Vascular Biomarkers Predictive of the Progression From Gestational Hypertension to Preeclampsia in Pregnant Women

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Hypertension in pregnancy is defined by PAS ?140 mmHg and/or PAD ? 90 mmHg, mild to moderate hypertension by PAS = 140-159 mmHg and/or PAD = 90-109 mmHg and severe hypertension by PAS ? 160 mmHg and/or PAD ? 110 mmHg. During gestational hypertension (GE) there is no pathologic elevation of proteinur...

Hypertension in pregnancy is defined by PAS ?140 mmHg and/or PAD ? 90 mmHg, mild to moderate hypertension by PAS = 140-159 mmHg and/or PAD = 90-109 mmHg and severe hypertension by PAS ? 160 mmHg and/or PAD ? 110 mmHg. During gestational hypertension (GE) there is no pathologic elevation of proteinuria (after 20 weeks of amenorrhea). Preeclampsia (PE) is defined as high blood pressure (controlled or uncontrolled) associated with proteinuria discovered after the 20th week of amenorrhea. The cause of hypertension during pregnancy and in particular of preeclampsia remains poorly understood. Endothelial dysfunction and abnormal blood levels of several biomarkers are associated with PE, such as: soluble Fms-like- tyrosine kinase 1 (sFlt-1), Placental Growth Factor (PIGF) and Vascular Endothelial Growth Factor (VEGF). VEGF is of particular importance due to its direct vasodilating effect at systemic level through its interaction with nitric oxide (NO). There is a bi-directional regulation between VEGF and NO, which has direct implications for endothelium, capillary permeability and angiogenesis. sFlt-1 (circulating form of VEGF receptor) has the property of neutraliting the growth factors VEGF and PIGF. Inhibition of VEGF has a known biological effect on endothelial function in adults and is believed to be a key factor in explaining elevated blood pressure. This has been demonstrated in patients undergoing anti-angiogenic therapy in combination with chemotherapy. Other biomarkers of preeclampsia are less known and could be involved in pathophysiological mechanisms; mainly hypervolemia, renal dysfunction and activation of inflammation. The progression of gestational hypertension to preeclampsia is difficult to predict; between 15 and 40 % of gestational hypertension cases progress to preeclampsia, suggesting that it is a single worsening disease. Preeclampsia is known to be one of the few diseases in which acute placental abnormalities manifest at the mother's vascular and renal system levels. These abnormalities are attributable to generalized vascular endothelial activation and vasospasm, resulting in hypertension and hypoperfusion of organs. Endothelial dysfunction could be at the origin of gestational hypertension, and subsequently itself contribute to the subsequent development of preeclampsia through an imbalance between pro- and anti-angiogenic factors likely in relation with increased oxidative stress. It is now accepted that angiogenic biomarkers (such as soluble fms-like tyrosine kinase 1, Placenta growth factor and soluble endoglin) contribute to endothelial dysfunction through VEGF antagonizing among others. The dosage of these angiogenic biomarkers in the maternal bloodstream is highly predictive and significantly abnormal from the 23th week of amenorrhea on average, and with a maximum peak between the 32th and 36th week of amenorrhea. Endothelial dysfunction contributes to cardiovascular risk and can be measured by Laser-Doppler technique coupled with transdermal administration of acetylcholine by iontophoresis. This non-invasive technique has been validated and has already been used in models of hypertension, including preeclamptic women. The main objective is to assess whether the alteration of endothelium-dependent vasodilatation in women with gestational hypertension is correlated with the occurrence of preeclampsia later during pregnancy. Endothelium-dependent vasodilation can be achieved by a validated method using Doppler-Laser skin blood flow measurement coupled with transdermal iontophoresis of acetylcholine. The investigators further explore a possible correlation of endothelium dysfunction with other biomarkers of pre-eclampsia endothelial dysfunction and vascular involvement in pregnancy hypertension.

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