The present study is a single-centre prospective study that will enrol pregnant women during their first trimester of pregnancy (11+0 - 13+6 weeks of gestation). During pregnancy, women will undergo standard clinical evaluation and management. During the two study visits (enrollment and 24+0 - 27+6 weeks of gestation) the investigators will perform arterial tonometry (Pulsepen) and in vivo darkfield microscopy (Glycocheck) to evaluate endothelial and vascular function. A urine sample and a blood sample for specific study analyses on metabolic profile, endothelial and angiogenic markers will be collected. Pregnancy outcomes will be collected at delivery and five years after delivery all the participants will be interview to collect long-term cardiovascular outcomes. Serum endothelial and angiogenic markers will be evaluated only in participants who will develop hypertensive disorders of pregnancy and in an equal number of controls matched for age and body mass index at the time of conception.
Primary aim: To determine the role of the combination of arterial tonometry and endothelial glycocalyx measurement in predicting the risk of developing hypertensive disorders in pregnancy. Secondary aims: * To determine the association between circulating markers of angiogenesis and endothelial dysfunction (ANG-1, ANG-2, ET-1, ICAM-1 and VCAM-1) and the development of hypertensive disorders of pregnancy. * To define the trends of serum uric acid, lipids and xanthine oxidase activity in normotensive and hypertensive pregnancies. * To determine the ability of the combination of arterial tonometry and endothelial glycocalyx measurement, performed in the two study visits during pregnancy, in predicting the risk of long-term maternal cardiovascular disease.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
400
Arterial applanation tonometry will be performed at the carotid and femoral level by the PulsePen device (Software WPulsePen version 2.3.1, DiaTecne, Milan, Italy), while the subject is lying in the horizontal position and after 5 minutes of rest.
The in vivo microscopy (GlycoCheck system) is performed in the sublingual capillaries during the morning, with the participant sitting on a chair. The sublingual capillaries are visualized using an SDF video microscope (Capiscope handheld, KK Research technology Ltd).
ELISA assays to measure serum circulating markers of angiogenesis and endothelial dysfunction (ANG-1, ANG-2, ET-1, ICAM-1 and VCAM-1).
Immunochemistry analysis of serum levels of uric acid, total cholesterol, LDL-cholesterol, HDL-cholesterol, Triglycerides, Lipoprotein (a)
Serum xanthine oxidase (XO) activity will be assessed in blood samples measuring the ability of XO to produce uric acid
Cardiovascular Internal Medicine Unit, IRCCS University Hospital of Bologna, Bologna, Italy
Bologna, Italy
RECRUITINGPerfused Boundary Region (PBR)
Micron
Time frame: Baseline visit (11/13+6 weeks of pregnancy)
Perfused Boundary Region (PBR)
Micron
Time frame: Follow-up visit (24/27+6 weeks of pregnancy)
Carotid-femoral pulse wave velocity (cf-PWV)
m/s
Time frame: Baseline visit (11/13+6 weeks of pregnancy)
Carotid-femoral pulse wave velocity (cf-PWV)
m/s
Time frame: Follow-up visit (24/27+6 weeks of pregnancy)
Number of participants with hypertensive disorders of pregnancy
Number of participants diagnosed during pregnancy with any hypertensive disorder of pregnancy
Time frame: From date of enrolment until the date of first documented diagnosis of hypertensive disorder of pregnancy, according to the International Society for the Study of Hypertension in Pregnancy Criteria, assessed up to one week after delivery
Number of participants with preeclampsia
Number of participants diagnosed during pregnancy with preeclampsia according to the International Society for the Study of Hypertension in Pregnancy (ISSHP) criteria.
Time frame: From date of enrolment until the date of first documented diagnosis of preeclampsia, according to the International Society for the Study of Hypertension in Pregnancy Criteria, assessed up to one week after delivery
Serum Angiopoietin 1 (ANG-1)
ng/ml
Time frame: Baseline visit (11/13+6 weeks of pregnancy)
Serum Angiopoietin 1 (ANG-1)
ng/ml
Time frame: Follow-up visit (24/27+6 weeks of pregnancy)
Serum Angiopoietin 2 (ANG-2)
ng/ml
Time frame: Baseline visit (11/13+6 weeks of pregnancy)
Serum Angiopoietin 2 (ANG-2)
ng/ml
Time frame: Follow-up visit (24/27+6 weeks of pregnancy)
Serum Endothelin-1 (ET-1)
Serum concentration assessed by ELISA (pg/ml)
Time frame: Baseline visit (11/13+6 weeks of pregnancy)
Serum Endothelin-1 (ET-1)
pg/ml
Time frame: Follow-up visit (24/27+6 weeks of pregnancy)
Serum Intercellular adhesion molecule-1 (ICAM-1)
ng/ml
Time frame: Baseline visit (11/13+6 weeks of pregnancy)
Serum Intercellular adhesion molecule-1 (ICAM-1)
ng/ml
Time frame: Follow-up visit (24/27+6 weeks of pregnancy)
Serum Vascular Cell Adhesion Molecule-1 (VCAM-1)
ng/ml
Time frame: Baseline visit (11/13+6 weeks of pregnancy)
Serum Vascular Cell Adhesion Molecule-1 (VCAM-1)
ng/ml
Time frame: Follow-up visit (24/27+6 weeks of pregnancy)
Number of participants with long-term cardiovascular outcomes
Number of participants diagnosed with stroke, myocardial infarction, heart failure or hospitalized for cardiovascular disease in the 5 years after delivery
Time frame: Interview 5 years after delivery
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