TABLE 3.
Associations between non-dietary covariates and AMD transitions from severity group 2 or group 3 to higher severity groups over 5 years (616 events/2697 eyes), adjusting for other covariates1.
| Variables | Non-progressing eyes (n = 2081), n (%) | Progressing eyes (n = 616), n (%) | Model 12, HR (95% CI) | P | Model 23, HR (95% CI) | P |
|---|---|---|---|---|---|---|
| Non-genetic factors | ||||||
| Age (years) | ||||||
| Mean (SD), range | 69.1 (5.2), 55–81 | 70.5 (5.1), 56–81 | 1.05 (1.03, 1.06) | <0.001 | 1.05 (1.03, 1.07) | <0.001 |
| 55 to 64 | 75 (3.6) | 17 (2.8) | 1.00 (Ref) | 1.00 (Ref) | ||
| 65 to 74 | 1110 (53.3) | 246 (39.9) | 1.57 (1.22, 2.01) | <0.001 | 1.69 (1.30, 2.12) | <0.001 |
| ≥75 | 896 (43.1) | 353 (57.3) | 1.90 (1.44, 2.50) | <0.001 | 2.04 (1.52, 2.73) | <0.001 |
| P-trend | <0.001 | <0.001 | ||||
| Sex | ||||||
| Female | 1179 (56.7) | 332 (53.9) | 1.00 (Ref) | 1.00 (Ref) | ||
| Male | 902 (43.3) | 284 (46.1) | 0.94 (0.81, 1.10) | 0.43 | 0.97 (0.80, 1.16) | 0.71 |
| Race | ||||||
| Other | 63 (3.0) | 11 (1.8) | 1.00 (Ref) | 1.00 (Ref) | ||
| Non-Hispanic White | 2018 (97.0) | 605 (98.2) | 1.45 (0.82, 2.59) | 0.20 | 1.07 (0.53, 2.16) | 0.85 |
| Education | ||||||
| ≤High school | 693 (33.3) | 238 (38.6) | 1.00 (Ref) | 1.00 (Ref) | ||
| >High School | 1388 (66.7) | 378 (61.4) | 0.84 (0.71, 0.98) | 0.03 | 0.90 (0.76, 1.06) | 0.21 |
| Smoking | ||||||
| Never | 963 (46.3) | 253 (41.0) | 1.00 (Ref) | 1.00 (Ref) | ||
| Past | 1027 (49.3) | 309 (50.2) | 1.12 (0.95, 1.32) | 0.17 | 1.10 (0.92, 1.32) | 0.28 |
| Current | 91 (4.4) | 54 (8.8) | 2.13 (1.60, 2.83) | <0.001 | 1.67 (1.22, 2.30) | 0.002 |
| Caloric intake (kcal/d) | ||||||
| Mean (SD), range | 1510.09 (567.56), 600.36–3994.63 | 1557.82 (574.07), 622.64–3869.29 | 1.19 (1.00, 1.41)4 | 0.05 | 1.08 (0.90, 1.30)4 | 0.42 |
| AREDS treatment group | ||||||
| Placebo | 491 (23.6) | 149 (24.2) | 1.00 (Ref) | 1.00 (Ref) | ||
| Active5 | 1590 (76.4) | 467 (75.8) | 0.97 (0.81, 1.16) | 0.74 | 0.95 (0.78, 1.15) | 0.61 |
| Multivitamin intake | ||||||
| No | 1089 (52.3) | 315 (51.1) | 1.00 (Ref) | 1.00 (Ref) | ||
| Yes | 992 (47.7) | 301 (48.9) | 1.02 (0.87, 1.19) | 0.83 | 0.98 (0.83, 1.15) | 0.78 |
| Fellow eye status at baseline | ||||||
| Non-advanced | 1887 (90.7) | 445 (72.2) | 1.00 (Ref) | 1.00 (Ref) | ||
| Advanced | 194 (9.3) | 171 (27.8) | 2.90 (2.44, 3.45) | <0.001 | 2.37 (1.97, 2.87) | <0.001 |
| AMD family history | ||||||
| No family member affected | 1503 (72.2) | 390 (63.3) | 1.00 (Ref) | 1.00 (Ref) | ||
| 1 family member affected | 401 (19.3) | 146 (23.7) | 1.39 (1.15, 1.68) | <0.001 | 1.18 (0.97, 1.45) | 0.10 |
| ≥2 family members affected | 177 (8.5) | 80 (13.0) | 1.60 (1.23, 2.01) | <0.001 | 1.38 (1.07, 1.78) | 0.02 |
| P-trend6 | <0.001 | 0.006 | ||||
| Genetic risk score7 | ||||||
| GRS_continuous | ||||||
| Mean (SD), range | 1.60 (0.46), 0.26–3.11 | 1.84 (0.45), 0.28–2.99 | 2.83 (2.35, 3.41) | <0.001 | 2.40 (1.96, 2.93) | <0.001 |
| GRS tertiles | ||||||
| GRS tertile 1 | 775 (37.2) | 124 (20.1) | 1.00 (Ref) | 1.00 (Ref) | ||
| GRS tertile 2 | 718 (34.5) | 182 (29.5) | 1.53 (1.22, 1.92) | <0.001 | 1.39 (1.10, 1.77) | 0.006 |
| GRS tertile 3 | 588 (28.3) | 310 (50.3) | 2.87 (2.32, 3.55) | <0.001 | 2.38 (1.89, 3.00) | <0.001 |
| P-trend8 | <0.001 | <0.001 | ||||
Abbreviations: AMD, age-related macular degeneration; AREDS, Age-Related Eye Disease Study; CI, confidence interval; GRS, genetic risk score; HR, hazard ratio; SD, standard deviation.
Progression defined as eye in AMD severity group 2 or group 3 at baseline progressing to higher severity groups at 2 consecutive visits over a 5 year follow-up period.
Model 1: Cox proportional hazard analyses adjusted for age groups and baseline AMD severity group.
Model 2: multivariate Cox proportional hazard analyses adjusted for baseline AMD severity group in addition to all non-dietary and genetic covariates in the table.
Relative risk normalized per 1340 kcal/d (average caloric intake of females and males combined).
Active group consists of subjects treated by antioxidants only, zinc only, or a combination of antioxidants and zinc.
Estimate indicates an increased incidence of progression with each additional family member affected with AMD.
GRS calculated as sum of β coefficients multiplied by number of minor alleles for 12 genetic variants [37], after adjusting for age, sex, and race.
Estimate indicates an increased incidence of progression with increase in GRS tertile.