Obesity is associated with increased mortality. Weight loss improves cardiovascular risk factors, but no prospective interventional studies have reported whether weight loss decreases overall mortality. In fact, many observational studies suggest that weight reduction is associated with increased mortality.

Most epidemiological studies have shown that obesity is associated with increased cardiovascular morbidity and mortality.^1,2 Weight loss improves diabetes and other intermediate risk factors for cardiovascular disease,^3-6 suggesting that weight loss could also reduce the incidence of cardiovascular events. However, weight loss has been paradoxically associated with an increased incidence of cardiovascular events in most epidemiological studies,^7-9 even in participants who were overweight or obese at baseline.¹⁰ Some observational studies suggest that self-reported intentional weight loss is associated with a decreased incidence of cardiovascular events.¹¹ Other studies suggest the opposite.^12,13 Results of these studies might be confounded by inclusion of participants with unintentional weight loss.^11-13

Research from JAMA — Association of Bariatric Surgery With Long-term Remission of Type 2 Diabetes and With Microvascular and Macrovascular Complications

The obesity paradox refers to the epidemiological evidence that obesity compared with normal weight is associated with counter-intuitive improved health in a variety of disease conditions. The aim of this study was to investigate the relationship between body mass index (BMI) and mortality in patients with acute coronary syndromes (ACSs). We extracted data from the Swedish Coronary Angiography and Angioplasty Registry and identified 64 436 patients who underwent coronary angiography due to ACSs. In 54 419 (84.4%) patients, a significant coronary stenosis was identified, whereas 10 017 (15.6%) patients had no significant stenosis. 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 3 years was compared using Cox proportional hazards regression with the lean BMI category (21.0 to <23.5 kg/m²) as the reference group. Regardless of angiographic findings [significant or no significant coronary artery disease (CAD)] and treatment decision, the underweight group (BMI <18.5 kg/m²) had the greatest risk for mortality. Medical therapy and PCI-treated patients with modest overweight (BMI category 26.5–<28 kg/m²) had the lowest risk of mortality [hazard ratio (HR) 0.52; 95% CI 0.34–0.80 and HR 0.64; 95% CI 0.50–0.81, respectively]. When studying BMI as a continuous variable in patients with significant CAD, the adjusted risk for mortality decreased with increasing BMI up to ∼35 kg/m² and then increased. In patients with significant CAD undergoing coronary artery by-pass grafting and in patients with no significant CAD, there was no difference in mortality risk in the overweight groups compared with the normal weight group. In this large and unselected group of patients with ACSs, 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.