Are Early Pregnancy Blood Pressure Patterns a Crystal Ball for Predicting Preeclampsia and Gestational Hypertension?

HomeJournal of the American Heart AssociationAhead of PrintAre Early Pregnancy Blood Pressure Patterns a Crystal Ball for Predicting Preeclampsia and Gestational Hypertension? Open AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citations ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toOpen AccessEditorialPDF/EPUBAre Early Pregnancy Blood Pressure Patterns a Crystal Ball for Predicting Preeclampsia and Gestational Hypertension? William E. AckermanIV, Irina A. Buhimschi and Catalin S. Buhimschi William E. AckermanIVWilliam E. AckermanIV *Correspondence to: William E. Ackerman IV, MD, Department of Obstetrics and Gynecology, University of Illinois College of Medicine – Chicago, 820 South Wood St MC 808, Chicago, IL 60612. Email: E-mail Address: [email protected] https://orcid.org/0000-0001-7366-3903 , Department of Obstetrics and Gynecology, , University of Illinois College of Medicine at Chicago, , Chicago, , IL, Search for more papers by this author , Irina A. BuhimschiIrina A. Buhimschi https://orcid.org/0000-0002-1701-1326 , Department of Obstetrics and Gynecology, , University of Illinois College of Medicine at Chicago, , Chicago, , IL, Search for more papers by this author and Catalin S. BuhimschiCatalin S. Buhimschi https://orcid.org/0000-0001-6751-8072 , Department of Obstetrics and Gynecology, , University of Illinois College of Medicine at Chicago, , Chicago, , IL, Search for more papers by this author Originally published12 Jul 2023https://doi.org/10.1161/JAHA.123.031068Journal of the American Heart Association. 2023;0:e031068In the United States, hypertension is responsible for more cardiovascular disease deaths than any other modifiable cardiovascular disease risk factor.1 Much has been debated about the 2017 American College of Cardiology/American Heart Association guidelines, which define normal blood pressure (BP) as systolic <120 mm Hg and diastolic <80 mm Hg.2 For most clinical practitioners, controlling BP within this range has become an attainable goal. The obstetrical community, however, has been required to confront how the 2017 American College of Cardiology/American Heart Association guidelines would impact the definitions and therapeutic recommendations for pregnancy‐associated hypertensive conditions, considering that disease classifications in the pregnant population have been based on different BP cut‐offs.3During the last century, the definitions for hypertensive disorders of pregnancy (HDP) have changed several times, with the most recent guidelines from the American College of Obstetricians and Gynecologists published in 2013.4 According to these recommendations, HDP is diagnosed when BPs are ≥140 mm Hg systolic or ≥90 diastolic mm Hg on 2 occasions at least 4 hours apart after 20 weeks of gestation in a pregnant person with a previously normal BP.4, 5 Unsurprisingly, and in contrast to the general population, the threshold for initiating antihypertensive therapy during pregnancy continues to be debated. Unlike other specialties, obstetricians are frequently challenged to balance maternal and fetal risks simultaneously. For example, maternal BP should be therapeutically lowered to prevent serious risks (such as maternal stroke, myocardial infarction, or placental abruption) and maintain an adequate placental–fetal blood flow during gestation (which decreases significantly when maternal BPs reach severe elevations due to vasoconstriction)6, 7, 8; however, antihypertensive use in pregnancy can confer risks such as fetal growth restriction through direct exposure of the fetus to medication or poor placental perfusion.9Outside of pregnancy, evidence supports the concept that reducing target BP thresholds decreases cardiovascular disease burden; during pregnancy, the beneficial effects of more tightly controlled BP have only recently been demonstrated.10, 11 To date, however, this evidence applies only in the context of chronic hypertension, leaving unresolved the need for tight BP control in other pregnancy‐associated hypertension disorders such as gestational hypertension (GHTN) and early‐onset preeclampsia (PE). From a pragmatic standpoint, it is reasonable to consider initiating therapeutic or preventive interventions soon after pregnancy is confirmed or, if that opportunity is missed, when a specific hypertensive condition is first identified clinically. This concept is not new, but aligns with the 2023 US Preventive Services Task Force recommendations to screen for hypertensive disorders in asymptomatic pregnant persons with BP measurements throughout pregnancy.12In this issue of the Journal of the American Heart Association JAHA, Gunderson and colleagues examined the utility of early pregnancy BP trajectory (BPT) groups for predicting HDP, specifically GHTN and PE, among low‐to‐moderate‐risk pregnancies.13 This report complements and extends their recent work14 in which 6 BPT groups associated with HDP were identified using latent class growth modeling.The current study leveraged a large and diverse retrospective cohort of parous subjects (n=249 892) from the Kaiser Permanente Northern California health system collected over 10 years. The cohort included singleton gestations with prenatal care entry ≤14 weeks. To focus on a population with a low‐to‐moderate risk for HDP, the study excluded individuals with serious medical conditions, pre‐existing stage 2 BP elevations, antihypertensive use <20 weeks, and personal history of HDP. Longitudinal BP patterns were constructed using BP measurements from prenatal outpatient visits during the first 20 weeks' gestation. A random 70 to 30 data split was used to generate training and validation sets for multivariable, multinominal logistic regression modeling, assessed according to transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) criteria.15 Relevant predictor variables were selected using the least absolute shrinkage and selection operator (LASSO) machine learning method, and separate models were fit for predicting the risk of the 3 major HDP outcomes: GHTN, early‐onset PE (<34 weeks), and late‐onset PE (≥34 weeks).The authors found that for these low‐to‐moderate‐risk individuals, predictive models incorporating BPT groups in addition to select risk factors (body mass index >30 kg/m2, nulliparity, age ≥35 years, race and ethnicity, and presence of diabetes) exhibited substantially better discriminative ability for GHTN and both early‐ and late‐onset PE (C‐statistic ranging from 0.731 to 0.770) than models based on risk factors alone (C‐statistic ranging from 0.688 to 0.695). Discrimination was also improved over models using only an initial BP measurement plus standard risk factors (C‐statistic ranging from 0.713 to 0.744). For each of the 3 major HDP outcomes considered, the adjusted odds ratios increased stepwise along a gradient of the named BPT groups: ultra‐low‐declining (lowest odds), low‐declining, moderate‐fast‐decline, low‐increasing, moderate‐stable, and elevated‐stable (highest odds). The absolute observed HDP risk, which ranged broadly in accordance with the BPT group strata, was closely approximated by the model predictions; this held across a variety of clinical risk factor stratifications, demonstrating the excellent model calibration.The highest 3 BPT groups (low‐increasing, moderate‐stable, and elevated‐stable) identified 77% of the HDP cases in the internal validation cohort with a specificity of 51%. For a given moderate risk factor, BPT group stratification revealed subsets of individuals at significantly higher risk for PE and GHTN than risk factors alone would suggest. Additionally, the BPT‐informed models reduced HDP risk for a substantial proportion of patients relative to that predicted based on current US Preventive Services Task Force guidelines.16 Sensitivity analysis showed that while the accuracy of BPT group assignment improved proportionally with the number of serial BP measurements available, as few as 3 to 4 BP measurements could be predictive: 85.2% and 93.3% of subjects retained their original BPT assignments when the analysis was restricted to ≤3 and ≤4 BP measurements, respectively.The current findings by Gunderson and colleagues are provocative. As with any promising area of inquiry, more research is required to determine how robust the presented models might prove to be in practice. External validation cohorts, particularly those comprising racial and ethnic compositions different from those available in this study, are needed to determine the applicability of the models beyond the internal validation group. Evaluation of the models in prospective settings likewise awaits further investigation. Additional research into predictive model development may help optimize the number of BPT groups needed and refine the requirements for BP measurement in terms of quantity and timing. Further improvements in model performance may also be realized through integration with other routinely collected electronic medical record data.17Predicting PE and GHTN in the general population remains highly challenging in clinical practice. Multimarker methods for HDP risk stratification have yet to be widely adopted, partly due to low positive predictive values in low‐risk populations, associated costs, lack of standardization, and limited evidence for generalizability.5 However, serial antenatal BP measurements early in gestation have shown potential for HDP discrimination, even when as few as 3 to 4 BP measurements are used. For example, data from the EAGeR (Effects of Aspirin in Gestation and Reproduction) trial demonstrated an association between preconception and early pregnancy BP changes and subsequent HDP.18 Similarly, a report from the nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers‐to‐Be) study found that BP trajectories during preconception and early pregnancy were independently associated with a later risk of GHTN and PE.19 Using routine, serial BP measurements to supplement standard risk factors is an attractive solution to improve HDP screening, considering that these measures are inexpensive and nearly universally available. Nevertheless, reaching these goals may not be easy. Predicting risk for GHTN or PE among low‐ or moderate‐risk groups in the first half of pregnancy may yet require combination screening involving ultrasound measurements as well as biochemical markers. In addition, increasing access to and compliance with prenatal care to allow for BP monitoring may prove challenging. However, the continuous development and improvement of wearable technologies might fill some of these gaps in the future.A need for the development of improved methods for early risk stratification during pregnancy has been recognized by the American College of Obstetricians and Gynecologists4 and endorsed by the US Preventive Services Task Force.20 We recognize that algorithmic risk stratification by the 20th week of gestation could improve precision medicine. It could help identify patients in need of enhanced surveillance and personalized care while reducing monitoring and treatment of bona fide low‐risk pregnancies. Although models such as those developed by Gunderson and colleagues likely require refinement before full implementation, it is reasonable to expect that clinical assessment tools incorporating longitudinal BP measurements will one day be available to help guide personalized decision‐making during pregnancy.DisclosuresNone.Footnotes*Correspondence to: William E. Ackerman IV, MD, Department of Obstetrics and Gynecology, University of Illinois College of Medicine – Chicago, 820 South Wood St MC 808, Chicago, IL 60612. Email: [email protected]eduThis manuscript was sent to Jennifer Tremmel, MD, Associate Editor, for editorial decision and final disposition.See article by Gunderson et al.For Disclosures, see page 3.References1 Facts about hypertension Centers for Disease Control and Prevention. 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Screening for preeclampsia: US Preventive Services Task Force recommendation statement. JAMA. 2017; 317:1661–1667. doi: 10.1001/jama.2017.3439CrossrefMedlineGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. 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Published on behalf of the American Heart Association, Inc., by Wiley BlackwellThis is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.https://doi.org/10.1161/JAHA.123.031068PMID: 37435794 Manuscript receivedJune 8, 2023Manuscript acceptedJune 12, 2023Originally publishedJuly 12, 2023 KeywordsEditorialshypertensionpredictionpreeclampsiapregnancyPDF download SubjectsHigh Blood PressureHypertensionPreeclampsiaPulmonary Hypertension