title: Association of Dietary Nitrate Intake With Primary Open-Angle Glaucoma: A Prospective Analysis From the Nurses' Health Study and Health Professionals Follow-up Study.
abstract: OBJECTIVE
  Nitric oxide signaling alterations in outflow facility and retinal blood flow autoregulation are implicated in primary open-angle glaucoma (POAG). Nitric oxide donation has emerged as a POAG therapeutic target. An exogenous source of nitric oxide is dietary nitrates.
  
  
  OBJECTIVE
  To evaluate the association between dietary nitrate intake, derived mainly from green leafy vegetables, and POAG.
  
  
  METHODS
  We followed up participants biennially in the prospective cohorts of the Nurses' Health Study (63 893 women; 1984-2012) and the Health Professionals Follow-up Study (41 094 men; 1986-2012) at each 2-year risk period. Eligible participants were 40 years or older, were free of POAG, and reported eye examinations.
  
  
  METHODS
  The primary exposure was dietary nitrate intake. Information on diet and potential confounders was updated with validated questionnaires.
  
  
  METHODS
  The main outcome was the incidence of POAG and POAG subtypes; 1483 cases were confirmed with medical records and classified into subtypes defined by intraocular pressure (IOP) (≥22 or <22 mm Hg) or by visual field (VF) loss pattern at diagnosis (peripheral loss only or early paracentral loss). Cohort-specific and pooled multivariable rate ratios (MVRRs) and 95% CIs were estimated.
  
  
  RESULTS
  During 1 678 713 person-years of follow-up, 1483 incident cases of POAG were identified. The mean (SD) age for the 1483 cases was 66.8 (8.3). Compared with the lowest quintile of dietary nitrate intake (quintile 1: approximately 80 mg/d), the pooled MVRR for the highest quintile (quintile 5: approximately 240 mg/d) was 0.79 (95% CI, 0.66-0.93; P for trend = .02). The dose response was stronger (P for heterogeneity = .01) for POAG with early paracentral VF loss (433 cases; quintile 5 vs quintile 1 MVRR = 0.56; 95% CI, 0.40-0.79; P for trend < .001) than for POAG with peripheral VF loss only (835 cases; quintile 5 vs quintile 1 MVRR = 0.85; 95% CI, 0.68-1.06; P for trend = .50). The association did not differ (P for heterogeneity = .75) by POAG subtypes defined by IOP (997 case patients with IOP ≥22 mm Hg: quintile 5 vs quintile 1 MVRR = 0.82; 95% CI, 0.67-1.01; P for trend = .11; 486 case patients with IOP <22 mm Hg: quintile 5 vs quintile 1 MVRR = 0.71; 95% CI, 0.53-0.96; P for trend = .12). Green leafy vegetables accounted for 56.7% of nitrate intake variation. Compared with consuming 0.31 servings per day, the MVRR for consuming 1.45 or more servings per day was 0.82 for all POAG (95% CI, 0.69-0.97; P for trend = .02) and 0.52 for POAG with paracentral VF loss (95% CI, 0.29-0.96; P for trend < .001).
  
  
  CONCLUSIONS
  Higher dietary nitrate and green leafy vegetable intake was associated with a lower POAG risk, particularly POAG with early paracentral VF loss at diagnosis.
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Jae H
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts2Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts3Department of Epidemiology, Harvard.
authors.forename: Walter C
authors.initials: WC
authors.lastname: Willett
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts4Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Rosner
authors.affiliation: Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Boston.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Buys
authors.affiliation: Glaucoma Service, Massachusetts Eye and Ear Infirmary, Boston.
authors.forename: Janey L
authors.initials: JL
authors.lastname: Wiggs
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts6Glaucoma Service, Massachusetts Eye and Ear Infirmary, Boston.
authors.forename: Louis R
authors.initials: LR
authors.lastname: Pasquale
mesh_terms: D000328:Adult; D000368:Aged; D004032:Diet; D005247:Feeding Behavior; D005260:Female; D005500:Follow-Up Studies; D005902:Glaucoma, Open-Angle / Q000453:epidemiology*; D006282:Health Personnel / Q000706:statistics & numerical data*; D006801:Humans; D015994:Incidence; D007429:Intraocular Pressure; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000008:administration & dosage*; D011446:Prospective Studies; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014065:Tonometry, Ocular; D014481:United States / Q000453:epidemiology; D014675:Vegetables
chemical_list: D009566:Nitrates