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Setup of Capillary Electrophoresis-Inductively Coupled Plasma Mass Spectrometry CE-ICP-MS for Quantification of Iron Redox Species FeII, FeIII
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Setup of Capillary Electrophoresis-Inductively Coupled Plasma Mass Spectrometry CE-ICP-MS for Quantification of Iron Redox Species FeII, FeIII

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Associations between genetically predicted iron status and cardiovascular disease risk: A Mendelian randomization

Alexa Barad1, Andrew G Clark2,3, Kimberly O O'Brien1

  • 1Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA.

Medrxiv : the Preprint Server for Health Sciences
|February 19, 2024
PubMed

Insights

Higher iron status increases cardioembolic stroke risk, independent of other cardiovascular disease risk factors. Diastolic blood pressure partially mediates this iron-stroke association, suggesting iron is a modifiable risk factor.

Area of Science:

  • Cardiovascular disease genetics
  • Iron metabolism and cardiovascular health
  • Mendelian randomization studies

Background:

  • Mendelian randomization (MR) studies suggest iron (Fe) status influences cardiovascular disease (CVD) risk.
  • Potential confounding by pleiotropic effects of instrumental variables (IVs) on CVD risk factors requires investigation.
  • This study investigates the effect of Fe status on CVD risk, controlling for established CVD risk factors.

Approach:

  • Utilized two-sample univariate (UV) and multivariate (MV) Mendelian randomization (MR) analyses.
  • Employed Fe biomarker IVs (TIBC, TSAT, SI, ferritin) and large-scale GWAS data for CVD outcomes (stroke, coronary heart disease).
  • Implemented MVMR by conditioning on six CVD risk factors to assess confounding and mediation effects.

Key Points:

  • Higher genetically predicted iron status is associated with increased cardioembolic stroke (CES) risk (e.g., TSAT OR 1.17, SI OR 1.21).
  • These detrimental effects of iron status on CES risk persist after adjusting for CVD risk factors.
  • Diastolic blood pressure partially mediates 7.1-8.8% of the iron status-CES risk association.

Conclusions:

  • Elevated iron status is linked to a higher risk of cardioembolic stroke, independent of common CVD risk factors.
  • Diastolic blood pressure is an identified mediator in the pathway between iron status and CES.
  • Iron status emerges as a potentially modifiable risk factor for cardioembolic stroke.
Abstract

Keywords:
Mendelian randomizationcardioembolic stroke riskiron statusischemic stroke

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