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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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Self-citationDihydroergotamine (DHE) Use During Gestation and the Risk of Adverse Pregnancy Outcomes
Bérard, A., & Kori, S. H. (2012) · Headache The Journal of Head and Face Pain · doi:10.1111/j.1526-4610.2012.02172.x · Cited by 29
“pitalization data for all Quebec residents, including gestational age (defined from the first day of the last menstrual period to the end of pregnancy, confirmed by ultrasound) for planned and spontaneous abortions, and deliveries.(17) The Fichier des événements démographiques, administered by the ISQ, provides data o…”
BackgroundMethodGarbe, E., & Suissa, S. (2005) · Springer eBooks · doi:10.1007/978-3-540-26577-1_31 · Cited by 29
Self-citationApplication of the matched nested case-control design to the secondary analysis of trial data
Partlett, C., Hall, N. J., Leaf, A., Juszczak, E., & Linsell, L. (2020) · BMC Medical Research Methodology · doi:10.1186/s12874-020-01007-w · Cited by 28
“These controls may develop the outcome later and become a case themselves, and they may also act as a control for other cases [6, 7].”
BackgroundD-Dimer Is Associated With First-Ever Intracerebral Hemorrhage
Johansson, K., Jansson, J., Johansson, L., Wiklund, P.-G., Nilsson, T. K., & Lind, M. M. (2018) · Stroke · doi:10.1161/strokeaha.118.021751 · Cited by 27
Patterns of warfarin use and subsequent outcomes in atrial fibrillation in primary care practices
Ewen, E. F., Simon, 。., Weintraub, Kolm, P., Zhang, Z., & Liu, X. (2012) · Vascular Health and Risk Management · doi:10.2147/vhrm.s34280 · Cited by 27
β 2-Agonists and the Incidence of Parkinson Disease
Giorgianni, F., Ernst, P., Dell’Aniello, S., Suissa, S., & Renoux, C. (2020) · American Journal of Epidemiology · doi:10.1093/aje/kwaa012 · Cited by 23
“In this context, the nested case-control approach is computationally more efficient than a time-dependent survival analysis while producing equivalent estimates (12, 14).”
Self-citationNakhai-Pour, H. R., Rey, É., & Bérard, A. (2009) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2009.05.019 · Cited by 23
Rutten, F. H., Vonken, E. J., Cramer, M. J., Moons, K. G. M., Velthuis, B. K., Prakken, N. H. J., Lammers, J. J., Grobbee, D. E., Mali, W. P. T. M., & Hoes, A. W. (2008) · American Heart Journal · doi:10.1016/j.ahj.2008.04.021 · Cited by 22
“85 (322/41), we constructed new 2 by 2 tables to calculate diagnostic accuracy parameters of CMR measurements.(17) Multivariable logistic regression was then used to quantify the independent contribution of each of the CMR variables to the diagnosis of CHF.”
Risk of Multiple Sclerosis Among Users of Antitumor Necrosis Factor α in 4 Canadian Provinces
Li, L., Aviña-Zubieta, J. A., Bernstein, C. N., Kaplan, G. G., Tremlett, H. L., Xie, H. W., Peña-Sánchez, J. N., Marrie, R. A., & Etminan, M. (2022) · Neurology · doi:10.1212/wnl.0000000000201472 · Cited by 22
“Cohort studies require much larger sample sizes when the outcome is rare.(30)”
BackgroundMethodInfluentialvan Zaane, B., Vergouwe, Y., Donders, A. R. T., & Moons, K. G. M. (2012) · BMC Medical Research Methodology · doi:10.1186/1471-2288-12-166 · Cited by 21
“By applying a nested case–control design in diagnostic accuracy studies the number of patients undergoing the index test can be substantially reduced, hereby increasing the efficiency of the particular study [6,8,10,11].”
BackgroundMethodGarbe, E., & Suissa, S. (2013) · Springer eBooks · doi:10.1007/978-0-387-09834-0_31 · Cited by 22
Self-citationEtminan, M., Sodhi, M., Samii, A., Carleton, B., Kezouh, A., & Aviña-Zubieta, J. A. (2018) · Seminars in Arthritis and Rheumatism · doi:10.1016/j.semarthrit.2018.09.006 · Cited by 20
Levothyroxine dose and risk of atrial fibrillation: A nested case-control study
Gong, I. Y., Atzema, C. L., Lega, I. C., Austin, P. C., Na, Y., Rochon, P. A., & Lipscombe, L. L. (2020) · American Heart Journal · doi:10.1016/j.ahj.2020.09.016 · Cited by 21
Clarke, S. L., Tcheandjieu, C., Hilliard, A. T., Lee, K. M., Lynch, J. A., Chang, K.-M., Miller, D. R., Program, V. M. V., Knowles, J. W., O’Donnell, C. J., et al. (2022) · Circulation Genomic and Precision Medicine · doi:10.1161/circgen.121.003501 · Cited by 21
Wang, W., Zhu, S., He, Q., Wang, M., Kang, Y., Zhang, R., Ji, P., Zou, K., Klompas, M., Zong, Z., et al. (2021) · Critical Care Medicine · doi:10.1097/ccm.0000000000005227 · Cited by 19
“Therefore, we used a nested case-control study design to ensure identical duration of MV treatment between cases and controls and to improve statistical efficiency (23).”
MethodAzoulay, L., Schneider‐Lindner, V., Dell’Aniello, S., Filion, K. B., & Suissa, S. (2009) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.1883 · Cited by 19
Self-citationEngel, T., Raffenberg, M., Schoepf, I. C., Kootstra, N. A., Reiss, P., Thorball, C. W., Hasse, B. K., Hirzel, C., Wissel, K., Roth, J. A., et al. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa1034 · Cited by 18
The Use of Antidepressants and the Risk of Idiopathic Pulmonary Arterial Hypertension
Fox, B. D., Azoulay, L., Dell’Aniello, S., Langleben, D., Lapi, F., Benisty, J. I., & Suissa, S. (2014) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2014.09.031 · Cited by 18
Self-citationCrash rates of quebec drivers with medical conditions.
Dow, J., Gaudet, M., & Turmel, É. (2013) · Europe PMC (PubMed Central) · Cited by 17
Azoulay, L., Dell’Aniello, S., Simon, T. A., Langleben, D., Renoux, C., & Suissa, S. (2012) · BMC Cardiovascular Disorders · doi:10.1186/1471-2261-12-49 · Cited by 17
“In comparison to a full cohort approach using a survival analysis with time-dependent variables, a nested case–control analysis is computationally more efficient [17], while producing odds ratios (ORs) that are unbiased estimators of incidence rate ratios (RRs) with little or no loss in precision [16–18].”
MethodSelf-citationBudiman‐Mak, E., Epstein, N. U., Brennan, M. B., Stuck, R. M., Guihan, M., Huo, Z., Emanuele, N., & Sohn, M. (2016) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2016.01.010 · Cited by 19
“Research Design and Methods We used a nested case-control design to account for the time-dependent nature of SBP variability and to minimize selection bias (11; 12).”
BackgroundMethodWilliams, P. T., PENDYALA, L. K., & Superko, H. R. (2011) · BMC Medical Genetics · doi:10.1186/1471-2350-12-42 · Cited by 16
“In addition to their being costeffective, case-control studies may be the only reasonable approach to study rare diseases [3].”
BackgroundAssociation between blood transfusion and ventilator-associated events: a nested case-control study
Wang, W. J., He, Q., Zhu, S., Wang, M., Kang, Y., Zhang, R., Ji, P., Zou, K., Zong, Z., & Sun, X. (2021) · Infection Control and Hospital Epidemiology · doi:10.1017/ice.2021.178 · Cited by 16
Mangoni, A. A., Woodman, R. J., Gilbert, A. L., & Knights, K. (2010) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.1945 · Cited by 16
“Estimates of risk obtained from nested case-control designs are also similar to those obtained with cohort designs that use time-varying covariates and Cox regression, particularly when approximately 20 controls per case are sampled as was the case here.(42) Since exposure information is available prior to study comme…”
MethodJohansson, K., Johansson, L., Pennlert, J., Söderberg, S., Jansson, J., & Lind, M. M. (2020) · Stroke · doi:10.1161/strokeaha.120.029630 · Cited by 17
Bittner, V., Wenger, N. K., Waters, D. D., DeMicco, D. A., Messig, M., & LaRosa, J. C. (2012) · American Heart Journal · doi:10.1016/j.ahj.2012.06.016 · Cited by 15
RetractedSchoepf, I. C., Thorball, C. W., Ledergerber, B., Engel, T., Raffenberg, M., Kootstra, N. A., Reiss, P., Hasse, B. K., Marzolini, C., Thurnheer, C., et al. (2021) · Clinical Infectious Diseases · doi:10.1093/cid/ciab521 · Cited by 15
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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