Cardiovascular function and biomarkers in women with preeclampsia

Background: Preeclampsia (PE) is a multisystem disorder peculiar to human pregnancy and characterized by the onset of hypertension and proteinuria after the 20th week of gestation. The pathophysiology of this disorder is still not clear. PE is not only associated with significant maternal and fetal morbidity and mortality during the index pregnancy but also with higher risk of cardiovascular disease later in life.

Overall aim: To study PE-related changes in the function of cardiovascular system and to measure the levels of different biomarkers of PE during pregnancy and after delivery.

Papers I and II: Eighteen women with a history of PE and 17 age-matched controls were enrolled one year after the index pregnancy. All underwent non-invasive ultrasound examination of the brachial artery for evaluation of flow-mediated vasodilatation (FMD). Ambulatory blood pressure and plasma concentrations of lipoproteins, inflammation markers, adhesion molecules, glucometabolic and hemostatic factors, thrombin generation and the levels of microparticles were determined during specific menstrual phases. Women with a history of PE had lower FMD, higher systolic, diastolic and mean arterial pressure during daytime, and a higher degree of insulin resistance. In addition they had a higher total amount of thrombin and platelet-derived microparticles, with no variation during follicular and luteal phases.

Papers III and IV: Thirty-five pregnant women with PE and 30 with normal pregnancy were examined during pregnancy and 3-6 months after delivery. Transthoracic echocardiography and Doppler tissue imaging were performed, and FMD of the brachial artery was examined. The blood levels of amino-terminal pro-brain natriuretic peptide (NT-pro-BNP), C-reactive protein, cystatin C, troponin I and inflammatory and angiogenic markers were measured. Women with PE showed structural and functional alterations in left ventricle and left atrium. They had a higher ratio of early transmitral diastolic flow velocity to early diastolic myocardial velocity (E/E), higher levels of NT-pro-BNP and cystatin C, and lower glomerular filtration rate as estimated using cystatin C both during pregnancy and at follow-up. In addition, the lateral E/E ratio and NT-pro-BNP were higher in women with early-onset, severe PE than in those with late PE. The FMD was decreased in the preeclamptic group at inclusion and at follow-up. Pentraxin 3 (PTX3) and ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (P1GF) were elevated in women with PE pregnancy. Furthermore FMD was lower and PTX3 and ratio of sFlt-1/P1GF were higher in women with early-onset, severe PE than in those with late PE.

Conclusion: Women with a history of PE had persisting identifiable abnormalities of vascular function as well as signs of hypercoagulability and excess platelet-derived microparticles, during both follicular and luteal phases of the menstrual cycle. PE was associated with alterations in the left ventricular structure and function, impaired endothelial function and elevation of cardiovascular biomarkers. These alterations persisted months after delivery and were more clearly visible in women with early-onset and severe PE. In addition, elevated inflammatory and antiangiogenic markers were present in those women, and were especially pronounced in early-onset PE.

List of scientific papers

I. Hamad RR, Eriksson MJ, Silveira A, Hamsten A, Bremme K (2007). "Decreased flow-mediated dilation is present 1 year after a pre-eclamptic pregnancy." J Hypertens 25(11): 2301-7
https://pubmed.ncbi.nlm.nih.gov/17921826

II. Rafik Hamad R, Curvers J, Berntorp E, Eriksson M, Bremme K (2009). "Increased thrombin generation in women with a history of preeclampsia." Thromb Res 123(4): 580-6. Epub 2008 May 22
https://pubmed.ncbi.nlm.nih.gov/18501408

III. Rafik Hamad R, Larsson A, Pernow J, Bremme K, Eriksson MJ (2009). "Assessment of left ventricular structure and function in preeclampsia by echocardiography and cardiovascular biomarkers." J Hypertens Oct 3: Epub ahead of print
https://pubmed.ncbi.nlm.nih.gov/19809366

IV. Rafik Hamad R, Eriksson MJ, Larsson A, Bremme K (2009). "Impaired endothelial function and elevated Pentraxin 3 in early-onset preeclampsia." (Submitted)