Faculty, Staff and Student Publications

Language

English

Publication Date

1-8-2026

Journal

Journal of Thrombosis and Haemostasis

DOI

10.1016/j.jtha.2025.12.016

PMID

41519271

Abstract

Background: Fibrinogen is a critical coagulation factor that plays an essential role in thrombosis and is elevated in individuals with chronic inflammation. Here, we used fibrinogen as a representative quantitative measure of pro-coagulant risk and evaluated metabolites associated with fibrinogen levels through non-targeted plasma metabolomic profiling (Broad and Metabolon platforms).

Methods: Our analysis included 10,533 individuals across six U.S. based cohorts representing diverse population groups. The cross-sectional relationship between each of 789 tested metabolites and plasma fibrinogen concentration was assessed with adjustment for relevant covariates such as age, sex, body mass index, and circulating lipoprotein levels.

Results: Meta-analysis of per-cohort results revealed 270 metabolites significantly associated with fibrinogen level (FDR adjusted p-value < 0.05). Lipid species such as glycerophospholipids, sphingolipids, and fatty acyls were prevalent among significantly associated metabolites; some of these may capture effects of inflammation, as supported by sensitivity analyses adjusted for C-reactive protein. Significant associations between fibrinogen levels and serotonin, thyroxine, and sex-hormone derivatives may capture endogenous influences on fibrinogen levels. Exogenous compounds and microbial co-metabolites significantly associated with fibrinogen also implicate lifestyle and microbiome risk-factors. Only a portion of fibrinogen-associated metabolites (30%) have been associated with a cardiovascular disease outcome in a prior study, suggesting the associations discovered here may provide insights on vascular biology which case-control studies may not yet be powered to detect.

Conclusions: These findings contribute to a growing list of metabolite biomarkers that may influence coagulation and inflammation pathways and may thereby contribute to vascular risk.

Keywords

Biomarkers, Cardiovascular diseases, Fibrinogen, Hemostasis, Inflammation, Metabolomics

Published Open-Access

yes

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