By Julie Reynolds, MD and Laney Poye

As the Foundation often shares, research shows that women with a history of preeclampsia are two to four times more likely to develop cardiovascular disease (CVD). Researchers and patients both ask, “but why?” Some research suggests that women who get preeclampsia may have an underlying reason that hypertension appears during pregnancy. Other research looks at whether preeclampsia itself may cause damage to a patient’s blood vessels.

In this research study, which was conducted by 2021 Vision Grant recipient Dr. Anum Minhas of Johns Hopkins University, researchers looked at preeclampsia patients’ underlying heart function three to six months after delivery. The study asked two questions:

1. Do women with a history of preeclampsia have impaired coronary endothelial function?
2. Do women with a history of preeclampsia continue to have circulating angiotensin II receptor 1 antibodies after delivery?

Impaired coronary endothelial function is a condition in which the inner lining (known as the endothelium) of the major blood vessels that bring blood to your heart does not work properly. The arteries are unable to expand adequately in response to the body’s blood flow needs. This leads to reduced blood flow to the heart. Other research shows that impaired coronary endothelial function may predict CVD – and that therapies to heal the endothelium may be a way to reduce long-term CVD. This condition is often seen in patients with risk factors such as smoking, diabetes, and high cholesterol. This study examined whether patients with a history of preeclampsia also showed impaired coronary endothelial function.

Angiotensin II receptor 1 (AT1) is a protein in the bloodstream that helps to regulate blood pressure by tightening blood vessels, reabsorbs salt and water, and supports cardiovascular remodeling. Angiotensin II receptor 1 antibodies (AT1R-Ab) are another type of protein created by the body’s immune system. AT1R-Ab binds to the same receptors as AT1. Usually, antibodies block receptors; however, AT1R-Ab actually activates the receptor. When this happens, these antibodies cause the blood vessels to mistakenly tighten up.

The authors evaluated cardiac performance in 52 women (29 with and 23 without preeclampsia) who had delivered three to six months before the study. The authors used a noninvasive, MRI-based approach to measure the shape of the coronary artery and blood flow before and after a simple handgrip exercise. The study found that women who previously had preeclampsia had less change in blood flow between the before and after MRI. This suggests that their blood vessels are not expanding like they should, and may be affecting their cardiac output.

The researchers found that women with a history of preeclampsia had:

1. Higher systolic blood pressure readings (134±16 versus 119±16 mm Hg) than the control population.
2. Greater impaired coronary endothelial function,
3. Higher levels of AT1R-Ab in their blood stream.

Significantly, these changes were measured in women three to six months out from their deliveries, when immediate physical changes caused by pregnancy have resolved.

Take home:

This study showed that an immune system protein found in pregnant women with preeclampsia continues to have a negative impact on blood vessel function and blood pressure for at least several months after delivery.

The strength of this study is that the noninvasive approach used by researchers to measure coronary function could help in developing new techniques to measure blood vessel function in women who have had preeclampsia. It also builds off other research into AT1R-Ab to present a possible pathway for why preeclampsia survivors continue to experience CVD after pregnancy. The weakness of the study includes the small sample size (52 patients), and that there may be other unknown factors influencing the outcomes of the study.

What the study does suggest is the importance of timely postpartum follow. While preeclampsia survivors cannot change the fact that they experienced a hypertensive disorder of pregnancy, modifiable risk factors like blood pressure control, diet, and exercise are warranted. Early postpartum treatment could reduce future risk of CVD, including ischemic heart disease and heart failure.

Association of Coronary Endothelial Function and Angiotensin Receptor Autoantibody With Preeclampsia Among Postpartum Women

Citation: Minhas AS, Vaught AJ, Schär M, Soleimani-Fard A, Fedarko N, Bennett W, Darla Esteban M, Zakaria S, Coresh J, Hays AG. Association of Coronary Endothelial Function and Angiotensin Receptor Autoantibody With Preeclampsia Among Postpartum Women. J Am Heart Assoc. 2024 Nov 5;13(21):e035799. doi: 10.1161/JAHA.124.035799. Epub 2024 Oct 18. PMID: 39424423.

LINK: https://www.ahajournals.org/doi/10.1161/JAHA.124.035799