FNOA: Assessment of Overweight/Obesity (2012)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To evaluate the association of general and abdominal adiposity with the risk of death in Europeans.

Inclusion Criteria:
  • Europeans from the general population residing in a town or province in 23 centers in 10 European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom)
  • Men and women ages 25 to 70 at enrollment (1992 to 2000) in the EPIC (European Prospective Investigation into Cancer and Nutrition) study.
Exclusion Criteria:
  • 2,088 participants who withdrew from the study and for whom there was no follow-up information on vital status
  • 25,720 persons from the Umea, Sweden cohort because the information on leisure-time physical activity provided on the questionnaire completed by this cohort was not compatible with that provided on the other EPIC questionnaires
  • Subjects for whom data on measured height or weight were missing (all 37,205 from the Norwegian cohort, 52,872 from French cohorts and 8,451 from other cohorts)
  • Those with missing waist circumference 3,833 (1.07%) and missing waist-to-hip ratio 6,466 (1.8%) were excluded from analysis of these variables
  • 7,659 participants in the top or bottom 1% of the total cohort with respect to the ratio of energy intake to estimated energy requirement to reduce the effect of implausible extreme values
  • 25,155 participants who reported a history of cancer, heart disease or stroke at baseline to avoid confounding by pre-existing chronic diseases.
Description of Study Protocol:

Recruitment

Participants were recruited from the general population residing in given geographic areas in Europe.

Design: 

Prospective cohort study:

  • Participants gave written informed consent, underwent anthropometric measurements, and completed a questionnaire that asked for information regarding socio-demographic and lifestyle characteristics, medical history, alcohol consumption and physical activity
  • Vital status and the cause and date of death were ascertained by means of record linkages with cancer registries, boards of health and death indexes (in the case of Denmark, Italy, the Netherlands, Spain, Sweden and the United Kingdom) or by active follow-up (in the case of Germany, Greece and France)
  • Active follow-up included inquiries by mail or telephone to participants, municipal registries, regional health departments, physicians and hospitals. 

Blinding Used

Implied with measurements.

Statistical Analysis

  • Associations between anthropometric variables and the risk of death were analyzed with the use of a Cox regression model, with age as the underlying time variable
  • The cohort was divided into categories of BMI, incorporating current definitions of underweight, normal, overweight and obesity
  • The likelihood-ratio test was used to assess the statistical significance of an association between BMI and the risk of death. In addition, subjects were grouped into sex-specific quintiles according to waist circumference and waist-to-hip ratio.
  • To assess performance in the prediction of death, the C statistic, the Hosmer-Lemeshow statistic and Nagelkerke's generalized model R statistic were calculated, and net reclassification indexes for a follow-up time of five years, using logistic-regression models, adjusted for the covariates described above
  • All P-values presented are two-tailed, and P-values of less than 0.5 were considered to indicate statistical significance. 
Data Collection Summary:

Timing of Measurements

After giving informed consent, participants underwent anthropometric measurements and completed the questionnaire (regarding socio-demographic and lifestyle characteristics, medical history and alcohol consumption).

Dependent Variables

Risk of death: Vital status and the cause and date of death were ascertained by means of record linkages with cancer registries, boards of health, and death indexes or by active follow-up. 

Independent Variables

  • BMI: Weight and height measured with subjects not wearing shoes
  • Waist and hip circumferences were measured and waist-to-hip ratio calculated
  • Waist circumference was measured horizontally at the level of the largest lateral extension of the hips or over the buttocks. Body weight and waist and hip circumferences were corrected for the clothing worn during measurement in order to reduce heterogeneity due to protocol differences among centers. 

Control Variables

  • Age
  • Sex
  • Medical history
  • Alcohol consumption
  • Smoking status
  • Educational level
  • Physical activity.
Description of Actual Data Sample:
  • Initial N: 519,978 in the initial cohort
  • Attrition (final N): 359,387, 65.4% women
  • Age: 25 to 70 at enrollment from 1992 to 2000, mean age at baseline was 51.5±10.4 years
  • Ethnicity: Not described other than "Europeans"
  • Location:  Europeans from the general population residing in a town or province in 23 centers in 10 European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom).
Summary of Results:

Key Findings

  • During a mean follow-up of 9.7 years, 14,723 participants died
  • The lowest risks of death related to BMI were observed at a BMI of 25.3 for men and 24.3 for women
  • After adjustment for BMI, waist circumference and waist-to-hip ratio were strongly associated with the risk of death
  • Relative risks among men and women in the highest quintile of waist circumference were 2.05 (95% CI: 1.80 to 2.33) and 1.78 (95% CI: 1.56 to 2.04), respectively, and in the highest quintile of waist-to-hip ratio, the relative risks were 1.68 (95% CI: 1.53 to 1.84) and 1.51 (95% CI: 1.37 to 1.66), respectively
  • BMI remained significantly associated with the risk of death in models that included waist circumference or waist-to-hip ratio (P<0.001).

Other Findings

  • General obesity was more strongly related to the risk of death among participants who had never smoked, whereas underweight was more strongly related to the risk of death among current smokers
  • After adjustment for BMI, the association of waist circumference with the risk of death was stronger among smokers. Smokers tend to have a metabolically more adverse fat-distribution profile, with higher central adiposity, than non-smokers.
  • Obesity appeared to be more strongly related to the risk of death among younger men than among older men, whereas no such difference was observed among women. The reasons for these sex differences are unclear and may reflect biologic factors or the play of chance.
  • The absolute risk of death in the reference category varied across subgroups.
Author Conclusion:

These data suggest that both general adiposity and abdominal adiposity are associated with the risk of death and support the use of waist circumference or waist-to-hip ratio in addition to BMI in assessing the risk of death.

Funding Source:
Government: European Commission: Public Health and Consumer Protection Directorate 1993–2004; Research Directorate-General 2005–present; Deutsche Krebshilfe; German Cancer Research Center; German Federal Ministry of Education and Research; Danish Cancer Society; Health Research Fund of the Spanish Ministry of H
University/Hospital: Aalborg Hospital, Aarhus University Hospital System, University Medical Center Utrecht, University of Oxford, University of Athern Medical School, Harvard School of Pubic Health, Imperial College London, University of Turin, Univarsita di Napoli, University of Tromso, University of Cambridge, Imperi
Not-for-profit
Research Directorate-General 2005–present; Deutsche Krebshilfe; German Cancer Research Center; German Federal Ministry of Education and Research; Danish Cancer Society; Health Research Fund of the Spanish Ministry of H
Other non-profit:
Reviewer Comments:
  • Very large multi-site European cohort study
  • Multi-sites may result in differences in how anthropometrics were measured (especially in Greece), but the relative-risk estimates for the overall cohort did not change substantially when the participants from Greece were excluded from the analysis
  • Participants were only excluded with a history of cancer, heart disease or stroke; this may have included other serious diseases
  • Supported from grants from numerous sources.
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) No
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) N/A
 
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? Yes
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? Yes
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? Yes
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? N/A
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? N/A
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? ???
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes