The findings of this study demonstrate that in women destined to develop PE, during the second-trimester of pregnancy there is an increase in maternal arterial stiffness as assessed by PWV of the carotid-femoral and carotid-radial parts of the arterial tree. The magnitude of the PWV increase of about 17% is similar to that reported in women with established PE 
and although small, is likely to be clinically significant considering the fact that aortic PWV increases by only ~6% per decade in healthy individuals 
Overall, women with impaired placentation, as detected by Doppler examination of the uterine arteries, had increased arterial stiffness (PWV) suggesting that women at risk of developing PE have a high resistance circulation affecting different vascular beds including the fetoplacental unit and the maternal conduit arteries. It is likely that other, multiple factors such as maternal genetic susceptibility will eventually determine which women will develop PE. Mean uterine artery PI was a significant independent predictor of PWV but despite that, PWV was still increased in women who subsequently developed PE implying that this vascular index provides additional information regarding the maternal cardiovascular adaptation to pregnancy over and above the Doppler examination of the uterine arteries.
The increased maternal arterial stiffness in women destined to develop PE may be related to the aberrant maternal physiological and biochemical adaptation to pregnancy that these women demonstrate. Maternal endothelial dysfunction, as assessed by flow-mediated dilatation of the brachial artery 
, increased levels of asymmetric dimethyl-arginine, an endogenous inhibitor of nitric oxide synthase 
, elevated concentrations of homocysteine and marked insulin resistance are all features of the pre-clinical state of PE 
and have also been shown to be associated with increased arterial stiffness 
. However, it is uncertain whether all these factors including maternal arterial stiffness are the cause or the phenotypic expression of the already existing underlying pathophysiological mechanisms of PE. Only studies in women prior, during and following pregnancy will be able to address this question.
Previous studies have shown that in non-pregnant populations increased PWV is predictive of cardiovascular mortality 
. Furthermore, studies in women with established and previous history of PE have shown increased maternal arterial stiffness, as assessed by PWV 
. Our study, which is the first to assess maternal PWV prior to the clinical manifestation of PE, is also consistent with the above findings. Consequently, it could be hypothesised that increased arterial stiffness, as assessed by PWV, provides a plausible link between the development of PE in the index pregnancy and the increased propensity to cardiovascular events that these women experience later on in life 
. Only studies assessing maternal arterial stiffness prior to, during and many years following a pregnancy complicated by PE can confirm the above concept.
In addition to increased arterial stiffness, women who subsequently developed PE demonstrated increased peripheral and central BP. Studies in non-pregnant hypertensive patients have shown that central and peripheral BP are not synonymous and antihypertensive agents can exert differential effects on the two types of BP 
. In patients with end-stage renal disease, central aortic pulse pressure was of greater predictive value for cardiovascular outcomes than brachial pulse pressure 
. Previous studies assessing peripheral BP have reported that in women destined to develop PE, the BP is higher than in the non-PE group both during the second but also in the first-trimester of pregnancy 
. It would be interesting to investigate the extent to which the prediction of PE can be improved by the measurement of central rather than peripheral BP.
In contrast to PWV, there were no significant differences in the AIx between the PE and non-PE groups. This is compatible with the results of our previous study in women with established PE where there was an increase in PWV but not in AIx 
. However, it is in contrast with other studies that suggested that AIx is elevated in women with established PE 
and one study that suggested that AIx could be used as a first trimester predictor of PE 
. Augmentation index provides an indirect measure of arterial stiffness and in both healthy individuals and in those with a disease such as hypercholesterolemia 
and essential hypertension 
, there is usually an association between PWV and AIx. However, AIx depends on the intensity of the reflected wave and as such it will depend on the diameter and elasticity of the small muscular arteries/arterioles at the major sites of pressure wave reflection. Therefore, alterations in muscular smooth muscle tone affecting mainly the small muscular arteries but not the elastic aorta might influence reflected wave intensity and hence AIx independently of PWV. In accordance to this, administration of vasoactive substances will affect AIx and PWV differently 
. Furthermore, the dissociation between PWV and AIx observed in our study has also been described in individuals with metabolic syndrome 
, a condition that is also present in a number of women who develop PE 
The aim of the current study was to investigate the maternal cardiovascular adaptation and in particular arterial stiffness in women destined to develop PE and not to assess whether arterial stiffness indices could be used as predictors of PE development. Therefore, we did not attempt to create predictive models and receiver-operating characteristics curve analysis. Furthermore, this was a cross-sectional study and as such we cannot comment on the longitudinal changes of maternal arterial stiffness during pregnancy complicated by PE. However, our results should encourage further research, involving larger number of women, to establish the predictive value of PWV in PE development and its use in patient's management.
The study demonstrated significant maternal hemodynamic/arterial stiffness differences between women destined to develop PE and those did not. The extent to which arterial stiffness is useful in screening for PE in unselected and high risk populations remains to be determined.