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Integrative metabolomics differentiate coronary artery disease, peripheral artery disease, and venous thromboembolism

Jiwoo Lee1,2, Thomas Gilliland1,2, Satoshi Koyama1

  • 1Program in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.

Medrxiv : the Preprint Server for Health Sciences
|July 10, 2023
PubMed

Insights

This study reveals overlapping metabolomic profiles in arterial and venous cardiovascular diseases. Remnant cholesterol plays a key role in arterial diseases like coronary artery disease and peripheral artery disease, but not venous thromboembolism.

Area of Science:

  • Cardiovascular Science
  • Metabolomics
  • Genetics

Background:

  • Arterial and venous cardiovascular diseases share genetic correlations, suggesting common underlying mechanisms.
  • Understanding distinct and overlapping pathways in coronary artery disease (CAD), peripheral artery disease (PAD), and venous thromboembolism (VTE) is crucial for novel therapeutic targets.

Approach:

  • Utilized UK Biobank metabolomic data from 95,402 individuals to assess epidemiologic associations between 249 metabolites and incident CAD, PAD, and VTE.
  • Employed bidirectional two-sample Mendelian randomization (MR) and multivariable MR (MVMR) to investigate causal genetic relationships between metabolites and these cardiovascular conditions.

Key Points:

  • 194, 111, and 69 metabolites showed epidemiologic links to CAD, PAD, and VTE, respectively, with varying degrees of overlap between disease pairs.
  • MR identified 28 metabolites associated with increased risk for both CAD and PAD, and 2 for CAD but decreased risk for VTE.
  • MVMR highlighted shared causal effects of metabolites, particularly remnant cholesterol in very-low-density lipoprotein particles, on CAD and PAD.

Conclusions:

  • Overlapping metabolomic profiles exist between arterial and venous cardiovascular diseases.
  • Remnant cholesterol is implicated as a causal factor in arterial diseases (CAD, PAD) but not in venous thromboembolism.
  • Metabolomic profiling and MR provide insights into shared and distinct etiological pathways for cardiovascular diseases.
Abstract

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