**4.3 Noncompliant cardiovascular system as a cause of preeclampsia**

In preeclampsia there may be an impaired vasodilator response to endotheliumdependent agonists such as acetylcholine and bradykinin (**Figure 7**). Various adaptive mechanisms are employed at the fetomaternal interphase, and subsequently after 20 weeks, a clinically evident maternal syndrome of hypertension, edema, and proteinuria develops. The development of second stage of late vascular dysfunction can also happen independent of first stage. The uterine artery Doppler waveform becomes transformed into a high flow with low resistance at 22–24 weeks in normal gestation. However, in preeclampsia there is a latent preclinical stage with impaired intravascular volume expansion, hyperdynamic circulation, and a decreased cardiac output as clinical disease develops. This decreased cardiac output leads to renal and uteroplacental insufficiency. There may also be leaky capillaries leading to pulmonary and cerebral edema. Severe and early-onset preeclampsia has abnormal uterine artery waveform in preclinical stage and hypertension in clinical stage. Abnormal Doppler of uterine artery may be considered as a local noninvasive imaging of a more generalized systemic vasculopathy. This may mediate further cardiovascular risks. Women with preeclampsia are also two and a half times likely to die from ischemic heart disease in later life [27–29]. Several studies have been conducted showing preeclampsia association with the high pulsatility index of uterine artery.

Raised uterine artery impedance is a marker of early endothelial dysfunction. It is associated with increased aortic pulse wave velocity and augmentation index in the first trimester of pregnancy that is the marker of future cardiovascular risk [30–32]. Increased homocysteine levels have also been implicated in both cardiovascular risks and preeclampsia [33].
