Heart failure with preserved ejection fraction (HFpEF) appears to develop as a result of changes in the biology of a person's internal fat tissue, according to the Adipokine Hypothesis, a new way of understanding how fat may impact the heart.
"Up to now, there has been no unifying hypothesis to explain HFpEF. That has resulted in significant misunderstanding and a lack of direction in both diagnosis and therapy," said Milton Packer, MD, FACC, Distinguished Scholar in Cardiovascular Science at Baylor University Medical Center（达拉斯贝勒大学医学中心） and Visiting Professor at Imperial College（伦敦帝国理工学院）.
HFpEF is the most common type of heart failure, affecting nearly 4 million people in the United States and 32 million globally. With HFpEF, the heart's muscle becomes stiff, unable to accommodate incoming blood properly. This causes cardiac overfilling, elevated internal pressures, exertional dyspnea（劳力性呼吸困难）, and fluid accumulation in the lungs, abdomen or legs.
Adipokines（脂肪因子）, signaling molecules released by fat tissue, exhibit functional transformation in patients with excess visceral fat. In healthy individuals, these molecules protect the heart and kidneys by reducing stress and inflammation while maintaining sodium-fluid balance. However, pathological adipose tissue produces pro-inflammatory adipokines that promote cardiac fibrosis and dysfunction.
Experimental studies demonstrate that effective HFpEF treatment should target fat tissue rather than the heart itself. GLP-1 receptor agonists（GLP-1受体激动剂） including semaglutide（司美格鲁肽） and tirzepatide（替泽帕肽） show therapeutic potential by modulating adipokine secretion profiles.
Clinicians should prioritize waist-to-height ratio measurements（腰高比测量） over BMI（体质指数） for risk assessment. A ratio exceeding 0.5 (waist circumference over half the height) indicates significant visceral adiposity and HFpEF risk, even with normal BMI. Packer emphasized: "Many patients misattribute exertional dyspnea to obesity when it actually signals treatable HFpEF."
This research builds upon Packer's seminal 1993 neurohormonal hypothesis（神经激素假说） for reduced ejection fraction heart failure. The current Adipokine Hypothesis paper is published in JACC, accompanied by two companion studies on eicosanoid adipokines and adipoexosomal microRNAs in JACC: Heart Failure.
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