Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of the diagnosed heart failure patients. In contrast to heart failure with reduced ejection fraction (HFrEF), there are currently no approved therapies for reducing mortality of HFpEF patients. In the last two decades several experimental studies have investigated the role of comorbidities in HFpEF, which seem to be highly prevalent and play a crucial role in the pathophysiology and development of this heart failure phenotype.