Angiogenic Factors and Long-Term Cardiovascular Risk in Women That Developed Preeclampsia During Pregnancy

Abstract

Preeclampsia is caused by placental impairment with increased expression of sFlt-1 (soluble fms-like tyrosine kinase 1) and decreased PlGF (placental growth factor); it has been associated with cardiovascular morbidity and mortality later in life, but the underlying mechanism remains unknown. The aim of this study was to determine whether sFlt-1 and PlGF levels during preeclampsia are associated to long-term cardiovascular risk. We prospectively recruited 43 women with previous preeclampsia and 21 controls with uncomplicated pregnancies. Cardiovascular risk assessment ≈12 years later included maternal hemodynamic, cardiac function and structure, biomarker analysis, and carotid-intima thickness evaluation. Women with previous preeclampsia had higher prevalence of hypertensive disorders and dyslipidemia than controls. In addition, they had worse global longitudinal strain, thicker left ventricular septal and posterior walls, more myocardial mass and increased carotid intima-media thickness compared with controls. PlGF during pregnancy correlated positively with high-density lipoprotein ( r =0.341; P =0.006), and negatively with global longitudinal strain ( r =−0.581; P <0.001), carotid intima-media thickness ( r =−0.251; P =0.045), and mean arterial blood pressure ( r =−0.252; P =0.045), when adjusted by study group. sFlt correlated negatively with high-density lipoprotein ( r =−0.372; P =0.002) and apolipoprotein A-1 ( r =−0.257; P =0.040), and positively with carotid intima-media thickness ( r =0.269; P =0.032) and left ventricular posterior wall thickness ( r =0.368; P =0.003). The antiangiogenic state present in preeclampsia is related to greater prevalence of cardiovascular risk factors ≈12 years after delivery. The knowledge of altered angiogenic factors may help detect women with a higher risk for premature cardiovascular disease, who will require earlier follow-up after delivery.

ceRNA Network and Functional Enrichment Analysis of Preeclampsia by Weighted Gene Coexpression Network Analysis

“…If PE progresses to eclampsia, symptoms such as coma, convulsions, and even death may arise. Furthermore, previous studies have revealed that women who have experienced PE during pregnancy have a higher risk for developing hypertension and dyslipidemia in the future than their healthy counterparts [10]. Many epidemiological studies have also revealed that PE has long-term adverse effects on the offspring [11,12].…”

Placental Pathology as a Tool to Identify Women for Postpartum Cardiovascular Risk Screening Following Preeclampsia: A Preliminary Investigation

“…Anti-angiogenic imbalance in the maternal circulation, including elevated soluble Fms-like tyrosine kinase-1 (sFlt-1) and reduced placental growth factor (PlGF), may contribute to lasting cardiovascular dysfunction after PE. Alternations in circulating angiogenic factors during pregnancy are associated with cardiovascular changes including increased blood pressure 6 to 12 years after pregnancy [46,47]. Although angiogenic factor levels significantly drop following delivery, a recent study suggests that angiogenic imbalance may persistent in the postpartum period [48].…”

Cardiac dysfunction and remodeling regulated by anti-angiogenic environment in patients with preeclampsia: the ANGIOCOR prospective cohort study protocol

“…Studies conducted in patients with heart failure and in patients with PE have found a possible common pathophysiological pathway mediated by angiogenic/anti-angiogenic placental markers like PIGF and sFlt-1 [ 42 , 43 ]. Our group has recently shown that 12 years after delivery, lower levels of PlGF in pregnancy affected by PE were are associated with worse maternal hemodynamics (higher BP) and lower high-density lipoprotein cholesterol concentrations and with subclinical myocardial dysfunction (worse global longitudinal strain) and increased carotid intima-media thickness [ 16 ]. The results of this study corroborate that angiogenic imbalance in pregnancies complicated by PE is related to a negative impact in future CV risk, long term after pregnancy.…”

“…This leads to an increase in the sFlt-1/PlGF ratio, which has been described as better predictor for PE severity than either marker alone [ 15 ]. Recently, our group reported an association between angiogenic factors during pregnancy and CV disease 12 years post-partum, suggesting angiogenic factors are important players in PE-associated CV risk later in life [ 16 ].…”