Low body mass index (BMI) and high body fat percentage, not just high BMI, are independently associated with increased mortality in both men and women, a new study suggests.

Raj Padwal, MD, from the University of Alberta, Edmonton, Canada, and colleagues published the results of their observational study online March 7 in the Annals of Internal Medicine.

"The major finding was that when BMI and body fat percentage were included in the same fully adjusted models, low BMI and high body fat percentage were both associated with increased all-cause mortality. Mortality increased as BMI decreased and body fat percentage increased," the authors write. "This suggests that after adjustment for BMI, higher adiposity may have a detrimental effect on survival and that after adjustment for body fat percentage, a lower BMI may likewise be associated with decreased survival."

Previous studies in middle-aged and older adults, and studies in patients with chronic diseases such as heart failure, have reported that overweight (BMI, 25.0 - 29.9 kg/m2) and mildly or moderately obese (BMI, 30.0 - 34.5 kg/m2) patients had a lower risk for mortality than those who had a normal weight (BMI, 18.5 - 24.9 kg/m2), the so-called obesity paradox.

These findings have been the source of much debate, in particular with respect to whether clinicians should advise obese patients to lose weight, especially if they are older or have chronic disease, to prolong their life.

However, according to the authors, BMI is an imperfect measure of adiposity because it does not directly measure body fat. "Therefore, more sophisticated body fat measurements must be used in studies examining the relationship between adiposity and mortality so that this relationship can be more confidently and accurately assessed."

As a consequence, they conducted a study to examine the relationship of BMI and body fat percentage (alone and in combination) with mortality.

They measured BMI and body fat percentage (by using dual-energy x-ray absorptiometry) in 49,476 women (mean age, 63.5 years; mean BMI, 27.0 kg/m2; mean body fat, 32.1%) and 4944 men (mean age, 65.5 years; mean BMI, 27.4 kg/m2; mean body fat, 29.5%).

The researchers followed up the participants until death or the end of the study; 4965 women died over a median of 6.7 years, and 984 men died over a median of 4.5 years.

Overall, the results of the study showed that having a higher body fat percentage was independently associated with reduced survival, as was having a low BMI.

In fully adjusted models examining BMI and body fat percentage separately, low BMI (hazard ratio [HR], 1.48 [95% confidence interval (CI), 1.36 - 1.61] for quintile 1; HR, 1.13 [95% CI, 1.03 - 1.23] for quintile 2) and low body fat percentage (HR, 1.36 [95% CI, 1.25 - 1.49] for quintile 1; HR, 1.17 [95% CI, 1.07 - 1.28] for quintile 2) were each associated with an increased risk for death in women. However, the risk for death was not significantly increased for those in the highest BMI or body fat percentage quintiles. Among men, mortality was significantly higher for those with a lower BMI (HR, 1.26 [95% CI, 1.04 - 1.52] for quintile 1) and those with a higher body fat percentage (HR, 1.40 [95% CI, 1.16 - 1.71] for quintile 5).

Similarly, in fully adjusted models examining BMI and body fat percentage together, low BMI (HR, 1.44 [95% CI, 1.30 - 1.59] for quintile 1; HR, 1.12 [95% CI, 1.02 - 1.23] for quintile 2) and high body fat percentage (HR, 1.19 [95% CI, 1.08 - 1.32] for quintile 5) were significantly associated with increased risk for death in women. Among men, mortality was still significantly higher for those with a lower BMI (HR, 1.45 [95% CI, 1.17 - 1.79] for quintile 1) and those with a higher body fat percentage (HR, 1.59 [95% CI, 1.28 - 1.96] for quintile 5).

"[O]ur findings underscore that the risk for all-cause mortality increases with both increasing adiposity and decreasing BMI in a general population of middle-aged and older adults," the authors write.

They also emphasized that BMI may be an inappropriate surrogate for adiposity, and that this limitation may help explain the presence of the obesity paradox in many studies. "These findings also suggest the importance of using direct measures of adiposity when building prognostic or even exploratory models," the authors conclude.

This study received no funding. One coauthor has received grants from Genzyme and Amgen and speaker fees from Amgen, Eli Lilly, and Novartis for work outside this study. The other authors have disclosed no relevant financial relationships.

Ann Intern Med. Published online March 7, 2016. Abstract