CV complications of pregnancy: A call for greater awareness

CV complications during pregnancy pose unique challenges for women and their health care professionals. Although the complications can affect both the mother and the child, adverse pregnancy outcomes such as preeclampsia, gestational hypertension, gestational diabetes and preterm delivery may serve as an indicator for future maternal CV risk.

Whether adverse pregnancy outcomes affect a woman before, during or after pregnancy, it is important to screen and diagnose this female population, then treat to reduce risk for CVD, experts told Cardiology Today.

One such CV complication is preeclampsia, which is diagnosed in 4% of pregnant women in the United States. Women who experience preeclampsia have a three-to eightfold increased risk for developing CVD later in life.

In April, the U.S. Preventive Services Task Force released recommendations on preeclampsia screening, including screening women with BP measurements at every prenatal visit.

“The most important take-home of the recent USPSTF guidelines is that women with preeclampsia require early diagnosis and treatment,” Margo B. Minissian, PhD, ACNP, CLS, AACC, FAHA, nurse scientist, cardiology nurse practitioner, clinical lipid specialist who oversees the Postpartum Heart Health Program at Barbra Streisand Women’s Heart Center at Cedars-Sinai Heart Institute, told Cardiology Today. “What’s currently happening, and why the position statement was triggered, is that women with preeclampsia are not identified right away, they are not treated right away and, therefore, have really severe complications and severe preeclampsia.”

The complications have implications for the mother, fetus or both. CV complications that affect the placenta may lead to issues with the child’s vascular development, the effects of which may present itself in childhood of mid-adulthood. Treatment options are somewhat limited during pregnancy and lactation, but medications are available to treat the woman safely and effectively. Women who have had hypertension or other CV complications before becoming pregnant are recommended to alter their treatment during pregnancy, but often return to their original treatment after they deliver, finish breast-feeding or finish childbearing, depending on the level components of treatment. Even after a woman is treated for pregnancy complications and delivers the baby, they remain at risk for CVD later in life.

Common CV complications

Although CV complications in pregnant women are known and are screened for throughout the pregnancy, the effects can severely harm the mother and even the child if left untreated. Pregnancies in women who are not treated for preeclampsia or gestational hypertension may result in placenta abruption, fetal mortality, preterm delivery and a baby born small for gestational age.

“If BP is left untreated for too long in pregnancy, elevated [BP] can increase the risk for maternal stroke and HF,” Ki Park, MD, clinical assistant professor of medicine in interventional cardiology at University of Florida, Gainesville, and a Cardiology Today Next Gen Innovator, said in an interview. “There are also effects within the placenta such that reduced blood flow can lead to a baby born small for gestational age amongst other neonatal complications.”

During a normal pregnancy, a woman’s systolic and diastolic BP lowers by 10 mm Hg to 15 mm Hg.

“We tend to see those BP numbers fall, and when that doesn’t fall, that indicates an abnormal response. We expect a decrease in vascular resistance or a vasodilation type of response,” Martha Gulati, MD, MS, FACC, FAHA, FASPC, cardiologist and chief of the division of cardiology at the University of Arizona in Phoenix, told Cardiology Today.

Hypertension, the most common CV complication of pregnancy, occurs in 12% to 22% of pregnancies. Gestational hypertension is typically diagnosed after 20 weeks’ gestation. In chronic hypertension, a woman has the condition before, during and after pregnancy. More serious forms of hypertension include preeclampsia and eclampsia, which can lead to seizures. Preeclampsia can also present itself as HELLP syndrome, during which a woman has a low platelet count, hemolysis and elevated liver enzymes (see Sidebar).

Moreover, women with prior preeclampsia, chronic hypertension or prior gestational hypertension have an increased risk for CV complications during subsequent pregnancies, Janet Wei, MD, FACC, cardiologist at the Barbra Streisand Women’s Heart Center at Cedars-Sinai Heart Institute and a Cardiology Today Next Gen Innovator, said in an interview. Women aged 35 years and older are also at increased risk for CV complications.

“One in three women at the age of 60 years will have heart disease, and it [tends to be] the woman who had a history of an adverse pregnancy outcome,” Minissian told Cardiology Today. “If we do nothing and we leave them untreated, they develop diabetes, they develop hypertension and they go on to develop heart disease, and oftentimes it’s premature heart disease.”

Exposure to hypertension during pregnancy also contributes to a fourfold increased risk for hypertension, a threefold increased risk for type 2 diabetes and a three- to eightfold increased risk for heart disease later in life, Minissian said.

Guidelines for diagnosis

The first step to diagnosing pregnant women with a CV complication is BP measurements at every appointment, regardless of whether measurements are taken at a cardiologist’s or OB-GYN’s office. Although this has been an established standard of care, the USPSTF guidelines emphasize the importance of regular BP screening in pregnant women.

“People should get screened because about 30% of women have adverse pregnancy outcomes,” Puja K. Mehta, MD, FACC, FAHA, assistant professor of medicine in the division of cardiology at Emory University School of Medicine and director of Women’s Translational Cardiovascular Research at Emory Women’s Heart Center, told Cardiology Today. “This number is huge, especially if you think about the number of women who are getting pregnant.”

Although there is no harm or added cost to regular BP measurements in the pregnant population, debate persists among OB-GYNs as to the exact measurement to prompt clinicians to begin BP treatment. This may be due to how each woman reacts to elevated BP.

“If a woman already had high BP going into pregnancy, then they tend to tolerate elevated values a little bit more as opposed to a woman whose normal systolic BP pre-pregnancy is 100 mm Hg and then they go up to 150 mm Hg, as opposed to a baseline of 140 mm Hg,” Park told Cardiology Today. “Obviously if the woman is experiencing symptoms relating to her high BP, that is an indication for treatment.”

Additionally, many obstetricians try to avoid additional treatment that may affect the fetus, Park said.

The new USPSTF guidelines do not provide an exact BP measurement to start treatment. In 2013, the American College of Obstetricians and Gynecologists recommend a systolic BP between 120 mm Hg and 160 mm Hg. Those guidelines also suggest using medical history in addition to measurements of BP and proteinuria to diagnose preeclampsia. However, how to particularly screen for hypertension in pregnant women is not detailed.

The USPSTF guidelines highlighted evidence that screening for proteinuria does not confer diagnostic accuracy as do BP measurements.

“The takeaway message from that was not to rely so much on screening of protein in the urine,” Park said in an interview. “Most women, if you are going to 39, 40 weeks’ gestation, it’s not uncommon that you are going to have some protein in your urine, so it’s not a very specific test.”

Since BP measurements have been established as a reliable method of determining women at high risk for hypertension, it is important that the OB-GYN community increase its awareness of identifying those at high risk, as pregnant women do not immediately see a cardiologist, experts told Cardiology Today.

Use of imaging during pregnancy

Pregnant women diagnosed with adverse pregnancy outcomes or are at high CV risk occasionally must undergo imaging, which may expose them to radiation.

“There’s no indication for routinely imaging the woman with hypertensive complications,” Nanette K. Wenger, MD, MACC, MACP, FAHA, professor of medicine (emeritus) at Emory University School of Medicine, consultant at Emory Heart and Vascular Center, founding consultant at Emory Women’s Heart Center and Cardiology Today Editorial Board Member, said in an interview. “If you’re worried, you may do an ECG, which exposes the woman to no radiation.”

Women with peripartum or postpartum cardiomyopathy presenting with HF can be diagnosed with an ECG, Wenger said. Peripartum cardiomyopathy, which occurs in about one in every 1,000 to 1,300 live births in the United States, can be diagnosed late in pregnancy or after the woman has delivered, Gulati said.

Most cases of hypertension, preeclampsia and other CV complications require bloodwork or imaging technology like ECG or cardiac ultrasound, which do not expose the woman and fetus to radiation. However, some conditions may call for imaging with radiation. For example, a coronary angiogram is used to diagnose women with spontaneous coronary artery dissection, which is especially life-threatening in pregnant women.

Risk for radiation exposure in pregnant women mainly occurs in those with suspected MI, which occurs in an estimated 35,000 pregnancies in the United States.

In these cases, in which the fetus is exposed to radiation, clinicians can use a shield to protect the fetus while using the minimum amount of contrast needed and limiting exposure to radiation. The as low as reasonably achievable (ALARA) code, an effort to make radiation exposure as far below dose limits as practical, should also be followed to limit exposure.

Further, the risk for radiation to the fetus is highest within the first trimester.

“If there is another imaging modality that doesn’t use radiation, then that should absolutely be performed,” Park told Cardiology Today.

Optimal medication use

Once a pregnant woman is diagnosed with a adverse pregnancy outcomes or other CV complications, treatment should keep in mind the safety of both the mother and child. A number of medications should be avoided during pregnancy, including ACE inhibitors, statins and angiotensin II receptor blockers, as these medications may be associated with fetal abnormalities. These treatments should also be stopped in women who are trying to conceive. Diuretics should also be avoided during pregnancy because they can reduce placenta volume and placenta perfusion.

The safety of treatment options should also be considered in women who remain hypertensive after pregnancy, especially if they are breast-feeding, Gulati said.

It is difficult to determine exactly which medications should be avoided or used as substitutions, as there are limited data on therapies on pregnant women. The safety of medications has mostly been determined by experience and animal studies.

Some NSAIDs like ibuprofen should be avoided during pregnancy because they may increase BP and CV events later in life, experts said.

Beta-blockers can be safely used in pregnant women diagnosed with arrhythmias and peripartum cardiomyopathy.

Currently, the American College of Obstetricians and Gynecologists recommends methyldopa, labetalol and nifedipine to treat pregnant women with high BP. Nifedipine is sometimes preferred in the treatment of severe hypertension or preeclampsia in pregnant women, as it comes in an immediate-release dose, Minissian said. She added that nifedipine and labetalol can also be used together.

Acetaminophen can be used as a substitute for ibuprofen and other NSAIDs, since it “does not have the specific COX inhibitor that’s part of the pathway through how NSAIDs work,” Park said.

Recent research has shown that low-dose aspirin taken during pregnancy may reduce the risk for preterm preeclampsia.

In women with familial hypercholesterolemia, it is recommended that statin treatment cease, especially during the first trimester, but statin treatment may be reintroduced after delivery depending on risk and cholesterol levels, according to Mehta, also a Cardiology Today Next Gen Innovator. Other clinicians recommend that statins be stopped completely in women with familial hypercholesterolemia until after delivery, although there is no substitution for this therapy.

“There is no indication for any other drugs, including the newer PCSK9 inhibitors, because none of them have been studied during pregnancy, but as prudence would advise to stop it until after the pregnancy,” Wenger told Cardiology Today.

In this case, a bile acid sequestrant could be used for the treatment of this patient population, Minissian said. Other options for pregnant women include soluble fiber or a plant sterol or stanol, but women being considered for those treatments should be referred first to a lipid specialist.

Team-based approach

A team-based approach to treating preeclampsia and other CV complications in pregnant women can be beneficial.

“It’s very important for OB-GYNs, cardiologists, primary care physicians and anesthesiologists to collaborate together because some of these CV complications may be prevented or risk reduced in patients who have had a history of cardiomyopathy, valvular heart disease, congenital heart disease or ischemic heart disease,” Wei told Cardiology Today.

Oftentimes, OB-GYNs treat women with high BP during pregnancy, but cardiologists are consulted when the BP cannot be easily controlled or persists postpartum.

Many centers across the United States use this collaborative approach to treatment. At the Emory Women’s Health Center, Wenger and colleagues work with OB-GYNs even after a woman has delivered. A similar program has been set up at the Postpartum Heart Health Clinic at Cedars-Sinai, Wei said. The cardiologists visit a preeclampsia clinic, where women with the complication have their 6-week follow-up, and discuss with the women their increased CV risk and the importance of evaluating and managing their conventional CV risk factors. Cardiologists at the clinic recommend that women return to their pre-pregnancy weight, exercise and stop smoking. Routine BP, lipid and glucose measurements should also be performed.

Centers that do not have direct communication between cardiologists and OB-GYN can discuss with the leadership of their cardiology program to identify cardiologists within their division who are interested in treating pregnant women. However, many cardiologists are hesitant to treat pregnant women because “the comfort is not there,” Mehta said.

Increased training and awareness during cardiology fellowship can help increase the comfort in treating pregnant women with high BP, gestational diabetes and other CV complications, experts said.

When adverse outcomes occur, it is important that it be noted in electronic medical records for all clinicians so they can monitor and treat their patients accordingly. History of all adverse pregnancy outcomes, including preeclampsia, gestational hypertension, spontaneous preterm delivery and gestational diabetes, should be recorded, especially because they increase CV risk in women later in life, although the problem may not be present. A detailed pregnancy history is an intrinsic component of CV risk assessment for women, Wenger said.

“It’s very difficult for women to recall these things for themselves, so if we’re able to help document it earlier in the process and then ensure that women who had preeclampsia are evaluated for diabetes, hypertension and lipid disorders annually,” Minissian said.

Awareness should also increase between clinicians and patients before, during and after pregnancy, especially since many women do not know that they are at increased CV risk due to preeclampsia or other adverse pregnancy outcomes even after they deliver and BP, lipid and glucose levels elevate.

When it comes to future CV risk, “pregnancy is your free stress test ... because it is telling us that there is some abnormal vascular response,” Gulati told Cardiology Today. – by Darlene Dobkowski

• References:
• American College of Obstetricians and Gynecologists. Obstet Gynecol. 2013;doi:10.1097/01.AOG.0000437382.03963.88.
• Irgens HU, et al. BMJ. 2001;doi:10.1136/bmj.323.7323.1213.
• Rolnik DL, et al. N Engl J Med. 2017;doi:10.1056/NEJMoa1704559.
• US Preventive Services Task Force. JAMA. 2017;doi:10.1001/jama.2017.3439.

• For more information:
• Martha Gulati, MD, MS, FACC, FAHA, FASPC, can be reached at University of Arizona College of Medicine, 550 E. Van Buren St., Phoenix, AZ 85004; email: marthagulati@email.arizona.edu.
• Puja K. Mehta, MD, FACC, FAHA, can be reached at Emory Clinical Cardiovascular Research Institute, 1462 Clifton Road NE, Suite 505, Atlanta, GA 30322; email: puja.kiran.mehta@emory.edu.
• Margo B. Minissian, PhD, ACNP, CLS, AACC, FAHA, can be reached at Barbra Streisand Women’s Heart Center at Cedars-Sinai Heart Institute, 127 S. San Vincente Blvd., Los Angeles, CA 90048; email: margo.minissian@cshs.org.
• Ki Park, MD, can be reached at University of Florida Division of Cardiovascular Medicine, 1600 SW Archer Road, Gainesville, FL 32610; email: ki.park@medicine.ufl.edu.
• Janet Wei, MD, FACC, can be reached at Barbra Streisand Women’s Heart Center at Cedars-Sinai Heart Institute, 127 S. San Vincente Blvd., Los Angeles, CA 90048; email: janet.wei@cshs.org.
• Nanette K. Wenger, MD, MACC, MACP, FAHA, can be reached at Emory University School of Medicine, 49 Jesse Hill Jr. Drive, Atlanta, GA 30303; email: nwenger@emory.edu.

Disclosures: Gulati, Minissian, Park, Wei and Wenger report no relevant financial disclosures. Mehta reports receiving research support from Gilead in the past 2 years.