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Association of apolipoproteins C-I, C-II, C-III and E with coagulation markers and venous thromboembolism risk

Authors Orsi FA, Lijfering WM, Van der Laarse A, Ruhaak LR, Rosendaal FR, Cannegieter SC, Cobbaert C

Received 28 November 2018

Accepted for publication 23 May 2019

Published 22 July 2019 Volume 2019:11 Pages 625—633


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Professor Vera Ehrenstein

Fernanda A Orsi,1,2 Willem M Lijfering,2,3 Arnoud Van der Laarse,4,5 L Renee Ruhaak,4 Frits R Rosendaal,2 Suzanne C Cannegieter,2–3,6 Christa Cobbaert4

1Department of Clinical Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil; 2Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands; 3Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands; 4Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands; 5Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; 6Department of Internal Medicine, Section of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands

Purpose: Apolipoproteins C-I, C-II, C-III and E have been associated with risk of arterial thrombotic diseases. We investigated whether these apolipoproteins have prothrombotic properties and are associated with risk of venous thromboembolism (VTE).
Patients and methods: A total of 127 VTE patients and 299 controls were randomly selected from the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis study (1999–2004), in the Netherlands. The apolipoproteins were quantified using mass spectrometry (LC/MS/MS), and their levels were analyzed as continuous variable (per SD increase).
Results: In controls, increases in levels of apolipoproteins were associated with increases in levels of vitamin K-dependent factors, factor XI, antithrombin and clot lysis time. Additionally, increasing apolipoproteins C-III and E levels were associated with higher factor VIII and von Willebrand factor levels. Levels of C-reactive protein were not associated with any apolipoprotein. The age- and sex-adjusted odds ratios of apolipoproteins E, C-III, CII and CI to the risk of venous thrombosis were 1.21 (95% CI, 0.98–1.49), 1.19 (95% CI, 0.99–1.44), 1.24 (95% CI, 0.95–1.61) and 1.06 (95% CI, 0.87–1.30) per SD increase, respectively. These odds ratios did not attenuate after adjustments for statin use, estrogen use, BMI, alcohol use, and self-reported diabetes.
Conclusions: Levels of apolipoproteins C-I, C-II, C-III and E are associated with those of several coagulation factors. However, whether these apolipoproteins are also associated with an increased risk of VTE remains to be established.

Keywords: thrombosis, proteomics, lipids, cholesterol, coagulation, risk factors

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