PMID- 26767881 OWN - NLM STAT- MEDLINE DCOM- 20160805 LR - 20220330 IS - 2168-6173 (Electronic) IS - 2168-6165 (Print) IS - 2168-6165 (Linking) VI - 134 IP - 3 DP - 2016 Mar TI - Association of Dietary Nitrate Intake With Primary Open-Angle Glaucoma: A Prospective Analysis From the Nurses' Health Study and Health Professionals Follow-up Study. PG - 294-303 LID - 10.1001/jamaophthalmol.2015.5601 [doi] AB - IMPORTANCE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. EXPOSURES: The primary exposure was dietary nitrate intake. Information on diet and potential confounders was updated with validated questionnaires. MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: Higher dietary nitrate and green leafy vegetable intake was associated with a lower POAG risk, particularly POAG with early paracentral VF loss at diagnosis. FAU - Kang, Jae H AU - Kang JH AD - Channing Division of Network Medicine, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts. FAU - Willett, Walter C AU - Willett WC AD - 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. FAU - Rosner, Bernard A AU - Rosner BA AD - 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. FAU - Buys, Emmanuel AU - Buys E AD - Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Boston. FAU - Wiggs, Janey L AU - Wiggs JL AD - Glaucoma Service, Massachusetts Eye and Ear Infirmary, Boston. FAU - Pasquale, Louis R AU - Pasquale LR AD - 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. LA - eng GR - EY015473/EY/NEI NIH HHS/United States GR - EY09611/EY/NEI NIH HHS/United States GR - UM1 CA186107/CA/NCI NIH HHS/United States GR - R01 EY015473/EY/NEI NIH HHS/United States GR - R01 EY009611/EY/NEI NIH HHS/United States GR - R21 EY022766/EY/NEI NIH HHS/United States GR - UM1 CA167552/CA/NCI NIH HHS/United States GR - R01 EY022746/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Ophthalmol JT - JAMA ophthalmology JID - 101589539 RN - 0 (Nitrates) SB - IM MH - Adult MH - Aged MH - *Diet MH - Feeding Behavior MH - Female MH - Follow-Up Studies MH - Glaucoma, Open-Angle/*epidemiology MH - Health Personnel/*statistics & numerical data MH - Humans MH - Incidence MH - Intraocular Pressure MH - Male MH - Middle Aged MH - Nitrates/*administration & dosage MH - Prospective Studies MH - Risk Factors MH - Surveys and Questionnaires MH - Tonometry, Ocular MH - United States/epidemiology MH - *Vegetables PMC - PMC4966649 MID - NIHMS801754 COIS- None of the authors have conflicts of interest, including financial interests, activities, relationships and affiliations. EDAT- 2016/01/16 06:00 MHDA- 2016/08/06 06:00 PMCR- 2017/03/01 CRDT- 2016/01/16 06:00 PHST- 2017/03/01 00:00 [pmc-release] PHST- 2016/01/16 06:00 [entrez] PHST- 2016/01/16 06:00 [pubmed] PHST- 2016/08/06 06:00 [medline] AID - 2480455 [pii] AID - 10.1001/jamaophthalmol.2015.5601 [doi] PST - ppublish SO - JAMA Ophthalmol. 2016 Mar;134(3):294-303. doi: 10.1001/jamaophthalmol.2015.5601.