Preeclampsia During Pregnancy Linked With CV Consequences Many Years Later

Pregnant women who experience preeclampsia—a condition marked by high blood pressure and protein in the urine—appear to be particularly vulnerable to developing cardiovascular disease far down the line, according to two new studies.

At 5 years after pregnancy, female patients with a history of the complication are more likely to have comorbidities that put them at higher CV risk, report researchers led by Karlee Hoffman, DO (Allegheny Health Network, Pittsburgh, PA), in an abstract released today ahead of next week’s American College of Cardiology (ACC) 2018 Scientific Session.

Additionally, in separate work, results from the multicenter, prospective CREW-IMAGO study recently showed that 10 to 20 years after preeclampsia women see an uptick in coronary artery calcification (CAC), with nearly half showing signs of plaque on coronary CT angiography (CTA) at ages 45 to 55 years.

“These findings demonstrate that early coronary atherosclerosis precedes the development of subclinical ischemic heart disease in women with previous preeclampsia,” Gerbrand A. Zoet, MD, PhD (University Medical Center Utrecht, the Netherlands), and colleagues write in a research letter published last week in Circulation. “Early identification of these women at high risk may facilitate timely prevention to reduce future CAD events.”

What’s new here, Zoet noted in an email to TCTMD, is the time frame for when cardiovascular repercussions begin to appear. While it was known that women aged 60 and older were at higher risk, he said, “for us it came as a surprise that such a large proportion of women after preeclampsia have subclinical coronary artery disease from 45 years onwards already, while they are still asymptomatic.”

According to vascular neurologist Eliza Miller, MD (Columbia University Medical Center, New York, NY), awareness that preeclampsia can precede stroke or heart disease is still poor among neurologists and cardiologists. “There’s a growing awareness, . . . but this is in its early stages. People are just starting to wake up,” she told TCTMD. “[Nephrologists] have been sounding the alarm for years on this, that there is something really bad going on in preeclampsia.”

Hoffman, a cardiology fellow, also urges clinicians to be more vigilant. “As providers, we’re missing the boat if we’re not adequately following up with these patients on their cardiovascular risk factors,” she said in an ACC press release. “Women are highly motivated to take care of themselves when they are pregnant and after they deliver their babies, so it’s a great time to educate them on long-term cardiovascular risks and potentially intervene with aggressive lifestyle modification.”

Yet as Hoffman noted to TCTMD, cardiologists “most likely are not going to see these young females in the hospital when they’re diagnosed with preeclampsia. . . . Right now, the way that we’re seeing these patients is when they come back when they’re 55, 60 years old [either] because of a strong family history or they had an abnormal stress test.”

For these middle-aged women, it’s important to ask whether they’ve ever been diagnosed with preeclampsia or heart-related complications during pregnancy, she emphasized. “That’s a question I can bet you nobody asks.”

Charting the Timeline

For the first study, Hoffman et al identified 329 patients with preeclampsia treated by the Allegheny Health Network in 2012, collecting data retrospectively by chart review. Mean age at the time of diagnosis was 30 years, and 75% of the women were Caucasian. These patients were matched with 329 controls by age and race, with the preeclampsia group showing higher prevalence of obesity and being more likely to have babies of low birth weight, have a preterm delivery, and experience postdelivery complications.

At 5-year follow-up, the women with prior preeclampsia were more likely to have new-onset diabetes (21.0% vs none), hypertension (32.8% vs 0.3%), and hyperlipidemia (3.0% vs none; P < 0.001 for all comparisons). Multivariate logistic regression analysis identified several factors that appeared to predispose the patients with preeclampsia to developing hypertension: older age at diagnosis, African-American race, and history of diabetes.

CREW-IMAGO looked at a longer time horizon and notably was prospective; it included 164 asymptomatic women (mean age 48.4 years at the time of enrollment) who had experienced preeclampsia 10 to 20 years earlier. Zoet et al compared this population with 387 women of similar age and ethnicity (all were white) without a history of preeclampsia who had taken part in the Multi-Ethnic Study of Atherosclerosis (MESA).

Compared with the MESA population, women who’d had preeclampsia were more likely to have a CAC score above zero (31% vs 18%; RR 1.7; 95% CI 1.2-2.3) or of at least 100 (6% vs 2%; RR 2.8; 95% CI 0.4-19.3) at 10 to 20 years after experiencing the complication. On coronary CTA, 47% of the preeclampsia group had plaque and 4% showed evidence of a significant stenosis ≥ 50%.

“They have done a terrific job of identifying a cohort of women who have really been followed very carefully and closely,” Miller said of the CREW-IMAGO study. “So you can know for sure the timeline of the development of risk.”

The Allegheny Health Network analysis, she added, “is good in pointing out the racial disparities” in preeclampsia, given that earlier research has shown minority women to be at higher risk of developing this complication and of experiencing poor outcomes once they do. In this study, where one-quarter of subjects were non-Caucasian, the average annual incidence of preeclampsia was 10.4% from 2009 to 2015.

Risk Marker or an Active Participant?

Asked by TCTMD whether preeclampsia is in fact the root cause of subsequent cardiovascular disease—or if there might be a shared risk factor for both conditions—Miller called this “the great controversy in preeclampsia.”

There are “two schools of thought,” she explained. “One is that preeclampsia is a marker of women who are at increased risk. That’s sort of the ‘pregnancy stress test’ hypothesis, that they’ve failed their stress test by developing preeclampsia and . . . are then going to go on to be at very high risk later.” The other idea, Miller continued, is that preeclampsia itself causes or contributes to cardiovascular disease “by virtue of this pathophysiological disorder.”

It’s possible that both explanations are true, or that what falls under the blanket of “preeclampsia” could be a variety of diseases, Miller suggested. Regardless, “the point is that people have preeclampsia when they’re young [in their 20s or 30s], far earlier than when risk is ordinarily being detected.” What matters most is that these people are being identified and followed more closely than usual, she stressed.

And while it’s not common practice now, Hoffman said, ideally women who have preeclampsia should receive extra attention to cardiovascular health early on. “When they’re in the hospital and they’re diagnosed with preeclampsia, they should have a touch point with a cardiologist or some type of cardiology consult at that index admission,” she suggested, even if just to make them aware of their heightened long-term risk. But if not, “I think we capture a lot of these patients retrospectively, too, when we see them in the office.”

Another lesson, said Zoet, is that this screening of CV health “should start before the age of 45 years at least, as vascular damage has already occurred by then in a lot of women after preeclampsia.”