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Updated: May 5, 2026

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Elevated Homocysteine: A Critical Risk Factor for Stroke Types and Subtypes - A Systematic Review and Meta-Analysis

Manyata Srivastava1, Annu Gulia, Pradeep Kumar

  • 1Clinical Research Unit, All India Institute of Medical Sciences, New Delhi, India.

Acta Neurologica Taiwanica
|June 5, 2025
PubMed

Insights

High homocysteine (Hcy) levels are linked to increased stroke risk. This meta-analysis confirms Hcy as a significant predictor for ischemic and hemorrhagic stroke, highlighting its potential role in stroke prevention strategies.

Area of Science:

  • Neurology
  • Cardiovascular Medicine
  • Biochemistry

Background:

  • The link between homocysteine (Hcy) and stroke risk is debated.
  • Previous investigations have yielded inconclusive results regarding this association.

Purpose of the Study:

  • To systematically review and meta-analyze studies assessing the association between elevated Hcy levels and stroke risk.
  • To investigate the relationship for stroke subtypes, including ischemic stroke (IS) and hemorrhagic stroke (HS).

Main Methods:

  • A comprehensive literature search was performed across major databases (PubMed, MEDLINE, EMBASE, Cochrane Library) up to April 2024.
  • Included case-control studies were analyzed using standardized mean difference (SMD) with 95% confidence intervals (CIs).
  • Publication bias and trial sequential analysis (TSA) were conducted to assess the robustness of findings.

Main Results:

  • Analysis of 96 studies revealed a significant association between higher Hcy levels and increased risk of IS (SMD = 1.35) and HS (SMD = 1.14).
  • Elevated Hcy levels were also significantly linked to Trial of ORG 10172 in Acute Stroke Treatment (TOAST) subtypes of IS (SMD = 1.48).
  • Trial sequential analysis confirmed sufficient statistical power for the observed associations across stroke types and subtypes.

Conclusions:

  • Elevated homocysteine levels are significantly associated with an increased risk of all stroke types and subtypes.
  • Homocysteine shows potential as a predictive biomarker for stroke risk.
  • Future research should explore hyperhomocysteinemia detection and Hcy-lowering strategies for stroke prevention.
Abstract

Keywords:
Hemorrhagic strokeTrial of ORG 10172 in Acute Stroke Treatment classificationhomocysteineischemic stroke

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