Obese Heart Failure With Preserved Ejection Fraction Phenotype
From Pariah to Central Player
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- diastolic function
- exercise intolerance
- heart failure with preserved ejection fraction
Article, see p 6
There has long been deep-seated suspicion that patients presenting with signs and symptoms of heart failure with preserved ejection fraction (HFpEF) who were also obese didn’t really have HF but instead were merely obese, deconditioned, and misdiagnosed. Increased body mass index (BMI) has even been a common exclusion criterion in past and ongoing large clinical HFpEF trials.1 However, it has become increasingly difficult to ignore obese HFpEF. In the United States, >80% of patients with HFpEF are overweight or obese, more than twice the general population.1,2 Even before the recent obesity epidemic, the population attributable risk for HF because of obesity was nearly as great as for hypertension.3 However, hypertension has received far more attention as a causative agent for HFpEF than obesity, which has been treated largely as a pariah. Indeed, all large clinical trials to date have utilized medications that had antihypertensive properties and yet were neutral on their primary outcomes. This disappointing experience suggests it may be worthwhile to finally examine what we can learn regarding the role of obesity in HFpEF.
There have been 2 key barriers to embracing the obese HFpEF phenotype. Because of mechanisms not fully understood, natriuretic peptide levels are much lower in obese than nonobese patients with definitively documented HFpEF and are frequently below standard diagnostic cut-points. There also seemed to be relative lack of obvious mechanisms whereby excess adipose could cause HFpEF. However, in reality, numerous pathophysiological links exist between obesity and HFpEF. Increased adiposity promotes inflammation, hypertension, insulin resistance, and dyslipidemia and also impairs diastolic, systolic, arterial, skeletal muscle, and physical function,1,4,5 all of which are abnormal in HFpEF and contribute to its pathophysiology. Furthermore, reducing excess adipose tissue prevents development of HF and improves established …