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.