Epidemiological, clinical, and mechanistic preclinical studies conducted in the field of cardiovascular medicine have led to remarkable progress in our understanding of nonmodifiable and modifiable risk factors for cardiovascular disease (CVD). For instance, although the prevalence of CVD had reached devastating levels in the 1950s, proper focus on the major CVD risk factors first identified at the time, such as smoking, hypertension, and high cholesterol levels, has allowed these risk factors to be targeted both at the clinical level and through public health policies. 1 As a consequence, coronary heart disease mortality has decreased by 50% over the past 50 years. 2 Ford et al2 have suggested that better screening and medical management of these CVD risk factors and the medical procedures developed to treat the various acute manifestations of CVD have had a favorable impact on its related mortality rates. However, the current overconsumption of processed and energy-dense food products of poor nutritional value combined with our sedentary lifestyle have contributed to the emergence of new drivers of CVD risk: obesity and type 2 diabetes mellitus (Figure 1). 3, 4 It has been proposed that our medical progress at tackling CVD could be offset, at least to a certain extent, by the dramatic consequences of our toxic lifestyle, which includes poor nutrition or excess caloric consumption and a sedentary lifestyle, both leading to obesity and type 2 diabetes mellitus. 2 Thus, the mosaic of modifiable CVD risk factors has evolved over the past 50 years with, on the one hand, less influence of smoking, and of untreated hypertension and high cholesterol, as well, but, on the other hand, an increased prevalence of sedentary overweight/obese patients having either type 2 diabetes mellitus or a constellation of metabolic abnormalities linked to insulin resistance: the so-called metabolic syndrome. 5

The exploding obesity epidemic has put this emerging risk factor at the front of CVD risk assessment and management. Accordingly, the American Heart Association has published several position papers to document and emphasize the health hazards of obesity. 6–8 At the population level, although it is clear that more obesity is associated with more type 2 diabetes mellitus and with a greater risk of developing a variety of cardiovascular health outcomes, this condition (obesity) is very complex and heterogeneous as a phenotype.