title: The nested case-control study in cardiology.
abstract: BACKGROUND
  The nested case-control study is an efficient epidemiological design whereby a case-control approach is employed within an established cohort. The large number of recent prospective studies and randomized trials conducted in cardiology provide cohorts within which the nested case-control approach is increasingly used.
  
  
  METHODS
  This paper describes the design of the nested case-control study, and evaluates its role in cardiology by reviewing all such studies indexed in Medline from 1966 to 2000. The example of homocysteine is used to illustrate how discrepancies between results of nested case-control and case-control studies played an important role in the decisions and recommendations of national and international organizations.
  
  
  RESULTS
  Seventy-seven nested case-control studies in cardiology were reviewed. The number of studies per year has been increasing since the first publication in 1987. The majority (96%) of studies evaluated potential risk factors for cardiovascular disease while the remainder evaluated drugs with cardiac adverse effects. In studies of homocysteine and coronary artery disease, nested case-control studies did not confirm the strong association suggested by early case-control studies that may have been influenced by bias (eg, selection, publication, or reverse causality). This led national and international organizations to advise against routine screening.
  
  
  CONCLUSIONS
  The nested case-control study is increasingly used to study causal relationships in cardiology. The large cohorts of cardiac patients created by prospective studies, clinical trials, and administrative databases should be exploited using this methodology to assess potential cardiac risk factors and other causal relationships that cannot be studied in randomized trials.
authors.affiliation: Division of Cardiology, McGill University Health Center, Montreal, Quebec, Canada.
authors.forename: Vidal
authors.initials: V
authors.lastname: Essebag
authors.forename: Jacques
authors.initials: J
authors.lastname: Genest
authors.forename: Samy
authors.initials: S
authors.lastname: Suissa
authors.forename: Louise
authors.initials: L
authors.lastname: Pilote
mesh_terms: D015415:Biomarkers / Q000097:blood; D002309:Cardiology; D016022:Case-Control Studies; D003327:Coronary Disease / Q000097:blood / Q000209:etiology*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D015201:Meta-Analysis as Topic; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D006710:Homocysteine