Angiogenic biomarker concentrations and their relation to coronary atherosclerosis in women with a history of preeclampsia: Findings from the CPH ‐ PRECIOUS study

INTRODUCTION: Preeclampsia is known to be associated with a two- to fourfold elevated risk of developing cardiovascular disease in the first 15 years following pregnancy. In this cross-sectional study of 892 women with prior preeclampsia, we aimed to assess differences in circulating angiogenic biomarker concentrations according to CT-assessed coronary atherosclerosis in women up to 28 years after an index pregnancy complicated by preeclampsia. MATERIAL AND METHODS: Women were identified from clinical databases consisting of data from all deliveries within the Capital Region of Denmark from 1995 onwards. Women with prior preeclampsia and a current age between 35 and 55 years were included from the CPH-PRECIOUS cohort. The primary outcome was differences in circulating angiogenic biomarkers according to CT-assessed coronary atherosclerosis. RESULTS: The median time since the pregnancy complicated by preeclampsia was 12.5 years (range: 0-28 years). PlGF concentrations were significantly higher in women with coronary atherosclerosis (9.6 pg/mL [IQR 4.9-12.6] vs. 7.4 pg/mL [IQR 3.9-11.3], p = 0.001), and subsequently a lower calculated sFlt-1/PlGF ratio (4.2 [IQR 3.1-6.3] vs. 5.0 [IQR 3.6-6.9], p = 0.001) was found. No differences in sFlt-1 concentrations were observed. Higher PlGF concentrations were significantly associated with coronary atherosclerosis; however, associations were attenuated in adjusted analysis. CONCLUSIONS: This is the first large study to investigate long-term differences in circulating angiogenic biomarker concentrations after preeclampsia, highlighting the complex relationship between angiogenic biomarkers, preeclampsia, and later atherosclerotic burden.