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Placental growth factor as an indicator of maternal cardiovascular risk after pregnancy

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    • Abstract:
      BACKGROUND: Angiogenic placental growth factor (PlGF) concentrations rise during pregnancy, peaking at the end of mid-pregnancy. Low PlGF concentrations during pregnancy are associated with pregnancy complications with recognized later life cardiovascular risk. We hypothesized that low PlGF concentrations, especially in mid-pregnancy identify not only a subset of women at risk for pregnancy complications, but also women with greater cardiovascular risk factor burden after pregnancy regardless of pregnancy outcome. METHODS: In a population-based prospective cohort study of 5529 women, we computed gestational-age-adjusted multiple of the medians of early pregnancy and mid-pregnancy PlGF concentrations. Information on pregnancy complications (pre-eclampsia, small for gestational age and spontaneous preterm birth) was obtained from hospital registries. Six years after pregnancy we measured maternal systolic and diastolic blood pressure (SBP and DBP), cardiac structure (aortic root diameter [AOD], left atrial diameter [LAD], left ventricular mass [LV mass] and fractional shortening ), carotid-femoral pulse wave velocity and central retinal arteriolar and venular calibers. Blood pressure was also measured nine years after pregnancy. RESULTS: Women were on average 29.8 (SD5.2) years of age in pregnancy, mostly European (55.2%) and 14.8% developed a pregnancy complication. Quartile analysis showed that especially women with mid-pregnancy PlGF in the lowest quartile (the low PlGF subset) had a larger AOD (0.40mm [95%CI; 0.08, 0.73]), LAD (0.34mm [95%CI; −0.09, 0.78]), LV mass (4.6g [95%CI; 1.1, 8.1]) and SBP (2.3mmHg [95%CI; 0.93, 3.6]) six years after pregnancy than women with the highest PlGF. Linear regression analysis showed that higher mid-pregnancy PlGF concentrations were associated with a smaller AOD (−0.24mm [95%CI; −0.39, −0.10]), LAD (−0.75mm [95%CI; −0.95, −0.56]), lower LV mass (−3.9g [95%CI; −5.5, −2.3]) and SBP (−1.1mmHg [95%CI; −1.7, −0.46]). These differences persisted after exclusion of women with complicated pregnancies. CONCLUSIONS: Women with low PlGF in mid-pregnancy have a greater AOD, LAD, and LV mass, and higher SBP six and nine years after pregnancy compared to women with higher PlGF, including women with uncomplicated pregnancies. The pathophysiological implications of lower PlGF concentrations in mid-pregnancy might provide insight towards identifying pathways contributing to greater cardiovascular risk factor burden.
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