Obesity and obesity-induced inflammatory disease contribute to atherosclerosis: a review of the pathophysiology and treatment of obesity.

Two billion people worldwide older than 18 years of age, or approximately 30% of the world population, are overweight or obese. In addition, more than 43 million children under the age of 5 are overweight or obese. Among the population in the United States aged 20 and greater, 32.8 percent are overweight and 39.8 percent are obese. Blacks in the United States have the highest age-adjusted prevalence of obesity (49.6%), followed by Hispanics (44.8%), whites (42.2%) and Asians (17.4%). The impact of being overweight or obese on the US economy exceeds $1.7 trillion dollars, which is equivalent to approximately eight percent of the nation's gross domestic product. Obesity causes chronic inflammation that contributes to atherosclerosis and causes >3.4 million deaths/year. The pathophysiologic mechanisms in obesity that contribute to inflammation and atherosclerosis include activation of adipokines/cytokines and increases in aldosterone in the circulation. The adipokines leptin, resistin, IL-6, and monocyte chemoattractant protein activate and chemoattract monocytes/macrophages into adipose tissue that promote visceral adipose and systemic tissue inflammation, oxidative stress, abnormal lipid metabolism, insulin resistance, endothelial dysfunction, and hypercoagulability that contribute to atherosclerosis. In addition in obesity, the adipokines/cytokines IL-1β, IL-18, and TNF are activated and cause endothelial cell dysfunction and hyperpermeability of vascular endothelial junctions. Increased aldosterone in the circulation not only expands the blood volume but also promotes platelet aggregation, vascular endothelial dysfunction, thrombosis, and fibrosis. In order to reduce obesity and obesity-induced inflammation, therapies including diet, medications, and bariatric surgery are discussed that should be considered in patients with BMIs>35-40 kg/m if diet and lifestyle interventions fail to achieve weight loss. In addition, antihypertensive therapy, plasma lipid reduction and glucose lowering therapy should be prescribed in obese patients with hypertension, a 10-year CVD risk >7.5%, or prediabetes or diabetes.