Heart failure, platelet activation and inhibition of the renin-angiotensin-aldosterone system.

Heart failure is a highly prevalent disease in aging western populations, associated with a substantially increased risk of thromboembolic events, not only in severe but even in mild to moderate stages. This can partly be attributed to concomitant atrial fibrillation, a well-known risk factor for stroke, as well as a "hypercoagulable state" including formation of intraventricular thrombi. Left ventricular dysfunction results in decreased cardiac output, pulmonary congestion and neurohumoral activation with marked stimulation of the renin-angiotensin-aldosterone system. Besides its contribution to progressive left ventricular remodelling, activation of the renin-angiotensin-aldosterone system is enhanced in the development of vascular endothelial dysfunction in heart failure, resulting in decreased nitric oxide bioavailability. Nitric oxide, however, controls vascular tone and inhibits platelet activation. Enhanced platelet activation has recently been described in patients with heart failure in sinus rhythm. This article summarises the potential contribution to platelet activation of vascular endothelial dysfunction and reduced formation of the platelet inhibitor nitric oxide, which increase further the risk for thromboembolic events in heart failure. Beneficial modulation of cardiac remodelling, left ventricular function, neurohumoral activation, endothelial dysfunction and platelet activation can be achieved by inhibition of the renin-angiotensin-aldosterone system.