Cardiac Measures Offer No Added Value to Preeclampsia Screening

Women who develop preeclampsia (PE) during pregnancy have some cardiovascular red flags long before PE appears, particularly peripheral vascular resistance and mild reduction in left ventricular (LV) function. However, these indices do not appear to improve the performance of current preeclampsia screening, new research suggests.

Investigators analyzed data from more than 4700 pregnancies in women who presented for a routine visit between 19- and 23-weeks' gestation. After adjusting for covariates, they found that peripheral vascular resistance was significantly higher and LV functional cardiac indices were lower in women who subsequently went on to develop PE.

However, these cardiac indices did not actually augment the performance of PE screening on top of maternal risk factors, mean arterial pressure (MAP), and biomarkers of placental perfusion and function.

"Our study showed that pregnant women at risk for preeclampsia, compared to those who had a normotensive pregnancy, long before the development of this pregnancy complication had mild deterioration of their left ventricular systolic function and increased peripheral resistance — cardiovascular changes not fully accounted for by their underlying risk factor profile and unrelated to markers of placental perfusion and function," senior author Marietta Charakida, MD, PhD, senior clinical lecturer and consultant in fetal and pediatric cardiology, Kings College, London, England, told theheart.org | Medscape Cardiology.

"Despite this observation, however, regular assessment of maternal cardiovascular system in pregnancy is not justified by our results, as these measurements did not improve the performance of screening for PE, which was based on maternal characteristics and medical history, or a combination of maternal risk factors and mean arterial pressure and markers of placental perfusion and function," she said.

The study was published online January 4 in the Journal of the American College of Cardiology.

What Increases Cardiovascular Risk?

"Observations have shown that women with preeclampsia are at increased risk for adverse cardiovascular outcome, but it remains unclear whether preeclampsia or the preexisting 'fragile' cardiovascular system of a woman increases her risk," Charakida said.

"In the current study, we investigated whether women who subsequently develop preeclampsia have evidence of preexisting cardiovascular alterations and examined the contribution of cardiovascular changes in the development of preeclampsia," she said.

Commenting for theheart.org | Medscape Cardiology, Karen Florio, DO, MPH, associate professor and assistant program director of the Maternal-Fetal Medicine Fellowship Program, Department of Obstetrics and Gynecology, Saint Luke's Hospital, University of Missouri–Kansas City, said that "the authors' current individualized, first-trimester SPREE [screening program for preeclampsia] risk model has outperformed all other risk prediction models in the detection of both term and preterm preeclampsia."

In the current model, the risk of development of PE arises in the presence of several factors: advancing maternal age; increasing weight; Black and South Asian origin; history of chronic hypertension, diabetes mellitus, systemic lupus erythematosus, or antiphospholipid syndrome; conception by in vitro fertilization; and family or personal history of PE, the authors state.

MAP, mean uterine artery pulsatility index (UtA-PI), placental growth factor (PIGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) are "useful biomarkers" for the subsequent development of PE.

In an accompanying editorial, Florio noted that prior research has shown that "women destined to develop preeclampsia experience an increase in LV mass and filling pressures identified in late gestation, so the next logical step [for the researchers] was to assess whether cardiac indices were useful in predicting impending disease at mid-gestation and whether the addition of these parameters would contribute to the predictive value of the SPREE model."

No Added Predictive Value

The researchers studied women at King's College Hospital, who presented for a routine visit at 19 to 23 weeks' gestation (n = 4795; mean gestational age, 21.3 weeks). Information collected during this visit included:

Maternal demographics
Medical history
Ultrasonographic examination for fetal anatomy and growth
Maternal cardiovascular assessment
Measurement of MAP
Blood pressure (BP)
Weight and body mass index (BMI)
Transvaginal color Doppler ultrasonography of the left and right uterine arteries and calculation of the UtA-PI
Measurement of the serum concentration of PIGF and sFlt-1

The outcome measure was delivery with PE, with a diagnosis of PE based on the finding of new-onset hypertension developing after 20 weeks' gestation or chronic hypertension with one of several conditions (e.g., proteinuria, thrombocytopenia, or pulmonary edema).

Of the women, 2.6% developed PE (including 0.6% of deliveries with PE at < 37 weeks' gestation), and 2.3% developed gestational hypertension (GH).

Compared with unaffected women, those in the PE group had a higher median maternal weight (70.6 [IQR, 63.5 - 79.9] vs 76.0 [68.0 - 88.7] kg, respectively) and BMI (25.5 [23.1 - 28.7] vs 27.5 [24.3 - 31.8] kg/m2, respectively; both Ps < .0001), as well as a higher incidence of chronic hypertension, family history of PE, conception by in vitro fertilization, nulliparity, and previous history of PE.

Compared with unaffected pregnancies, those with GH also had higher median maternal weight and BMI (77.0 [69.3 - 87.0] and 28.0 [20.9 - 21.6] kg, respectively; both Ps < .0001).

Both the PE and the GH groups had higher UtA-PI, systolic and diastolic BP, and MAP compared with unaffected pregnancies.

Multivariable analyses showed that peripheral vascular resistance was "significantly higher and LV global longitudinal systolic strain, ejection fraction, cardiac output, and left atrial area were mildly lower" in women who went on to develop PE, compared with those who did not, the authors state. But after accounting for multiple testing for all cardiac indices, peripheral vascular resistance was the only measurement that remained significantly higher.

A "weak association was found between maternal cardiovascular indices and biomarkers of placental perfusion and function," the authors report.

The detection rates of delivery with PE at < 37 weeks' gestation or delivery with PE at any gestational age (at a 10% screening positive rate) in screening by maternal demographic characteristics and medical history or combinations of maternal risk factors with MAP, UtA-PI, PIGF, and sFlt-1 "were not improved by the addition of peripheral vascular resistance," the authors report.

Charakida noted that women at risk of PE commonly have a "constellation of adverse risk factors," such as increased BMI and BP, which "need to be monitored during pregnancy and thereafter." Moreover, women at risk of PE "have evidence of increased afterload, and this likely places a higher strain in their left ventricular function during pregnancy."

However, she cautioned, "there is no evidence as yet that routine cardiovascular assessment of women during pregnancy can improve the prediction of who is likely to develop preeclampsia."

Take-Home Messages for US Clinicians

Florio said she has "the utmost respect for this group, which has done incredible work in the prediction of preeclampsia and has produced an amazing article looking at adding or attempting to add additional predictors to their model."

She noted that the "most important takeaway for those of us residing in America is that implementing these types of predictor models for the development of preeclampsia at this juncture in our healthcare system is not feasible to implement, due to cost — especially since many of the women at highest risk are poverty-stricken or minorities and underinsured or uninsured."

For clinicians practicing in the United States, "the take-home message is to continue using the guidelines of the USPSTF to inform which women at major or minor risk should receive preventive treatment with aspirin."

This study was supported by a grant from the Fetal Medicine Foundation. Charakida, her coauthors, and Florio have disclosed no relevant financial relationships.

J Am Coll Cardiol. 2022;79:63-65, 52-62. Abstract, Editorial

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