Early-onset preeclampsia predisposes to preclinical diastolic left ventricular dysfunction in the fifth decade of life: An observational study

PLoS One. 2018 Jun 12;13(6):e0198908. doi: 10.1371/journal.pone.0198908. eCollection 2018.


Background: Systemic inflammation, endothelial dysfunction and deficient vascularization of either uterus or myocardium are mechanistic hallmarks of early-onset preeclampsia and heart failure with preserved ejection fraction (HFpEF). HFpEF is especially prevalent in elderly women and preceded in middle age by preclinical left ventricular (LV) diastolic dysfunction. To detect if preeclampsia predisposes to HFpEF at later age, echocardiographic indices of LV function and of LV structure and biomarkers of systemic inflammation and of endothelial dysfunction were compared in middle-aged women with a history of early-onset preeclampsia or uncomplicated pregnancy.

Methods and findings: Middle-aged women with a history of early-onset preeclampsia (n = 131) or uncomplicated pregnancy (n = 56) were prospectively recruited 9 to 16 years after pregnancy. Women with a history of preeclampsia had higher body mass index (p = 0.006), blood pressure (p<0.001) and plasma levels of interleukin-6 (p = 0.005) and soluble intercellular adhesion molecule-1 (sICAM-1) (p = 0.014). They had thicker septal (p = 0.001) and posterior (p = 0.003) LV walls and worse diastolic LV function evident from reduced mean mitral annular lengthening velocity (E'mean; p = 0.007) and higher ratio of early diastolic mitral flow velocity (E) over E'mean (E/E'mean; p<0.001). Differences of sICAM-1, E'mean and E/E'mean remained significant after accounting for BMI and blood pressure.

Conclusions: History of preeclampsia predisposes in middle age to worse LV diastolic function, which could increase the likelihood of later HFpEF development. This predisposition derives not only from persistent cardiovascular risk but may also be caused by persistent endothelial dysfunction hindering adequate vascularization in the uterus during pregnancy and in the myocardium in middle age.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Case-Control Studies
  • Diastole*
  • Disease Susceptibility*
  • Echocardiography, Doppler
  • Female
  • Heart Failure / etiology*
  • Heart Failure / physiopathology
  • Humans
  • Middle Aged
  • Pre-Eclampsia / physiopathology*
  • Pregnancy
  • Prospective Studies
  • Ventricular Dysfunction, Left / etiology*
  • Ventricular Dysfunction, Left / physiopathology

Grant support

This research was funded, in part, by a grant from the Dutch Heart Association. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for this study.