Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis

N Engl J Med. 1995 Feb 2;332(5):286-91. doi: 10.1056/NEJM199502023320502.


Background: Epidemiologic studies have identified hyperhomocysteinemia as a possible risk factor for atherosclerosis. We determined the risk of carotid-artery atherosclerosis in relation to both plasma homocysteine concentrations and nutritional determinants of hyperhomocysteinemia.

Methods: We performed a cross-sectional study of 1041 elderly subjects (418 men and 623 women; age range, 67 to 96 years) from the Framingham Heart Study. We examined the relation between the maximal degree of stenosis of the extracranial carotid arteries (as assessed by ultrasonography) and plasma homocysteine concentrations, as well as plasma concentrations and intakes of vitamins involved in homocysteine metabolism, including folate, vitamin B12, and vitamin B6. The subjects were classified into two categories according to the findings in the more diseased of the two carotid vessels: stenosis of 0 to 24 percent and stenosis of 25 to 100 percent.

Results: The prevalence of carotid stenosis of > or = 25 percent was 43 percent in the men and 34 percent in the women. The odds ratio for stenosis of > or = 25 percent was 2.0 (95 percent confidence interval, 1.4 to 2.9) for subjects with the highest plasma homocysteine concentrations (> or = 14.4 mumol per liter) as compared with those with the lowest concentrations (< or = 9.1 mumol per liter), after adjustment for sex, age, plasma high-density lipoprotein cholesterol concentration, systolic blood pressure, and smoking status (P < 0.001 for trend). Plasma concentrations of folate and pyridoxal-5'-phosphate (the coenzyme form of vitamin B6) and the level of folate intake were inversely associated with carotid-artery stenosis after adjustment for age, sex, and other risk factors.

Conclusions: High plasma homocysteine concentrations and low concentrations of folate and vitamin B6, through their role in homocysteine metabolism, are associated with an increased risk of extracranial carotid-artery stenosis in the elderly.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carotid Stenosis / blood
  • Carotid Stenosis / diagnostic imaging
  • Carotid Stenosis / etiology*
  • Confidence Intervals
  • Cross-Sectional Studies
  • Female
  • Folic Acid / blood
  • Homocysteine / blood*
  • Humans
  • Male
  • Odds Ratio
  • Pyridoxal Phosphate / blood
  • Pyridoxine / blood
  • Risk Factors
  • Ultrasonography
  • Vitamin B 12 / blood


  • Homocysteine
  • Pyridoxal Phosphate
  • Folic Acid
  • Pyridoxine
  • Vitamin B 12