During 859,164 person years of follow-up, we documented 939 incident cases of diverticulitis, and 256 incident cases of diverticular bleeding. Baseline characteristics of the cohort are summarized in according to regular use of aspirin and NSAIDs and standardized for age. Approximately 29% of participants reported regular aspirin use (2 or more times per week) and 5% reported regular NSAID use. On average, regular users of aspirin were more likely to have a history of coronary heart disease than non-users, and users of aspirin and NSAIDs were more likely to have osteoarthritis and to consume more alcohol than non-users.
Baseline Characteristics of the Study Cohort in 1986 According to Regular Use of Aspirin and NSAID
After controlling for other potential risk factors for diverticular complications, we observed a significantly higher risk of diverticulitis among regular users of NSAIDs (multivariable HR 1.72; 95% CI, 1.40–2.11), and to a lesser degree among regular users of aspirin (multivariable HR 1.25; 95% CI, 1.05–1.47) when compared with men who denied use of either drug (). In analyses according to subtypes of diverticulitis, we observed that regular NSAID use appeared to be more strongly associated with risk of complicated diverticulitis (multivariable HR 2.55; 95% CI, 1.32–4.95) than uncomplicated diverticulitis (multivariable HR 1.65; 95% CI, 1.32–2.05) compared to non-use of either NSAIDs or aspirin. For both subtypes, we found comparable risk estimates for regular aspirin use, with a multivariable HR of 1.13 (95% CI, 0.61–2.10) for complicated diverticulitis and 1.24 (95% CI, 1.04–1.47) for uncomplicated diverticulitis.
Aspirin and NSAID Use and the Risk of Diverticulitis and Diverticular Bleedinga
For diverticular bleeding, the associations of regular use of NSAIDs and aspirin were similar (multivariable HR 1.74; 95% CI, 1.15–2.64 and multivariable HR 1.70; 95% CI, 1.21–2.39, respectively). Combined use of aspirin and NSAIDs was associated with a multivariable HR for diverticulitis of 1.65 (95% CI, 1.36–2.01) and for bleeding of 2.02 (95% CI, 1.38–2.96). A formal test of whether the concurrent use of aspirin and NSAIDs was associated with greater risk than use of each drug alone was not statistically significant for diverticulitis (p=0.06) or for bleeding (p=0.145)..
The association between aspirin use and diverticular complications did not display a linear dose-relationship in the multivariable analyses excluding NSAID users (p=0.28 for trend for diverticulitis and p=0.10 for trend for diverticular bleeding) (). However, we observed that men who took intermediate doses of aspirin (2–5.9 standard (325 mg) tablets per week) had the highest risk of diverticular bleeding (multivariable HR 2.32; 95% CI, 1.34–4.02) when compared to men who reported no aspirin use.
Dose of Aspirin and the Risk of Diverticulitis and Diverticular Bleedinga
To better assess the effect of consistency of use on the risk of diverticular complications, we also examined frequency of regular aspirin use in non-NSAID users (). Compared to non-regular users, men who used aspirin daily had a significantly higher risk of diverticulitis (multivariable HR 1.46; 95% CI, 1.13–1.88, p =0.002 for trend). Similar to the findings for aspirin dose, we found that moderately frequent use of aspirin was strongly associated with the risk of diverticular bleeding. Men who reported aspirin use 4–6 days per week had a multivariable HR of 3.13 (95% CI, 1.82–5.38) when compared to men who denied aspirin use.
Frequency of Aspirin Use and the Risk of Diverticulitis and Diverticular Bleedinga
In addition, we found that increasing duration of regular aspirin and NSAID use was associated with greater risk of diverticular complications among non-users of NSAIDs and aspirin, respectively. Ten years or more of aspirin use was associated with a multivariable HR of 1.51 (95% CI, 1.13–2.03, p=0.01 for trend) for diverticulitis, and 2.53 (95% CI, 1.43–4.46, p=0.003 for trend) for bleeding compared to non-regular use. Likewise, after 10 years of NSAID use the HR of diverticulitis was 1.80 (95% CI, 1.30–2.51, p<0.001 for trend), and of diverticular bleeding was 2.17 (95% CI, 1.23–2.85, p=0.006 for trend).
To address the possibility of confounding by comorbid illness, we additionally adjusted our analyses for cardiovascular disease and osteoarthritis, the two most common indications for aspirin use in this cohort. In this analysis, the relationships between aspirin and NSAID use and diverticulitis remained largely unchanged (multivariable HR 1.20; 95% CI, 1.01–1.42 for aspirin and multivariable 1.64; 95% CI, 1.33–2.02 for NSAIDs). For diverticular bleeding, the association with aspirin use was not materially altered (multivariable HR 1.66; 95% CI, 1.18–2.33), but the association with NSAIDs was somewhat attenuated (multivariable HR 1.42; 95% CI, 0.92–2.18).