CHIP in Endothelial Dysfunction Associated With HEpEF

Heart failure is responsible of 70,000 deaths every year in France. Heart failure can be divided into 2 categories depend on whether the ejection fraction is reduced (HFrEF) or preserved (HFpEF). Most of the treatments efficient in HFrEF are unable to prevent decompensating or reduce mortality associated with HFpEF. HFpEF pathophysiology remains poorly understood, which represents an obstacle to their management and to reduce cardiovascular events they are associated with. Currently, it is admitted that cardiovascular risk factors (CVRF such as aging, female gender, diabetes mellitus, high blood pressure, hypercholesterolemia, obesity) are responsible of a low grade chronic inflammatory state that causes an endothelial dysfunction that contributes to the development of HFpEF. However, not all patients with these CVRF develop HFpEF. Moreover, the mechanisms linking CVRF to inflammation or alteration of cardiomyocyte function by endothelial dysfunction remain unknown. This suggests that it exists a role for another factor that remains to be identified. Clonal Hematopoiesis of Indeterminate Potential (CHIP) result from the acquisition in hematopoietic stem cells of mutations associated with hematological malignancies, in the absence of any hematological disease. This situation initially described with a frequency of \<5% before 60 years and \>20% after 80 years old appears to be more frequent (\>40% of people over 65 years). CHIP are mainly associated with the occurrence of cardiovascular events such as atherothrombosis and heart failure, possibly due to the induction of a chronic inflammation. Because CHIP are very frequent in the elderly and because CHIP are associated with inflammation and cardiovascular events, they could represent the missing link in the pathophysiology sequence that leads to the appearance of endothelial dysfunction and HFpEF development.