Table 2. Cumulative Mean Aspirin Dose and Risk of Hepatocellular Carcinoma in 13 371 Women (1980-2012) and Men (1986-2012) in the Pooled NHS and HPFS Cohorts.

Characteristic	No. of Weekly Aspirin Tablets (Cumulative Mean)				P Value for Trenda
	<0.5	0.5 to <1.5	1.5 to <5	≥5
Cases per person-years	46/1 425 726	23/867 338	24/1 207 350	15/731 776
Model 1, HR (95% CI)b	1 [Reference]	0.83 (0.49-1.40)	0.50 (0.30-0.84)	0.55 (0.30-1.01)	.008
Model 2, HR (95% CI)c	1 [Reference]	0.86 (0.50-1.46)	0.48 (0.28-0.82)	0.48 (0.26-0.89)	.003
Model 3, HR (95% CI)d	1 [Reference]	0.87 (0.51-1.48)	0.51 (0.30-0.86)	0.49 (0.28-0.96)	.006
Model 4, HR (95% CI)e	1 [Reference]	1.20 (0.65-2.20)	0.56 (0.32-0.99)	0.37 (0.17-0.81)	.005

Abbreviations: HR, hazard ratio; HPFS, Health Professionals Follow-up Study; NHS, Nurses’ Health Study.

^aCalculated using cumulative mean aspirin dose (continuous), among regular aspirin users.

^bModel 1 was conditioned on age (continuous years), year of questionnaire return, and sex (ie, cohort).

^cModel 2 includes model 1 covariates plus race/ethnicity (white vs nonwhite), body mass index (continuous measure), alcohol intake (0-4.9, 5.0-14.9, ≥15.0 g/d), smoking status (current vs prior vs never), physical activity (<3.0, 3.0-8.9, ≥9 metabolic equivalent task–hours per week), diabetes (yes vs no), hypertension (yes vs no), dyslipidemia (yes vs no), regular multivitamin use (≥2 multivitamin tablets per week vs no), regular use of oral antidiabetic medications (yes vs no), and regular use of statins (yes vs no). All relevant covariates were updated over time.

^dModel 3 includes model 2 regular use of nonaspirin nonsteroidal anti-inflammatory drugs (≥2 nonaspirin nonsteroidal anti-inflammatory drug tablets per week vs no), assessed as a time-varying covariate.

^eModel 4 includes model 3 covariates plus duration of regular aspirin use (continuous, years).