Introduction

Preeclampsia, a hypertensive disorder of pregnancy defined as new-onset hypertension (systolic blood pressure ≥140 mmHg and/or diastolic ≥90 mmHg) with proteinuria or other specific end-organ dysfunction after 20 weeks of pregnancy, affects 5% to 7% of all pregnancies.¹ Preeclampsia significantly increases the risk of still birth and neonatal death and is a leading cause of maternal morbidity.^2,3

A diagnosis of preeclampsia has long-term implications for women's health, with an associated increase in lifetime risk of ischemic heart disease, stroke, and heart failure.^4,5 A large cohort study found a 3.6-fold increase in CVD death at age 60 for women who had been diagnosed with early onset preeclampsia (developed by week 34 of pregnancy) when compared to women without a preeclampsia diagnosis after adjustment for covariates.⁶ A proposed explanation for this increased CVD risk in patients with preeclampsia is the high prevalence of pre-existing cardiovascular risk factors such as hypertension, hyperlipidemia, and diabetes, which confer an increased risk independent of their association with preeclampsia.^7-9

Study Design and Findings

Women with a history of preeclampsia have been shown to be at increased risk for coronary artery calcification (CAC), a surrogate for CVD, but data has largely been limited to those ages 50-69,¹⁰ and the timing of CAC development in this population remains unknown.

In this study, Benschop et al. compared the prevalence of CAC in asymptomatic women ages 40-63 years with a history of preeclampsia to those without a history of preeclampsia.¹¹ Importantly, women with a history of preeclampsia were more likely to have CAC compared with women without prior preeclampsia (20% vs. 13%; p = 0.003), and women with a history of preeclampsia developed CAC an average of 5 years earlier (95% CI 1.8-8.0) compared to women with prior preeclampsia. A third of women with a history of preeclampsia were found to have visible plaque formation on coronary computed tomography angiogram (CTA), while 3% had significant stenosis.

The most significant difference in CAC between women with and without a history of preeclampsia was seen in women ages 40-45 years (23% vs. 10%; p = 0.003). After adjusting for covariates including smoking status, BMI, diabetes, hypertension, and hyperlipidemia, women with a history of preeclampsia ages 45-50 years were four times as likely to have some CAC compared to women ages 40-45 (OR 4.3, 95% CI 1.5-12.2). While the Framingham Risk Score (FRS) was higher for women with a history of preeclampsia in each age group, only the 55-63-year-old age group had a FRS greater than 10%, meeting current guidelines for preventive treatment.

Conclusions

While women with preeclampsia do appear to have increased risk for traditional cardiovascular risk factors (smoking, obesity, diabetes, hypertension, hyperlipidemia) to explain increased incidence of CVD, preeclampsia is an independent risk factor for early onset CAC and subclinical CVD. Many of the commonly used risk stratification algorithms do not account for preeclampsia; thus, women with such a history are not identified as having elevated CVD risk. This underestimation of risk may lead to less aggressive lifestyle and pharmacologic treatment of modifiable risk factors.

Clinical Significance and Future Directions

A history of preeclampsia in pregnancy has previously been associated with an increased risk of CAC 30 years post-pregnancy, after controlling for traditional risk factors.¹² This new study by Benschop et al. is the first study to shed light on the timing of early onset subclinical CVD in women with a history of preeclampsia. It makes a strong argument for earlier cardiovascular risk assessment for this population. Women with a history of preeclampsia would likely benefit from establishing care with a cardiologist before age 45 to optimize modifiable risk factors.

Additionally, this study stresses the importance of soliciting a thorough reproductive history for female patients in order to risk stratify patients more effectively. Prior preeclampsia, along with other adverse pregnancy outcomes including preterm birth and small for gestational age pregnancies, should be accounted for in risk assessment when initiating primary prevention strategies to reduce CVD.¹³ Among women with a history of preeclampsia, the presence of CAC may serve to identify those at a particularly high cardiovascular risk and should be the subject of future studies.

The generalizability of this study is limited by all participants being white women. The development and outcomes of CAD vary by race, and pregnancy complications including pre-eclampsia have been associated with CAD in Black women.¹⁴ Further research must be done to elucidate these differences and inform further risk stratification.

References

1. Rana S, Lemoine E, Granger JP, Karumanchi SA. Preeclampsia: pathophysiology, challenges, and perspectives. Circ Res 2019;124:1094-1112.
2. Ahmad AS, Samuelsen SO. Hypertensive disorders in pregnancy and fetal death at different gestational lengths: a population study of 2 121 371 pregnancies. BJOG 2012;119:1521-28.
3. Ghulmiyyah L, Sibai B. Maternal mortality from preeclampsia/eclampsia. Semin Perinatol 2012;36:56-59.
4. Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. BMJ 2007;335:974.
5. Brown MC, Best KE, Pearce MS, Waugh J, Robson SC, Bell R. Cardiovascular disease risk in women with pre-eclampsia: systematic review and meta-analysis. Eur J Epidemiol 2013;28:1-19.
6. Cirillo PM, Cohn BA. Pregnancy complications and cardiovascular disease death: 50-year follow-up of the Child Health and Development Studies pregnancy cohort. Circulation 2015;132:1234-42.
7. Barry DR, Utzschneider KM, Tong J, et al. Intraabdominal fat, insulin sensitivity, and cardiovascular risk factors in postpartum women with a history of preeclampsia. Am J Obstet Gynecol 2015;213:104.e1-104.e11.
8. Veerbeek JHW, Hermes W, Breimer AY, et al. Cardiovascular disease risk factors after early-onset preeclampsia, late-onset preeclampsia, and pregnancy-induced hypertension. Hypertension 2015;65:600-6.
9. Hermes W, Tamsma JT, Grootendorst DC, et al. Cardiovascular risk estimation in women with a history of hypertensive pregnancy disorders at term: a longitudinal follow-up study. BMC Pregnancy Childbirth 2013;13:126.
10. Cassidy-Bushrow AE, Bielak LF, Rule AD, et al. Hypertension during pregnancy is associated with coronary artery calcium independent of renal function. J Womens Health (Larchmt) 2009;18:1709-16.
11. Benschop L, Brouwers L, Zoet GA, et al. Early onset of coronary artery calcification in women with previous preeclampsia. Circ Cardiovasc Imaging 2020;13:e010340.
12. White WM, Mielke MM, Araoz PA, et al. A history of preeclampsia is associated with a risk for coronary artery calcification 3 decades later. Am J Obstet Gynecol 2016;214:519.e1-519.e8.
13. Park K, Wu P, Gulati M. Obstetrics and gynecological history: a missed opportunity for cardiovascular risk assessment. J Am Coll Cardiol Case Rep 2020;2:161-63.
14. Wichmann JL, Takx RAP, Nunez JH, et al. Relationship between pregnancy complications and subsequent coronary artery disease assessed by coronary computed tomographic angiography in Black women. Circ Cardiovasc Imaging 2019;12:e008754.

Clinical Topics: Anticoagulation Management, Cardiovascular Care Team, Congenital Heart Disease and Pediatric Cardiology, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Imaging, CHD and Pediatrics and Interventions, CHD and Pediatrics and Prevention, CHD and Pediatrics and Quality Improvement, Acute Heart Failure, Interventions and Imaging, Angiography, Nuclear Imaging, Hypertension

Keywords: Dyslipidemias, Pre-Eclampsia, Pregnancy Outcome, Cohort Studies, Premature Birth, Infant, Newborn, Incidence, Prevalence, Blood Pressure, African Americans, Cardiovascular Diseases, Reproductive History, Hyperlipidemias, Constriction, Pathologic, Gestational Age, Factor XII, Body Mass Index, Multiple Organ Failure, Risk Factors, Hypertension, Risk Assessment, Primary Prevention, Diabetes Mellitus, Life Style, Heart Failure, Proteinuria, Stroke, Angiography, Obesity, Tomography, Diagnostic Imaging

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