Comparison with existing literature
The similarities in pathophysiology and risk factors shared by uteroplacental insufficiency disorders and cardiovascular disease have prompted the search for treatments of uteroplacental insufficiency with agents used to treat vascular disease. The underlying mechanism of both conditions involves vascular endothelial dysfunction with endothelial inflammation. The American Heart Association included a history of preeclampsia as a risk factor for future cardiovascular disease. This association might relate to the shared risk factors for cardiovascular diseases preceding pregnancy, such as obesity, hypertension, diabetes, and dyslipidaemia or alternatively, to the metabolic and vascular changes that preeclampsia itself induces.
Numerous clinical studies have confirmed the multiple therapeutic benefits resulting from the pleiotropic effects of statins. Statins improve endothelial dysfunction by protecting vascular endothelium and stimulating its regeneration and its angiogenesis. The antioxidant action of statins relates to their antithrombotic and vasodilating activities and inhibition of free radical formation. The anti-inflammatory action of statins results from their impact on the immune response, which is expressed as increased blood level inflammatory markers and mediators. The latter include C-reactive protein, L-, E- and P-selectin, intercellular and vascular adhesion molecule and Hmox-1, which inhibits sFlt-1 and sEng. According to this pathophysiology, statins have been shown to directly improve endothelial dysfunction and angiogenic imbalance in human placenta. Thus, statins may be a promising agent in preventing and treating uteroplacental dysfunction.
The safety profile of statin exposure during pregnancy is not well defined. United States Food and Drug Administration labelling recommends against the use of statins during pregnancy, based on animal data showing teratogenic potential at high doses. Therefore, the current practice encompasses the advice to discontinue statins when trying to conceive. However, subsequent case registries did not demonstrate an association between congenital anomalies and statin exposure. The clinical benefits of statins in individuals with familial hypercholesterolemia or cardiovascular diseases should be considered, together with the growing evidence of statins’ potential benefit in preventing and treating uteroplacental insufficiency-associated disorders. Accordingly, their benefit may fairly overcome their controversial risk.