot study
Nick S Nurmohamed[SUP] 1 [/SUP], Didier Collard[SUP] 2 [/SUP], Laurens F Reeskamp[SUP] 2 [/SUP], Yannick Kaiser[SUP] 2 [/SUP], Jeffrey Kroon[SUP] 3 [/SUP], Tycho R Tromp[SUP] 2 [/SUP], Amsterdam UMC Covid-19 Biobank; Bert-Jan H van den Born[SUP] 2 [/SUP], Michiel Coppens[SUP] 2 [/SUP], Alexander P J Vlaar[SUP] 4 [/SUP], Martijn Beudel[SUP] 5 [/SUP], Diederik van de Beek[SUP] 5 [/SUP], Nick van Es[SUP] 2 [/SUP], Patrick M Moriarty[SUP] 6 [/SUP], Sotirios Tsimikas[SUP] 7 [/SUP], Erik S G Stroes[SUP] 8 [/SUP]
Affiliations
- PMID: 34995986
- PMCID: PMC8690577
- DOI: 10.1016/j.atherosclerosis.2021.12.008
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.
Keywords: COVID-19; IL-6; Lipoprotein(a); VTE.