Cardiovascular origins of Preeclampsia

Abstract

Preeclampsia is the leading cause of maternal mortality in industrialized countries, accounting for 42% of maternal deaths and 25% of overall neonatal morbidity. The definition of the disease is seemingly straightforward: the new onset of hypertension and proteinuria after 20 weeks of gestation. However, it is well known that the simplicity of this arbitrary definition does not reflect the complexity of the multisystem disorder. It has been shown recently that angiogenic and antiangiogenic factors have the highest accuracy in predicting pregnancy complications associated with preeclampsia in singletons and twins presenting with signs and symptoms for preeclampsia in the second and third trimester. Despite these advances, the pathophysiology of preeclampsia is still largely unresolved, being labelled a “disease of theories”. According to the two-stage theory of preeclampsia, the maternal syndrome, hypertension and proteinuria, constitutes the end-stage of a pathogenetic cascade beginning in the first trimester. The initial pathognomonic lesion, a failure in trophoblast invasion, is localized in the placenta. It has been proposed that placental dysfunction disorders such as early onset PE comprise a disease entity, which is more or less distinct from late onset PE.26 The latter has been attributed as “maternal” preeclampsia, while the first has been dubbed as “fetal” preeclampsia. We propose that this dichotomy is rather simplistic. It has been shown previously that women with a history of preeclampsia have an increased for cardiovascular diseases in later life. The prevalence of hypertension in women with previous preeclampsia is approximately 50% at an average of 14 years after pregnancy, which is 3–4 times the risk found in women without preeclampsia. Large epidemiologic studies have shown that the onset of the disease constitutes an important factor of cardiovascular mortality in later life. From public health perspective, cardiovascular disease due to preeclampsia constitutes a major burden. Recent studies focussing on the role of maternal cardiovascular adaptation to pregnancy might potentially change our perception of the maternal cardiovascular changes in normal pregnancy. Triggered by the known fact that women with a history of preeclampsia have a higher incidence of cardiovascular morbidity and mortality in later life, prospective studies have been initiated to further elucidate the role of cardiac function in hypertensive pregnancy diseases. The results of these studies have shed a light on firstly the extent of cardiovascular dysfunction in pregnancy and secondly the impact on long-term cardiovascular morbidity in later life. But most of all, thirdly, these new data haven given insights in the cardiovascular adaptations to pregnancy and thus the etiology of preeclampsia. In this talk, the recent understandings of maternal cardiovascular adaptation to pregnancy and its failure in preeclampsia are to be reviewed. The recent findings of our group on cardiac function in preeclampsia have confirmed and improved existing literature on cardiovascular adaptation of the maternal organism to pregnancy. With the introduction of up to date methods such as Tissue Doppler as well as the normalization of indices according to cardiological standards, we were able to clarify the central role of cardiac dysfunction for the pathogenesis of preeclampsia.