Preeclampsia Linked to Later Stroke Risk, Aspirin May Help

January 03, 2019

Having preeclampsia or other forms of hypertension during pregnancy puts women at increased risk of stroke, which may be mitigated by long-term use of aspirin, a new study suggests.

"Women at high risk of developing preeclampsia are given aspirin during pregnancy and we know this reduces their risk of developing the condition, but the aspirin is usually stopped after delivery. The question remains as to whether aspirin should be continued in these women," lead author Eliza C. Miller, MD, Columbia University Mailman School of Public Health, New York City, commented to Medscape Medical News.

"This study doesn't answer that question, but we show some interesting and thought-provoking findings," she said. "We saw a trend towards benefit of aspirin in women who had experienced hypertension in pregnancy in this study but the effect was not significant in the whole group. However, women in their 40s and 50s saw the most benefit and the effect was significant in this age group. It is possible that the effect gets diluted as women age."

In the younger group (under 60 years), women not on aspirin but with a history of hypertension in pregnancy had a 50% increased risk of stroke compared with women who did not have a history of hypertension during pregnancy, even after adjusting for many other risk factors, the study showed. However, women with a history of hypertension during pregnancy but who took aspirin did not show an increased stroke risk. "It therefore seems like aspirin has a beneficial effect in this group who are at increased risk of stroke in middle age," Miller commented.   

However, she cautioned that because this was an observational study, the data should be considered preliminary. "We cannot make definite recommendations that women who have experienced hypertension during pregnancy should take aspirin for the long-term based on these data, but I think we should take it into consideration when assessing cardiovascular and stroke risk in these women."

The study was published online on December 26 in Neurology.

Miller noted previous studies have suggested that preeclampsia and other types of hypertension in pregnancy increase cardiovascular risk later in life, but this is often ignored when assessing cardiovascular risk.  

"This is an important part of a women's health history, but it often gets forgotten and it is not part of the recommended cardiovascular risk calculation at present," she said. Miller believes that needs to change.     

"People think that when the pregnancy is over the occurrence of preeclampsia or other types of hypertension in pregnancy are not relevant anymore," she said. "It has not been on the neurology radar when assessing stroke risk, but as more women are going into neurology, interest is growing in this area."

She noted that prior studies have not been conducted specifically in the US population, where preeclampsia rates are rising. "We analyzed data from a US study which specifically asked participants about preeclampsia, and previous studies have not focused specifically on stroke, which is what we did here," she added.

Miller says there are two time points when a history of hypertension in pregnancy should be considered. "After delivery, it would be advisable to discuss future risk with these women. They can be told that the fact they had hypertension in pregnancy puts them at increased cardiovascular risk in the future, so they need to be more vigilant about other risk factors.

"And then at middle age, when assessing cardiovascular risk women should be asked about a history of hypertension disorders in pregnancy. If they have experienced this, then it should be a red flag which should be considered together with other risk factors when making the decision on whether or not to give aspirin."

While this alone may not be enough to prescribe aspirin, she noted, "if there were other risk factors and I wasn't sure whether aspirin was justified or not — for example, someone who may have had a transient ischemic attack but isn't sure — then a history of hypertension in pregnancy might push me to prescribe it."

She reminds that use of aspirin is not without risk and is known to be associated with gastrointestinal bleeding. "We didn't look at that in this study," she added. "We did, however, look at hemorrhagic stroke and there didn't appear to be an increased risk of that with aspirin use in this population."

For the study, researchers analyzed data from the California Teachers Study, a prospective cohort study, to investigate whether hypertensive disorders of pregnancy increased long-term stroke risk in women and whether aspirin or statin use modified this risk.

A total of 83,749 women aged 60 years or younger at time of enrollment in 1995 were include in the analysis. They were followed-up prospectively for validated stroke outcomes obtained through linkage with California hospital records through to 2015.

Results showed that 4070 (4.9%) women had a history of hypertension during pregnancy, and women with such a history had an increased risk of all stroke (adjusted hazard ratio [HR], 1.3; 95% CI, 1.2 - 1.4).

There was an interaction between aspirin use and hypertension during pregnancy on risk of stroke before age 60 years: nonusers of aspirin had a higher risk (adjusted HR, 1.5; 95% CI, 1.0 - 2.1) but aspirin users did not (adjusted HR, 0.8; 95% CI, 0.4 - 1.7).

This effect was not seen with statins.

Miller noted that other studies of primary prevention of cardiovascular disease have suggested a benefit of aspirin in women older than 45 years of age, but not in men. "There may be a sex-specific effect, and this group of women with a history of hypertension in pregnancy may account for part of it," she suggests.   

"We don't know if these women who get hypertension during pregnancy were already at increased cardiovascular risk and the pregnancy has just unmasked this or if the pregnancy causes the risk. It might be a bit of both. But it doesn't really matter why it occurs — only that we recognize it as a risk factor for future stroke," she added.

Stroke Prevention Limbo

In an accompanying editorial, Steven K. Feske, MD, Harvard Medical School, Boston, and Cheryl Bushnell, MD, Wake Forest Baptist Health, Winston-Salem, North Carolina, say they "applaud all efforts to understand the importance of hypertension disorders of pregnancy and to identify treatable risk factors that might allow us to go yet lower in the stroke prevention limbo."

They point out that the effect of aspirin in this study is relatively small but would probably have been considerably underestimated for many reasons because of the study design.

They suggest that a randomized trial is unlikely to detect such a small effect, but they recommend that future epidemiologic studies of stroke and cardiovascular disease include hypertension disorders of pregnancy as a potential risk factor.

"The findings here are too preliminary to drive clinical decision making," they conclude. "However, taking the findings of the Women's Health Study into consideration, the use of aspirin for primary prevention in women > 45 years of age is reasonable, increasingly so as they accumulate risk factors."

Miller, Feske, and Bushnell have reported no relevant financial relationships.

Neurology. Published online December 26, 2018. Abstract, Editorial

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