Homocysteine levels and leukocyte telomere length.

OBJECTIVE Elevated plasma homocysteine is a risk factor for vascular diseases, possibly due to homocysteine-mediated increase in oxidative stress and inflammation. As leukocyte telomere length (LTL) registers the cumulative oxidative stress and inflammation, we examined the relationship between homocysteine and LTL. METHODS LTL was measured using the Southern blot method. The relationship between LTL and homocysteine levels was considered for confounding with the following covariates: age, sex, smoking, obesity, physical activity, menopause, hormone replacement therapy use and creatinine clearance. RESULTS 1,319 healthy subjects were recruited from a population-based cohort. LTL was negatively correlated with plasma homocysteine levels, after adjustment for smoking, obesity, physical activity, menopause, hormone replacement therapy use and creatinine clearance. The difference in multiply-adjusted LTL between the highest and lowest tertile of homocysteine levels was 111 base pairs (p=0.004), corresponding to 6.0 years of telomeric aging. This relationship was further accentuated by decreased concentrations of serum folate and increased levels of C-reactive protein. CONCLUSIONS Increased homocysteine levels are associated with shortened LTL, further supporting the tenet that LTL is an index of cardiovascular risk.