Depression and Heart Failure With Preserved Ejection Fraction: An Inflammatory Perspective

Depression is a common comorbidity in patients with heart failure with preserved ejection fraction (HFpEF), suggesting potential epidemiological and pathophysiological connections between these two age-related chronic diseases. Extensive clinical evidence demonstrates that depression is closely associated with both the incidence and prognosis of HFpEF. It is currently believed that depression may contribute to the pathogenesis of HFpEF through various interconnected mechanisms, including intestinal dysfunction, endothelial dysfunction, disturbances in fat and energy metabolism, autonomic nervous system dysfunction, hypothalamic-pituitary-adrenal (HPA) axis imbalance, and sex differences. Both conditions often share common comorbidities and genetic predispositions. Notably, inflammation is implicated in all these mechanisms and processes, playing a key role at different stages and facilitating the interaction between the two diseases during their onset and progression. However, the connections between depression and HFpEF have not yet been systematically and thoroughly elucidated. This review aims to comprehensively summarize the associations between depression and HFpEF, focusing particularly on elucidating their interplay in pathogenesis from an inflammation perspective, with special emphasis on the adverse effects of depression on the development of HFpEF. Additionally, we evaluate the management approaches for patients with comorbid depression and HFpEF, which include both pharmacological and nonpharmacological treatments, highlighting that personalized and integrated interventions may offer significant benefits. The review underscores the importance of increased attention and early identification of patients with comorbid depression and HFpEF and is expected to provide valuable insights and guidance for the clinical management of this significant patient population.