title: 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.
abstract: BACKGROUND
  Studies have raised concerns that medications with anticholinergic property have potential adverse effects on health outcomes.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  Observational study.
  
  
  METHODS
  Community cohort.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Medicine and Dentistry, University of Aberdeen, Aberdeen AB25 2ZD, UK Clinical Gerontology Unit, Department of Public Health and Primary Care, University of Cambridge, Addenbrooke's Hospital, Cambridge, Cambridgeshire CB2 0QQ, UK.
authors.forename: Phyo Kyaw
authors.initials: PK
authors.lastname: Myint
authors.affiliation: School of Medicine, University of East Anglia, Norwich, Norfolk NR47TJ, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Fox
authors.affiliation: Institute of Cardiovascular Sciences, University of Manchester, Manchester, Lancashire, M13 9WL, UK.
authors.forename: Chun Shing
authors.initials: CS
authors.lastname: Kwok
authors.affiliation: Clinical Gerontology Unit, Department of Public Health and Primary Care, University of Cambridge, Addenbrooke's Hospital, Cambridge, Cambridgeshire CB2 0QQ, UK.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Luben
authors.affiliation: MRC Epidemiology Unit, Cambridge, Cambridgeshire, UK.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
authors.affiliation: Clinical Gerontology Unit, Department of Public Health and Primary Care, Clinical Gerontology Unit, University of Cambridge, Cambridge CB2 2QQ, UK School of Clinical Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK.
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
mesh_terms: D000328:Adult; D017677:Age Distribution; D000367:Age Factors; D000368:Aged; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000401:mortality*; D002423:Cause of Death; D018680:Cholinergic Antagonists / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004739:England / Q000453:epidemiology; D005260:Female; D019538:Health Care Surveys; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D017678:Sex Distribution; D012737:Sex Factors; D013997:Time Factors
chemical_list: D018680:Cholinergic Antagonists
keywords: anticholinergic burden; cardiovascular diseases; epidemiology; mortality; older people