Higher anticholinergic burden from medications is associated with significant increase in markers of inflammation in the EPIC-Norfolk prospective population-based cohort study

Abstract

Background: Higher anticholinergic burden from medications is associated\nwith increased risk of cardiovascular disease and cognitive function\ndecline. A mechanistic pathway has never been established. We aimed to\ndetermine whether chronic inflammation may mediate these associations.\nMethods: Participants were drawn from the European Prospective\nInvestigation into Cancer, Norfolk cohort (40-79 years at baseline). The\nanticholinergic cognitive burden score (ACB) was calculated at\nbaseline/first (1HC) (1993/97) and second (2HC) (1998/2000) health\nchecks. Plasma fibrinogen and C-reactive protein (CRP) were measured\nduring 1HC and Tumour Necrosis Factor alpha (TNF-α) and interleukin 6\n(IL-6) during 2HC. Cross-sectional associations between ACB and\ninflammatory markers were examined for 1HC and 2HC, respectively. The\nprospective association was also examined between 1HC ACB and 2HC\ninflammatory markers. All models adjusted for age, sex, lifestyle\nfactors, co-morbidities and medications. Results: 17,678 and 22,051\nparticipants were included in cross-sectional analyses for CRP, and\nfibrinogen, respectively. A total of 5,101 participants with available\ndata for TNF-α and IL-6 were included in the longitudinal analyses.\nCross-sectionally, a point increase in the ACB was associated with a\nsignificant increase in all inflammatory markers (beta (standard error):\nfibrinogen – 0.035g/l (0.006), p<0.001; CRP 0.284mg/l\n(0.044), p<0.001; TNF-α 0.031pg/ml (0.010), p=0.002; and IL-6\n0.112pg/ml (0.033), p=0.001. Longitudinally, a unit increase in the ACB\nwas associated with a significant increase in TNF-α 0.028pg/ml (0.011),\np=0.013 and IL-6 0.076 pg/ml (0.035), p=0.029. Conclusion: Higher\nanticholinergic burden was significantly associated with higher\ninflammatory markers. Inflammation may mediate the relationship between\nexposure to anticholinergic medications and adverse outcomes