A Systematic Review of Vascular Structure and Function in Pre-eclampsia: Non-invasive Assessment and Mechanistic Links

Hypertensive disorders of pregnancy, such as pre-eclampsia, are known to be independently associated with the development of premature cardiovascular disease (CVD) in women. In pre-eclampsia, the placenta secretes excess anti-angiogenic factors into the maternal circulation, leading to widespread endothelial damage, and inflammation. This endothelial damage is evidenced to persist beyond the acute illness. However, whether it is permanent and responsible for the elevated rates of premature CVD seen in this at-risk group remains unclear. A systematic review of the available literature with respect to vascular structure and function prior to, during and after a pregnancy complicated by pre-eclampsia was performed. Studies non-invasively assessing vascular structure using carotid intima-media thickness (CIMT), retinal microvasculature caliber, CT coronary angiogram, or coronary calcium scores were included. Vascular function was assessed using brachial flow-mediated dilation (FMD), pulse wave analysis (PWA), and peripheral arterial tonometry (PAT). In total 59 articles were included (13 CIMT, 5 CTCA/Ca score, five retinal microvasculature, 27 FMD, 7 PAT, and 14 PWV/PWA), consisting of prospective and retrospective cohort, and case-control studies. Change in vascular structure was evidenced with significant increases in CIMT by 73-180 μm greater than that of non-affected women. This is tempered by other studies reporting resolution of structural changes postpartum, highlighting the need for further research. Accelerated coronary calcification and plaque deposition was identified, with greater rates of increased calcium scores and subclinical coronary artery disease shown by CTCA in women with a history of pre-eclampsia at 30 years postpartum. Impaired endothelial function was consistently reported prior to, during and immediately after pregnancy as evidenced by differences in FMD of 1.7-12.2% less than non-affected women, an increase in PWV by 13.2-26%, and reduced retinal microvascular caliber and arterial elasticity indices. The evidence was less conclusive for the persistence of long-term endothelial dysfunction. Understanding the underlying mechanistic links between pre-eclampsia and CVD is a key step to identifying targeted therapies aimed at "repairing the endothelium" and attenuating risk. This review has highlighted the need for a greater understanding of vascular structure and function following pre-eclampsia through high quality studies with large sample sizes, particularly in the longer postpartum period when clinical CVD disease starts to manifest.