The Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction study (RELAX) (NCT00763867) highlighted that patients with HFpEF and diabetes have elevated levels of endothelin-1 (ET-1), inflammatory markers, and profibrotic indicators, correlating with worse left ventricular diastolic function, increased left ventricular mass, and reduced exercise tolerance compared to non-diabetic HF patients [49,50]. Here, EDN1 is linked to diabetes mellitus.