Endothelial dysfunction in cardiovascular disease: risk factor, risk marker, or surrogate end point?

Endothelial dysfunction is a feature of the early stages of atherosclerotic cardiovascular disease. It also is almost invariably associated with recognized cardiovascular risk factors, including those that are irreversible (such as age and family history) and those that are reversible (such as hypertension and hypercholesterolemia). It remains the subject of debate whether endothelial dysfunction can be considered an independent risk factor or, perhaps more plausibly, an intermediate or surrogate end point. However, although the relevance to research into cardiovascular pathophysiology is not in dispute, there remains uncertainty about its relevance as a therapeutic target. Overall, the available evidence suggests that targeting of the conventional major risk factors remains the primary strategy, but an ancillary effect on intermediate end points, such as an improvement or reversal of endothelial dysfunction, constitutes an additional potential benefit.