Total anticholinergic burden and risk of mortality and cardiovascular disease over 10 years in 21,636 middle-aged and older men and women of EPIC-Norfolk prospective population study

BACKGROUND: studies have raised concerns that medications with anticholinergic property have potential adverse effects on health outcomes.

OBJECTIVES: the objective of this study is to examine the prospective relationships between total anticholinergic burden (ACB) from medications and mortality, and cardiovascular disease (CVD) in a general population.

DESIGN: observational study.

SETTING: community cohort.

SUBJECTS: we examined data collected from 21,636 men and women without cancer at the baseline who participated in a baseline survey 1993-97 in the European Prospective Investigation into Cancer (EPIC)-Norfolk. They were followed until 2009/11.

METHODS: we performed Cox-proportional hazards models to determine the associations between total ACB and the subsequent risk of all-cause mortality and incident CVD during the follow-up.

RESULTS: there were a total of 4,342 people died and 7,328 had an incident CVD during the study follow-up (total person years = 322,321 years for mortality and 244,119 years for CVD event). Compared with people with no anticholinergic burden (ACB = 0), people with total ACB ≥3 from medications had hazards ratios of 1.83 (1.53, 2.20) and 2.17 (1.87, 2.52) for mortality and CVD incidence outcomes, respectively, after adjusting for potential confounders. Repeating the analyses after excluding people with prevalent illnesses, and events occurring within the first 2 years of follow-up, only slightly attenuated the results.

CONCLUSION: there appear to be a class effect as well as dose-response relationship between the ACB and both outcomes. Future research should focus on understanding the relationship between ACB and mortality, and cardiovascular disease and possibly minimising ACB load where feasible.