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Higher anticholinergic burden from medications is associated with significant increase in markers of inflammation in the EPIC-Norfolk prospective population-based cohort study
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  • RIA SANGHAVI,
  • Tiberiu Pana,
  • Hulkar Mamayusuppova,
  • Ian Maidment,
  • Chris Fox,
  • S.Matthijs Boekholdt,
  • Mamas Mamas,
  • Nicholas Wareham,
  • Kay-tee Khaw,
  • Phyo Myint
RIA SANGHAVI
University of Central Lancashire
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Tiberiu Pana
University of Aberdeen
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Hulkar Mamayusuppova
University of Aberdeen
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Ian Maidment
Aston University
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Chris Fox
Medical School
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S.Matthijs Boekholdt
University of Amsterdam
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Mamas Mamas
Keel Cardiovascular group
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Nicholas Wareham
MRC Epidemiology Unit
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Kay-tee Khaw
University of Cambridge
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Phyo Myint
University of Aberdeen
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Abstract

Background: Higher anticholinergic burden from medications is associated with increased risk of cardiovascular disease and cognitive function decline. A mechanistic pathway has never been established. We aimed to determine whether chronic inflammation may mediate these associations. Methods: Participants were drawn from the European Prospective Investigation into Cancer, Norfolk cohort (40-79 years at baseline). The anticholinergic cognitive burden score (ACB) was calculated at baseline/first (1HC) (1993/97) and second (2HC) (1998/2000) health checks. Plasma fibrinogen and C-reactive protein (CRP) were measured during 1HC and Tumour Necrosis Factor alpha (TNF-α) and interleukin 6 (IL-6) during 2HC. Cross-sectional associations between ACB and inflammatory markers were examined for 1HC and 2HC, respectively. The prospective association was also examined between 1HC ACB and 2HC inflammatory markers. All models adjusted for age, sex, lifestyle factors, co-morbidities and medications. Results: 17,678 and 22,051 participants were included in cross-sectional analyses for CRP, and fibrinogen, respectively. A total of 5,101 participants with available data for TNF-α and IL-6 were included in the longitudinal analyses. Cross-sectionally, a point increase in the ACB was associated with a significant increase in all inflammatory markers (beta (standard error): fibrinogen – 0.035g/l (0.006), p<0.001; CRP 0.284mg/l (0.044), p<0.001; TNF-α 0.031pg/ml (0.010), p=0.002; and IL-6 0.112pg/ml (0.033), p=0.001. Longitudinally, a unit increase in the ACB was associated with a significant increase in TNF-α 0.028pg/ml (0.011), p=0.013 and IL-6 0.076 pg/ml (0.035), p=0.029. Conclusion: Higher anticholinergic burden was significantly associated with higher inflammatory markers. Inflammation may mediate the relationship between exposure to anticholinergic medications and adverse outcomes

Peer review status:UNDER REVIEW

30 Apr 2021Submitted to British Journal of Clinical Pharmacology
03 May 2021Assigned to Editor
03 May 2021Submission Checks Completed
03 Jun 2021Reviewer(s) Assigned