Obesity, health issues, and cardiovascular disease.

This issue is dedicated to obesity, health issues, and cardiovascular disease. Chapter 1, on epidemiology of obesity, provides proper information on classification of obesity and associated compromised health consequences. The prevalence of adult and childhood obesity in the world is highest in countries with a Western food pattern and lifestyle, and the lowest in poor, developing countries. In Western countries, obesity seems to be more common in groups of the population with relatively low socioeconomic status and lifestyle. In chapter 2, Considine reviews human leptin as an adipocyte hormone with weight regulatory and endocrine (metabolic) functions. Mutations in the leptin or leptin receptor genes results in no leptin, which is associated with hyperphagia, morbid obesity, and cold intolerance. Leptin promotes weight loss, lowers insulin and glucose, and inhibits food intake (satiety control). Hexosamine biosynthesis is the link between glucose metabolism and leptin production. Leptin levels are higher in women than in men, mainly because estradiol stimulates and testosterone inhibits leptin production in human abdominal adipose tissue. Obesity is associated with increased leptin levels, increased leptin gene expression in adipocytes, and resistance to weight-reducing activity of leptin (leptin resistance). Weight loss (by relative starvation) results in decreased adipose mass and decreased leptin levels. Leptin has several other metabolic effects: it enhances platelet activation/aggregation, increases nitro-oxide (NO) synthesis by endothelial cells, increases endothelin, stimulates angiogenesis and hematopoiesis, and influences insulin action in target tissues. In chapter 3, Douketis and Sharma shed some light on the relation between obesity and cardiovascular disease (CVD). A body mass index (BMI) above 30 has emerged as an important independent but modifiable risk factor for CVD. People with an abdominal (or central) pattern of obesity are at higher risk of developing the metabolic syndrome. Above the age of 65 years, there is no significant association between BMI and CVD, but an increased waist-to-hip ratio (WHR), indicative of abdominal obesity, has a threefold relative risk for CVD. Mechanisms for the association of obesity and CVD are the metabolic syndrome–related hypertension, hyperlipidemia, insulin resistance, diabetes, and components produced or expressed by adipocytes including leptin, adiponectin, TNFa, and components of the renin–angiotensin system. The relation between obesity and stroke is weak, but between central obesity (increasedWHR) and stroke the correlation is much stronger. In the NHANES I study, the population attributable risk of developing heart failure as a result of obesity was 8%, diabetes 3%, hypertension 10%, and coronary artery disease 62%. An association between peripheral artery disease and BMI is unclear. Increased BMI is associated with an increased risk on venous thrombo-embolic complications, in particular in those who had a waist circumference above 95 cm. Clinically important weight loss of 5–10% of baseline weight or 5–10 kg is associated with an improvement of lipid levels, glycemic control, hypertension control, and reduced risk of diabetes and CVD. Prospective studies in obese patients demonstrate that pharmacological weight-reduction therapy combined with dietary and lifestyle interventions is associated with a 5–10-kg weight loss over a few years. A large prospective study on the effect of surgical weight-loss intervention versus usual care on long-term morbidity and mortality is ongoing. In Chapter 4, the role of dietary fat in obesity is elucidated by Astrup. A 6% point reduction in dietary fat in conjunction with increased intake of fish, fruit, vegetables, and nuts is associated with weight loss of 4 kg over 1 year and a reduction of cardiovascular events and mortality of 40%. Dietary intervention should focus on a combination of fat reduction and an increase of whole-grain and fiber-rich food and the replacement of sugar-sweetened soft drinks and fruit juices by mineral water. Monounsaturated fats (MUFAs) and adiposity are positively related, though polyunsaturated fat is weakly related, to obesity. Body weight and insulin resistance are increased in a high-MUFA diet compared with in fat-reduced diets. A diet rich in safflower oil (PUFA) accumulates less body fat than a diet rich in beef