Cardiovascular disease (CVD) has been the leading cause of maternal death in the United States, with increasing rates over the past decades due to factors such as advancing age and increased CVD risk factors. Treatable comorbidities such as obesity, hyperlipidemia (HLD), hypertension (HTN), and diabetes mellitus (DM) contribute to most of these deaths.¹ The Journal of the American College of Cardiology (JACC) Focus Seminar 1/5 provided a broad overview of the appropriate counseling regarding maternal and fetal risks of pregnancy and highlighted the utilization of multidisciplinary cardio-obstetrics teams during the preconception period and pregnancy.¹ This expert analysis focuses on several of the most common driving factors of cardiometabolic health and how they contribute to pregnancy-related cardiovascular (CV) outcomes.

Cardiometabolic Risk Factors

Obesity

In a 2019 American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin, obesity (body mass index [BMI] ≥30 kg/m2) was among the top four risk factors for CVD-related death in pregnancy.² The prevalence of obesity among women in the United States between 20 and 39 years of age is 39.6% and rising.³

Increased BMI during pregnancy has been associated with long-term major adverse cardiovascular events (MACE) and premature death. In a sample of 4,216 pregnant patients enrolled in nuMoM2b-HHS (Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be Heart Health Study), early pregnancy obesity was associated with higher rates of postpartum HTN, HLD, and DM.⁴ These increased complications may be related to dysregulated metabolic, vascular, and inflammatory pathways because of excess adipose tissue.

Addressing preconception obesity requires a multifaceted approach focused on prevention and early intervention. The mainstays of treatment are a Mediterranean diet and regular moderate exercise. Metformin may be continued in pregnancy and may reduce gestational weight gain, although it has not been shown to improve outcomes.⁵ Other obesity medications (e.g., glucagon-like peptide-1 agonists) have not been studied in pregnancy.

Hyperlipidemia

Because of hormonal fluctuations and requirements for proper fetal development, lipid metabolism changes significantly throughout pregnancy, with low-density lipoprotein levels increasing up to 30-50% by the third trimester.⁶ This exposure during pregnancy may accelerate atherosclerosis and pose a significant risk of MACE, particularly for patients with existing coronary disease or inherited HLD disorders. Preconception dyslipidemia has also been associated with other complications during pregnancy such as gestational DM and pre-eclampsia.⁶

No clear recommendation currently exists for screening of lipid disorders in young patients, although it may be reasonable to obtain baseline testing in the preconception period. Management of HLD consists of dietary changes and medications. Bile acid sequestrants are the only lipid-lowering agent approved in pregnancy, although omega-3 fatty acids have also been safely used. Literature regarding statins has been evolving after results from several trials demonstrated a lack of teratogenicity; as such, the Food and Drug Administration (FDA) recently removed the black box warning surrounding statin use in pregnancy and recommends shared decision-making regarding use in pregnancy.⁶ Patients with familial hypercholesterolemia should undergo additional preconception counseling, medication adjustment, and close monitoring by a multidisciplinary team.

Hypertension

Chronic HTN is defined as blood pressure (BP) ≥140/≥90 mm Hg on two or more occasions ≥4 hours apart before 20 weeks of gestation or persisting for >12 weeks after a pregnancy; it is estimated to be present in 3-5% of pregnancies.⁷ Chronic, or prepregnancy, HTN contributes to hypertensive disorders of pregnancy (HDP), one of the fastest-growing subsets of CVD in the pregnant population. The most common complication in women with HTN is the development of pre-eclampsia/eclampsia during pregnancy, both of which, in rare cases, can result in heart failure (HF), stroke, seizures, kidney failure, or death. The risk of complications increases linearly with BP, even if mildly elevated or high-normal before conception. HDP are a sign of underlying susceptibility to CVD (HF, cerebrovascular disease).⁷

Women with HTN should be identified before conception to assess kidney function, identify secondary causes, and undergo a baseline cardiac evaluation. Treatment with medications with established safety profiles in pregnancy (e.g., labetalol, nifedipine) is recommended to target normotension prior to conception, as well as dietary modifications (Dietary Approaches to Stop Hypertension) and weight loss. A detailed toolkit on the management of postpartum HTN, including medication safety during lactation, follow-up, and medication titration, is available on the ACC website.

Diabetes Mellitus

DM has also been identified by ACOG as one of the top four risk factors for CVD-related death during pregnancy,³ which encompasses both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). DM affects 1-2% of women of childbearing age. Although it is well established that gestational DM is a risk factor for development of future CVD, pre-existing DM also places patients at increased risk of complications, particularly HDP. Pre-eclampsia is more than four times more likely to occur in patients with pre-existing DM, affecting 9-20% of pregnant women with T1DM and 7-14% of women with T2DM (which is >2-8% in the population without DM).^1,8

Tight glycemic control for a preconception hemoglobin A1c concentration of <6.5% is important to reduce both the development of HDP and other CV complications.⁸ Insulin remains the standard therapy during the preconception period and pregnancy because of its known safety profile, although metformin can be continued in the first trimester. Other oral agents have limited safety information and are thus avoided in the preconception period.

Multidisciplinary Team

To mitigate the CV complications associated with cardiometabolic disease states, it is imperative that patients at risk receive preconception counseling by a cardio-obstetrics team (including an obstetrician, cardiologist, anesthesiologist, maternal-fetal medicine specialist, and nurses) or health care providers experienced in high-risk pregnancies. The use of a cardio-obstetrics team is described and recommended in the JACC Focus Seminar 1/5 (Figure 1) and by the American Heart Association (AHA) given its important role in decreasing maternal mortality and morbidity.

Figure 1: The Cardio-Obstetrics Model of Care

Recent reports from a New York City–based multidisciplinary cardio-obstetrics program demonstrate low rates of both maternal and fetal complications, as well as low rates of 30-day and 90-day readmissions.⁹ Multidisciplinary clinics have also demonstrated high levels of patient-reported satisfaction and communication, as well as increases in patient-reported knowledge about heart disease.¹⁰ As the multidisciplinary team model becomes more widely available, the data will help guide improvement in outcomes for this patient population.

References

1. Davis MB, Arendt K, Bello NA, et al.; American College of Cardiology Cardiovascular Disease in Women Committee and the Cardio-Obstetrics Work Group. Team-based care of women with cardiovascular disease from pre-conception through pregnancy and postpartum: JACC Focus Seminar 1/5. J Am Coll Cardiol 2021;77:1763-77.
2. American College of Obstetricians and Gynecologists' Presidential Task Force on Pregnancy and Heart Disease and Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 212: Pregnancy and Heart Disease. Obstet Gynecol 2019;133:e320-e356.
3. Stierman B, Afful J, Carroll MD, et al. National Health and Nutrition Examination Survey 2017–March 2020 Prepandemic Data Files—Development of Files and Prevalence Estimates for Selected Health Outcomes (CDC website). 2021. Available at: https://stacks.cdc.gov/view/cdc/106273. Accessed 09/20/2024.
4. Khan SS, Petito LC, Huang X, et al.; NICHD nuMoM2b and NHLBI nuMoM2b Heart Health Study Networks. Body mass index, adverse pregnancy outcomes, and cardiovascular disease risk. Circ Res 2023;133:725-35.
5. Dodd JM, Louise J, Deussen AR, et al. Effect of metformin in addition to dietary and lifestyle advice for pregnant women who are overweight or obese: the GRoW randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol 2019;7:15-24.
6. Bashir M, Navti OB, Ahmed B, Konje JC. Hyperlipidaemia and severe hypertriglyceridaemia in pregnancy. The Obstetrician & Gynaecologist 2023;25:196-209.
7. Ackerman-Banks CM, Lipkind HS, Palmsten K, Ahrens KA. Association between hypertensive disorders of pregnancy and cardiovascular diseases within 24 months after delivery. Am J Obstet Gynecol 2023;229:65.e1-65.e15.
8. Do NC, Vestgaard M, Nørgaard SK, Damm P, Mathiesen ER, Ringholm L. Prediction and prevention of preeclampsia in women with preexisting diabetes: the role of home blood pressure, physical activity, and aspirin. Front Endocrinol (Lausanne) 2023;14:[ePub ahead of print].
9. Magun E, DeFilippis EM, Noble S, et al. Cardiovascular care for pregnant women with cardiovascular disease. J Am Coll Cardiol 2020;76:2102-13.
10. Florio KL, White D, Gosch K, et al. Patient-perceived satisfaction and knowledge uptake in a combined cardio-obstetrics clinic. J Cardiovasc Dev Dis 2022;9:433.