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Obesity paradox

Not all metabolisms are equal

Two studies including a combined 107,000 subjects have reported that people can be obese but metabolically healthy and fit, and patients with heart disease have a reduced risk of dying if they are overweight or obese, while underweight and normal weight heart disease patients have an increased risk.

The first study, published online in the European Heart Journal, reported that some patients are metabolically fit with no evidence of insulin resistance, diabetes, hypercholesterolemia or hypertension, despite being obese. These patients have no greater risk of developing or dying from cardiovascular disease or cancer than normal weight people, the research concludes.

As their obese status does not appear to have a detrimental effect on their health, the investigators said doctors should consider this when assessing possible treatments or interventions.

Lead investigator, Dr Francisco Ortega, University of Granada, Spain, explained that the prognosis of metabolically healthy but obese phenotype is limited due to the exclusive use of the body mass index to define obesity and the lack of information on cardiorespiratory fitness.

“We aimed to assess whether metabolically healthy but obese individuals have a higher fitness level than their metabolically abnormal and obese peers and after accounting for fitness, whether metabolically healthy but obese phenotype is a benign condition, in terms of cardiovascular disease and mortality,” he said.


Under the direction of Professor Steven Blair, University of South Carolina, Ortega and colleagues examined the metabolic status of 43,265 participants (24.3% women) who were recruited into the Aerobics Center Longitudinal Study (ACLS). The participants were recruited to the ACLS between 1979 and 2003, and completed a detailed questionnaire. The study participants were followed until they died or until the end of 2003.

Fitness was assessed by a maximal exercise test on a treadmill and body fat percentage (BF%) by hydrostatic weighing or skinfolds (obesity was defined as BF% ≥25 for mean and  ≥30% for women, respectively). Metabolically healthy was defined as having only one of the criteria for metabolic syndrome.

The investigators report that 46% of the obese patients were metabolically healthy and had better fitness than metabolically abnormal obese participants (p<0.001). When adjusting for fitness and other confounders, metabolically healthy but obese individuals had a lower risk (30–50%, estimated by hazard ratios) of all-cause mortality, non-fatal and fatal cardiovascular disease, and cancer mortality than their metabolically unhealthy obese peers.

“Our data support the idea that interventions might be more urgently needed in metabolically unhealthy and unfit obese people, since they are at a higher risk,” said Ortega. “This research highlights once again the important role of physical fitness as a health marker.”

No significant differences were observed between metabolically healthy but obese and metabolically healthy normal-fat participants.

The authors concluded that the data indicates that accurate BF% and fitness assessment can contribute to properly define a subset of obese individuals who do not have an elevated risk of cardiovascular disease or cancer.

Swedish study

The second study, also published in the European Heart journal, analysed patients on the Swedish Coronary Angiography and Angioplasty Registry, and investigated the relationship between BMI and mortality in patients with acute coronary syndrome (ACS).

The researchers from the University of Gothenburg and Uppsala University, Sweden, identified 64,436 patients who underwent coronary angiography due to ACS.

A significant coronary stenosis was identified in 54,419 (84.4%) patients. Patients were divided into nine different BMI categories. The patients with significant stenosis were further subdivided according to treatment received such as medical therapy, percutaneous coronary intervention (PCI), or coronary artery by-pass grafting.

Mortality for the different subgroups during a maximum of three years was compared using Cox proportional hazards regression with the lean BMI category (21.0 to <23.5) as the reference group. Regardless of angiographic findings and treatment decision, the underweight group (BMI <18.5) had the greatest risk for mortality.

Medical therapy and PCI-treated patients with modest overweight (BMI category 26.5–<28) had the lowest risk of mortality (hazard ratio 0.52; 95% CI 0.34–0.80 and hazard ratio 0.64; 95% CI 0.50–0.81, respectively).

When studying BMI as a continuous variable in patients with significant coronary artery disease, the adjusted risk for mortality decreased as BM rose up to 35, and then increased.

In patients with significant coronary artery disease undergoing coronary artery by-pass grafting and in patients with no significant coronary artery disease, there was no difference in mortality risk in the overweight groups compared with the normal weight group.

The researchers said that in this large and unselected group of patients with ACS, the relation between BMI and mortality was U-shaped, with the nadir among overweight or obese patients and underweight and normal-weight patients having the highest risk.

“These data strengthen the concept of the obesity paradox substantially,” they concluded.