Methods: Participants were drawn from the European Prospective Investigation into Cancer, Norfolk cohort (40-79 years at baseline). Anticholinergic burden score (ACB) was calculated at first (1HC) (1993/97) and second (2HC) (1998/2000) health checks. Fibrinogen and Creactive protein (CRP) were measured during 1HC and Tumour Necrosis Factor alpha (TNFα) and interleukin 6 (IL-6) during 2HC. Cross-sectional associations between ACB and
inflammatory markers were examined for both health checks. Prospective associations were also examined between 1HC ACB and 2HC inflammatory markers. Models were 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. 5,101 participants with data on TNF-α and IL-6 were included in the prospective analyses. Cross-sectionally, compared to ACB=0, ACB ≥4 was associated with higher fibrinogen, beta (95% confidence interval)=0.134 g/l (0.070, 0.199), CRP 1.175 mg/l (0.715, 1.634), IL-6 0.593 pg/ml (0.254, 0.932) and TNF-α 0.137 pg/ml (0.033, 0.241).
Furthermore, a point increase in ACB was associated with a higher levels of all markers.
Prospectively, compared to ACB=0, ACB ≥4 was associated with higher IL-6(pg/ml): 0.019 (-0.323, 0.361) and TNF-α(pg/ml): 0.202% (0.81, 0.323). In addition, a unit increase in ACB was associated with a significantly higher TNF-α and IL-6.
Conclusion: Higher ACB was associated with higher inflammatory markers. Inflammation may mediate the relationship between anticholinergic medications and adverse outcomes.
We are grateful to all the participants who have been part of the project and to the many members of the study teams at the University of Cambridge who have enabled this research. We would also like to acknowledge the principal investigators and staff of the EPIC-Norfolk study.
The EPIC-Norfolk study (DOI 10.22025/2019.10.105.00004) was funded by the Medical Research Council, Grant number (MR/N003284/1 and MC-UU_12015/1) and Cancer Research UK, Grant number (C864/A14136).
Data Availability StatementData available on request to EPIC-Norfolk Steering Committee for their approval.
- C-Reactive Protein
- Tumour Necrosis Factor-alpha
- cardiovascular diseases