Edward Yu, MS; Sylvia H. Ley, PhD, RD; JoAnn E. Manson, MD, DrPH; Walter Willett, MD, DrPH; Ambika Satija, ScD; Frank B. Hu, MD, PhD, MPH; Andrew Stokes, PhD
Note: The authors assume full responsibility for analyses and interpretation of these data.
Acknowledgment: The authors are grateful to Samuel Preston for helpful comments and suggestions and thank the participants and staff of the NHS, NHS II, and HPFS for their valuable contributions, as well as the following state cancer registries for their help: Alabama, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Idaho, Illinois, Indiana, Iowa, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Nebraska, New Hampshire, New Jersey, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, Tennessee, Texas, Virginia, Washington, and Wyoming.
Grant Support: By the National Institutes of Health, Bethesda, Maryland (UM1 CA186107, R01 HL034594, R01 HL088521, UM1 CA176726, UM1 CA167552, R01 HL35464, R01 AG040212, R03 SH000037, and P30 DK46200).
Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-1390.
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 and data set: Not available. Statistical code: Available from Dr. Hu (e-mail, firstname.lastname@example.org).
Requests for Single Reprints: Andrew Stokes, PhD, Boston University School of Public Health, 801 Massachusetts Avenue, Crosstown Center, Boston, MA 02118; e-mail, email@example.com.
Current Author Addresses: Mr. Yu and Drs. Satija and Hu: Department of Nutrition, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Building II, 3rd Floor, Boston, MA 02115.
Dr. Ley: Department of Nutrition, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Building II, Room 355A, Boston, MA 02115.
Dr. Manson: Brigham & Women's Hospital, 900 Commonwealth Avenue, 3rd Floor, Boston, MA 02215.
Dr. Willett: Department of Nutrition, Harvard T.H. Chan School of Public Health, 651 Huntington Avenue, Building II, Room 311, Boston, MA 02115.
Dr. Stokes: Boston University School of Public Health, 801 Massachusetts Avenue, Crosstown Center, Boston, MA 02118.
Author Contributions: Conception and design: E. Yu, J.E. Manson, W. Willett, F.B. Hu, A. Stokes.
Analysis and interpretation of the data: E. Yu, S.H. Ley, J.E. Manson, W. Willett, A. Satija, F.B. Hu, A. Stokes.
Drafting of the article: E. Yu, A. Stokes.
Critical revision of the article for important intellectual content: E. Yu, S.H. Ley, J.E. Manson, W. Willett, A. Satija, F.B. Hu, A. Stokes.
Final approval of the article: E. Yu, S.H. Ley, J.E. Manson, W. Willett, A. Satija, F.B. Hu, A. Stokes.
Obtaining of funding: F.B. Hu.
Administrative, technical, or logistic support: J.E. Manson, F.B. Hu.
Collection and assembly of data: J.E. Manson, W. Willett, F.B. Hu.
The relationship between body mass index (BMI) and mortality is controversial.
To investigate the relationship between maximum BMI over 16 years and subsequent mortality.
3 prospective cohort studies.
Nurses' Health Study I and II and Health Professionals Follow-Up Study.
225 072 men and women with 32 571 deaths observed over a mean of 12.3 years of follow-up.
Maximum BMI over 16 years of weight history and all-cause and cause-specific mortality.
Maximum BMIs in the overweight (25.0 to 29.9 kg/m2) (multivariate hazard ratio [HR], 1.06 [95% CI, 1.03 to 1.08]), obese I (30.0 to 34.9 kg/m2) (HR, 1.24 [CI, 1.20 to 1.29]), and obese II (≥35.0 kg/m2) (HR, 1.73 [CI, 1.66 to 1.80]) categories were associated with increases in risk for all-cause death. The pattern of excess risk with a maximum BMI above normal weight was maintained across strata defined by smoking status, sex, and age, but the excess was greatest among those younger than 70 years and never-smokers. In contrast, a significant inverse association between overweight and mortality (HR, 0.96 [CI, 0.94 to 0.99]) was observed when BMI was defined using a single baseline measurement. Maximum overweight was also associated with increased cause-specific mortality, including death from cardiovascular disease and coronary heart disease.
Residual confounding and misclassification.
The paradoxical association between overweight and mortality is reversed in analyses incorporating weight history. Maximum BMI may be a useful metric to minimize reverse causation bias associated with a single baseline BMI assessment.
National Institutes of Health.
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Yu E, Ley SH, Manson JE, Willett W, Satija A, Hu FB, et al. Weight History and All-Cause and Cause-Specific Mortality in Three Prospective Cohort Studies. Ann Intern Med. 2017;166:613-620. doi: 10.7326/M16-1390
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Published: Ann Intern Med. 2017;166(9):613-620.
Published at www.annals.org on 4 April 2017
Cardiology, Coronary Risk Factors, Obesity, Smoking, Tobacco, Alcohol, and Other Substance Abuse.
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