High-normal serum homocysteine concentrations are associated with an increased risk of early atherosclerotic carotid artery wall lesions in healthy subjects

J Hypertens. 2000 Apr;18(4):425-30. doi: 10.1097/00004872-200018040-00011.


Objective: Moderate hyperhomocysteinaemia is common in the general population and has been linked with systemic atherosclerotic vascular disease. We studied the relation of sonographically determined carotid intima-media wall thickness to serum homocysteine concentrations in asymptomatic, healthy subjects.

Methods and results: Seventy-five male and female untreated subjects (mean age 49 years, range 22-75) with normal serum folate concentrations were included. High-resolution duplex sonography was used to determine intima-media thickness of the common carotid artery. Serum homocysteine concentration was measured by high-performance liquid chromotography with fluorescence detection. Mean intima-media thickness (+/- SD) was 0.78 +/- 0.19 mm (range 0.5-1.35) and mean serum homocysteine concentration was 10.5 +/- 2.81 micromol/l (range 5.7-19.6). In stepwise regression models, statistically significant predictors of intima-media thickness included age, body mass index, LDL cholesterol and homocysteine (R2 = 0.51). Homocysteine concentration was independently associated with intima-media thickness after adjustment for the other variables (P < 0.001) and explained an additional 18% of the variation of intima-media thickness.

Conclusions: In healthy subjects, high-normal serum homocysteine concentrations are associated with an increased prevalence of carotid artery wall thickening. The significance of the contribution of homocysteine to the variation of carotid intima-media thickness, even at concentrations previously believed to be normal, suggests a role for homocysteine as an independent risk factor for early carotid artery atherosclerosis in the asymptomatic subjects.

MeSH terms

  • Adult
  • Aged
  • Carotid Artery Diseases / diagnostic imaging
  • Carotid Artery Diseases / etiology*
  • Carotid Artery, Common / diagnostic imaging
  • Female
  • Folic Acid / blood
  • Homocysteine / blood*
  • Humans
  • Intracranial Arteriosclerosis / diagnostic imaging
  • Intracranial Arteriosclerosis / etiology*
  • Male
  • Middle Aged
  • Osmolar Concentration
  • Reference Values
  • Risk Factors
  • Tunica Intima / diagnostic imaging
  • Tunica Media / diagnostic imaging
  • Ultrasonography


  • Homocysteine
  • Folic Acid