Prevention of vascular dysfunction after preeclampsia: a potential long-term outcome measure and an emerging goal for treatment

Abstract

Preeclampsia is increasingly being recognised as more than an isolated disease of pregnancy. In particular, preeclampsia has emerged as an independent risk factor for maternal cardiovascular disease and has recently been recognised as a risk factor for cardiovascular disease in children exposed in utero. Preeclampsia and cardiovascular disease may share important pathophysiological and molecular mechanisms and further investigation into these is likely to offer insight into the origins of both conditions. This paper considers the links between cardiovascular disease and preeclampsia and the implication of these findings for refinement of the management of patients whose care is complicated by preeclampsia.

Figure 1

Molecular and vascular mechanisms of endothelial dysfunction in preeclampsia. Defective placentation, a common feature of preeclampsia, triggers a cascade of events including oxidative stress and exaggerated inflammatory reaction and angiogenic imbalance which exacerbate endothelial dysfunction. Impaired endothelial function plays a central role in the clinical manifestations of preeclampsia such as hypertension and proteinuria.

Figure 2

Theoretical timelines of impairment of endothelial function and development of cardiovascular disease following preeclamptic pregnancy. (1) In the normal individuals there is a gradual age-related reduction in endothelial function, which can be exacerbated by the presence of cardiovascular risk factors and associates with the future risk of clinical cardiovascular disease. (2) Women who experience preeclamptic pregnancies are known to have impaired endothelial function during pregnancy and up to 3 years following an affected pregnancy. It is possible that these women begin life with normal endothelial function, which is acutely impaired during a preeclamptic pregnancy. This followed by ongoing age-related decreases in endothelial function may relate to the increased incidence of cardiovascular disease in these individuals. (3) Alternatively, women who develop preeclampsia may have primary endothelial dysfunction which both puts them at risk of preeclampsia, this may then be exacerbated by the preeclamptic pregnancy (solid line), or simply persist (dotted line), in either case leading to higher incidence of cardiovascular disease.