Table 3. Age-adjusted and multivariable adjusted relative risk (95% confidence interval) of subtypes of primary open-angle glaucoma, by quintiles of nitrate intake,* in Nurses' Health Study (1984-2012) and in Health Professionals' Follow-up Study (1986-2012).
Quintiles of dietary nitrate intake | |||||||||
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SUBTYPES DEFINED BY INTRAOCULAR PRESSURE† | Q1 | Q2 | Q3 | Q4 | Q5 | p-trend | p-heterogeneity¶ | ||
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High-tension glaucoma (intraocular pressure ≥ 22 mm Hg; n=998) | Women | Cases | 133 | 117 | 138 | 121 | 142 | 0.75 | |
Multivariable RR(95% CI)‡ | 1.00 (ref) | 0.83 (0.64, 1.06) | 0.89 (0.70, 1.14) | 0.75 (0.58, 0.96) | 0.87 (0.68, 1.11) | 0.29 | |||
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Men | Cases | 68 | 62 | 75 | 82 | 59 | |||
Multivariable RR (95% CI)‡ | 1.00 (ref) | 0.89 (0.62, 1.27) | 1.01 (0.72, 1.43) | 1.11 (0.79, 1.56) | 0.73 (0.51, 1.06) | 0.20 | |||
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Pooled§ | Multivariable RR (95% CI) | 1.00 (ref) | 0.85 (0.69, 1.04) | 0.93 (0.76, 1.13) | 0.90 (0.61, 1.32) | 0.82 (0.67, 1.01) | 0.11 | ||
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Normal-tension glaucoma (intraocular pressure < 22 mm Hg; n=487) | Women | Cases | 77 | 56 | 69 | 78 | 69 | ||
Multivariable RR(95% CI)‡ | 1.00 (ref) | 0.68 (0.48, 0.96) | 0.77 (0.55, 1.07) | 0.82 (0.59, 1.13) | 0.71 (0.51, 1.00) | 0.22 | |||
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Men | Cases | 30 | 27 | 26 | 29 | 25 | |||
Multivariable RR (95% CI)‡ | 1.00 (ref) | 0.90 (0.52, 1.56) | 0.84 (0.48, 1.47) | 0.98 (0.57, 1.70) | 0.72 (0.41, 1.28) | 0.34 | |||
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Pooled§ | Multivariable RR (95% CI) | 1.00 (ref) | 0.73 (0.55, 0.98) | 0.79 (0.59, 1.05) | 0.86 (0.65, 1.13) | 0.71 (0.53, 0.96) | 0.12 | ||
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SUBTYPES DEFINED BY INITIAL VISUAL FIELD LOSS PATTERN‖ | |||||||||
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POAG with peripheral visual field loss only (n=836 cases) | Women | Cases | 120 | 91 | 121 | 120 | 124 | 0.01 | |
Multivariable RR(95% CI)‡ | 1.00 (ref) | 0.71 (0.54, 0.93) | 0.86 (0.67, 1.12) | 0.83 (0.64, 1.07) | 0.84 (0.65, 1.09) | 0.60 | |||
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Men | Cases | 47 | 47 | 58 | 62 | 45 | |||
Multivariable RR (95% CI)‡ | 1.00 (ref) | 1.01 (0.67, 1.55) | 1.20 (0.80, 1.80) | 1.29 (0.86, 1.92) | 0.87 (0.57, 1.34) | 0.67 | |||
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Pooled§ | Multivariable RR (95% CI) | 1.00 (ref) | 0.82 (0.58, 1.15) | 0.98 (0.72, 1.34) | 1.00 (0.65, 1.54) | 0.85 (0.68, 1.06) | 0.50 | ||
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POAG with early paracentral visual field loss (n=433 cases) | Women | Cases | 61 | 64 | 58 | 56 | 49 | ||
Multivariable RR (95% CI)‡ | 1.00 (ref) | 0.95 (0.66, 1.35) | 0.79 (0.55, 1.14) | 0.74 (0.51, 1.07) | 0.64 (0.43, 0.94) | 0.01 | |||
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Men | Cases | 35 | 28 | 28 | 32 | 22 | |||
Multivariable RR (95% CI)‡ | 1.00 (ref) | 0.79 (0.47, 1.34) | 0.72 (0.42, 1.22) | 0.84 (0.50, 1.39) | 0.44 (0.25, 0.78) | 0.01 | |||
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Pooled§ | Multivariable RR (95% CI) | 1.00 (ref) | 0.89 (0.67, 1.20) | 0.77 (0.57, 1.04) | 0.77 (0.57, 1.04) | 0.56 (0.40, 0.79) | 0.0003 |
Abbreviations: RR = Relative Risk; CI = Confidence Interval; IOP=intraocular pressure; VF=visual field
Intake calculated using cumulative average (i.e., average of all available intake data from food frequency questionnaires completed before each two-year period at risk).
Based on the maximum untreated intraocular pressure at diagnosis.
All multivariable analyses were adjusted for the same variables as in Model 1 in Table 2.
Pooled results were calculated using Dersimonian and Laird methods with random effects.
Based on visual field (VF) loss pattern as of the earliest reliable VF at diagnosis that was reproduced at the latest reliable VF. Cases (n=216) with advanced VF loss at diagnosis who could not be categorized based on initial presenting VF loss as either peripheral VF loss only or early paracentral VF loss were censored during analyses. See Methods for how cases were categorized according to initial presenting VF loss.
For testing whether the associations between nitrate and one POAG subtype is significantly different from that with another subtype, we combined the two datasets into one, then conducted Cox regression analyses that stratified on the 2 cohorts, which allowed for the baseline hazard function to be different in the cohorts; we then used the Lunn-McNeil approach59 to test for heterogeneity in associations and derived p for heterogeneity.