Hypertensive pregnancy disorder, an under-recognized women specific risk factor for heart failure?

Abstract

During pregnancy, the maternal cardiovascular (CV) system undergoes major haemodynamic alterations ensuring adequate placental perfusion and a healthy pregnancy course. Hypertensive disorders of pregnancy (HDP) occur in almost 10% of gestations and preeclampsia, a more severe form, in 3-4%. Women with HDP demonstrated impaired myocardial function, biventricular chamber dysfunction and adverse biventricular remodelling. Shortly after delivery, women who experienced HDP express increased risk of classic CV risk factors such as hypertension, renal disease, abnormal lipid profile, and diabetes. Within the first two decades following a HDP, women experience increased rates of heart failure, chronic hypertension, ischaemic heart and cerebral disease. The mechanism underlying the relationship between HDP in younger women and CV disease later in life could be explained by sharing pre-pregnancy CV risk factors or due to a direct impact of HDP on the maternal CV system conferring a state of increased susceptibility to future metabolic or haemodynamic insults. Racial disparities in CV risk and social determinants of health also play an important role in their remote CV risk. Although there is general agreement that women who suffered from HDP should undertake early CV screening to allow appropriate prevention and timely treatment, a screening and intervention protocol has not been standardized due to limited available evidence. In this review, we discuss why women with hypertensive pregnancy may be disproportionately affected by heart failure with preserved ejection fraction and how cardiac remodelling during or after pregnancy may influence its development.

Keywords: Cardiovascular disease in women; Hypertensive pregnancy disorders; Preeclampsia; Pregnancy; Prevention.

Figure 1

In a normal pregnancy there is an increase in volume load and lower pressure load. The left ventricular mass (LVM) increases in these women with a minimum rise in relative wall thickness (RWT) resulting in eccentric hypertrophy. In a preeclamptic pregnancy, the change in volume load is shallow and pressure load increases significantly resulting in concentric remodelling, diastolic dysfunction, impaired left ventricular (LV) strain, increased right ventricular systolic pressure (RVSP) and right ventricular systolic (RVS) dysfunction (latest two mainly in severe/early preeclampsia). After preeclampsia, the prevalence of diastolic dysfunction, impaired LV and right ventricular (RV) strain and subclinical heart failure (HF stage B) remain high at a relative young age. These changes may not always be reversible and may persist or deteriorate, especially in persistent of metabolic, lifestyle or pressure factors and may contribute to the 2–7 times elevated risk for cardiovascular disease. The presenting symptoms and clinical signs of preeclampsia are thought to be triggered by abnormally high levels of soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and low placental growth factor (PlGF) – commonly referred to as ‘angiogenic imbalance’. sFlt‐1 is a protein that acts as an anti‐angiogenic factor, meaning it interferes with the formation of new blood vessels. In preeclampsia, sFlt‐1 levels become abnormally high, disrupting normal blood vessel function. PlGF is a protein that promotes the growth of blood vessels. In preeclampsia, PlGF levels are abnormally low, further worsening the blood vessel issues. Preeclampsia and cardiovascular disease also share several overlapping microRNA (miRNA) expression. Women who develop preeclampsia are more likely to carry protein‐altering mutations in genes associated with cardiomyopathy, particularly in titin (TTN). Whether these mutations relate to the associated aberrant cardiac remodelling seen in preeclampsia is currently unknown. CAD, coronary artery disease. Adapted from Ghossein‐Doha et al.

Figure 2

Global incidence rates of maternal hypertensive disorders per 100 000 females, 15 to 49 years of age, 2021. (Data courtesy of the Global Burden of Disease Study. Institute for Health Metrics and Evaluation. All rights reserved).

Figure 3

Pathophysiology of preeclampsia. Placental hypoperfusion either due to asymptomatic cardiac dysfunction or excessive pregnancy demand may lead to preeclampsia following the same translational mechanisms previously described for the placental aetiology hypothesis.

Figure 4

Approach to hypertension in pregnancy. Different societies vary in definition of chronic hypertension. AHA/ACC 2017 guidelines define Stage 1 hypertension as >130/80 mmHg and Stage 2 as >140/90 mmHg. ISSHP and ESC 2018 define hypertension as >140/90 mmHg. Women with chronic hypertension planning pregnancy should consider transitioning to a medication safe with pregnancy. For women without evidence for end‐organ damage traditional target goals for therapy are reasonable. In presence of end‐organ damage, tighter control is recommended. For women developing gestational hypertension, traditionally medication is started if blood pressure (BP) nears severe range. Based on the recent CHAP study, earlier therapy initiation should be considered.

Figure 5

Who should we screen after hypertensive pregnancy? Patients who may benefit from screening and primary prevention. Any patient with hypertensive disorders of pregnancy (HDP), including gestational hypertension (GHTN), preeclampsia, eclampsia or HELLP syndrome (haemolysis, elevated liver enzymes, low platelet count). Patients with gestational diabetes mellitus (GDM), intra‐uterine growth restriction (IUGR), preterm birth or placental abruption, obesity, excessive weight gain with pregnancy, obstructive sleep apnoea (OSA) or age >40 years.

Figure 6

How should we screen women after hypertensive disorders of pregnancy? Screening considerations for women with hypertensive disorders of pregnancy. A general cardiovascular risk assessment should be made of women with hypertensive disorders of pregnancy. The transfer of care to well prevention from obstetrics and gynaecology typically occurs by 6 weeks. Subsequent screening performed at 6 and 12 months. This should include usual risk factors for cardiovascular disease (CVD) including prior cardiovascular events, presence of chronic hypertension (HTN), diabetes mellitus (DM), smoking, physical inactivity, family history of CVD, mitigating factors such as breast feeding, physical parameters (body mass index [BMI], blood pressure [BP], waist circumference) and laboratory parameters including lipids, glucose/glycated haemoglobin and urine protein/creatinine ratio. HR, heart rate.