Paliz Nordlöf Callbo: Preeclampsia - in light of the cardiovascular system

Abstract

Preeclampsia affects 2–8% of all pregnancies worldwide. This multi-system disorder, increases the risk of adverse pregnancy outcomes, maternal death, and adverse short- and long-term consequences for the women and infants. Impaired cardiovascular adaptations to pregnancy may contribute to preeclampsia. These women run an elevated risk of future cardiovascular disease (CVD). The mechanisms connecting adverse cardiovascular adaptions, preeclampsia, and CVD remain unclear. To address the rising CVD prevalence in women, identification of sex-specific pathways is needed, particularly in women with prior preeclampsia.

This thesis explores the pathophysiological and predictive role of cardiovascular biomarkers before preeclampsia and preeclampsia´s impact on long-term CVD, using proteomics and register-based data.

In Papers I and II, 92 cardiovascular plasma proteins were analysed. In Paper I, machine learning approach identified Matrix metalloproteinase (MMP)-12 as a novel biomarker for subsequent preeclampsia, including early- and late-onset preeclampsia. In Paper II pathophysiological pathways were explored by comparing cardiovascular proteins in women with subsequent preeclampsia, small for gestational age (SGA) birth, or combined outcomes, with normotensive pregnancies. Only subsequent preeclampsia, was associated with dysregulation of several cardiovascular biomarkers. All outcomes were associated with MMP-12 and placental growth factor (PlGF).

In Paper III, the risk of future CVD in multi-fetal pregnancies complicated by preeclampsia was assessed by adjusted Cox proportional hazard models, comparing them to normotensive singleton pregnancies. Multi-fetal pregnancies complicated by preeclampsia were not associated with increased long-term CVD-risk as observed in singleton pregnancies with preeclampsia.

In Paper IV, a regression model assessed cardiovascular risk factors at the first-time myocardial infarction (MI), comparing women with to without prior pregnancy-induced hypertensive disorders (PIH). Chronic hypertension and elevated body mass index were more prevalent and smoking less prevalent, in those with prior PIH.

In conclusion, analysing cardiovascular biomarkers revealed MMP-12 as a promising predictive cardiovascular biomarker for preeclampsia, and dysregulation of the cardiovascular system specifically in women with subsequent preeclampsia. Women with multi-fetal pregnancies and preeclampsia lack the increased long-term CVD risk observed in corresponding singleton pregnancies, indicating different pathways to preeclampsia. The strong association between chronic hypertension and prior PIH at first MI, indicates its key role in their elevated MI-risk.