Abstract
The unique pathophysiology of heart failure with a preserved ejection fraction (HF-PEF) and the involvement of hypertension in its development are only poorly understood. The upregulation of the renin-angiotensin-aldosterone system (RAAS) has been identified as a key pathologic pathway contributing to fibrosis, cardiomyocyte abnormalities, inflammation, and endothelial dysfunction, all of which have been implicated in the progression of hypertension to HF-PEF. In addition, pharmacologic inhibition of the RAAS has been shown in animal models of diastolic dysfunction and in clinical trials to reduce these deleterious processes and to improve diastolic function. Despite these data, clinical trials performed with RAAS inhibitors in patients with HF-PEF have failed to demonstrate morbidity and mortality benefits. To date, there is no proven effective therapy specifically for HF-PEF. The deleterious effects of hypertension on mechanisms underlying the development of HF-PEF underscore the importance of effective and early control of hypertension for the prevention of HF-PEF.