Vitamin B12, homocysteine and carotid plaque in the era of folic acid fortification of enriched cereal grain products

Background: Carotid plaque area is a strong predictor of cardiovascular events. High homocysteine levels, which are associated with plaque formation, can result from inadequate intake of folate and vitamin B-12. Now that folic acid fortification is widespread in North America, vitamin B-12 has become an important determinant of homocysteine levels. We sought to determine the prevalence of low serum levels of vitamin B-12, and their relation to homocysteine levels and carotid plaque area among patients referred for treatment of vascular disease since folic acid fortification of enriched grain products. Methods: We evaluated 421 consecutive new patients with complete data whom we saw in our vascular disease prevention clinics between January 1998 and January 2002. We measured total carotid plaque area by ultrasound and determined homocysteine and serum vitamin B-12 levels in all patients. Results: The patients, 215 men and 206 women, ranged in age from 37 to 90 years ( mean 66 years). Most were taking medications for hypertension (67%) and dyslipidemia (62%). Seventy-three patients (17%) had vitamin B-12 deficiency ( vitamin B-12 level < 258 pmol/ L with homocysteine level > 14 mu mol/L or methylmalonic acid level > 271 nmol/L). The mean area of carotid plaque was significantly larger among the group of patients whose vitamin B-12 level was below the median of 253 pmol/ L than among those whose vitamin B-12 level was above the median: 1.36 ( standard deviation [SD] 1.27) cm(2) v. 1.09 (SD 1.0) cm(2); p= 0.016. Conclusions: Vitamin B-12 deficiency is surprisingly common among patients with vascular disease, and, in the setting of folic acid fortification, low serum vitamin B-12 levels are a major determinant of elevated homocysteine levels and increased carotid plaque area.