Aspirin, inflammation markers, and colorectal adenomas Free

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The goals of this ancillary study to the Aspirin/Folate Polyp Prevention Clinical Trial were to (a) examine the effects of daily low dose aspirin on circulating inflammation markers, namely C-reactive protein (CRP) and IL-6, and (b) assess associations of baseline levels of these markers with risk of recurrent colorectal adenomas.

The Aspirin/Folate Polyp Prevention Study was a randomized, double-blind, placebo-controlled trial of aspirin (and folate) to prevent recurrent colorectal adenomas in patients with an adenoma history. Patients were randomized to placebo (n=372), 81 mg of aspirin (n=377), or 325 mg of aspirin (n=372) daily, and an endpoint colonoscopy was conducted after 3 years. The aspirin component of the study showed that 81 mg of aspirin/day lowered the risk of recurrent adenomas. In this ancillary study, blood samples collected at baseline and Year 3 were assayed for CRP by high-sensitivity latex-enhanced immunonephelometry and for IL-6 by ELISA.

To study effects of aspirin on CRP and IL-6, levels of these inflammation markers at Year 3 were compared among randomization groups by linear regression, with adjustment for covariates associated with the markers (e.g., baseline levels, age, gender, and BMI). The adjusted geometric means for placebo, 81 mg, and 325 mg groups for CRP (mg/L) were 2.09, 2.17, and 2.11 (p = 0.841), and for IL-6 (pg/ml), they were 1.97, 2.06, and 2.02 (p = 0.575), respectively. There were no differences among randomization groups within subgroups defined by baseline levels of the marker, age, gender, and BMI. Results were similar when changes in marker levels between baseline and Year 3 were analyzed.

To study associations of baseline levels of CRP and IL-6 with risk of recurrent adenomas, individuals with and without adenomas at Year 3 were compared using log-binomial models, controlling for randomization group, smoking status, adenoma history, and age. In the entire study population, the risk ratio (RR) for the association between baseline CRP above the median (1.94 mg/L) and recurrent adenomas was 1.11 (95% CI = 0.97-1.27). In women, however, a high CRP (> 1.94 mg/L) was associated with recurrent adenomas (RR = 1.32, 95% CI = 0.99-1.76), number of adenomas at Year 3 (RR for ≥ 2 adenomas = 1.51, 95% CI = 1.05-2.17), and advanced adenomas (RR = 1.48, 95% CI = 1.03-2.12); no statistically significant associations were observed in men for any of these analyses (e.g., RR for recurrent adenomas = 1.05, 95% CI = 0.89-1.23). Baseline IL-6 was not related to recurrent adenomas in men or women (RR in all subjects = 1.05, 95% CI = 0.86-1.29 for highest vs. lowest quartiles).

Our data showed that long-term use of low-dose aspirin did

not affect CRP and IL-6 levels, suggesting that the chemopreventive effect of aspirin on colorectal adenomas is not mediated through modulation of these inflammation markers. Our results also suggest that relatively high levels of CRP are associated with increased risk of recurrent adenomas in women, but not in men.