University of Glasgow researchers challenge the obesity paradox

In both men and women, increased adiposity has a deleterious association with cardiovascular disease (CVD), and previous assertions that increased adiposity may protect against CVD should be banished, according to research published in the European Heart Journal.

Further, compared with other measures of adiposity, the association between body mass index (BMI) and CVD may be more affected by pre-existing comorbidities, including waist-to-hip ratio, waist-to-height ratio, and percentage of body fat mass.

“Any public misconception of a potential ‘protective’ effect of fat on heart and stroke risks should be challenged,” said lead researcher Dr. Stamatina Iliodromiti, clinical lecturer, Obstetrics and Gynecology, and MRC Fellow, University of Glasgow, Scotland, UK.

Recent studies have suggested an “obesity paradox,” which contends that being overweight or even obese may not affect mortality from CVD or other causes, and may even be protective, especially in the elderly.

In this study, researchers sought to assess the possible associations between body composition and CVD outcomes in healthy subjects. Using the UK Biobank, they identified 296,535 subjects (57.8% women) of white European descent who had no CVD at baseline.

Low BMI (18.5 kg/m² or less) was associated with a higher incidence of CVD. Surprisingly, the lowest risk of CVD was seen in subjects with a BMI of 22-23 kg/m². After this point, CVD risk only increased. Upon subgroup analyses, this association became stronger when patients with comorbidities were excluded.

For example, for a BMI above 22 kg/m², the risk of CVD increased by 13% for every 5.2 kg/m² increase in women, and 4.3 kg/m² in men. 

For the remaining adiposity measures, associations were more linear. A 1 SD increase in waist circumference was associated with a higher risk of CVD in women (HR: 1.16; 95% CI: 1.13-1.19) and in men (HR: 1.10; 95% CI: 1.08-1.13).

That increase translates to a CVD risk increase of 16% in women and 10% in men for every 12.6 cm and 11.4 cm, respectively, increase in waist circumference in women with a waist circumference of 74 cm, and in men with a waist circumference of 83 cm.

A similar magnitude of association was found for 1 SD increases in waist-to-hip ratios, waist-to-height ratios, and percentage of body fat mass.

“This is the largest study that provides evidence against the obesity paradox in healthy people. It is possible that the story may be different for those with pre-existing disease because there is evidence that in cancer patients, for instance, being slightly overweight is associated with lower risk, especially as cancer and its treatments can lead to unhealthy weight loss,” said Dr. Iliodromiti. “By maintaining a healthy BMI of around 22-23 kg/m², healthy people can minimize their risk of developing or dying from heart disease. In terms of other adiposity measures, the less fat, especially around their abdomen, they have, the lower the risk of future heart disease,” she added.

Maintaining a BMI of 22-23 kg/m² can be difficult, however, especially with increasing age.

Dr. Iliodromiti’s co-author, Naveed Sattar, professor, Metabolic Medicine, University of Glasgow, said: “We know many cannot get to such low BMIs, so the message is, whatever your BMI, especially when in the overweight or obese range, losing a few kilograms or more if possible, will only improve your health. There are no downsides to losing weight intentionally and the health professions needs to get better at helping people lose weight.”

These researchers noted that their findings may have implications for future guidelines in preventing and managing CVD.

“Even within the normal BMI category of between 18.5-25 kg/m², the risk of CVD increases beyond a BMI of 22-23 kg/m². The other adiposity measures show that the leaner the person the lower the risk of CVD, and this must be a public message, that healthy individuals should maintain a lean physique to minimize their risk of CVD,” concluded Dr. Iliodromiti.