BMI Weighs Heavily on All-Cause Mortality Risk, According to a Global Meta-Analysis

Not only is obesity linked with all-cause mortality across a range of body mass index (BMI) levels, but this relationship is consistent throughout different global populations, according to findings from a large meta-analysis spanning four continents.

With one-fifth of the world expected to be obese by 2025 and many cath labs ill-equipped to care for the very obese, cardiologists around the world face the mounting challenge of how to optimally treat these patients. Additionally, the so-called obesity paradox continues to confound practitioners who observe often better survival in certain cohorts of heart failure, PCI, and TAVR patients with higher versus lower BMIs.

For the meta-analysis, lead author Emanuele Di Angelantonio, MD, PhD (University of Cambridge, England), and colleagues included almost 4 million healthy people who had never smoked from 189 prospective studies conducted between 1970 and 2015. Within 5 years, all-cause mortality was 9.8% overall, but compared with individuals who had BMIs between 18.5 and 25 kg/m², those with higher BMIs had significantly greater risk. This risk increased in conjunction with rising BMI.

The patterns were consistent across Europe, North America, East Asia, and Australia and New Zealand for individuals classified as overweight (BMI 25 to < 30 kg/m²) and obesity grade 1 (BMI 30 to < 35 kg/m²). For example, in Europe, the hazard ratio was 1.07 for those with a BMI of 25 to < 27.5 kg/m² and ranged up to 3.04 for those with a BMI of 40 to < 60 kg/m². In North America, the hazard ratios for those BMIs were 1.06 and 2.58, and in East Asia, they were 1.07 and 2.38.

Notably, the risk of death was somewhat higher for both underweight (BMI 15 to < 18.5 kg/m²) and obesity grade 3 (BMI 40 to < 60 kg/m²) individuals in Europe compared with East Asia. 

In addition, each 5-kg/m² increase in BMI was more tightly associated with death in men (HR 1.51) than in women (HR 1.30), and in younger versus older patients. Lastly, while the researchers did not perform an in-depth analysis of the causes of death, BMI over 25 kg/m² was strongly positively correlated with coronary heart disease, stroke, and respiratory disease mortality.

Effects on Public Health

The meta-analysis “contradicts previous claims . . . that actually being overweight and morbidly obese doesn’t increase your risk of dying,” Di Angelantonio told TCTMD, referring to a 2013 study that caused some controversy in this regard. 

However, an accompanying editorial written by David Berrigan, PhD, Richard Troiano, PhD, and Barry Graubard, PhD—one of the authors of that 2013 study—from the National Institutes of Health, makes the point that this meta-analysis tackles two other main issues: “whether conclusions about the relation between BMI and mortality from analyses with extensive exclusions can be generalizable and unbiased” and “what sort of public health guidance can be obtained from analyses that pool data.”

While these questions remain open-ended even with these findings, they write, ultimately large epidemiological studies like this are limited by their broad nature, and “challenges in deriving global public health recommendations are unlikely to be resolved by ever-larger datasets without further developments in study data and design.” They recommend that future studies focus on specific ethnic populations and use statistical tools (eg, Mendelian randomization) and weight histories to better identify patterns to target with public health strategies.

But being the largest study of its kind looking at BMI and mortality that he knows of, Di Angelantonio said the results will have an effect on public health and, as the authors write, support “strategies to combat the entire spectrum of excess adiposity in many population.”

BMI Not Perfect, But Most Practical

Author of the book The Obesity Paradox, Carl J. Lavie, MD (Ochsner Medical Center, New Orleans, LA), told TCTMD in an email that obesity is something that cardiologists monitor on a clinical basis, but he said that they “should give even more attention to physical activity, which is the best way to prevent weight gain, and fitness, which corresponds better with survival than weight.”

While he uses BMI as one method of measuring obesity among his patients, Lavie pointed out that “it does not separate muscle from fat.” Waist circumference and physical activity are “more important than obesity parameters,” he added.

Di Angelantonio acknowledged that BMI is not necessarily the “best way” of measuring obesity, but said “it’s the most practical way at the moment.” Other measures of fat and fat distribution have not been evaluated on a large enough scale to reliably assess them from a physician viewpoint, he said, adding that future research should focus on this.

Lavie added that he would like to see researchers work on identifying “the optimal body composition for various cardiovascular disease profiles and different genders, ages, and races. For example, in CHD patients, there is very little data to suggest that a patient with a BMI of 29 reduces CHD events or mortality by dropping to 25, whereas there is substantial data supporting the benefits of increasing fitness.”

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