Acknowledgment: The authors thank the other investigators, staff, and participants of the REGARDS study for their valuable contributions. A full list of REGARDS investigators and institutions can be found at
www.regardsstudy.org.
Financial Support: This research project is supported by a cooperative agreement U01-NS041588 and investigator-initiated grant R01-NS061846 from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health. Additional funding was provided by an unrestricted research grant from The Coca-Cola Company.
Disclosures: Drs. Howard and Colabianchi report grants from the National Institutes of Health during the conduct of the study. Mr. Hutto and Dr. Blair report grants from the National Institutes of Health and The Coca-Cola Company during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed
www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-0212.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement: Study protocol: Available at
www.regardsstudy.org.
Statistical code: Available through written agreement with authors from Dr. Diaz (e-mail,
[email protected]).
Data set: Available through a data use agreement with University of Alabama at Birmingham (e-mail,
[email protected]).
Corresponding Author: Keith Diaz, PhD, Columbia University Medical Center, 622 West 168th Street, PH9-301, New York, NY 10032; email,
[email protected].
Current Author Addresses: Dr. Diaz: Columbia University Medical Center, 622 West 168th Street, PH9-301, New York, NY 10032.
Dr. Howard: Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, 1720 2nd Avenue South, Birmingham, AL 35294.
Mr. Hutto: Prevention Research Center, Arnold School of Public Health, University of South Carolina, 921 Assembly Street, Columbia, SC 29208.
Dr. Colabianchi: School of Kinesiology, University of Michigan, OBL 1145, 1402 Washington Heights, Ann Arbor, MI 48109.
Dr. Vena: Department of Public Health Sciences, Medical University of South Carolina, 135 Cannon Street, Suite 303, MSC 835, Charleston, SC 29425.
Dr. Safford: Department of Medicine, Weill Cornell Medical Center, 1300 York Avenue, New York, NY 10021.
Dr. Blair: Department of Exercise Science, Arnold School of Public Health, University of South Carolina, 921 Assembly Street, Columbia, SC 29208.
Dr. Hooker: College of Health Solutions, Arizona State University, 550 North 3rd Street, Phoenix, AZ 85004.
Author Contributions: Conception and design: V.J. Howard, N. Colabianchi, J.E. Vena, M.M. Safford, S.P. Hooker.
Analysis and interpretation of the data: K.M. Diaz, V.J. Howard, B. Hutto, N. Colabianchi, M.M. Safford, S.P. Hooker.
Drafting of the article: K.M. Diaz, S.P. Hooker.
Critical revision of the article for important intellectual content: V.J. Howard, B. Hutto, N. Colabianchi, J.E. Vena, M.M. Safford, S.N. Blair, S.P. Hooker.
Final approval of the article: K.M. Diaz, V.J. Howard, B. Hutto, N. Colabianchi, J.E. Vena, M.M. Safford, S.N. Blair, S.P. Hooker.
Provision of study materials or patients: M.M. Safford, S.P. Hooker.
Statistical expertise: B. Hutto.
Obtaining of funding: V.J. Howard, M.M. Safford, S.N. Blair, S.P. Hooker.
Administrative, technical, or logistic support: V.J. Howard, M.M. Safford.
Collection and assembly of data: V.J. Howard, B. Hutto, M.M. Safford, S.P. Hooker.
This article was published at
Annals.org on 12 September 2017.
Reverse causation and the association of sedentary behavior with mortality
In general, we would expect the shorter the time between measurement of sedentary and outcome, the greater likelihood that the sedentary behavior represents reverse causation. Currently, we do not know how long the period where reverse causation may be important, and the magnitude of the potential bias. Yet, lessons learned from body-mass index (BMI) and mortality studies can illustrate threats caused by reverse causation and point future directions for sedentary behavior studies. “The obesity paradox”, an inverse association between overweight (25.0 to 29.9 Kg/m2) and mortality has been reported in several studies [2]. This phenomenon is likely due to reverse causation bias (people unintentionally lose weight due to underlying diseases have increased risk of death[3]) and confounding by smoking (smokers tend to have lower body mass index). A recent paper [4] used repeated-measures of weight over time (weight history) in order to determine the optimal length of follow-up to minimize reverse causality. At least 16-year weight history was needed to address with confidence the temporal relationship between overweight and mortality, which actually increases the risk of death compared to participants with normal BMI. Importantly, the authors still found hints of reverse causation even after 24-year weight history[3]. Future studies with repeated-measures over time are needed to estimate optimal length of follow-up to minimize reverse causation in sedentary behavior and mortality analysis.
References
1. Diaz KM, Howard VJ, Hutto B, Colabianchi N, Vena JE, Safford MM, et al. Patterns of Sedentary Behavior and Mortality in U.S. Middle-Aged and Older Adults: A National Cohort Study. Ann Intern Med. 2017;[Epub ahead of print 12 September 2017] doi: 10.7326/M17-0212
2. Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA. 2013;309:71-82.
3. Wannamethee SG, Shaper AG, Lennon L. Reasons for intentional weight loss, unintentional weight loss, and mortality in older men. Arch Intern Med. 2005;165(9):1035-40.
4. Yu E, Ley SH, Manson JE, Willett W, Satija A, Hu FB, Stokes A. Weight History and All-Cause and Cause-Specific Mortality in Three Prospective Cohort Studies. Ann Intern Med. 2017;166(9):613-620.