Preeclampsia is a pregnancy complication widely known for its immediate impact on maternal and fetal health. However, scientific evidence accumulated recently has shown that preeclampsia is also associated with an increased long-term cardiovascular risk in women who have experienced it. Despite this, the mechanisms underlying this elevated risk remain incompletely defined.
Two recent studies conducted by the Perinatal and Women’s Medicine Research Group at the Institut de Recerca Sant Pau (IR Sant Pau) analyze how preeclampsia and angiogenic imbalance during pregnancy are linked to persistent changes in the female cardiovascular and renal systems several years after childbirth.
“In these studies, we aimed to analyze what happens to women’s cardiovascular health various years after a complicated pregnancy,” explains Dr. Pablo García Manau, researcher in the Perinatal and Women’s Medicine Research Group at IR Sant Pau and corresponding author of both articles. “Until now, we knew there was an increased long-term risk, but we lacked data to help us understand which changes persist and in which organs.”
It is well established that women who have had preeclampsia face, in the long term, a higher risk of hypertension, thrombosis, diabetes, kidney disease, and cardiovascular events. Available scientific evidence shows that this increased risk persists for decades and that preeclampsia has its independent prognostic value for a woman’s future health. In fact, previous epidemiological analyses have estimated that each episode of preeclampsia may be associated with an approximately three-year reduction in life expectancy.
One of the key elements in the pathophysiology of preeclampsia is angiogenic imbalance, an alteration in two factors that can impair endothelial function and vascular adaptation. This imbalance can be detected during pregnancy through the sFlt-1/PlGF ratio, even before clinical symptoms appear. However, not all women with this profile develop the disease.
“Pregnancy is a true stress test for a woman’s cardiovascular system,” explains Dr. Pablo García Manau. “Faced with the same biological stress, some women develop clinical manifestations such as preeclampsia and others do not, indicating that they do not all start from the same cardiovascular baseline.”
From this perspective, the two studies conducted at IR Sant Pau complement each other in analyzing which medium-term changes persist after pregnancy, both from a vascular functional standpoint and at the biochemical level. The aim is to advance understanding of the underlying mechanisms behind these differences.
The first article, published in Acta Obstetricia et Gynecologica Scandinavica, evaluated 354 women between three and six years postpartum. Of these, 148 had experienced preeclampsia or fetal growth restriction associated with placental insufficiency, while 206 had no history of these complications. In a subgroup of 249 participants, the sFlt-1/PlGF ratio during pregnancy was also available.
During postpartum follow-up, a noninvasive vascular assessment was performed, including Doppler ultrasound of the ophthalmic artery in both eyes and measurement of carotid intima-media thickness. In the ophthalmic Doppler, the OA-PSV ratio was analyzed, a parameter reflecting peripheral vascular resistance and indirectly assessing arterial elasticity.
“The ophthalmic artery provides a functional measure of the vascular system—that is, how blood vessels respond to the heartbeat,” notes Dr. Pablo García Manau.
The data showed that women with a history of placental insufficiency had significantly higher ratios between the two systolic peaks, indicating greater persistent vascular resistance years after pregnancy. This difference was particularly evident among those who had developed preeclampsia and, within this group, among those who also exhibited angiogenic imbalance during pregnancy.
In the combined analysis, the increase in the OA-PSV ratio was significant only in the group presenting both factors—clinical preeclampsia and angiogenic imbalance—whereas no relevant differences were observed in women with isolated angiogenic imbalance without clinical expression.
By contrast, no significant differences were observed in carotid intima-media thickness among the different groups, either according to obstetric history or angiogenic profile during pregnancy. This parameter measures the thickness of the inner layers of the carotid artery wall and is commonly used as a structural marker of vascular damage and long-term cardiovascular risk.
“Carotid intima-media thickness typically reflects changes that develop over time,” explains Dr. Pablo García Manau. “The absence of differences three to six years after delivery suggests that, at this stage, alterations associated with preeclampsia do not yet manifest as structural changes, but rather at a functional level, in the way vessels adapt to blood flow.”
The second study, published in the Journal of Clinical Medicine, analyzed the biochemical, metabolic, and cardiovascular profiles of 363 women assessed three to six years postpartum, 113 of whom had experienced preeclampsia. Multiple blood and urine parameters were examined, including cardiovascular biomarkers such as high-sensitivity troponin T (hs-TnT) and NT-proBNP, as well as indicators of renal function.
The results indicated that women with a history of preeclampsia had slightly higher concentrations of hs-TnT, indicative of subclinical cardiac stress, compared with those without prior preeclampsia. Although these values were within ranges considered normal and had no direct clinical relevance, the difference was statistically significant.
However, when results were analyzed according to angiogenic profile during pregnancy—regardless of whether clinical preeclampsia developed—a different pattern emerged. Women with an sFlt-1/PlGF ratio ≥38 during pregnancy showed slightly higher follow-up levels of proteinuria, potassium, and lactate dehydrogenase (LDH), along with a somewhat lower leukocyte count.
These variations were more pronounced with increasing degrees of angiogenic imbalance during pregnancy, particularly in the case of proteinuria, which showed a positive association with the sFlt-1/PlGF ratio.
“In women with angiogenic imbalance who do not go on to develop clinical preeclampsia, the heart does not appear to be affected, but we do detect subtle renal changes,” says Dr. Pablo García Manau. “The kidney is highly dependent on the endothelium and particularly sensitive to this type of alteration.”
No significant differences were observed in other cardiovascular biomarkers, such as NT-proBNP, consistent with the fact that the women evaluated did not have heart failure or overt cardiovascular disease at the time of follow-up.
Taken together, both studies suggest that placental dysfunction during pregnancy may be associated with persistent medium-term changes at both the functional and biochemical levels, and that these manifestations are not homogeneous across all women.
“Preeclampsia reveals a preexisting vulnerability and worsens the cardiovascular prognosis of these women,” concludes Dr. Pablo García Manau. “At the same time, we observe that women who do not develop the clinical disease are not completely free of risk.”
These findings are part of the CARDIOMOM study (Cardiovascular Risk Assessment in Young Women After Index Pregnancy with and without Placental Complications), a project at IR Sant Pau that prospectively follows the cardiovascular health of women after pregnancies with and without placental complications. The aim is to identify early risk markers and improve postpartum monitoring and prevention strategies.
“Current cardiovascular risk estimation tools have been developed primarily from data obtained in men,” explains Dr. Pablo García Manau. “Our goal with CARDIOMOM is to generate specific knowledge in women’s cardiovascular health to move toward monitoring and prevention strategies that better reflect women’s realities.”
