National Heart Research Institute Singapore, National Heart Centre Singapore, 5 Hospital Drive, Singapore, 169609, Singapore.
Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, 8 College Road, Singapore, 169857, Singapore.
Curr Heart Fail Rep. 2022 Jun;19(3):63-74. doi: 10.1007/s11897-022-00546-1. Epub 2022 Apr 11.
Heart failure with preserved ejection fraction (HFpEF) is a leading cause of morbidity and mortality. The current mechanistic paradigm supports a comorbidity-driven systemic proinflammatory state that evokes microvascular and myocardial dysfunction. Crucially, diabetes and obesity are frequently prevalent in HFpEF patients; as such, we review the involvement of a metabolic-inflammatory circuit in disease pathogenesis.
Experimental models of diastolic dysfunction and genuine models of HFpEF have facilitated discovery of underlying drivers of HFpEF, where metabolic derangement and systemic inflammation appear to be central components of disease pathophysiology. Despite a shared phenotype among these models, molecular signatures differ depending on type and combination of comorbidities present. Inflammation, oxidative stress, hypertension, and metabolic derangements have been positioned as therapeutic targets to suppress the metabolic-inflammatory circuit in HFpEF. However, the stratification of unique patient phenogroups within the collective HFpEF subgroup argues for specific interventions for distinct phenogroups.
射血分数保留的心力衰竭（HFpEF）是发病率和死亡率的主要原因。目前的机械论范式支持一种由合并症驱动的全身促炎状态，引起微血管和心肌功能障碍。至关重要的是，糖尿病和肥胖症在 HFpEF 患者中经常普遍存在；因此，我们回顾了代谢-炎症回路在疾病发病机制中的参与。
舒张功能障碍的实验模型和真正的 HFpEF 模型促进了 HFpEF 发病机制的潜在驱动因素的发现，其中代谢紊乱和全身炎症似乎是疾病病理生理学的核心组成部分。尽管这些模型具有共同的表型，但根据存在的合并症的类型和组合，分子特征存在差异。炎症、氧化应激、高血压和代谢紊乱已被定位为治疗靶点，以抑制 HFpEF 中的代谢-炎症回路。然而，在 HFpEF 的集体亚组中，独特的患者表型亚组的分层表明需要针对不同表型亚组进行特定干预。
