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The body-mass index (BMI) value associated with the lowest risk for all-cause mortality is now 27, up from 24 in the 1970s, according to a large Danish cohort study.

That means the lowest-risk BMI is now in the overweight category, said Børge Nordestgaard, MD, of Copenhagen University, Denmark, and colleagues in the Journal of the American Medical Association.

In addition, compared to BMIs in the conventional normal range, the hazard ratio for all-cause mortality associated with a BMI of 30 or higher has dropped from 1.3 to about 1.0 over the same time period, the Danish scientists said.

"To the extent these findings are replicable and generalizable, they raise both interesting hypotheses and reiterate points made in earlier work," said Tapan Mehta, PhD, an obesity researcher the University of Alabama at Birmingham, in an email to MedPage Today. Mehta is also on the advocacy committee of The Obesity Society.

"A potential explanation for the secular trend may be that while improved treatment for cardiovascular risk factors or complicating diseases has reduced mortality in all weight classes, the effects may have been greater at higher BMI levels than at lower BMI levels," Nordestgaard and colleagues wrote.

The Danish scientists analyzed data from three cohorts enrolled at different times: the Copenhagen City Heart Study in 1976-78 (n=13,704), the same study in 1991-1994 (n=9,482), and the Copenhagen General Population study in 2003-2013 (n=97,362). All participants were followed until November 2014, emigration, or death, whichever came first.

Except for cancer mortality, the association of BMI with all-cause, cardiovascular, and other mortality was U-shaped. The BMI associated with the lowest all-cause mortality risk increased by 3.3 points over the study period:

1976-1978 cohort: 23.7 (95% CI 23.4-24.3)

1991-1994 cohort: 24.6 (95% CI 24.0-26.3)

2003-2013 cohort: 27.0 (95% CI 26.5-27.6)

Nordestgaard and colleagues found a similar pattern for cardiovascular and other mortality.

The adjusted hazard ratios for all-cause mortality for BMI of 30 or more versus BMI in the normal range decreased during the study period:

1976-1978 cohort: HR 1.31 (95% CI 1.23-1.39)

1991-1994 cohort: HR 1.13 (95% CI 1.04-1.22)

2003-2013 cohort: HR 0.99 (95% CI 0.92-1.07)

Analyses stratified by age, sex, smoking, and presence of cardiovascular disease or cancer also yielded similar results, Nordestgaard and colleagues said.

They also noted that "a subgroup of never-smokers without history of cardiovascular disease or cancer" had the lowest mortality risk at BMI 26.1, supporting the results of the main analysis.

"If this finding is confirmed in other studies, it would indicate a need to revise the WHO [World Health Organization] categories presently used to define overweight, which are based on data from before the 1990s," Nordestgaard and colleagues concluded.

Mehta told MedPage Today that the study "reiterates the need to move away from a BMI-focused approach at the clinical-level. Recent work on obesity staging systems (cardiometabolic obesity staging system, Edmonton obesity staging system) addresses some of these by focusing not on BMI but the overall cardiometabolic health. Better measurements of body fat that can be applied in clinical settings may also be helpful."

He added, "It would have been interesting and helpful for the authors to do these analyses using waist circumferences that were available for the last two cohorts."

"Interesting questions or hypotheses are: To what extent do the improvements in cardiovascular disease and medications explain this change? Does an individual's BMI affect his propensity to get screened and diagnosed for underlying conditions through routine check-ups and monitoring?" Mehta said.