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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.
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“The nested case-control design is commonly used in pharmacosurveillance research and provides estimates of effects that are consistent with those obtained from time to event analysis.67 68 69 70”
From Levothyroxine dose and risk of fractures in older adults: nested case-control study (2011) · cites this paper as [68]
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“Thus, in comparison to a time-dependent survival analysis, a nested case–control analysis is computationally more efficient [16], while producing odds ratios that are unbiased estimators of incidence rate ratios (RR), with little or no loss in precision[15–17].”
BackgroundSelf-citation
Metadata
- Authors
- Essebag, V., Genest, J., Suissa, S., & Pilote, L.
- Affiliations
- McGill University Health Centre (CA)
- McGill University (CA)
- Corresponding author
- Pilote, Louise
- Venue
- American Heart Journal
- Publisher
- Elsevier BV
- Published
- 2003-10
- Volume
- 146
- Issue
- 4
- Pages
- 581-590
- ISSN
- 0002-8703 (ISSN-L)
- OpenAlex
- W2029994787
- Cited by
- 173
- References
- 56
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 7 · 2023: 6 · 2022: 7 · 2021: 6 · 2020: 12 · 2019: 7 · 2018: 12 · 2017: 7 · 2016: 7 · 2015: 7 · 2014: 9 · 2013: 12 · 2012: 11
- FWCI
- 4.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Heart Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
- Health Sciences › Nursing › Nutrition and Dietetics › Folate and B Vitamins Research
- Keywords
- nested case-control study, homocysteine, coronary artery disease, cardiovascular risk factors, selection bias, publication bias, reverse causality, causal inference
- MeSH terms
- Cardiology, Coronary Disease, Homocysteine, Humans, Prospective Studies, Risk Factors, Meta-Analysis as Topic, Biomarkers, Case-Control Studies
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