Implications on Cardiovascular Outcomes
Chronic hypertension, GH and PE have been shown to have adverse effects on pregnancy and associations with a higher risk for cardiovascular disease (CVD) outcomes. Many studies have shown an association between PE and CV disease in later life. A large meta-analysis from Wu et al. showed that women with a history of PE have a 71% increased risk of CV mortality, a 2.5-fold increase in risk of coronary artery disease (CAD), and a 4-fold increase in the development of heart failure when compared to normal cohorts. The Nurses' Health Study II reported that women with GH and PE had almost a 3-fold and 6-fold increased rate of chronic hypertension, respectively. It also showed that women who were hypertensive during their first pregnancy had a 70% increased risk of type 2 diabetes and 30% increased prevalence of hypercholesterolemia later in life. Recurrent PE is associated with a higher risk of future CVD events including hospitalization from heart failure or cardiac procedures compared with no PE, and significantly shorter time to a first cardiovascular event.
Recent data has shown that PE is associated with complications such as preterm delivery (PTD) or small for gestational age (SGA) infant. A Norwegian study with a mean follow-up of 17.2 years found that women with PE alone had a 2-fold increased risk of a major CV event, whereas women with PE plus PTD or SGA were 4 times as likely to have a major cardiac event compared to women with uncomplicated pregnancies.8 A large meta-analysis demonstrated that women with chronic hypertension had a higher incidence of superimposed PE, caesarean section, preterm delivery before 37 weeks' gestation, birth weight less than 2500 grams, neonatal unit admission and perinatal death.
In a recent prospective observational study, women with severe PE had higher right ventricular systolic pressure, decreased global right ventricular longitudinal systolic strain and lower mitral septal eʹ velocity when compared to the control cohort of normal pregnancies. Twelve percent of patients with PE also had grade II diastolic dysfunction and 9.5% had peripartum pulmonary edema. These data demonstrate that adverse outcomes of pregnancy are common and highlight the need for antenatal surveillance, risk stratification and close long term follow up of patients with these complications.
Guideline Directed Management
Hypertension is a key risk factor for CVD and its treatment reduces complications over time. However, the benefits of tight blood pressure control during pregnancy are controversial. During pregnancy, the goal of pharmacologic management of hypertension is to prevent acute complications while minimizing risk to the fetus. There is no evidence that treatment of mild to moderate hypertension during pregnancy improves maternal or perinatal outcomes (including preeclampsia, preterm birth and small for gestational age or infant mortality). In fact, most women with mild hypertension can stop their antihypertensive medications during the first and second trimesters due to the physiological drop in blood pressure that occurs during this time. Those who require treatment can continue their medical regimen except for renin angiotensin aldosterone system inhibitors including angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers and direct renin inhibitors. This class of pharmacotherapy is contraindicated during pregnancy due to the increased risk of fetal renal malformations. Severe hypertension should be aggressively treated to reduce the risk of progression to preeclampsia and hemorrhagic stroke.
Data on treatment of chronic hypertension during pregnancy is limited and there is no consensus on the optimal agent. The non-selective beta blocker labetalol and the calcium channel blocker (CCB) nifedipine have similar efficacy in controlling hypertension during pregnancy and are commonly used due to their good safety profiles. Methyldopa has a long history of use in pregnancy and is still used, although it is not as effective and considered a second line therapy after CCBs and beta blockers. Diuretics can be used but are also second line agents due to the theoretical risk of intravascular volume depletion and fetal growth restriction. Given the lack of conclusive evidence regarding specific antihypertensive medications during pregnancy, side effects, contraindications and familiarity of the drug should guide the provider to choose an appropriate agent. The influence of ethnicity in the choice of antihypertensive therapy during pregnancy is unknown and has not been adequately studied. For severe hypertension, intravenous labetalol, oral nifedipine and intravenous hydralazine are equally effective. In hypertensive emergencies, intravenous sodium nitroprusside or nitroglycerin can be used. Salt restriction and weight loss are not recommended during pregnancy due to the risk of volume contraction and neonatal growth restriction, respectively.
During the postpartum period, hypertension treatment is required and the treatment goals for hypertension are the same as those for the general non-pregnant population. Since breastfeeding is strongly encouraged by the American College of Obstetrics and Gynecologists (ACOG), medications that are not excreted into breast milk are preferred. Methyldopa, labetalol and propranolol are considered safe. Beta blockers such as metoprolol and atenolol can achieve high levels in breast milk and should be avoided for this reason. The angiotensin converting enzyme inhibitors captopril and enalapril are considered safe given their low concentrations in breast milk. There are limited data for calcium channel blockers, but nifedipine is commonly used during breastfeeding. Diuretics are discouraged because of the risk of reducing breast milk production. Nonsteroidal anti-inflammatories should also be avoided to prevent sodium retention and hypertension.
For primary prevention of PE, a recent meta-analysis showed a modest decrease in the risk of PE with the use of low dose aspirin in the late first trimester in high-risk populations. ACOG recommends the use of aspirin 60-80 mg daily in high risk women, defined as previous history of early onset PE and preterm delivery before 34 0/7 weeks of gestation or PE in more than one pregnancy.
1. Pregnancy provides a unique opportunity for both patients and providers to engage in improving overall health. Many studies have shown that women are motivated to change their lifestyle habits during pregnancy and the postpartum period. Obstetricians and cardiologists can improve the cardiovascular health of women through enhanced collaboration. A recent joint presidential advisory from ACOG and the American Heart Association called for a multidisciplinary approach in management incorporating lifestyle and behavioral modifications including diet, exercise and smoking cessation as well as electronic medical record based standardized algorithms targeting cardiovascular risk factors. Shared information between the two disciplines can be used to assess risk, initiate interventions and facilitate significant and lasting lifestyle changes.
2. Cardiologists and primary care physicians should partner to develop a comprehensive pregnancy history tool for cardiovascular risk assessment. Roberts et al. proposed a simple and effective questionnaire (Table 1) that can be incorporated for risk assessment of women when seen by primary care providers and cardiologists. Understanding pregnancy related complications could help categorize women into higher risk groups for targeted therapies. While a few of these questions are beyond the scope of this discussion, those that pertain to gestational history and hypertensive disorders during pregnancy may provide a window into non-traditional CV risk factors.
3. Evidence-based guidelines for screening and interventions remain an unmet need. More focused research on assessing biomarker profiles, vascular physiological and imaging parameters and successful lifestyle-directed interventions targeting this group must be pursued. A shared consensus statement written by key medical societies should be developed to guide management of this population.