Vascular damage and dysfunction in hypertensive emergencies

In Part I of this thesis we aimed to quantify the excess mortality risk in patients with a history of malignant hypertension and to investigate whether traditional cardiovascular risk factors contribute to excess mortality in these patients by comparing them with age, sex and ethnicity matched controls from the same area of residence. Our second aim was to assess the long term renal outcome and its predictors in patients with malignant hypertension. Although renal function may recover after the acute phase of malignant hypertension, little data exist on the long term renal prognosis. Thirdly, presence of grade III or IV hypertensive retinopathy has been shown to coincide with disturbed cerebral autoregulation, and is considered to distinguish hypertensive encephalopathy from other causes of encephalopathy. However, several case-reports suggested that grade III or IV hypertensive retinopathy may be absent in patients with hypertensive encephalopathy. We aimed to assess the frequency of grade III and IV hypertensive retinopathy in a relatively large series of patients with hypertensive encephalopathy.
The principal aim of Part II of this thesis was to investigate the mechanisms by which VEGF inhibition leads to BP elevation. To this end we aimed to assess whether alterations in glycocalyx composition contribute to sFLT-1-induced BP elevation and whether sFLT-1 induces changes in sphingolipid metabolism that subsequently contribute to hypertension and proteinuria in women with pre-eclampsia. A secondary aim was to investigate whether a recently developed technique for non-invasive real-time glycocalyx volume estimation could be used for assessment of the microcirculation in pregnant women with and without pre-eclampsia.