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Homocysteine is a risk factor for cerebral small vessel disease, acting via endothelial dysfunction

Ahamad Hassan1, Beverley J Hunt, Michael O'Sullivan

  • 1Department of Clinical Neurosciences, St George's Hospital Medical School, London SW17 ORE, UK.

Brain : a Journal of Neurology
|November 11, 2003
PubMed

Insights

Elevated homocysteine levels are a significant risk factor for cerebral small vessel disease (SVD), especially ischemic leukoaraiosis. This association may be linked to endothelial dysfunction, suggesting homocysteine-lowering therapy could benefit SVD patients.

Area of Science:

  • Neurology
  • Vascular Biology
  • Genetics

Background:

  • Cerebral small vessel disease (SVD) encompasses lacunar infarction and leukoaraiosis.
  • Endothelial dysfunction is a proposed mechanism in SVD pathogenesis.
  • Homocysteine is known to be toxic to the endothelium.

Purpose of the Study:

  • To investigate if elevated homocysteine and MTHFR C677T polymorphism are risk factors for SVD.
  • To examine associations with SVD subtypes: lacunar infarction and ischemic leukoaraiosis.
  • To determine if endothelial dysfunction mediates these associations.

Main Methods:

  • Study included 172 Caucasian SVD patients and 172 controls.
  • Serum homocysteine levels and MTHFR genotyping were performed.
  • Circulating endothelial markers (ICAM1, thrombomodulin) were measured in a subgroup.

Main Results:

  • Mean homocysteine levels were higher in SVD patients compared to controls.
  • Homocysteine was a stronger risk factor for ischemic leukoaraiosis than for lacunar infarction.
  • The MTHFR 677T allele was a risk factor for ischemic leukoaraiosis.
  • Including endothelial markers diminished the homocysteine-SVD association's significance.

Conclusions:

  • Hyperhomocysteinemia is an independent risk factor for SVD, particularly ischemic leukoaraiosis.
  • Endothelial dysfunction may mediate the link between homocysteine and SVD.
  • Homocysteine-lowering therapy might be especially effective for ischemic leukoaraiosis patients.

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