Obesity and heart failure with preserved ejection fraction

Heart failure (HF) can occur in the presence of normal pump function or preserved left ventricular ejection fraction (HFpEF). The prevalence of HFpEF continues to increase in the developed world because of the increasing prevalence of common risk factors, including older age, female sex, hypertension, metabolic syndrome, renal dysfunction and obesity. Obesityrelated HFpEF is an important phenotype present in the community, especially in people with metabolic disorders such as dyslipidemia and diabetes. They exhibit a marked expansion of plasma volume, but ventricular distensibility is limited, most likely as a result of cardiac microvascular dysfunction with myocardial and pericardial fibrosis. The increase in plasma volume causes a disproportionate increase in cardiac filling pressures, leading to HF, even though systolic ejection is not impaired. This syndrome appears to be related to the overproduction of adipocyte-derived cell-signalling molecules, including aldosterone and neprilysin, together with the increased effects of other adipocytokines. The diagnosis of HFpEF is made by confirming the clinical diagnosis of HF and finding a preserved ejection fraction (>50%) on echocardiography in the absence of significant valve or pericardial disease. Even the risk of HF increases with body mass index (BMI), patients with heart failure with reduced ejection fraction (HFrEF) who are overweight or obese usually have better outcomes than those who are normal weight or underweight. A meta-analysis from the Global Group in Chronic Heart Failure (MAGGIC) included 31 studies, both randomised controlled trials and observational studies revealed a relationship between BMI and mortality in both HFrEF and HFpEF. Another meta-analysis including 22,000 patients who had chronic HF (HFrEF and HFpEF) and follow-up for almost 3 years demonstrated the same outcome. The overweight patients presented with the lowest total and cardiovascular mortality rate compared with those who were normal weight, while underweight patients had the highest mortality rate. From these data, many investigators have tried to explore the mechanisms of the obesity paradox. The reason is related to the inaccuracy of the BMI in characterising the severity of obesity. The World Health Organization (WHO) definitions of obesity imply that individuals with a BMI of 25 kg/m or higher have increased fat mass. However, this implication is not necessarily true. BMI has several limitations because it considers a measurement of heaviness not of body composition. Patients with increased BMImay not necessarily have increased fat mass while normal BMI does not preclude an individual from having increased fat mass. Thus an accurate measurement of body composition, rather than BMI, may play a crucial role in the development and progression of HF (Table 1). When sarcopenia and increasing fat mass are combined this could induce body composition abnormalities, sarcopenia and obesity. Sarcopenic obesity is extremely prevalent and is related to poor outcomes in HF patients. A prospective cohort of studies with a large number of patients demonstrated that sarcopenic obesity had a 24% increased risk for all-cause mortality compared with those patients who had non-sarcopenic obesity. So, identifying patients with sarcopenic obesity as early as possible is a very important thing to do to improve the outcomes of these patients. In this issue of the journal, Campbell et al. report the results of an important study that focused on the threshold BMI and sex-specific waist circumference for the increased risk of HFpEF. The investigators addressed identifying BMI and waist circumference thresholds for the increased incidence of HFpEF that may guide HFpEF prevention strategies. They demonstrated that after a follow-up of 5.6 years in 3842 participants aged 60 years and older with one or more of the following: self-reported treatment for hypertension or diabetes for 2 years or longer; myocardial infarction or other ischaemic or valvular heart disease; irregular