Table 4 Development of bilateral visual impairment according to cotinine level.

Cotinine level	Person-years	Incident cases	Incidence density (per 1,000 person-years)	Age sex adjusted HR (95% CI)	Multivariable-adjusted HR^a (95% CI)	HR (95% CI)^b in the model using time-dependent variables
Total (n = 198,282)
< 50	757,397.9	4043	5.3	1.00 (reference)	1.00 (reference)	1.00 (reference)
50–99	10,199.4	44	4.3	1.05 (0.78–1.42)	1.04 (0.77–1.40)	1.29 (0.95–1.74)
≥ 100	216,012.5	1039	4.8	1.22 (1.13–1.31)	1.18 (1.09–1.27)	1.29 (1.19–1.40)
P for trend				< 0.001	< 0.001	< 0.001
Men (n = 115,228)
< 50	381,928.1	1386	3.6	1.00 (reference)	1.00 (reference)	1.00 (reference)
50–99	8620.6	31	3.6	0.99 (0.69–1.41)	0.98 (0.68–1.40)	1.27 (0.90–1.80)
≥ 100	204,317.1	934	4.6	1.20 (1.11–1.31)	1.17 (1.08–1.27)	1.30 (1.19–1.42)
P for trend				< 0.001	< 0.001	< 0.001
Women (n = 83,054)
< 50	375,469.8	2657	7.1	1.00 (reference)	1.00 (reference)	1.00 (reference)
50–99	1578.8	13	8.2	1.23 (0.72–2.13)	1.23 (0.71–2.12)	1.34 (0.72–2.49)
≥ 100	11,695.4	105	9.0	1.27 (1.04–1.54)	1.22 (1.002–1.48)	1.25 (1.02–1.53)
P for trend				0.014	0.038	0.022

The P value for the interaction of sex and cotinine levels for risk of bilateral visual impairment was 0.742.
BMI body mass index, CI confidence intervals, CVD cardiovascular disease, HR hazards ratio.
^aEstimated from parametric proportional hazard models. Multivariable model was adjusted for age, sex (only for total), center, year of screening exam, BMI, physical activity, alcohol intake, total energy intake, educational level, medication for dyslipidemia, history of CVD, history of diabetes, and history of hypertension.
^bEstimated from parametric proportional hazard models with cotinine levels category, physical activity, alcohol intake, total energy intake, BMI, medication for dyslipidemia, history of diabetes, history of hypertension, and history of CVD as time-dependent categorical variables and baseline age, sex, center, year of screening exam, and education level as time-fixed variables.

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