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

From the Department of Family Medicine, McMaster University, Hamilton, Ont. (Robertson); the Department of Neurology, General Hospital "R. Guzzardi" Vittoria, Ragusa, A.S.L 7 Sicilian Region, and the Department of Neurological Science of Catania University, Italy (Iemolo); the Stroke Prevention and Atherosclerosis Research Centre, Robarts Research Institute, and Department of Clinical Neurological Sciences, University of Western Ontario, London, Ont. (Spence); and the Department of Medicine, University of Colorado Health Sciences Center, Denver, Col., (Stabler, Allen)

Correspondence to: Dr. J. David Spence, Stroke Prevention and Atherosclerosis Research Centre, 1400 Western Rd., London ON N6G 2V2; fax 519 663-3018; dspence{at}robarts.ca

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 B₁₂. Now that folic acid fortification is widespread in North America, vitamin B₁₂ has become an important determinant of homocysteine levels. We sought to determine the prevalence of low serum levels of vitamin B₁₂, 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 B₁₂ 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 B₁₂ deficiency (vitamin B₁₂ level < 258 pmol/L with homocysteine level > 14 µmol/L or methylmalonic acid level > 271 nmol/L). The mean area of carotid plaque was significantly larger among the group of patients whose vitamin B₁₂ level was below the median of 253 pmol/L than among those whose vitamin B₁₂ level was above the median: 1.36 (standard deviation [SD] 1.27) cm² v. 1.09 (SD 1.0) cm²; p = 0.016.

Conclusions: Vitamin B₁₂ deficiency is surprisingly common among patients with vascular disease, and, in the setting of folic acid fortification, low serum vitamin B₁₂ levels are a major determinant of elevated homocysteine levels and increased carotid plaque area.

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