Maternal CV Risk After Adverse Pregnancy Outcome Can Last Over 40 Years

Approximately 30% of women have a major pregnancy complication such as preterm delivery, preeclampsia, or gestational diabetes in their reproductive years, which may confer elevated risk for ischemic heart disease that persists for decades, a Swedish national cohort study shows.

Despite the known association of some adverse pregnancy outcomes with higher future maternal risk of ischemic heart disease or traditional CV risk factors, these patients often slip through the cracks, with the long-term risks of pregnancy complications often unmentioned between women and their physicians in routine practice, noted lead author Casey Crump, MD, PhD (Icahn School of Medicine at Mount Sinai, New York, NY).

“The important thing is to recognize that all of these major adverse pregnancy outcomes are important lifelong risk factors for ischemic heart disease,” he said. “These should be considered when evaluating cardiovascular risk because it's an opportunity to identify high-risk women much earlier than with traditional risk factors alone.”

Crump and colleagues’ study of over 2 million women in Sweden, which was published in the BMJ, found that those with one or more adverse pregnancy outcomes had increased risk for CAD out to 46 years, with those who experienced multiple adverse pregnancy outcomes and combinations of certain adverse events having even greater increased risk.

Commenting on the study for TCTMD, Michael C. Honigberg, MD (Massachusetts General Hospital and Harvard Medical School, Boston, MA), said while the reasons behind the association aren’t entirely clear, he believes they reflect shared upstream risk factors.

“Others have speculated that there might be a causal effect of the adverse pregnancy outcome itself on future risk of cardiovascular disease, and it's possible that there is a bidirectional relationship, although how a pregnancy outcome could continue to impart enduring risk 46 years later seems a little bit hard to explain biologically,” Honigberg noted. “So, I think what these associations are actually showing us is that women who experience some of these adverse pregnancy outcomes have inherent genetic or other environmental risk factors that aren’t fully captured by conventional cardiovascular disease risk factors.”

Some Risk Interactions Seen

For the study, Crump and colleagues examined data on 2,195,266 Swedish women (median age 27 years at first delivery) who gave birth between 1973 and 2015.

While some prior studies have looked at the effect of individual adverse pregnancy outcomes on later CV risk, Crump and colleagues looked at five major types: preterm delivery (< 37 weeks gestation), small for gestational age, preeclampsia, other hypertensive disorders of pregnancy, and gestational diabetes.

Among the 30% of women who experienced at least one of the five complications, delivery of a small-for-gestational-age infant was the most common, followed by preterm delivery. Similarly, of the more than 8% of women who had two or more of the five complications, the most common combination was preterm delivery and delivery of a small-for-gestational-age infant.

Over the follow-up period (median 25 years, maximum 46 years), 3.8% of women were diagnosed with ischemic heart disease. The median age at diagnosis was 58 years.

The important thing is to recognize that all of these major adverse pregnancy outcomes are important lifelong risk factors for ischemic heart disease. Casey Crump

After adjustment for other adverse pregnancy outcomes and maternal factors, those who had hypertensive disorders of pregnancy had the greatest risk of a CAD diagnosis in the 10 years after pregnancy (HR 2.09; 95% CI 1.77-2.46), followed by those with preterm delivery (HR 1.72; 95% CI 1.55-1.90), preeclampsia (HR 1.54; 95% CI 1.37-1.72), gestational diabetes (HR 1.30; 95% CI 1.09-1.56), and a small-for-gestational-age infant (HR 1.10; 95% CI 1.00-1.21).

Looking further out from the pregnancy, having a small-for-gestational-age infant was associated with the highest risk of CAD at 10 to 19 years postpartum, and gestational diabetes was associated with the highest risk at 20 to 29 years. For women with longer follow-up, adjusted hazard ratios for CAD decreased but remained elevated compare with those without adverse pregnancy outcomes in the 30- to 46-year follow-up window.

The researchers also looked at interactions between adverse event types, finding that preterm delivery had positive additive interactions with preeclampsia, other hypertensive disorders of pregnancy, and gestational diabetes on CAD diagnosis. Additionally, preeclampsia accounted for significantly more CAD diagnoses in women who also had gestational diabetes, and vice versa.

Crump and colleagues also attempted to adjust for background risk by performing a co-sibling analysis, which found that most of the associations persisted after controlling for shared familial genetic and other environmental factors, although they acknowledge that these types of analyses “do not fully capture genetic risk, and it is possible that underlying genetic pathways may partly explain future risks of adverse pregnancy outcomes and ischemic heart disease or its precursors.”

Increased Awareness Needed

Crump told TCTMD that while the American Heart Association now recommends asking about pregnancy history when evaluating cardiovascular risk in women, “we know that's not consistently done in clinical practice, especially in primary care settings where most women receive their care.” He added that the exciting thing about the new findings “is it provides an opportunity to identify high-risk women potentially much earlier in their life, and then start preventive actions much earlier to hopefully improve their long-term outcomes.”

Even as someone who does research in this space, Honigberg said he recognized that he wasn’t always capturing reproductive history in his own patients, so he added it to his clinical templates as a prompt. Still, he said it’s unclear to many clinicians what they're supposed to do with this information.

“We need clear guidelines, clearer recommendations about how folks can incorporate this history in their clinical care, because if we had that, then [physicians] would be much more likely to ask about it,” he said.

Honigberg added that another glaring issue is that overt CVD risk factors are routinely ignored in younger people, including those who have just given birth and are otherwise healthy.

“The default is to say this is a young person who's at low short-term risk, so we don't have to be quite as aggressive about treating early or subclinical risk factors, and I think that's the wrong approach,” he explained. “We also now have mounting data . . . highlighting that the population with adverse pregnancy outcomes develops subclinical atherosclerosis detectable by CT imaging earlier than women with normotensive or uncomplicated pregnancies.”

Honigberg said those women may represent a prime population to employ early coronary artery calcium testing to look for premature development of subclinical atherosclerosis and begin early initiation of preventive therapies like statins.

Finally, a remaining issue that needs to be addressed is best practices for intervening soon after pregnancy for women who have had an adverse pregnancy outcome, knowing that it is a time of increased stress and too little self-care.

“We need to be thinking a little bit creatively about how care delivery systems can be optimized for when women are most receptive and able to incorporate education and lifestyle modification into their lives,” he added.