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. 2022 Jan:341:43-49.
doi: 10.1016/j.atherosclerosis.2021.12.008. Epub 2021 Dec 21.

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

Nick S Nurmohamed  1 , Didier Collard  2 , Laurens F Reeskamp  2 , Yannick Kaiser  2 , Jeffrey Kroon  3 , Tycho R Tromp  2 ; Amsterdam UMC Covid-19 Biobank; Bert-Jan H van den Born  2 , Michiel Coppens  2 , Alexander P J Vlaar  4 , Martijn Beudel  5 , Diederik van de Beek  5 , Nick van Es  2 , Patrick M Moriarty  6 , Sotirios Tsimikas  7 , Erik S G Stroes  8
Affiliations

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

Nick S Nurmohamed et al. Atherosclerosis. 2022 Jan.

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.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:

NSN and LFR are co-founders of Lipid Tools. MC reports grants from Bayer and grants and personal fees from Daiichi Sankyo. PM reports grants and personal fees from Regeneron, Amgen, Esperion, Kaneka, Stage II Innovations/Renew, grants from Novartis, Ionis Pharmaceuticals, FH Foundation, GB Life Sciences, Aegerion and personal fees from Amarin. ST is a co-inventor and receives royalties from patents owned by UCSD on biomarkers related to oxidized lipoproteins and is a co-founder and has an equity interest in Oxitope, Inc and its affiliates, Kleanthi Diagnostics, LLC and Covicept Therapeutics, Inc. ESGS reports advisory board/lecturing fees paid to the institution of ESGS by Amgen, Sanofi, Regeneron, Esperion, Novo-Nordisk, Esperion, IONIS.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Baseline Lp(a), IL-6 and CRP levels in COVID-19 patients. Depicted are the baseline Lp(a) (A; mg/dl), IL6 (B; ng/l) and CRP (C; mg/l) levels of the COVID-19 patients in in boxplots. Lp(a), lipoprotein(a); IL-6, Interleukin-6; CRP, C-reactive protein; COVID-19, coronavirus disease 2019.
Fig. 2
Fig. 2
Lp(a), IL-6 and CRP levels in COVID-19 patients during admission. Estimated marginal means of Lp(a), IL(6) and CRP in COVID-19 patients; derived from a mixed linear model of the time-course of these biomarkers following hospitalization. The black lines represent estimate of biomarker levels with standard error intervals shown in color during admission of COVID-19 patients. All models were significant (p < 0.001). Lp(a), lipoprotein(a); IL6, interleukin-6; CRP, C-reactive protein; COVID-19, coronavirus disease 2019.
Fig. 3
Fig. 3
Delta Lp(a) levels and VTE incidence in COVID-19 patients. Left panel: Barchart of delta Lp(a) levels and VTE incidence in the first 21 days after admission. Shown on the x-axis are the tertiles of Lp(a), with the relative VTE incidence within the tertile shown on the y-axis. Right panel: Kaplan Meier analysis of Lp(a) tertiles on VTE incidence in the first 21 days after admission. Patients with no delta Lp(a) available were excluded from the analysis. VTE, venous thromboembolism; Lp(a), Lipoprotein(a); COVID-19, coronavirus disease 2019.
See this image and copyright information in PMC

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