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Ask About Weight History to Learn More About Mortality Risk

Even shed pounds may come back to cause problems — a study measuring maximum BMI over 24 years of weight history found an association between obesity and all-cause mortality, even in once-obese people who later attained normal weight.

In a cohort of 6,197 participants from the original and offspring Framingham Heart Study, there were increasing risks across obese I and obese II categories compared with normal weight, and obese II status almost doubled risk, according to Andrew Stokes, PhD, of the Boston University School of Public Health, and colleagues.

In a monotonic association between increasing maximum BMI and mortality, obese I (BMI 30 to <35) status and obese II (BMI 35 to<40) status had hazard ratios of 1.27 (95% CI 1.14-1.41) and 1.93 (95% CI 1.68-2.20), respectively, they reported in JAMA Network Open.

For all participants, the HR of 1.22 (95% CI 1.17-1.27) suggested a 21.9% increased risk with each 5-unit increase in maximum BMI, they noted. The findings imply that eliciting patients’ weight history could identify those at increased risk of death, and that preventing weight gain in the first place needs to be a primary goal, the authors said.

“Our study findings indicate that failure to incorporate weight history may introduce substantial bias into assessment of risk,” they wrote. “Specifically, in analyses stratified by weight history, mortality risks were found to be substantially higher in normal-weight individuals who had a history of overweight or obesity compared with those who maintained a normal-weight status over time.”

Previous estimates based on weight at a single point in time have shown a paradoxical association between overweight and mortality, and attenuated associations with obese I and obese II. Some have suggested that reverse causality may play a role in the “obesity paradox,” a phenomenon entailing confounding by illness, in which a preexisting condition alters both weight and mortality risk.

This source of bias could explain the findings of a 2013 meta-analysis in which overweight was associated with lower all-cause mortality, and being categorized as obese I was not associated with higher mortality, the authors noted.

“Incorporating weight history into studies of obesity and mortality could effectively reduce the consequences of reverse causation due to weight loss from illness,” they wrote.

Study Details

At baseline, the mean age of study participants was 62.7 and 55.5% were female. By end of follow-up in December 2014, 3,478 (56.1%) had died.

Using maximum BMI, 77.3% (4,793 of 6,197) were overweight or obese, while 66.5%(4,118 of 6,197) were overweight or obese using baseline BMI. A higher proportion of women than men had maximum BMI in both the normal (30.7%, 1,055 of 3,439 versus 12.7%, 349 of 2,758) and obese II categories (10.2%, 350 of 3,439 versus 7.2%, 198 of 2,758).

No significant association was observed, however, for the overweight category (BMI of 25 to <30, HR 1.08, 95% CI 0.99-1.18).

For normal-weight (BMI 18.5-24.9) individuals who were formerly overweight or obese, the mortality rates were 47.48 and 66.67 per 1000 person-years, respectively, while individuals who never exceeded normal weight had a mortality rate of 27.93 per 1000 person-years.

“Maximum BMI in the normal-weight range was associated with the lowest risk of mortality in this cohort, highlighting the importance of obesity prevention,” Stokes’ group wrote.

As for weight loss, that people who fell into a lower category after attaining maximum BMI during the weight history period had a higher risk of mortality. For example, individuals who were once obese but were normal weight at baseline had an HR of 1.80 (95% CI 1.23-2.64) compared with individuals who belonged to the normal-weight category the whole time.

The authors pointed out that previous research has suggested that the correlation of obesity with all-cause and cardiovascular disease (CVD)-specific mortality has declined over time. “Given that CVD is a major pathway through which obesity influences mortality, it is possible that improvements in CVD treatment and risk factor control have contributed to reductions in the risks associated with obesity,” they wrote.

Study limitations included the 4- to 8-year intervals between adjacent examinations of the Framingham offspring cohort, which may have prevented capture of true maximum BMI in some individuals who reached maximum BMI at a point between two examinations. In addition, the sample had few underweight participants, limiting the ability to investigate associations in that weight group. Moreover, most in both cohorts were white, limiting the generalizability of the findings to other racial or ethnic groups.

The authors noted that additional information on the impact of intentionality of BMI change may further strengthen the association. “Therefore, one potential future direction would be to take intentionality of weight loss into consideration,” they wrote.

‘Weight Gain Prevention’

In an invited commentary, Mark A. Pereira, PhD, of the University of Minnesota School of Public Health in Minneapolis, noted that measuring maximum BMI over a lengthy period may permit clearer inferences on the longer-term effect of BMI on mortality risk.

“At least from these models, the bottom line is weight gain prevention, as the authors importantly included in their discussion of the study implications,” he wrote.

Pereira pointed out the study lacked potentially useful information, such as the dynamics of weight change, weight loss intentionality, and stratification based on Framingham’s original versus offspring cohorts.

“The key finding of those with stable overweight having similar risk as stable normal weight is an important observation in support of lifestyle and environment changes to prevent chronic diseases and mortality among overweight and obese individuals,” he wrote.

Pereira pointed to large-scale randomized clinical trials of diabetes prevention that have shown that decreased disease incidence is possible through improved diet and physical activity among overweight and obese individuals, whether weight loss is achieved or not.

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute (NHLBI), the National Institute on Aging, and the Robert Wood Johnson Foundation.

Stokes disclosed support from Johnson & Johnson. A co-author disclosed support from the Veterans Administration, NHLBI, and the NIH, and relevant relationships with Boston Heart Diagnostics and The Dyslipidemia Foundation.

Pereira disclosed no relevant relationships with industry.

2018-11-19T17:30:00-0500

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