Imbalanced Angiogenesis in Peripartum Cardiomyopathy - Diagnostic Value of Placenta Growth Factor

Circ J. 2017 Oct 25;81(11):1654-1661. doi: 10.1253/circj.CJ-16-1193. Epub 2017 May 27.

Abstract

Background: Concentrations of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) are altered in peripartum cardiomyopathy (PPCM). In this study we investigated changes in the angiogenesis balance in PPCM.Methods and Results:Plasma concentrations of sFlt-1 and the pro-angiogenic placenta growth factor (PlGF) were determined in patients with PPCM during the post-partum phase (n=83), in healthy women at delivery (n=30), and in patients with acute heart failure (AHF; n=65). Women with cardiac failure prepartum or associated with any form of hypertension, including pre-eclampsia, were excluded. Compared with non-pregnant women, in women with AHF and PPCM, median PlGF concentrations were greater (19 [IQR 16-22] and 98 [IQR 78-126] ng/mL, respectively; P<0.001) and the sFlt-1/PlGF ratio was lower (9.8 [6.6-11.3] and 1.2 [0.9-2.8], respectively; P<0.001). The sFlt-1/PlGF ratio was lower in PPCM than in normal deliveries (1.2 [0.9-2.8] vs. 94.8 [68.8-194.1], respectively; P<0.0001). The area under the curve for PlGF (cut-off value: 50ng/mL) and/or the sFlt-1/PlGF ratio (cut-off value: 4) to distinguish PPCM from either normal delivery or AHF was >0.94. Median plasma concentrations of the anti-angiogenic factor relaxin-2 were lower in PPCM and AHF (0.3 [IQR 0.3-1.7] and 0.3 [IQR 0.3-1] ng/mL, respectively) compared with normal deliveries (1,807 [IQR 1,101-4,050] ng/mL; P<0.001).

Conclusions: Plasma of PPCM patients shows imbalanced angiogenesis. High PlGF and/or low sFlt-1/PlGF may be used to diagnose PPCM.

Keywords: Angiogenesis; Peripartum cardiomyopathy (PPCM); Placental growth factor; Relaxin-2.

MeSH terms

  • Cardiomyopathies / blood*
  • Cardiomyopathies / diagnosis
  • Female
  • Heart Failure / diagnosis
  • Humans
  • Neovascularization, Pathologic / blood*
  • Peripartum Period
  • Placenta Growth Factor / blood*
  • Pregnancy
  • Vascular Endothelial Growth Factor Receptor-1 / blood*

Substances

  • Placenta Growth Factor
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1