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Combined associations of body weight and lifestyle factors with all cause and cause specific mortality in men and women: prospective cohort study

BMJ 2016; 355 doi: (Published 24 November 2016) Cite this as: BMJ 2016;355:i5855
  1. Nicola Veronese, research fellow1 2,
  2. Yanping Li, research scientist3,
  3. JoAnn E Manson, professor4 5 6,
  4. Walter C Willett, professor3 4 5,
  5. Luigi Fontana, professor1 7 8,
  6. Frank B Hu, professor3 4 5
  1. 1Division of Geriatrics and Nutritional Science, Washington University, St Louis, MO, USA
  2. 2Division of Geriatrics, Department of Medicine, University of Padua, Italy
  3. 3Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
  4. 4Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
  5. 5Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
  6. 6Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
  7. 7Department of Clinical and Experimental Sciences, Brescia University Medical School, Brescia, Italy
  8. 8CEINGE Biotecnologie Avanzate, Naples, Italy
  1. Correspondence to: Frank B Hu{at}
  • Accepted 21 October 2016


Objective To evaluate the combined associations of diet, physical activity, moderate alcohol consumption, and smoking with body weight on risk of all cause and cause specific mortality.

Design Longitudinal study with up to 32 years of follow-up.

Setting Nurses’ Health Study (1980-2012) and Health Professionals Follow-up Study (1986-2012).

Participants 74 582 women from the Nurses’ Health Study and 39 284 men from the Health Professionals Follow-up Study who were free from cardiovascular disease and cancer at baseline.

Main outcome measures Exposures included body mass index (BMI), score on the alternate healthy eating index, level of physical activity, smoking habits, and alcohol drinking while outcome was mortality (all cause, cardiovascular, cancer). Cox proportional hazard models were used to calculate the adjusted hazard ratios of all cause, cancer, and cardiovascular mortality with their 95% confidence intervals across categories of BMI, with 22.5-24.9 as the reference.

Results During up to 32 years of follow-up, there were 30 013 deaths (including 10 808 from cancer and 7189 from cardiovascular disease). In each of the four categories of BMI studied (18.5-22.4, 22.5-24.9, 25-29.9, ≥30), people with one or more healthy lifestyle factors had a significantly lower risk of total, cardiovascular, and cancer mortality than individuals with no low risk lifestyle factors. A combination of at least three low risk lifestyle factors and BMI between 18.5-22.4 was associated with the lowest risk of all cause (hazard ratio 0.39, 95% confidence interval 0.35 to 0.43), cancer (0.40, 0.34 to 0.47), and cardiovascular (0.37, 0.29 to 0.46) mortality, compared with those with BMI between 22.5-24.9 and none of the four low risk lifestyle factors.

Conclusion Although people with a higher BMI can have lower risk of premature mortality if they also have at least one low risk lifestyle factor, the lowest risk of premature mortality is in people in the 18.5-22.4 BMI range with high score on the alternate healthy eating index, high level of physical activity, moderate alcohol drinking, and who do not smoke. It is important to consider diet and lifestyle factors in the evaluation of the association between BMI and mortality.


  • We thank the participants and staff of the Nurses’ Health Study and the Health Professionals Study who contributed data for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY.

  • Contributors: LF jointly conceived the study with FBH. NV, YL, LF, and FBH were involved in the study design. WCW, FBH, and JEM obtained funding. WCW, FBH, and JEM provided study materials or patients and collected and collated data. NV and YL contributed equally to the paper. All authors were involved in analysis and interpretation of the data. NV drafted the article; all authors revised it critically for important intellectual content and approved the final version. LF and FBH are guarantors.

  • Funding: The cohorts were supported by grants of UM1 CA186107, P01 CA87969, R01 HL088521, UM1 CA167552, HL60712, and R01 HL35464 from the National Institutes of Health. LF and NV were supported by grants from the Bakewell Foundation and the Longer Life Foundation (an RGA/Washington University Partnership). The funders play no role in the design of the study; the collection, analysis, and interpretation of the data; and the decision to approve publication of the finished manuscript. The authors assume full responsibility for analyses and interpretation of these data.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare: no support from any organization for the submitted work other than those detailed above; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: The study protocol was approved by the institutional review boards of the Brigham and Women’s Hospital and the Harvard School of Public Health. Completion of the self administered questionnaire was considered to imply informed consent.

  • Data sharing: No additional data available.

  • Transparency statement: The lead authors (the manuscript’s guarantors) affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

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