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Association Between Elevated Total Homocysteine and Heart Failure Risk in the Multi-Ethnic Study of Atherosclerosis

Amy B Karger1, Sarah O Nomura1, Weihua Guan2

  • 1Department of Laboratory Medicine & Pathology University of Minnesota Minneapolis MN USA.

Journal of the American Heart Association
|February 19, 2025
PubMed

Insights

Elevated total homocysteine (tHcy) is linked to heart failure (HF) risk, particularly HF with preserved ejection fraction (HFpEF). The study highlights differing impacts of tHcy and dysglycemia on HF subtypes.

Area of Science:

  • Cardiovascular Medicine
  • Metabolic Disorders
  • Epidemiology

Background:

  • Limited research links elevated total homocysteine (tHcy) to heart failure (HF) risk.
  • No studies have investigated if this association varies by HF subtype (HFpEF, HFrEF).

Purpose of the Study:

  • To examine the relationship between tHcy and the risk of overall HF, HFpEF, and HFrEF.
  • To assess if the impact of tHcy on HF risk differs by HF subtype.
  • To investigate the combined effects of elevated tHcy and dysglycemia on HF incidence.

Main Methods:

  • Utilized data from 6765 participants in the Multi-Ethnic Study of Atherosclerosis with baseline tHcy and HF data.
  • Employed Cox proportional hazards regression to calculate hazard ratios for tHcy and HF risk.
  • Stratified models by impaired fasting glucose/type 2 diabetes status to examine combined impacts.

Main Results:

  • Elevated tHcy (>12 micromol/L) was significantly associated with overall HF and HFpEF.
  • Individuals with both elevated tHcy and dysglycemia showed increased risk for overall HF and HFrEF, with a trend for HFpEF.
  • tHcy was a stronger contributor to HFpEF risk, while dysglycemia was more critical for HFrEF risk.

Conclusions:

  • Confirms the association between hyperhomocysteinemia and HF risk in a large, multi-ethnic cohort.
  • First study to show that tHcy's impact on HF risk differs by subtype.
  • tHcy appears to contribute more significantly to HFpEF risk than HFrEF risk.
Abstract

Keywords:
dysglycemiaejection fractionheart failurehomocysteine

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