The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction by Milton Packer MD instant download

The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction by Milton Packer MD instant download

HYPOTHESIS The paper proposes a novel unifying hypothesis—that heart failure with preserved ejection fraction(HFpEF) arises primarily from the expansion and dysfunctional transformation of visceral adipose tissue, leading to thesecretion of altered suite of signaling molecules (adipokines), which causes systemic inflammation, plasma volumeexpansion, and cardiac hypertrophy and fibrosis.ELEMENTS OF THE FRAMEWORK The framework groups adipokines into 3 domains. Domain I adipokines are cardioprotective molecules but are suppressed in patients with excess adiposity. Domain II adipokines are cardioprotectivemolecules that are up-regulated by adiposity as a compensatory response mechanism. Domain III adipokines, whosesecretion is heightened in adiposity, have proinflammatory, prohypertrophic, profibrotic, and antinatriuretic effects.HFpEF results from an adiposity-driven imbalance that promotes Domain III adipokines but suppresses Domain I adipokines, with Domain II adipokines representing an inadequate counter-regulatory response.KEY LINES OF EVIDENCE 1) Obesity and dietary nutrient excess are the major drivers of experimental HFpEF; 2)changes in visceral adiposity and circulating adipokines are observed years before and predict the diagnosis of HFpEF(but not heart failure with a reduced ejection fraction) in the general community; 3) central obesity or visceral adiposityis present in >95% of patients with HFpEF and tracks with disease severity; 4) obesity and HFpEF exhibit strikingparallelism in their molecular, pathophysiological, and clinical features; 5) characteristic changes in the adipokine profileoccur in parallel in central obesity and heart failure and are correlated with disease severity; 6) adipokines haveestablished effects on cardiac structure and function that can lead to HFpEF; 7) bariatric surgery or drug treatments forHFpEF cause shrinkage of visceral f