Low concentrations of folate, not hyperhomocysteinemia, are associated with carotid intima-media thickness

Aim: We examined whether total homocysteine, B vitamins and the 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C → T polymorphism are related to common carotid intima-media thickness, a marker of atherosclerosis, and carotid distension, a marker of arterial stiffness. Methods: We used cross-sectional data from 819 individuals aged 50–70 years. B-mode ultrasound of the distal common carotid arteries was performed to determine maximum carotid intima-media thickness, mean carotid intima-media thickness and distension. Results: Carotid intima-media thickness and distension did not differ across homocysteine, serum folate, vitamin B6 and vitamin B12 quartiles or between MTHFR C677T genotype. Erythrocyte folate was independently associated with maximum carotid intima-media thickness (mean difference first versus third quartile, 0.03 mm, 95% CI 0.004–0.06 mm; first versus fourth quartile, 0.03 mm, 95% CI −0.002 to 0.06 mm). Further adjustment for homocysteine did not affect this association. Folate deficient subjects had greater maximum carotid intima-media thickness than those with high-normal folate concentrations (serum folate: mean difference 0.05 mm, 95% CI 0.01–0.08 mm; erythrocyte folate: mean difference 0.04 mm, 95% CI −0.03 to 0.11 mm). Conclusion: Low folate concentrations, independent of hyperhomocysteinemia, may promote atherogenesis. Our findings confirm the null association of homocysteine with carotid intima-media thickness observed in other population-based studies, suggesting that hyperhomocysteinemia does not perpetuate atherosclerosis or arterial stiffness.