Long‐Term Postpartum Cardiac Function and Its Association With Preeclampsia

Abstract

Background Preeclampsia is a prominent risk factor for long‐term development of cardiovascular disease. Although existing studies report a strong correlation between preeclampsia and heart failure, the underlying mechanisms are poorly understood. One possibility is the glycoprotein growth factor activin A. During pregnancy, elevated activin A levels are associated with impaired cardiac global longitudinal strain at 1 year, but whether these changes persist beyond 1 year is not known. We hypothesized that activin A levels would remain increased more than 1 year after a preeclamptic pregnancy and correlate with impaired cardiac function. Methods and Results To test our hypothesis, we performed echocardiograms and measured activin A levels in women approximately 10 years after an uncomplicated pregnancy (n=25) or a pregnancy complicated by preeclampsia (n=21). Compared with women with a previously normal pregnancy, women with preeclampsia had worse global longitudinal strain (−18.3% versus −21.3%, P =0.001), left ventricular posterior wall thickness (0.91 mm versus 0.80 mm, P =0.003), and interventricular septal thickness (0.96 mm versus 0.81 mm, P =0.0002). Women with preeclampsia also had higher levels of activin A (0.52 versus 0.37 ng/mL, P =0.02) and activin/follistatin‐like 3 ratio (0.03 versus 0.02, P =0.04). In a multivariable model, the relationship between activin A levels and worsening global longitudinal strain persisted after adjusting for age at enrollment, mean arterial pressure, race, and body mass index ( P =0.003). Conclusions Our findings suggest that both activin A levels and global longitudinal strain are elevated 10 years after a pregnancy complicated by preeclampsia. Future studies are needed to better understand the relationship between preeclampsia, activin A, and long‐term cardiac function.

Defective Uteroplacental Vascular Remodeling in Preeclampsia: Key Molecular Factors Leading to Long Term Cardiovascular Disease

“…An in vitro study using human umbilical vein endothelial cells (HUVECs) has suggested that activin A up-regulates transcription of endothelial vasoconstrictors such as ET-1 [ 75 ]. Moreover, an elevated activin A level had been reported to be strongly correlated with myocardial dysfunction at 1 year after preeclamptic pregnancy, and a recent follow up study confirmed that the activin A level still remained elevated with impaired cardiac function 10 years after preeclamptic pregnancy, implying its potential use as a tool for monitoring women at risk for postpartum CVD [ 76 , 77 ].…”

Pregnancy Complications Lead to Subclinical Maternal Heart Dysfunction—The Importance and Benefits of Follow-Up Using Speckle Tracking Echocardiography

“…A recent report found that blood pressure variability affects the right ventricle as well [69,70]. Recent data shows that, compared to uncomplicated pregnancies, the ones complicated by preeclampsia affect cardiac function in the long-term, at 10 years post-partum [71]. Moreover, women with early onset preeclampsia showed reduced longterm left ventricular global longitudinal strain associated with a low coronary flow velocity reserve, as a sign of microvascular dysfunction [63] and of higher left ventricular mass [72].…”

Sustained Elevated Circulating Activin A Impairs Global Longitudinal Strain in Pregnant Rats: A Potential Mechanism for Preeclampsia-Related Cardiac Dysfunction

“…These associations between circulating placental-derived factors and cardiac dysfunction remain significant after multivariable adjustment for clinically relevant confounders, including blood pressure [ 21 , 59 , 60 ]. Importantly, while circulating levels of other placental factors are similar between normal pregnancy and PE [ 59 ], activin A levels are comparable at one year postpartum but significantly elevated at approximately 10 years after a pregnancy complicated by PE [ 20 , 21 ]. These clinical data provide strong evidence of a relationship between plasma activin A and a lifelong risk of cardiac dysfunction.…”

“…Indeed, it was found that GLS gradually deteriorates from normotensive pregnancy to gestational hypertension (GH, allegedly without placental compromise) to PE [ 9 , 14 , 15 ], despite comparable blood pressure in these hypertensive groups [ 14 ]. Additionally, GLS remains impaired postpartum even after adjustment for blood pressure and other clinically and biologically relevant variables [ 19 , 20 , 21 ], further supporting a role for placental factors in the development of cardiac dysfunction in PE.…”

“…Moreover, circulating levels of activin A are higher from 10 to 26 weeks of gestation in women who subsequently developed PE [ 33 , 35 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ]. We previously showed that serum activin A levels during the third trimester in normotensive pregnancy, gestational or chronic hypertension, and PE correlate positively with abnormal GLS at one year postpartum [ 21 ] and this relationship persists 10 years after pregnancy [ 20 ]. Earlier studies demonstrated sustained infusion of activin A-induced PE-like features in pregnant mice, including hypertension, proteinuria, preterm birth, and fetal growth restriction [ 51 ].…”