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ORIGINAL RESEARCH COMMUNICATION |
1 From the Department of Medical and Surgical Critical Area, Center for the Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Diseases to Develop Novel Therapies, University of Florence, Florence, Italy (AMG, SF, AG, FS, GFG, and RA); the Laboratory of Clinical Epidemiology, Geriatric Department, National Institute of Research and Care on Aging, Florence, Italy (AMC and SB); the Division of Nutritional Sciences, Cornell University, Ithaca, NY (BB); and the Longitudinal Studies Section, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD (LF)
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 µmol/L; odds ratio: 2.6; 95% CI: 1.1, 5.6; P = 0.024) or in the intermediate range 15–30 µmol/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 
-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.
Key Words: Homocysteine • inflammation • cytokines • macronutrients • micronutrients • vitamin concentrations • InCHIANTI Study
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