OC 63.1 - The plasma proteome and risk of venous thromboembolism (VTE)

Tuesday, June 27, 2023

14:45 – 15:00 ET

Room: 520

Session Available As: On-Demand

Presenting Author(s)

Sigrid K. Brækkan, PhD (she/her/hers)

Professor
Thrombosis Research Center (TREC), Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
Tromsø, Troms, Norway

Co-Author(s)

AO

Asbjørn L. Onsaker

PhD-Student
Thrombosis Research Group, Department of Clinical Medicine, UiT - the Arctic University of Norway, Tromso, Norway
Tromso, Troms, Norway
TN

Therese H. Nøst

Researcher
K.G. Jebsen Center for Genetic Epidemiology, Norwegian University of Science and Technology, Trondheim, Norway
Trondheim, Sor-Trondelag, Norway
Vânia M. Morelli, MD PhD

Researcher
Thrombosis Research Group (TREC), Department of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, Norway
Tromsø, Troms, Norway
WT

Weihong Tang

Associate Professor
Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN 55454, USA
Minneapolis, Minnesota, United States
WG

Weihua Guan

Associate Professor
Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, MN, 55455, USA
Minneapolis, Minnesota, United States
AF

Aaron R. Folsom

Professor
Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN 55454, USA
Minneapolis, Minnesota, United States
CJ

Christian Jonasson

Researcher
HUNT Research Center, Norwegian University of Science and Technology, Levanger, Norway
Trondheim, Sor-Trondelag, Norway
KH

Kristian Hveem

Professor
Department of Public Health, K. G. Jebsen Center for Genetic Epidemiology, Norwegian University of Science and Technology, Trondheim, Norway
Trondheim, Nord-Trondelag, Norway
JH

John-Bjarne Hansen, MD, PhD

Professor
Thrombosis Research Center (TREC), Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
Tromsø, Troms, Norway

Background: Proteomics can provide new insight into molecular pathways involved in the pathogenesis of VTE and reveal potential predictive biomarkers or drug targets for prevention.

Aims: The aim of this study was to identify plasma proteins associated with first-lifetime VTE.

Methods: We used a case-cohort design with incident VTE-cases (n=286), and a randomly sampled age- and sex-weighted subcohort (n=1066) from the Trøndelag Health Study cohort (HUNT3). Ethical approval and informed consent was obtained. Blood samples (EDTA plasma) were collected at baseline inclusion in 2006/08, and participants were followed for a maximum of 5 years. The 7k SomaScan® v4.1 aptamer-based platform was used for protein measurements. For proteome-wide analyses, weighted Cox-regression models adjusted for age and sex were conducted, with the Bonferroni method applied to account for multiple testing (significance threshold: p< 6.9x10-6). Hazard ratios (HR) with 95% confidence intervals (CI) were estimated according to increasing quartiles (Q) with Q1 as reference group.

Results: In total, 7288 human proteins were measured. The proteome-wide analyses identified five proteins that were associated with significantly higher VTE risk. These proteins displayed a dose-response relationship to VTE risk and included coagulation factor VIII (FVIII) (procoagulant function) and collagen alpha-3(VI):BPTI/Kunitz inhibitor (antifibrinolytic function) where individuals with plasma concentrations in Q4 had a 4.9- (HR 4.94, 95% CI 3.20-7.64) and 2.6-fold (HR 2.61, 95 CI: 1.72-3.97) higher VTE risk, respectively, compared to those with plasma concentration in Q1. The remaining three proteins were considered novel biomarker candidates, all with plausible functions in the pathophysiology of VTE.

Conclusion(s): In a proteome-wide analysis, we identified five proteins that were differentially expressed in individuals who developed VTE within five years. Of these, three were considered novel candidates with plausible function in VTE pathogenesis. As the next step, we will validate our findings with conventional protein quantification assays in an external population.

Learning Objectives:

Identify knowledge gaps for risk stratification and prevention of venous thromboembolism
Describe an omics-based approach to detect new biomarkers for venous thromboembolism
List potentially important proteins and pathways associated with venous thromboembolism