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Raising the Awareness of Severe Preeclampsia and Recognizing Potential Long-Term Impacts

SAP Partner | <b>Mayo Clinic</b>

Vesna Garovic, MD, PhD, chair of the nephrology division at Mayo Clinic, discussed the appropriate reaction to data suggesting late-life elevated inflammation and neurovascular damage from severe preeclampsia.

In 2017, Vesna Garovic, MD, PhD, and colleagues published research that investigated the combined effect of both preeclampsia and late-life hypertension. Findings indicated that total gray matters were smaller in women with a history of preeclampsia and late-life hypertension compared with a history of normotensive pregnancy regardless of hypertension status. Additionally, using voxel-based morphometry, findings showed that the volume changes were localized to the posterior brain regions, particularly the occipital lobe gray matter in women with a history of preeclampsia with or without late-life hypertension.1

Garovic, chair of the nephrology division at Mayo Clinic, used that cohort again in an additional study presented at the 2022 Alzheimer’s Association International Conference (AAIC), July 31 to August 4, in San Diego, California. Here, findings showed that severe cases of preeclampsia elevated markers of neuroinflammation and neurovascular damage, while demonstrating increased amyloid-ß concentration. More specifically, severe cases had significantly higher concentration of amyloid-ß carrying extracellular vesicles (P <.003) compared with all groups, and total amyloid-ß compared with mild cases (P = .037).2

Garovic sat down for an interview with NeurologyLive® to discuss the findings, but more importantly, how the clinical community should react to them. She brought up aspects of improving awareness, while also stressing that not everyone is prone to the effects of preeclampsia. She also provided insight on how inflammation is viewed within the community and whether it’s still held with high regard.

NeurologyLive®: Do these findings change the way clinicians treat preeclampsia?

Vesna Garovic, MD, PhD: Despite the increasing body of evidence that preeclampsia has long term effects, not only on cardiovascular risks, but now as we are learning, cognition, it's very important to educate primary care providers about the risks associated with preeclampsia. Also, educate the patients to bring that history to physicians who are taking care of that, because we may not understand exactly what's happening at the molecular level, but there are some other coexisting risk factors that can be effectively treated, such as hypertension, diabetes. We can maybe introduce some lifestyle modifications with respect to optimal body weight or exercise regimen. In other words, if you identify that as the risk factor for cognitive decline, and there are some other risk factors in that context that can be treated better, and according to current guidelines, can give better outcomes. Increasing the awareness of the relevance of preeclampsia when it comes to cognitive decline, I think it's highly relevant.

What are the community’s views on neuroinflammation? Is it still talked about regarding preeclampsia?

When it comes to preeclampsia, inflammation is kind of recognized as one of the possible pathophysiological events when it comes to the pathophysiology of this particular disease. We know that, in general, even normal pregnancy, per se, is pro inflammatory. And it makes sense because we are talking about a woman developing reaction, or getting adjusted, or being immuno-tolerant, to semi-allergenicities. Chances are that a part of the inflammatory response, even in normal pregnancy, is the reaction to send semi-allergenitic features. We know that in preeclampsia, the pro-inflammatory response is further elevated. And we know that even after preeclamptic pregnancy, some of the markers of inflammation may be elevated, such as C reactive protein, TNF-α, and other interleukins that have been known to be associated with inflammation. It's a very interesting angle to approach as to whether or not that the proinflammatory milieu that occurs in preeclampsia that persists throughout the reproductive years ultimately adds to increased risk for cognitive decline. Alternatively, you can argue that women with preeclampsia had proinflammatory milieu prior to their disease that resulted in different disease entities in different times of a woman's life, ie, preeclampsia in reproductive age, and then some cardiovascular and cerebrovascular outcomes later in life, ie, after reproductive age.

Transcript edited for clarity.

REFERENCES
1. Raman MR, Tosakulong N, Zuk S, et al. influence of preeclampsia and late-life hypertension on MRI measures of cortical atrophy. J Hypertens. 2017;35(12)2479-2485. doi:10.1097/HJH. 0000000000001492.
2. Suvokov S, Norby A, Abou-Hassan C, et al. Circulating extracellular vesicles of neurovascular origin are elevated in women with severe preeclampsia years after their affected pregnancies. Presented at: 2022 Alzheimer’s Association International Conference; July 31 to Aug 4; San Diego, CA. 62360