Homocysteine is a determinant of ApoA-I and both are associated with ankle brachial index, in an Ambulatory Elderly Population

Objective: The ankle brachial index (ABI) is an indicator of lower extremity peripheral arterial disease (PAD) and a predictor of atherothrombosis. ApoA-I and HDL are associated with PAD, in humans. Homocysteine influences the liver expression of ApoA-I and decreases its blood level and HDL in genetic mice models. We aimed therefore to evaluate whether homocysteine and its nutritional determinants, folate and vitamin B12 are associated with ABI by influencing HDL metabolism, in an ambulatory elderly population. Methods: 667 elderly volunteers from rural Sicily were assessed for ABI, homocysteine and its determinants, lipid markers and other predictors of PAD. HDL size was assessed in 15 sera in upper and lower quartiles of Hcy distribution. Results: In multivariate analysis, ApoA-I and homocysteine were two predictors of ABI (β-coefficient = 2.86, p<0.004 and β-coefficient = -3.41, p<0.001, respectively). Homocysteine correlated negatively with ApoA-I (R = -0.147, p<0.001) and with HDL-Cholesterol (R = -0.113, P = 0.003). The associations of homocysteine, vitamin B12 and methylmalonic acid with ApoA-I and HDL2a particles and that of homocysteine with increased small size HDL3c suggested mechanisms related with impaired synthesis of ApoA-I and HDL and abnormal maturation of HDL particles. Conclusion: The influence of homocysteine on ApoA-I and HDL metabolism provides new insights on its role on vascular diseases, at a cross-point between atherosclerosis and atherothrombosis.