Objective
We sought to assess vascular structure and function in early- and late-onset preeclampsia (PE) at the time of diagnosis.
Study Design
We evaluated 100 PE cases subdivided into 50 early- and 50 late-onset cases according to gestational age at onset (</>34 weeks), and 100 controls paired by maternal age and gestational age at scan with cases. Carotid intima-media thickness (IMT), distensibility, and circumferential wall stress together with inferior vena cava (IVC) collapsibility were assessed by ultrasound.
Results
Early PE was characterized by increased carotid IMT diameters, and arterial stiffness with no significant changes in IVC parameters as compared to normotensive pregnancies. Late PE was characterized by significantly increased carotid IMT and lumen diameters as compared to controls while arterial stiffness, as expressed by distensibility, did not provide pronounced changes. A significant decrease of IVC collapsibility index was also observed in late PE as compared to controls.
Conclusion
The current data suggest that distinct vascular adaptations in early and late PE could reflect different pathophysiologic mechanisms. Future studies are warranted to further assess the complex etiologies and clinical expressions of the 2 entities.
Preeclampsia (PE) is a multisystem disorder complicating 5-10% of pregnancies and a leading cause of maternal mortality and morbidity. A substantial body of literature has elucidated in recent years that PE is a cardiovascular risk factor, predictive of subsequent cardiovascular disease and death. Two recent metaanalyses established a 3-fold risk for hypertension and a 2-fold risk of ischemic heart disease and stroke in women with a history of PE. The positive association between PE and later-life cardiovascular disease has been attributed to shared cardiovascular risk factors. Cardiovascular morbidity is currently assessed by carotid intima-media thickness (IMT) and arterial stiffness indices such as pulse wave velocity, augmentation index, distensibility, and circumferential wall stress (CWS). Additionally, inferior vena cava (IVC) is a compliant vein reflecting venous responsiveness to hemodynamic changes. Evaluation of these parameters in preeclamptic women has provided conflicting results, which could possibly be explained by the heterogeneity of PE syndrome.
Recent data have supported that classifying PE into early- and late-onset disease differentiates 2 distinct clinical forms with pathophysiological specific features. Thus, early PE is commonly associated with placental insufficiency, intrauterine growth restriction, and adverse maternal and perinatal outcomes. Conversely, late-onset PE is associated with minor placental involvement and milder clinical disease. Intrinsic placental factors are more frequently altered in early PE while late PE is usually associated with predisposing maternal factors.
In this study, we hypothesized that early and late PE present distinct types of vascular structural and functional changes already at the time of diagnosis. Thus, we sought to comprehensively describe carotid IMT, carotid distensibility, CWS, and IVC collapsibility in normotensive, early-onset preeclamptic, and late-onset preeclamptic women to explore the existence of these differences.
Materials and Methods
Study population
This prospective cohort study included 100 normotensive and 100 preeclamptic pregnancies. PE was defined according to the International Society for the Study of the Hypertension in Pregnancy as a resting blood pressure of ≥140/90 mm Hg on 2 occasions at least 4 hours apart and proteinuria of ≥300 mg/L or a 2+ urine dipstick >20 weeks of gestation in a previously normotensive woman. Further, the affected pregnancies were subdivided into: (1) 50 cases of early-onset PE defined as PE occurring <34th week of gestation; and (2) 50 cases of late-onset PE occurring >34th week of gestation.
The pregnant women with PE were recruited and evaluated within ≥24 hours of diagnosis while admitted to the Department of Obstetrics at the Hospital Clinic, University of Barcelona. All were receiving intravenous fluids and anticonvulsive and/or antihypertensive medication. Women without confirmed history of PE, diabetes mellitus, and renal and connective tissue disease were included in the study. Smokers and women with history of chronic hypertension were considered initially eligible. Women were considered as having chronic hypertension if hypertension (blood pressure of ≥140/90 mm Hg) predated pregnancy or developed <20th week of pregnancy.
The normotensive group comprised women attending antenatal clinic with uncomplicated pregnancies matched 1 to 1 by maternal age and gestational age at exploration to preeclamptic women. Only healthy nonsmoking women, not affected by current or anterior pregnancy complications or intrauterine growth restriction, were included in the control group.
Information on maternal demographic characteristics, reproductive history, and current pregnancy clinical data was obtained in the interview at the day of the scan and through medical history notes. Fetoplacental Doppler examination included uterine arteries, umbilical artery, and middle cerebral artery. Cerebroplacental ratio was calculated as a simple ratio of the middle cerebral artery pulsatility index divided by the umbilical artery pulsatility index. Pregnancy outcome such as gestational age at delivery, mode of delivery, birthweight, birthweight centile, Apgar score, and umbilical pH were recorded a posteriori. In all pregnancies gestational age was calculated based on the crown-rump length at first-trimester ultrasound. Fetal and neonatal weight centile were calculated according to local reference curves. Ethics approval was received by the local research ethics committee and written informed consent form was obtained from patients.
Vascular assessment
The study was designed to evaluate several components of vascular structure and function. Remodeling is defined as the modification of arterial shape and size (IMT and lumen diameters) to adapt to hemodynamic changes. Arterial distensibility and CWS are measures of arterial stiffness and consequently of arterial function. IVC collapsibility is defined as venous distensibility in response to hemodynamic changes. And finally, “responsiveness” is considered a generic term applied to both arterial and venous structural and functional changes.
The exploration was performed in a quiet environment with the pregnant women in a supine position with slight hyperextension and rotation of the neck in an opposite direction to the probe. The assessment protocol included initially blood pressure measurement by a validated ambulatory automated Omron 5 Series device (Omron Healthcare, Kyoto, Japan). Carotid ultrasound assessment was subsequently performed by a single experienced investigator using a Siemens Sonoline Antares (Siemens Medical Systems, Malvern, PA). Longitudinal clips of the far wall of both carotid arteries were obtained approximately 1 cm proximal to the bifurcation using a 13-MHz linear-array transducer. Carotid IMT measurements were performed offline according to a standardized protocol based on a trace method with the assistance of a computerized program (Siemens Syngo Arterial Health Package; Siemens Medical Systems). To obtain IMT, 3 end-diastolic frames were selected across a length of 10 mm and analyzed for mean and maximum IMT in end-diastole, and the average reading from these 3 frames was calculated. Simultaneous electrocardiogram recording ensured an accurate R-wave still-frame selection. Systolic and diastolic arterial diameters were acquired at the sites corresponding at the IMT measurements. They were evaluated offline with the same computerized program at end-systole and end-diastole.
Arterial distensibility was calculated as: 2 × 1000 × (systolic carotid artery diameter – diastolic carotid artery diameter)/ (diastolic carotid artery diameter) × (brachial pulse pressure). Pulse pressure denotes the difference between systolic and diastolic blood pressure and was converted from millimeters of mercury to kilopascals (kPa; 1 mm Hg = 0.133 kPa). CWS was calculated as: CWS = MBP × dD/2 × carotid IMT, where MBP denotes mean blood pressure and was also converted from millimeters of mercury to kilopascals, and dD denotes diastolic diameter.
IVC diameter changes were evaluated during the respiratory cycle by ultrasound M-mode as depicted in Figure 1 . All examinations were performed in the supine position with 6-MHz curvilinear transducer placed in a subxyphoid plane. Sagittal sections of the upper part of IVC behind the liver were obtained. Respiratory variations of the vessel diameter were evaluated offline during inspiration (IVCi) and expiration (IVCe) with Siemens Syngo Arterial Health Package. The difference between IVCe and IVCi is defined as collapsibility and collapsibility index is the ratio IVCe – IVCi/IVCe.
