title: Plasma homocysteine, dietary B vitamins, betaine, and choline and risk of peripheral artery disease.
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.
  
  
  CONCLUSIONS
  Homocysteine levels were positively associated and dietary folate intake was inversely associated with risk of PAD in men but not in women.
authors.affiliation: 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.
authors.forename: Monica L
authors.initials: ML
authors.lastname: Bertoia
authors.affiliation: 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.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Pai
authors.affiliation: Houston Methodist Research Institute, Houston, TX, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Cooke
authors.affiliation: 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.
authors.forename: Michel M
authors.initials: MM
authors.lastname: Joosten
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Murray A
authors.initials: MA
authors.lastname: Mittleman
authors.affiliation: 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.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Rimm
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Mukamal
mesh_terms: D000328:Adult; D000368:Aged; D001622:Betaine / Q000627:therapeutic use*; D016022:Case-Control Studies; D002794:Choline / Q000627:therapeutic use*; D015331:Cohort Studies; D004032:Diet; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000737:chemistry; D005500:Follow-Up Studies; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000453:epidemiology* / Q000517:prevention & control*; D016016:Proportional Hazards Models; D012256:Riboflavin / Q000627:therapeutic use; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014803:Vitamin B Complex / Q000627:therapeutic use*
chemical_list: D006710:Homocysteine; D014803:Vitamin B Complex; D001622:Betaine; D005492:Folic Acid; D002794:Choline; D012256:Riboflavin
keywords: Betaine; Choline; Folate; Homocysteine; Peripheral artery disease; Riboflavin; Vitamin B12; Vitamin B6