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.