A U-shaped association of body mass index and all-cause mortality in heart failure patients: A dose-response meta-analysis of prospective cohort studies

The prevalence of obesity has increased worldwide and is a source of concern since the negative consequences of obesity start as early as in childhood. The most commonly used anthropometric tool to assess relative weight and classify obesity is the body mass index (BMI); BMI alone shows a U- or a J-shaped association with clinical outcomes and mortality. Such an inverse relationship fuels a controversy in the literature, named the 'obesity paradox', which associates better survival and fewer cardiovascular (CV) events in patients with elevated BMI afflicted with chronic diseases compared to non-obese patients. However, BMI cannot make the distinction between an elevated body weight due to high levels of lean vs. fat body mass. Generally, an excess of body fat (BF) is more frequently associated with metabolic abnormalities than a high level of lean body mass. Another explanation for the paradox is the absence of control for major individual differences in regional BF distribution. Adipose tissue is now considered as a key organ regarding the fate of excess dietary lipids, which may determine whether or not body homeostasis will be maintained (metabolically healthy obesity) or a state of inflammation/insulin resistance will be produced, with deleterious CV consequences. Obesity, particularly visceral obesity, also induces a variety of structural adaptations/alterations in CV structure/function. Adipose tissue can now be considered as an endocrine organ orchestrating crucial interactions with vital organs and tissues such as the brain, the liver, the skeletal muscle, the heart and blood vessels themselves. Thus, the evidence reviewed in this paper suggests that adipose tissue quality/function is as important, if not more so, than its amount in determining the overall health and CV risks of overweight/obesity. © 2013.

Immune activation in patients with chronic heart failure may be secondary to endotoxin (lipopolysaccharide) action. We investigated the hypothesis that altered gut permeability with bacterial translocation and endotoxaemia would be increased in patients with oedema secondary to congestive heart failure. We compared 20 patients who had chronic heart failure with recent-onset peripheral oedema (mean age 64 years [SD 10], New York Heart Association [NYHA] class 3.3 [0.7]), 20 stable non-oedematous patients with chronic heart failure (mean age 63 years [19], NYHA class 2.6 [0.7]), and 14 healthy volunteers (mean age 55 years [16]). Biochemical markers of endotoxaemia, inflammation, and immune activation were measured. Ten patients were studied within 1 week of complete resolution of oedema. Five patients survived longer than 6 months and were restudied again after remaining free of oedema for more than 3 months. Mean endotoxin concentrations were higher in oedematous patients with chronic heart failure than in stable patients with chronic heart failure (0.74 [SD 0.45] vs 0.37 EU/mL [0.23], p=0.0009) and controls (0.46 EU/mL [0.21], p=0.02). Oedematous patients had the highest concentrations of several cytokines. After short-term diuretic treatment, endotoxin concentrations decreased from 0.84 EU/mL [0.49] to 0.45 EU/mL [0.21], p<0.05) but cytokines remained raised. After freedom of oedema for more than 3 months after oedema resolved, endotoxin concentrations remained unchanged from the previous visit (0.49 EU/mL [0.06], p=0.45). Raised concentrations of endotoxin and cytokines are found in patients with chronic heart failure during acute oedematous exacerbation. Intensified diuretic treatment can normalise endotoxin concentrations. Our preliminary findings suggest that endotoxin may trigger immune activation in patients with chronic heart failure during oedematous episodes.