# High-density lipoprotein subfractions and risk of future venous thromboembolism—the HUNT study

**Authors:** Inga A. Røstvold, Ben Brumpton, Kristian Hveem, Bjørn Olav Åsvold, Guro F. Giskeødegård, George Davey Smith, Nicholas J. Timpson, Kaitlin H. Wade, John-Bjarne Hansen, Sigrid K. Brækkan

PMC · DOI: 10.1016/j.rpth.2025.103295 · 2025-12-09

## TL;DR

This study found no link between HDL subfractions and future venous thromboembolism risk in a large population cohort.

## Contribution

The study provides new evidence that HDL subfractions are not predictive of venous thromboembolism risk.

## Key findings

- No associations were found between HDL particle size, concentration, or lipid composition and venous thromboembolism risk.
- Quartile analyses of HDL particles and ApoA1 showed no significant risk differences for venous thromboembolism.
- Findings suggest HDL metrics may not influence the development of venous thromboembolism.

## Abstract

Previous studies on high-density lipoprotein (HDL) cholesterol levels and the risk of venous thromboembolism (VTE) have shown conflicting results, and it has been suggested that specific HDL subfractions and lipid composition may be more informative with regards to VTE risk.

We aimed to investigate the association between HDL subfractions (including particle size, concentration, and lipid composition) and risk of VTE in a population-based cohort.

The study included 17,032 participants from the Trøndelag Health Study (HUNT3) cohort conducted in 2006-2008 who were followed up until December 31, 2019. HDL subfractions were analyzed in serum using nuclear magnetic resonance spectroscopy. All incident VTEs during follow-up were validated and recorded. Cox proportional hazards regression models estimated hazard ratios (HRs) for the association between HDL metrics and incident VTE, adjusting for age, sex, and body mass index.

During a median follow-up of 12.0 years, 342 incident VTE cases were confirmed. No associations were found among HDL particle size, HDL concentration, HDL lipid composition, apolipoprotein (Apo)A1 levels, and VTE risk. All HRs per 1-SD increase in HDL metrics were within the range of 0.83 to 1.16 and had 95% CIs that included 1. Furthermore, quartile analyses of HDL particles (Q4 vs Q1—HR, 0.89; 95% CI, 0.65-1.21) and ApoA1 (Q4 vs Q1—HR, 0.94; 95% CI, 0.68-1.29) showed no associations with VTE risk.

HDL subfractions, including particle size, concentration, lipid composition, and ApoA1, were not associated with the risk of a first-lifetime VTE event.

•High-density lipoprotein (HDL) subfractions may affect venous thromboembolism (VTE) risk.•This study analyzed 17,032 participants from the HUNT3 cohort over 12 years.•HDL subfractions showed no association with first-lifetime VTE risk.•Findings suggest that HDL metrics may not play a role in the pathogenesis of VTE.

High-density lipoprotein (HDL) subfractions may affect venous thromboembolism (VTE) risk.

This study analyzed 17,032 participants from the HUNT3 cohort over 12 years.

HDL subfractions showed no association with first-lifetime VTE risk.

Findings suggest that HDL metrics may not play a role in the pathogenesis of VTE.

## Linked entities

- **Proteins:** APOA1 (apolipoprotein A1)
- **Diseases:** venous thromboembolism (MONDO:0005399)

## Full-text entities

- **Genes:** APOA1 (apolipoprotein A1) [NCBI Gene 335] {aka AMYLD3, HPALP2, apo(a)}
- **Diseases:** VTE (MESH:D054556)
- **Chemicals:** cholesterol (MESH:D002784), lipid (MESH:D008055)

## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12804113/full.md

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Source: https://tomesphere.com/paper/PMC12804113