Pulse Check: Arterial Health After Preeclampsia

There is an extensive body of literature linking pregnancy outcomes with future maternal disease.1,2 Seemingly disparate pregnancy complications that range from gestational diabetes3 to placental abruption and birth of a small for gestational age newborn4 have been associated with future cardiovascular disease, highlighting the importance of reproductive history in primary and specialty care. Hypertensive disorders of pregnancy (HDP), in particular preeclampsia (PE), have been shown to be significantly associated with future cardiovascular disease, including ischemic heart disease, hypertension, and stroke.5,6 The American College of Cardiology/American Heart Association (ACA/AHA) guidelines on the prevention of cardiovascular disease consider PE a potential risk-enhancing event that could be overlooked by current risk stratification tools that do not contain HDP as a variable.7 They further recommend that providers consider additional testing for subclinical cardiovascular disease if they feel the risk has been underestimated in a particular individual. What remains less clear is when risk is most appropriately evaluated postpartum and by what means, questions that Paquin et al. try to address in their current study.8 The study by Paquin et al. recruited 40 women with history of PE and 40 age-matched controls with normotensive pregnancies 6 months to 6 years postpartum. They evaluated arterial hemodynamics including central blood pressure (BP), aortic stiffness, carotid–femoral pulse wave velocity, pulsatile and steady arterial load, and peripheral wave reflections, including augmentation index. Their main analysis compared women with PE who continued to have chronic hypertension postpartum (PE-HTN; n = 8), patients with PE who returned to a normotensive state (PE-noHTN; n = 32), and patients without hypertensive disorder. They found that the PE-HTN group had significantly worse cardiometabolic profiles than controls, with higher body mass index (BMI), low-density lipoprotein (LDL), and non-high-density lipoprotein (HDL) cholesterol levels. Women with PE-noHTN similarly had higher BMI and cholesterol levels, but at a lower magnitude than PE-HTN, as compared with controls (P < 0.05 for each comparison). They found a similar trend in certain hemodynamic parameters—women with PE-HTN had higher central BP, aortic stiffness, wave reflections, and steady arterial loads than women with PE-noHTN and controls, with a stepwise decrease in adjusted mean difference across categories. In logistic regression models, central systolic BP, followed by augmentation index, were the measures with the highest discriminatory ability for women with PE-HTN as compared with controls (threshold of 115 mm Hg and 15% for maximum sensitivity and specificity, respectively). Central diastolic BP and augmentation index had the highest discriminatory ability for women with PE-noHTN vs. controls (threshold 57 mm Hg and 4%, respectively, for maximum sensitivity and specificity, respectively). Markers of arterial health, including stiffness, pulse wave velocity, and central BP, have been shown to be predictive of future cardiovascular disease in other populations.9,10 Previous work in patients with prior HDP has demonstrated significant differences in left ventricular remodeling a decade after pregnancy as compared with controls, which could be related to systemic arterial dysfunction.11 The authors highlight the discrepancy between the brachial and central BPs and point out that there is evidence that brachial BP may not be the most meaningful reflection of arterial health in young people.12 Central BP reflects the arterial load delivered to target organs, including the heart,13 though large scale, epidemiologic studies linking central BP to cardiovascular outcomes are limited as it is not routinely measured in clinical practice. Isolated systolic hypertension of the young, also known as ISHY, is another condition where there may a significant discrepancy between brachial and central BP.14 In some patients with ISHY, there may be elevated brachial pressures with normal central BP, which is thought to be due to increased arterial elasticity.15 Paquin et al. describe the opposite scenario in patients with prior PE, where their arterial health profile is characterized by increased arterial stiffness, augmentation index, and central BP, out of proportion to brachial BP. The results of this study add to the body of work demonstrating that conventional risk stratification tools may not be sufficient in patients with prior PE, particularly those that rely on brachial definitions of hypertension. This paper has several strengths, including a uniform definition of PE as defined by the Society of Obstetricians and Gynecologists of Canada, and a standard definition for hypertension, which larger registry-based studies and meta-analyses lack, limiting their generalizability and clinical utility.16 The diagnosis and management of hypertension in pregnancy are currently at an inflection point, where we have both better evidence as to the safety of treatment for hypertension in pregnancy17 and momentum to treat chronic hypertension more aggressively.18 It is not difficult to imagine a future where, acknowledging the safety of treatment and significant future cardiovascular risk associated with HDP even after BP elevations appear to “resolve,” the definition of hypertension in pregnancy will shift to a lower threshold of ≥130/80 mm Hg. Additional studies that evaluate maternal and fetal outcomes, long-term maternal health, and subclinical, noninvasive markers of cardiovascular disease at lower BP targets, either brachial or central, will be important tools in evaluating the evidence for and implications of such a significant shift in practice. One limitation of this analysis, as in all studies evaluating women solely postpartum, is that it is difficult to identify whether alterations in vascular health preceded the onset of PE or whether PE caused the vascular dysfunction. It is highly likely that there is a combination of both confounding and causal pathways that link arterial health and PE. For example, women in this study with PE had significantly higher BMI, waist-to-hip ratios, and lipids, all of which are associated with PE risk and future cardiovascular disease, and furthermore, were not adjusted for in this analysis. On the other hand, the PE-noHTN group experienced a seemingly transient hypertensive episode, but still have clearly identifiable alterations in aortic stiffness, wave reflections, and steady arterial load, suggesting PE may be causing direct damage to the arterial system. Additional clarity on cause and effect could be gleaned from studies linking phenotypes of PE, including preterm PE, PE with severe features, or PE superimposed on chronic hypertension, to certain hemodynamic profiles. In this study, only 4 women with PE had known hypertension prior to PE, limiting the ability to draw significant conclusions from this cohort. This study focuses on markers of arterial dysfunction and their potential use in risk stratification, but the question of what interventions are needed to mitigate future cardiovascular risk are still unclear. Should patients with prior PE be treated the same as other high-risk patients, such as those with prior smoking or diabetes? The authors do mention the importance of lifestyle interventions in modulating arterial hemodynamics in patients with history of PE. However, PE disproportionately affects black populations and populations with lower socioeconomic status who may have poor access to care.19 Recommending healthy diet and exercise without pushing for larger structural changes in the healthcare system is unlikely to fully address the needs of this high-risk group. While HDP and other pregnancy complications should be independently assessed when evaluating a patient’s cardiovascular risk, a deeper understanding of different PE phenotypes is needed. HDP encompasses a spectrum of disease and studies have shown a direct link between the severity, onset and recurrence of the disease and the association to cardiovascular risk.1,5,20 However, there is no consensus on long-term surveillance for patients based on the manifestation of their HDP. After patients graduate from their obstetric care, they get grouped into a singular category of “history of preeclampsia” leaving little to no clinical utility for their primary providers. Deepening our knowledge on the relationship between HDP and cardiovascular disease, and increasing the precision of our risk prediction, can drive change to a more individualized care approach. A large subset of the younger population is captured into healthcare during pregnancy. A nuanced understanding of the associations that includes an understanding of pathophysiology will allow us to meaningfully incorporate obstetric history into risk stratification and offer surveillance and primary interventions accordingly. There is a long way to go in that pursuit, but this paper does take us decidedly in the right direction. The authors declared no conflict of interest.

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