Baseline anticholinergic burden from medications predicts incident fatal and non-fatal stroke in the EPIC-Norfolk general population

Background: Stroke is primarily a disease of older age with a substantial impact on global mortality and morbidity. Whilst medications with anticholinergic effects are widely used, no studies have been conducted to examine the relationship between anticholinergic burden (ACB) and stroke in a general population. Method: The sample was drawn from the EPIC-Norfolk cohort. Baseline assessments were carried out during 1993-1997 and participants were followed up until March 2016. Participants were divided into 4 groups according to their total ACB score at baseline, these groups were those with a total ACB score of 0, 1, 2-3 and >3. After exclusion, Cox-proportional hazards models were constructed to determine the associations between the ACB score groups and the risk of incident stroke and stroke mortality. Sensitivity analysis and propensity score matched analyses were performed. Results: In total 25,639 participants attended the first health check, 3,917 participants were excluded, leaving 21,722 participants to be included. Participants had a mean age (SD) of 58.9 (9.2) years (54.4% women). Of these, 2,131 suffered incident stroke and 562 died from stroke. Mean follow up was approximately 18 years for both outcomes. In the fully adjusted model, those with an ACB of >3 had 59% relative risk of incident stroke (HR (95% CI) 1.59 (1.34 - 1.89)) and 86% relative risk of stroke mortality (1.86 (1.37 - 2.53)) compared to those in ACB 0 category. Sensitivity analyses and propensity score matched analyses showed similar results. Conclusions: Our results provide an incentive for the cautious use of medications with anticholinergic properties to help reduce the global burden of stroke.