U of A researcher looks at pre-eclampsia as risk factor for cardiovascular disease

Pregnant women who experience a common complication known as pre-eclampsia are twice as likely to develop heart disease and stroke later in life. Amanda de Oliveira, a University of Alberta post-doctoral researcher, is looking at why this is the case.

De Oliveira is pursuing a post-doctoral fellowship in Sandra Davidge‘s laboratory in the department of obstetrics and gynaecology. She is receiving funding through a Banting Postdoctoral Fellowship via the Canadian Institute of Health Research (CIHR).

Pre-eclampsia is a complication associated with pregnancy that can begin around week 20. Symptoms of pre-eclampsia include high blood pressure and excessive levels of proteins in urine, de Oliveira said.

The condition affects five to seven per cent of pregnancies and is one of the leading causes of severe illness. In some cases, it is also the cause of fatal consequences such as death among pregnant women and their babies.

De Oliveira previously completed a PhD studying cardiovascular disease in male and female animal models. She was drawn to examining the differences in cardiovascular disease manifestation in males and females.  

“I was primarily focused on the blood vessels. There are sex differences in the manifestation of cardiovascular disease. A female being exposed to a complicated pregnancy can exacerbate this problem,” de Oliveira said.

Pre-existing conditions and high cholesterol levels increase risk for pre-eclampsia

According to de Oliveira, pre-existing conditions such as obesity and Type 2 diabetes, lipid level imbalances, and advanced maternal age are some of the risk factors for developing pre-eclampsia. Women are also at an increased risk during their first pregnancy, compared to any other pregnancy, de Oliveira said.

With high blood pressure levels being one of the defining features of pre-eclampsia during pregnancy, de Oliveria highlighted the need to test lipid levels in pregnant women. Lipids are fats in the blood that perform several functions throughout the body.

“Right now we know that excessive lipid levels [during] pregnancy [is a risk factor] for the development of pre-eclampsia. But, surprisingly, the maternal lipid profile is not a standard test during pregnancy,” de Oliveira said.

New research shows that pre-eclampsia increases the likelihood of pregnant women developing cardiovascular disease later in life. De Oliveira is “particularly interested in the excessive-high cholesterol levels in pregnancy, which is a risk factor [for pre-eclampsia], but it is still poorly characterized.”

According to de Oliveira, two theories potentially explain the increased likelihood of developing cardiovascular disease later in life in women who experienced pre-eclampsia during pregnancy. 

One potential reason is that “pregnancy is a stress test [that] will reveal pre-existing conditions. The second theory is that pre-eclampsia itself impairs the maternal cardiovascular system,” de Oliveira said. 

More research is needed to inform clinical practice for preventing pre-eclampsia

De Oliveira highlighted the importance of gathering more information to support the development of new clinical guidelines and policies for preventing and managing pre-eclampsia. 

She said that before important clinical and policy implications are introduced, more information on the mechanisms contributing to the development of pre-eclampsia and its impact on life-long cardiovascular health is required.

De Oliveira’s research involves feeding pregnant rats a high-cholesterol diet to mimic increased circulating cholesterol levels in the mother. Researchers are then able to induce pre-eclampsia in the animals.

Currently, there are no treatments for pre-eclampsia except for the delivery of the baby. 

“If you are diagnosed with pre-eclampsia, the only cure would be the delivery of the placenta and the baby,” de Oliveira said.

As for preventative strategies, “if a woman is considered at an increased risk of developing pre-eclampsia, [clinicians may] prescribe Aspirin.”

De Oliveira is exploring the effectiveness of TLR4 deactivation and Aspirin for treating pre-eclampsia

De Oliveira is interested in investigating potential preventative strategies throughout her post-doctoral studies. Firstly, she is studying the role of toll-like receptor 4 (TLR4), an immune system protein, in pre-eclampsia. 

According to de Oliveira, when activated, TLR4 contributes to maternal blood vessel dysfunction. The team will explore whether the deactivation of TLR4 could provide a potential treatment strategy for pre-eclampsia. 

Additionally, de Oliveira is researching the effectiveness of Aspirin, also known as acetylsalicylic acid, for preventing pre-eclampsia. She is most interested in exploring the role of Aspirin in preventing the development of pre-eclampsia in the context of excessive maternal cholesterol levels during pregnancy. 

Aspirin “has been shown to reduce the incidence of pre-eclampsia. It does not work in all cases and we don’t know why,” de Oliveira said. 

For de Oliveira, researching the exact mechanisms that contribute to the risk of developing cardiovascular disease later in life, and those that contribute to potential treatment and preventative strategies, is a large motivator — especially for informing new clinical practice guidelines.