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

Abstract 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 B 6 and vitamin B 12 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.