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Overweight and Obesity Linked With an Increased Risk of All-Cause Death

December 2, 2010 |

Being too fat–as well as possibly being too skinny–is associated with an increased risk of all-cause mortality, according to the results of a new study [1]. Among the underweight individuals, the increased risk of all-cause mortality was likely the result of preexisting disease, according to investigators, with the association attenuated when adjusted for potential confounders.

Speaking to heartwire about the results, from a large meta-analysis of nearly 1.5 million white adults now published in the December 2, 2010 issue of the New England Journal of Medicine, lead investigator Dr Amy Berrington de Gonzalez (National Cancer Institute, Bethesda, MD) said there are some possible interpretations of the underweight data.

“One of them is that what we’re really seeing is a bias, that’s it’s not really that being underweight puts you at increased risk of death,” said Berrington de Gonzalez. “It’s that you’re underweight because you have a preexisting illness of some sort, which is what is actually putting you at the increased risk of death. There is some suggestion from our findings that might be the explanation, we can’t say for certain, but when we excluded people with preexisting conditions, the magnitude of that risk decreased. When we followed up people for longer periods of time, the risk became even smaller still, which might mean that people with these preexisting conditions have died off earlier in the study, and we get a cleaner analysis as we go into longer follow-up.”

Past Studies Conflicting

Prior studies examining the relationship between all-cause mortality and weight have shown a clearly increased risk of death from heart disease, stroke, and specific cancers among obese individuals, those with a body-mass index (BMI) >30 kg/m2. The relationship among overweight individuals, however, is less clear, according to the investigators, with some studies suggesting that being overweight, defined as a BMI between 25 and 29.9, might be beneficial or have little effect on all-cause mortality. Other studies have suggested that being underweight might also put individuals at an increased risk of death, as reported previously by Heartwire .

In this new meta-analysis, the researchers examined prospective studies in the National Cancer Institute Cohort Consortium having more than five years of follow-up and including more than 1000 deaths among non-Hispanic white individuals and ascertained height, weight, and smoking status at baseline. Overall, 19 studies were included, with 1.46 million individuals, of whom 58% were female. The median age at baseline was 58 years old, and the median BMI was 26.2.

The median follow-up was 10 years, and in this time there were 160 087 deaths. The age-standardized rate of death was lowest among individuals with a BMI ranging from 22.5 to 24.9, and this was used as the referent BMI when researchers assessed the risk of being underweight, overweight, or obese. Overall, there was a J-shaped relationship between BMI and all-cause mortality, and the hazard ratios increased when individuals who smoked or were current smokers, as well as those with cancer or heart disease at baseline, were excluded from the analysis.

Among healthy women who never smoked, being underweight was associated with a 47% higher risk of death compared with the referent women, while being obese was associated with a 44% higher risk of death. The morbidly obese, those with a BMI >40, had a 2.5-fold greater risk of all-cause mortality than those with a BMI ranging from 22.5 to 24.9. Among men, the hazard ratios were similar, report investigators.

Hazard Ratio for All-Cause Mortality Among Healthy Women Who Never Smoked

BMI (kg/m2)  All-cause mortality, hazard ratio (95% CI) 
15.0–18.4 1.47 (1.33–1.62)
18.5–19.9 1.14 (1.07–1.22)
20.0–22.4 1.00 (0.96–1.04)
22.5–24.9 1.00 (reference)
25.0–29.9 1.13 (1.09–1.17)
30.0–34.9 1.44 (1.38–1.50)
35.0–39.9 1.88 (1.77–2.00)
40.0–49.9 2.51 (2.30–2.73)

Commenting on the findings, specifically the relationship between overweight and all-cause mortality, Berrington de Gonzalez told heartwire that they had expected to see an increased risk of death in this cohort, despite past studies suggesting a little bit of extra padding might be beneficial.

“When we excluded the smokers and people with existing conditions, we did find that being overweight was associated with a small increased risk of death,” she said. “It’s about a 10% increased risk, but highly statistically significant with our very large numbers.”

As noted, in a follow-up of 15 years or greater for underweight individuals, only those with a BMI of 15.0 to 18.4 remained at an increased risk of death compared with the referent group. Similarly, the hazard ratios for all underweight individuals were lower among those who reported higher levels of physical activity, although this trend did not reach statistical significance.

The study was designed to examine the association between all-cause mortality and BMI, but investigators did tease out deaths from cardiovascular disease and cancer. Like the overall findings, those with the lowest BMI, from 15.0 to 18.4, had a higher risk of dying from cardiovascular disease and cancer, as did individuals who were overweight and obese. The study also helps provide some data on an optimal BMI for lowering the risk of death. Based on the meta-analysis, the optimal BMI appears to be between 20 and 25, or between 135 and 170 lbs for a 5’9″ individual.


1.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; 363:2211-2219.

Authors and Disclosures

by Michael O’Riordan for Heartwire on Medscape Today

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