Obesity Second Only to Smoking as Cause of Premature Death
Overweight and obesity are associated with a significantly increased risk of premature death, particularly among men, with the effect seen across Europe, North America, East Asia, Australia, and New Zealand, confirms an individual-participant data meta-analysis.
Collating data on almost four million who took part in 189 studies, the researchers found that individuals with a body mass index (BMI) of more than 25 kg/m2 had a significantly increased risk of all-cause mortality, with approximately one in six premature deaths potentially avoidable through weight loss.
Coauthor Sir Richard Peto, FRS, professor of medical statistics and epidemiology at the University of Oxford, United Kingdom, said in a press release: “Obesity is second only to smoking as a cause of premature death in Europe and North America.
“Smoking causes about a quarter of all premature deaths in Europe and in North America, and smokers can halve their risk of premature death by stopping. But overweight and obesity now cause about one in seven of all premature deaths in Europe and one in five of all premature deaths in North America.”
And lead author Emanuele Di Angelantonio, MD, PhD, University of Cambridge, United Kingdom, told Medscape Medical News that he hopes the findings will help to “put to rest” the discussion over the association between BMI and obesity.
He said: “Of course, there’s a lot of research that needs to be done in trying to understand other factors implicated with obesity, especially, for example, fat distribution and visceral fat, which we haven’t been able to study in this paper.”
Dr Di Angelantonio added, however, that this is “possibly one of the largest” studies of BMI and mortality, “and I hope that it will be a starting point to moving above and beyond the simple measure of BMI.”
The current findings, which were published online in the Lancet on July 13, are in contrast to those of a previous study by Flegal et al that suggested that overweight and grade 1 obesity were not associated with increased mortality and indeed that overweight was associated with significantly lower all-cause mortality (JAMA. 2013;309: 71-82).
Dr Di Angelantonio believes that the reasons for the difference in findings between the two are not simply that the current analysis is much larger in terms of both the number of studies and patients included, but also because he and his colleagues “adopted a much stricter methodology.”
He said that the “risk of the message” from the earlier paper is that “being overweight and slightly obese is normal.” He emphasized: “Actually, it’s not,” adding, “I think here we are reinforcing this message, and we are reinforcing the need to have public-health measures to try to implement a strategy to reduce body weight.”
Mortality Increases Linearly W ith BMI Once Greater Than 25.0 kg/m2
To provide a standardized comparison of associations between BMI and mortality across different populations, the Global BMI Mortality Collaboration was established, which brought together 500 investigators from 300 institutions in 32 countries.
After agreeing on an analysis plan for combining individual-participant data from contributing studies, they conducted a search of the MedLine, Embase, and Scopus databases for relevant studies. From this, 10,625,411 million adults from 239 prospective cohort studies in 32 countries with a median follow-up of 13.7 years were identified.
Of the participants, 3,951,455 from 189 studies were never-smokers aged 20 to 90 years with a BMI between 15 kg/m2 and 60 kg/m2 who did not report chronic diseases at recruitment and were still being followed up 5 years later. A total of 385,879 individuals died.
Obesity grade 1 was defined as BMI 30.0 kg/m2 to < 35.0 kg/m2, obesity grade 2 was 35.0 kg/m2 to < 40.0 kg/m 2, and obesity grade 3 as 40.0 kg/m2 to < 60.0 kg/m2. Premature deaths were defined as those between ages 35 and 69 years.
Relative to a BMI of 22.5 kg/m2 to <25.0 kg/m2, underweight was associated with an increased all-cause mortality risk, at a study-, age-, and sex-adjusted hazard ratio (HR) of 1.13 for BMI 18.5 kg/m2 to < 20.0 kg/m2 and 1.51 for BMI 15.0 kg/m2 to < 18.5 kg/m2.
The risk of all-cause mortality was also increased in individuals who were overweight, at HRs of 1.07 for BMI 25.0 kg/m2 to < 27.5 kg/m 2 and 1.20 for BMI 27.5 kg/m2 to < 30.0 kg/m2.
The risk was further raised for those in obesity grade 1 (HR, 1.45), obesity grade 2 (HR, 1.94), and obesity grade 3 (HR, 2.76).
The team found that the population-attributable fractions of all-cause mortality associated with overweight or obesity were 19% in North America vs 16% in Australia and New Zealand, 14% in Europe, and 5% in East Asia.
Over a BMI of 25.0 kg/m2, mortality increased approximately log-linearly in line with BMI, such that the HR per 5-kg/m2 increase in BMI was 1.39 in Europe, 1.29 in North America, 1.39 in East Asia, and 1.31 in Australia and New Zealand.
It was estimated that the proportion of premature deaths that could be avoided by the overweight and obese population having a normal BMI would be one in five in America, one in six in Australia and New Zealand, one in seven in Europe, and one in 20 in East Asia.
Main Difference in Survival Is Seen Between Genders
Dr Di Angelantonio described the differences in survival outcomes between continents as “minor.” He said: “I think those differences, in some ways, are not as big as people as people might have thought before, and the main difference that we find is actually between men and women.”
The HR per 5-kg/m2 increase in BMI over 25 kg/m2 was greater in men compared with women, at 1.51 vs 1.20. Furthermore, the HR per 5-kg/m2 increase was greater in younger than older people, at 1.52 for BMI measured at 35 to 49 years vs 1.21 for BMI measured at 70 to 89 years.
Over 25 kg/m2, BMI was strongly and positively associated with death from coronary heart disease, stroke, and respiratory disease and moderately positively associated with cancer mortality, with the associations lately similar across Europe, North America, and East Asia.
The team writes that “wherever overweight and obesity are common, their associations with higher all-cause mortality are broadly similar in different populations, supporting strategies to combat the entire spectrum of excessive adiposity worldwide.”
What Kind of Guidance Can Be Derived From Analyses Pooling Global Data?
In an accompanying commentary, David Berrigan, PhD, MPH, Richard Troiano, PhD, and Barry Graubard, PhD, from the National Cancer Institute, National Institutes of Health, Bethesda, Maryland, applaud the study methodology and point out that the results “are broadly similar to other recent studies…with increased risk of mortality for both low BMI and obesity.”
Nevertheless, the paper raises two important issues.
“The first is whether conclusions about the relation between BMI and mortality from analyses with extensive exclusions can be generalizable and unbiased. The second is what sort of public-health guidance can be obtained from analyses that pool global data.”
Noting that “substantial research and conceptual questions remain” over both of these issues, they say that “ever-larger” data sets are not likely to resolve the challenges of developing global public-health recommendations “without further developments in study data and design.”
Yet despite the limitations of observational studies, many crucial questions about BMI will continue to rely on such data, because few sufficiently sized randomized trials have been done to address whether weight-loss interventions reduce mortality or morbidity, they note.
And weight-loss interventions have only modest long-term effectiveness and generally target behaviors, such as diet and physical activity, that can lead to change in BMI rather than directly targeting BMI itself. Therefore, clinical trials “are limited in their capacity to address causal relations between BMI and mortality.”
They conclude: “Important challenges remain in the effort to translate epidemiological evidence of excess body weight and mortality into effective guidelines and public-health interventions.”
Global BMI Mortality Collaboration provides links to websites of the component studies (or consortia), many of which describe their funding. The coordinating center at the University of Cambridge was funded by the UK Medical Research Council, British Heart Foundation, British Heart Foundation Cambridge Cardiovascular Centre of Excellence, and National Institute for Health Research Cambridge Biomedical Research Centre. The work of the coordinating center at the Harvard TH Chan School of Public Health was funded by grants from the National Institutes of Health. This research has been conducted using the UK Biobank resource. Dr Angelantonio received research funding from the UK Medical Research Council, British Heart Foundation, National Institute of Health Research, NHS Blood and Transplant, and the European Commission Framework Programme during the conduct of the study and personal fees from Elsevier (France). Dr Peto reports no relevant financial relationships. Disclosures for the coauthors are listed in the article. Drs Berrigan, Troiano, and Graubard report no relevant financial relationships.
Lancet. Published online July 13, 2016. Article