Associations of plasma homocysteine level with brachial-ankle pulse wave velocity, LDL atherogenicity, and inflammation profile in healthy men

Abstract

AIMS: To investigate the association of plasma total homocysteine (tHcy) with arterial stiffness, measured as brachial-ankle pulse wave velocity (baPWV), LDL atherogenicity, and inflammation profile in healthy men.

METHODS AND RESULTS: In this cross-sectional study, 612 healthy men aged 31-79 years were classified into quartiles according to plasma tHcy concentration. In the total study population, tHcy concentration showed positive correlation with age (r=0.083, P=0.040), interleukin (IL)-1β (r=0.249, P<0.001), TNF-α (r=0.150, P<0.001), IL-6 (r=0.154, P<0.001), oxidized LDL (oxLDL) (r=0.161, P=<0.001), and baPWV (r=0.087, P=0.032); and negative correlation with folate (r=-0.353, P<0.001) and vitamin B(12) (r=-0.269, P<0.001). In subgroup analysis based on plasma tHcy level, tHcy was associated with baPWV in men with high levels of tHcy (≥ 13.1μmol/L, n=153; r=0.258, P=0.001), but not in those with low-tHcy (<13.1 μmol/L, n=459; r=-0.033, P=0.478). The association between tHcy and baPWV in the high-tHcy group remained significant after adjustment for age, BMI, smoking, drinking, folate, and vitamin B₁₂. In the high-tHcy group, tHcy level was also positively correlated with IL-1β, TNF-α, oxLDL, and blood pressure; and negatively correlated with LDL particle size. In addition, baPWV showed negative correlation with LDL particle size and positive correlation with oxLDL in the high-tHcy group.

CONCLUSION: This study shows an association between high levels of plasma tHcy and more advanced arterial stiffness, smaller LDL particle size, and higher levels of oxLDL and cytokines in men with hyperhomocysteinemia. Enhanced arterial stiffness in hyperhomocysteinemia might be attributed, in part, to Hcy-related LDL atherogenicity.