Plasma homocysteine, dietary B vitamins, betaine, and choline and risk of peripheral artery disease

Abstract

ObjectiveFew studies have examined the roles of homocysteine and related nutrients in the development of peripheral artery disease (PAD). We examined the associations between plasma homocysteine, dietary B vitamins, betaine, choline, and supplemental folic acid use and incidence of PAD. MethodsWe used two cohort studies of 72,348 women in the Nurses' Health Study (NHS, 1990–2010) and 44,504 men in the Health Professionals Follow-up Study (HPFS, 1986–2010). We measured plasma homocysteine in nested matched case–control studies of clinically recognized PAD within both cohorts, including 143 PAD cases and 424 controls within the NHS (1990–2010) and 143 PAD cases and 428 controls within the HPFS (1994–2008). We examined the association between diet and risk of incident PAD in the cohorts using a food frequency questionnaire and 790 cases of PAD over 3.1 million person-years of follow-up. ResultsHigher homocysteine levels were positively associated with risk of PAD in men (adjusted IRR 2.17; 95% CI, 1.08–4.38 for tertile 3 vs. 1). There was no evidence of an association in women (adjusted IRR 1.14; 95% CI, 0.61–2.12). Similarly, higher folate intake, including supplements, was inversely associated with risk of PAD in men (adjusted HR 0.90; 95% CI, 0.82–0.98 for each 250 μg increase) but not women (HR 1.01, 95% CI, 0.88–1.15). Intakes of the other B vitamins, betaine, and choline were not consistently associated with risk of PAD in men or women. ConclusionHomocysteine levels were positively associated and dietary folate intake was inversely associated with risk of PAD in men but not in women.