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Atherosclerosis. 2014 Jul;235(1):94-101. doi: 10.1016/j.atherosclerosis.2014.04.010. Epub 2014 Apr 28.

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

Author information

1
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA. Electronic address: mbertoia@hsph.harvard.edu.
2
Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
3
Houston Methodist Research Institute, Houston, TX, USA.
4
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA; Top Institute Food and Nutrition, Wageningen, The Netherlands; Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
5
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
6
Department of Nutrition, Harvard School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
7
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.

Abstract

OBJECTIVE:

Few 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.

METHODS:

We 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.

RESULTS:

Higher 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.

CONCLUSION:

Homocysteine levels were positively associated and dietary folate intake was inversely associated with risk of PAD in men but not in women.

KEYWORDS:

Betaine; Choline; Folate; Homocysteine; Peripheral artery disease; Riboflavin; Vitamin B12; Vitamin B6

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