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Greenberg  JA.  Correcting biases in estimates of mortality attributable to obesity.  Obesity (Silver Spring). 2006;14(11):2071-2079.PubMedGoogle ScholarCrossref
Flegal  KM, Graubard  BI, Williamson  DF, Gail  MH.  Impact of smoking and preexisting illness on estimates of the fractions of deaths associated with underweight, overweight, and obesity in the US population.  Am J Epidemiol. 2007;166(8):975-982.PubMedGoogle ScholarCrossref
Flegal  KM, Graubard  BI, Williamson  DF, Cooper  RS.  Reverse causation and illness-related weight loss in observational studies of body weight and mortality.  Am J Epidemiol. 2011;173(1):1-9.PubMedGoogle ScholarCrossref
Berrington de Gonzalez  A, Hartge  P, Cerhan  JR,  et al.  Body-mass index and mortality among 1.46 million white adults.  N Engl J Med. 2010;363(23):2211-2219.PubMedGoogle ScholarCrossref
Boggs  DA, Rosenberg  L, Cozier  YC,  et al.  General and abdominal obesity and risk of death among black women.  N Engl J Med. 2011;365(10):901-908.PubMedGoogle ScholarCrossref
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(1):71-82.PubMedGoogle ScholarCrossref
Jee  SH, Sull  JW, Park  J,  et al.  Body-mass index and mortality in Korean men and women.  N Engl J Med. 2006;355(8):779-787.PubMedGoogle ScholarCrossref
Pischon  T, Boeing  H, Hoffmann  K,  et al.  General and abdominal adiposity and risk of death in Europe.  N Engl J Med. 2008;359(20):2105-2120.PubMedGoogle ScholarCrossref
Whitlock  G, Lewington  S, Sherliker  P,  et al; Prospective Studies Collaboration.  Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies.  Lancet. 2009;373(9669):1083-1096.PubMedGoogle ScholarCrossref
Winter  JE, MacInnis  RJ, Wattanapenpaiboon  N, Nowson  CA.  BMI and all-cause mortality in older adults: a meta-analysis.  Am J Clin Nutr. 2014;99(4):875-890.PubMedGoogle ScholarCrossref
Zheng  W, McLerran  DF, Rolland  B,  et al.  Association between body-mass index and risk of death in more than 1 million Asians.  N Engl J Med. 2011;364(8):719-729.PubMedGoogle ScholarCrossref
Gregg  EW, Cheng  YJ, Cadwell  BL,  et al.  Secular trends in cardiovascular disease risk factors according to body mass index in US adults.  JAMA. 2005;293(15):1868-1874.PubMedGoogle ScholarCrossref
Mehta  NK, Chang  VW.  Secular declines in the association between obesity and mortality in the United States.  Popul Dev Rev. 2011;37(3):435-451.PubMedGoogle ScholarCrossref
Su  D.  Body mass index and old-age survival: a comparative study between the Union Army Records and the NHANES-I Epidemiological Follow-Up Sample.  Am J Hum Biol. 2005;17(3):341-354.PubMedGoogle ScholarCrossref
Nordestgaard  BG, Palmer  TM, Benn  M,  et al.  The effect of elevated body mass index on ischemic heart disease risk: causal estimates from a Mendelian randomisation approach.  PLoS Med. 2012;9(5):e1001212.PubMedGoogle ScholarCrossref
Zacho  J, Tybjaerg-Hansen  A, Jensen  JS, Grande  P, Sillesen  H, Nordestgaard  BG.  Genetically elevated C-reactive protein and ischemic vascular disease.  N Engl J Med. 2008;359(18):1897-1908.PubMedGoogle ScholarCrossref
Pedersen  CB.  The Danish Civil Registration System.  Scand J Public Health. 2011;39(7)(suppl):22-25.PubMedGoogle ScholarCrossref
Global status report on noncommunicable diseases 2010. World Health Organization. http://www.who.int/nmh/publications/ncd_report_full_en.pdf. Accessed March 26, 2015.
Fall  T, Hägg  S, Mägi  R,  et al; European Network for Genetic and Genomic Epidemiology (ENGAGE) consortium.  The role of adiposity in cardiometabolic traits: a Mendelian randomization analysis.  PLoS Med. 2013;10(6):e1001474.PubMedGoogle ScholarCrossref
Lu  Y, Hajifathalian  K, Ezzati  M, Woodward  M, Rimm  EB, Danaei  G; Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration (BMI Mediated Effects).  Metabolic mediators of the effects of body-mass index, overweight, and obesity on coronary heart disease and stroke: a pooled analysis of 97 prospective cohorts with 1.8 million participants.  Lancet. 2014;383(9921):970-983.PubMedGoogle ScholarCrossref
Timpson  NJ, Harbord  R, Davey Smith  G, Zacho  J, Tybjaerg-Hansen  A, Nordestgaard  BG.  Does greater adiposity increase blood pressure and hypertension risk? Mendelian randomization using the FTO/MC4R genotype.  Hypertension. 2009;54(1):84-90.PubMedGoogle ScholarCrossref
Varbo  A, Benn  M, Smith  GD, Timpson  NJ, Tybjaerg-Hansen  A, Nordestgaard  BG.  Remnant cholesterol, low-density lipoprotein cholesterol, and blood pressure as mediators from obesity to ischemic heart disease.  Circ Res. 2015;116(4):665-673.PubMedGoogle ScholarCrossref
Afzal  S, Bojesen  SE, Nordestgaard  BG.  Low plasma 25-hydroxyvitamin D and risk of tobacco-related cancer.  Clin Chem. 2013;59(5):771-780.PubMedGoogle ScholarCrossref
Madsen  M, Davidsen  M, Rasmussen  S, Abildstrom  SZ, Osler  M.  The validity of the diagnosis of acute myocardial infarction in routine statistics: a comparison of mortality and hospital discharge data with the Danish MONICA registry.  J Clin Epidemiol. 2003;56(2):124-130.PubMedGoogle ScholarCrossref
Asnaes  S.  Uncertainty of determining mode and cause of death without autopsy: an autopsy study of medically unattended non-medicolegal deaths.  Forensic Sci Int. 1980;15(3):191-196.PubMedGoogle ScholarCrossref
Afzal  S, Brøndum-Jacobsen  P, Bojesen  SE, Nordestgaard  BG.  Genetically low vitamin D concentrations and increased mortality: Mendelian randomisation analysis in three large cohorts.  BMJ. 2014;349:g6330.PubMedGoogle ScholarCrossref
Durrleman  S, Simon  R.  Flexible regression models with cubic splines.  Stat Med. 1989;8(5):551-561.PubMedGoogle ScholarCrossref
Akaike  H. Information theory and an extension of the maximum likelihood principle. In: Parzen  E, Tanabe  K, Kitagawa  G, eds.  Selected Papers of Hirotugu Akaike. New York, NY: Springer; 1998:199-213.
DerSimonian  R, Laird  N.  Meta-analysis in clinical trials.  Control Clin Trials. 1986;7(3):177-188.PubMedGoogle ScholarCrossref
DiCiccio  TJ, Efron  B.  Bootstrap confidence intervals.  Stat Sci. 1996;11(3):189-212.Google ScholarCrossref
Mehta  T, Fontaine  KR, Keith  SW,  et al.  Obesity and mortality: are the risks declining? evidence from multiple prospective studies in the United States.  Obes Rev. 2014;15(8):619-629.PubMedGoogle ScholarCrossref
Flegal  KM, Graubard  BI, Williamson  DF, Gail  MH.  Excess deaths associated with underweight, overweight, and obesity.  JAMA. 2005;293(15):1861-1867.PubMedGoogle ScholarCrossref
Flegal  KM, Kit  BK, Graubard  BI.  Body mass index categories in observational studies of weight and risk of death.  Am J Epidemiol. 2014;180(3):288-296.PubMedGoogle ScholarCrossref
Physical status: the use and interpretation of anthropometry [Technical Report Series No. 854]. World Health Organization. http://www.who.int/childgrowth/publications/physical_status/en/. Accessed April 18, 2016.
Deaths and life expectancy. Statistics Denmark. https://www.dst.dk/en/Statistik/emner/doedsfald-og-middellevetid/doedsfald#. Accessed March 8, 2016.
Original Investigation
May 10, 2016

Change in Body Mass Index Associated With Lowest Mortality in Denmark, 1976-2013

Author Affiliations
  • 1Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  • 2Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  • 3Section for Molecular Genetics, Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  • 4Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  • 5Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Frederiksberg, Denmark
JAMA. 2016;315(18):1989-1996. doi:10.1001/jama.2016.4666

Importance  Research has shown a U-shaped pattern in the association of body mass index (BMI) with mortality. Although average BMI has increased over time in most countries, the prevalence of cardiovascular risk factors may also be decreasing among obese individuals over time. Thus, the BMI associated with lowest all-cause mortality may have changed.

Objective  To determine whether the BMI value that is associated with the lowest all-cause mortality has increased in the general population over a period of 3 decades.

Design, Setting, and Participants  Three cohorts from the same general population enrolled at different times: the Copenhagen City Heart Study in 1976-1978 (n = 13 704) and 1991-1994 (n = 9482) and the Copenhagen General Population Study in 2003-2013 (n = 97 362). All participants were followed up from inclusion in the studies to November 2014, emigration, or death, whichever came first.

Exposures  For observational studies, BMI was modeled using splines and in categories defined by the World Health Organization. Body mass index was calculated as weight in kilograms divided by height in meters squared.

Main Outcomes and Measures  Main outcome was all-cause mortality and secondary outcomes were cause-specific mortality.

Results  The number of deaths during follow-up was 10 624 in the 1976-1978 cohort (78% cumulative mortality; mortality rate [MR], 30/1000 person-years [95% CI, 20-46]), 5025 in the 1991-1994 cohort (53%; MR, 16/1000 person-years [95% CI, 9-30]), and 5580 in the 2003-2013 cohort (6%; MR, 4/1000 person-years [95% CI, 1-10]). Except for cancer mortality, the association of BMI with all-cause, cardiovascular, and other mortality was curvilinear (U-shaped). The BMI value that was associated with the lowest all-cause mortality was 23.7 (95% CI, 23.4-24.3) in the 1976-1978 cohort, 24.6 (95% CI, 24.0-26.3) in the 1991-1994 cohort, and 27.0 (95% CI, 26.5-27.6) in the 2003-2013 cohort. The corresponding BMI estimates for cardiovascular mortality were 23.2 (95% CI, 22.6-23.7), 24.0 (95% CI, 23.4-25.0), and 26.4 (95% CI, 24.1-27.4), respectively, and for other mortality, 24.1 (95% CI, 23.5-25.9), 26.8 (95% CI, 26.1-27.9), and 27.8 (95% CI, 27.1-29.6), respectively. The multivariable-adjusted hazard ratios for all-cause mortality for BMI of 30 or more vs BMI of 18.5 to 24.9 were 1.31 (95% CI, 1.23-1.39; MR, 46/1000 person-years [95% CI, 32-66] vs 28/1000 person-years [95% CI, 18-45]) in the 1976-1978 cohort, 1.13 (95% CI, 1.04-1.22; MR, 28/1000 person-years [95% CI, 17-47] vs 15/1000 person-years [95% CI, 7-31]) in the 1991-1994 cohort, and 0.99 (95% CI, 0.92-1.07; MR, 5/1000 person-years [95% CI, 2-12] vs 4/1000 person-years [95% CI, 1-11]) in the 2003-2013 cohort.

Conclusions and Relevance  Among 3 Danish cohorts, the BMI associated with the lowest all-cause mortality increased by 3.3 from cohorts enrolled from 1976-1978 through 2003-2013. Further investigation is needed to understand the reason for this change and its implications.