INTRODUCTION
Chronic hypertension (CH) complicates 1-2% of pregnancies and represents one of the most significant risk factors for the development of preeclampsia (PE).1 We have proposed that women with CH fall into four categories in relation to their first trimester blood pressure (BP) control. Group 1 includes women without a preceding history of CH presenting with BP of ≥140/90mmHg. Groups 2-4 have pre-pregnancy CH; in group 2 the BP is <140/90mmHg without antihypertensive medication, in group 3 the BP is <140/90mmHg with antihypertensive medication and in group 4 the BP is ≥140/90mmHg despite antihypertensive medication.2 We have previously demonstrated that, across these four groups, the prevalence of superimposed PE is not uniformly distributed with group 4 having the highest rate of 27% compared to only 13% for group 1.2 We hypothesised that this stratification reflects the severity of endothelial disease in women with CH.
The pathophysiology of PE is thought to involve a tendency towards an anti-angiogenic state.3 Utero-placental hypoxia in pregnancies destined to develop PE plays an important role in shifting the production in favour of the anti-angiogenic soluble fms like tyrosine kinase-1 (sFLT-1) at the expense of a reduction in the pro-angiogenic placental growth factor (PLGF).4 This has lead to considerable interest in their ability to predict PE, with PLGF already being incorporated into screening algorithms.5-7 However, it has been demonstrated both outside and in pregnancy that differences in the levels of angiogenic factors exist in patients with CH.8, 9 This could impact upon the predictive performance of PLGF and sFLT-1 and requires further clarification prior to their incorporation into screening models.
Outside of pregnancy, the pathophysiology of CH involves a coordinated interaction between the endothelium and circulating inflammatory mediators that include interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α).10, 11 TNF-α promotes both the endothelial expression of vascular cell adhesion molecule (VCAM)10, an early event in the development of the atherosclerotic plaque, and the production of endothelin, a potent vasoconstrictor.12 TNF-α, VCAM and endothelin all induce the production of IL-610, 13, which through its effects on vascular remodelling, contributes to the chronic elevation of BP.11 Thus, these inflammatory mediators, as markers of endothelial dysfunction outside of pregnancy, have been identified as possible biomarkers, in addition to angiogenic factors, for the prediction of PE.
Our objective was to examine differences in angiogenic and inflammatory factors in women with CH at 11+0-13+6 weeks according to BP control.