A proinflammatory state is associated with hyperhomocysteinemia in the elderly.

BACKGROUND The mechanism by which high circulating homocysteine concentrations are a risk factor for atherothrombosis is incompletely understood. A proinflammatory state is related to atherosclerosis, and recent studies suggest that acute phase reactants correlate with circulating concentrations of homocysteine. OBJECTIVE We determined whether high concentrations of inflammatory markers are associated with hyperhomocysteinemia independently of dietary vitamin intakes, vitamin concentrations, and cardiovascular disease risk factors in a large, representative sample of the general population. DESIGN Five hundred eighty-six men and 734 women were randomly selected from the inhabitants of 2 small towns near Florence, Italy. RESULTS After adjustment for multiple potential confounders, interleukin 1 receptor antagonist (IL-1ra) and interleukin 6 (IL-6) concentrations were significantly (P < 0.001) associated with plasma homocysteine concentrations in older (>65 y) populations. Compared with participants in the lowest IL-6 tertile, those in the highest tertile had a higher risk of having homocysteine concentrations that were high (>30 micromol/L; odds ratio: 2.6; 95% CI: 1.1, 5.6; P = 0.024) or in the intermediate range 15-30 micromol/L (odds ratio: 1.6; 95% CI: 1.2, 2.2; P = 0.0014). Sedentary state, intakes of vitamin B-6 and folic acid, and serum folate, vitamin B-12, vitamin B-6, and alpha-tocopherol concentrations were significant independent correlates of homocysteine. CONCLUSIONS High circulating concentrations of IL-1ra and IL-6 are independent correlates of hyperhomocysteinemia and may explain, at least in part, the association between homocysteine and atherosclerosis.