Multiplex Analysis of Circulating Maternal Cardiovascular Biomarkers Comparing Preeclampsia Subtypes

Abstract

Preeclampsia, a hypertensive pregnancy disorder, links to increased long-term maternal cardiovascular disease (CVD). The risk is further increased with early-onset preeclampsia (EPE) and delivery of a growth-restricted child. We hypothesized that circulating biomarkers associated with CVD risk differed between preeclampsia subtypes and controls. We compared EPE; n=37, delivery <week 34, late-onset preeclampsia (LPE); n=29, delivery ≥week 34, and normotensive controls (n=49) using Olink Proseek multiplex CVD I assay (targeting 92 biomarkers). We stratified analysis to uteroplacental spiral artery acute atherosis presence in preeclampsia patients, sharing morphological similarities with atherosclerosis. We found 47 CVD-related biomarkers differing between the groups, 42 markers between normotensive controls and EPE, 28 markers between normotensive controls and LPE, and 9 markers between EPE and LPE. Among these 9 markers, ST2 (ST2 protein), MMP (matrix metalloproteinase) 1, MMP3, and fractalkine (CX3CL1) were uniquely dysregulated in EPE. Principal component (PC) analysis of the differing markers identified 4 clusters (named PC1–PC4) that largely separated the preeclampsia and control groups as well as pregnancies with low and high circulating PlGF (placental growth factor). The combination of the single markers PlGF, ST2, MMP1, MMP3, and CX3CL1 had a high discriminatory property to differentiate between EPE and LPE. Preeclampsia with acute atherosis or with fetal growth restriction could be differentiated by Olink biomarkers as compared with preeclampsia without these features. We identified specific CVD-related biomarkers in pregnancy depending on preeclampsia subtypes and uteroplacental acute atherosis. Assessment of these pregnancy measured biomarkers’ relation to long-term cardiovascular dysfunction and hard end points is warranted.

Failure of physiological transformation and spiral artery atherosis: their roles in preeclampsia

“…Another of our recent papers suggests that older women with decidual acute atherosis (both preeclamptic and normotensive pregnancies) have a lipidemic profile resembling that of patients with atherosclerosis, including elevated levels of apolipoprotein B and LDL. 94 Furthermore, we recently showed that the presence of decidual acute atherosis or other evidences of placental dysfunction (eg, low levels of PlGF) was associated with dysregulated patterns of circulating cardiovascular diseaseerelated multiplex biomarkers at delivery, 95 supporting our model of potentially shared mechanisms.…”

Differences in maternal soluble ST2 levels in the third trimester of normal pregnancy versus preeclampsia

“…This difference may have been caused by a disproportionate occurrence of early- and late-onset preeclampsia in our sample. Women with early-onset preeclampsia had higher sST2 concentrations than those with late-onset preeclampsia [18] , [19] . This phenomenon resulted from higher cytokine concentrations (such as IL-12, TNF-α, and IL-1β) in early- versus late-onset preeclampsia [11] .…”

Maternal Blood-Based Protein Biomarkers in Relation to Abdominal Fat Distribution Measured by Ultrasound in Early Mid-Pregnancy

“…A possible limitation is that the Olink biomarkers are reported as relative values and not absolute values, which could complicate comparisons with other studies. However, a study investigating preeclampsia subtypes using an Olink CVD biomarker panel compares the result of one biomarker (PlGF) with that from an immunochemiluminescence assay and reports an excellent correlation [47]. Another limitation is that the Olink protein biomarkers were measured only once.…”