Judith Blaauw

Increased Intima-Media Thickness After Early-Onset Preeclampsia

OBJECTIVE: Preeclampsia is associated with cardiovascular atherosclerotic events later in life. However, little is known about earlier subclinical signs of atherosclerosis. We aimed to investigate whether women who recently had preeclampsia show increased intima-media thickness (IMT), as marker of early atherosclerosis, compared with women with normal pregnancies or nulliparous women. METHODS: Intima-media thickness of carotid and femoral arteries measured by ultrasonography, and possible confounding risk factors as body mass index, blood pressure, serum lipids, smoking status, and family history of cardiovascular disease were compared among 22 nulliparous women, 22 primiparous women with normal pregnancy, and 22 primiparous women with early-onset preeclampsia at least 3 months postpartum and 6 weeks after ending lactation RESULTS: Except for slightly higher values for blood pressure, triglycerides, and homocysteine in the formerly preeclamptic women, no other clinical or biochemical differences were observed. The preeclampsia group showed an increased IMT (mean ± standard deviation, 0.63 ± 0.14 mm) of the common femoral artery compared with the normal pregnancy group (0.55 ± 0.06 mm, P = .005) and to the nulliparous group (0.52 ± 0.06 mm, P < .001). These differences remained significant after correction for possible confounders by multiple linear regression analyses. An increase in IMT of the common carotid artery between the normal pregnancy and the nulliparous group was observed, which became significant after adjustment for confounders. CONCLUSION: Preeclampsia and, to a lesser degree, normal pregnancy are associated with increased IMT. The association between increased IMT and (preeclamptic) pregnancy leads to the question of which comes first, which should be addressed in follow-up studies. LEVEL OF EVIDENCE: II-2

Abnormal endothelium-dependent microvascular reactivity in recently preeclamptic women

OBJECTIVE: To assess endothelial function at the level of skin microvasculature, using iontophoretic administration of acetylcholine (endothelium-dependent vasodilator) and sodium nitroprusside (endothelium-independent vasodilator), in women who recently had a preeclamptic pregnancy. METHODS: Microvascular skin reactivity was assessed by laser Doppler perfusion monitoring and iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) in 25 women with a history of early onset preeclampsia and 23 women with previous uncomplicated pregnancies, all of whom were between 3 and 11 months postpartum. RESULTS: Mean (± standard error of the mean) ACh-mediated vasodilatation, expressed as a percentage increase in flux, was higher in women who recently had a preeclampsia than in controls (535 ± 46% versus 314 ± 29%, P < .001). In contrast, SNP-mediated vasodilatation was not significantly different (560 ± 71% versus 483 ± 69%, P = .4) in both groups. Linear regression analysis revealed that the difference in ACh-mediated vasodilatation was explained by preeclampsia (P = .004), whereas vascular risk factors such as maternal age, diastolic blood pressure, and family history of premature cardiovascular diseases had no significant effect. CONCLUSION: The increased ACh-mediated vasodilatation in the microcirculation of recently preeclamptic women indicates abnormal endothelial function. Furthermore, it may represent a compensatory response to an impaired vasodilatory response of the macrocirculation, thereby supporting the hypothesis of an underlying (micro)angiopathy. LEVEL OF EVIDENCE: II-2

Abnormal endothelium-dependent microvascular dilator reactivity in pregnancies complicated by normotensive intrauterine growth restriction

OBJECTIVE Normotensive intrauterine growth restriction and preeclampsia share a similar placenta pathophysiology, whereas maternal clinical manifestations differ. Clinical symptoms of preeclampsia are partly attributed to vascular endothelial dysfunction, but it is unclear whether this phenomenon plays a role in intrauterine growth restriction. Therefore, we investigated microvascular endothelial function in women with intrauterine growth restriction. STUDY DESIGN Laser Doppler fluxmetry was used combined with iontophoresis of acetylcholine and sodium nitroprusside, namely, endothelium-dependent and endothelium-independent vasodilators. We studied 12 women with intrauterine growth restriction and 16 controls in the third trimester of pregnancy. All women had prepregnancy body mass indexes < 26. RESULTS Acetylcholine-mediated vasodilatation was significantly increased in women with intrauterine growth restriction compared with controls (743% +/- 120% vs 390% +/- 67%, P = .01); sodium nitroprusside-mediated vasodilatation was not different (360% +/- 55% vs 363% +/- 65%, P > .99). CONCLUSION Nonobese women with normotensive intrauterine growth restriction show abnormal endothelium-dependent microvascular vasodilatation, suggesting endothelial dysfunction as in preeclampsia. Obviously, for the clinical manifestation of preeclampsia additional factors are required, and a role of metabolic syndrome and obesity has been suggested.

Decreased arterial elasticity in formerly early‐onset preeclamptic women

Objective. Preeclampsia is associated with cardiovascular atherosclerotic events later in life. Impaired arterial elasticity is considered to be a marker of vascular (endothelial) dysfunction and to be involved in the atherosclerotic process. We investigated whether previously preeclamptic women have lower arterial elasticity indices in comparison with controls. Design. Case‐control study. Setting. University Medical Center Groningen, the Netherlands. Sample. 14 non‐pregnant women with a history of early‐onset preeclampsia (cases) and 16 non‐pregnant women (controls) with an uncomplicated pregnancy in 2003–2004. Methods. Measurement of radial artery elasticity indices combined with the brachial blood pressure using pulse wave contour analysis. The assessment of traditional risk factors for cardiovascular diseases (CVD) including body mass index, serum high‐sensitivity C‐reactive protein (hsCRP), serum insulin and plasma homocysteine. Mean outcome measures. Arterial elasticity indices and traditional risk factors for CVD in cases and controls. Results. Arterial elasticity was impaired in cases as compared with controls. Body mass index, blood pressure, pulse pressure, hsCRP and triglycerides were significantly higher in cases. Conclusion. Arterial elasticity indices are reduced in formerly preeclamptic women, indicating vascular dysfunction. This and the more established risk factors for CVD are likely to contribute to a higher risk of CVD in women with a history of early‐onset preeclampsia.

Vascular responsiveness in the microcirculation of patients with systemic lupus erythematosus is not impaired

As endothelial dysfunction is one of the earliest signs of atherosclerosis, which is accelerated in systemic lupus erythematosus (SLE), we assessed whether vascular responses of the cutaneous microcirculation are disturbed in SLE patients and influenced by Raynaud’s phenomenon (RP). Laser Doppler fluxmetry (LDF) was used in combination with iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), an endothelium-dependent and endothelium-independent vasodilator respectively. 42 SLE patients with inactive disease, 12 of whom had RP and 19 age- and sex-matched controls were included. Furthermore, traditional and non-traditional risk factors for cardiovascular disease (CVD) were assessed, and markers of inflammation and endothelial activation were measured. Vascular responses of SLE patients without RP did not differ from controls. However, SLE patients with RP exhibited decreased vasodilatation compared with controls. SLE patients with RP also had longer arrival times of ACh and SNP than controls. Markers of inflammation and von Willebrand factor were increased in SLE patients. Smoking, the presence of SLE and RP were negatively associated with vascular responses in univariate analysis. In multivariate analyses, the only independent variable of vascular responses to ACh and SNP was the presence of RP. Despite signs of endothelial activation, SLE patients with inactive disease do not have altered vascular responses in the microcirculation compared with controls. In SLE patients with RP, cutaneous vascular responses to both ACh and SNP are impaired. Therefore, LDF of the microcirculation seems not to be the appropriate method to distinguish those SLE patients with an increased risk to develop CVD.

Diffusion model for iontophoresis measured by laser-Doppler perfusion flowmetry, applied to normal and preeclamptic pregnancies

We present a physical model to describe iontophoresis time recordings. The model is a combination of monodimensional material diffusion and decay, probably due to transport by blood flow. It has four adjustable parameters, the diffusion coefficient, the decay constant, the height of the response, and the shot saturation constant, a parameter representing the relative importance of subsequent shots (in case of saturation). We test the model with measurements of blood perfusion in the capillary bed of the fingers of women who recently had preeclampsia and in women with a history of normal pregnancy. From the fits to the measurements, we conclude that the model provides a useful physical description of the iontophoresis process.

Skin Autofluorescence as Marker of Tissue Advanced Glycation End-Products Accumulation in Formerly Preeclamptic Women

Condensation. In women with a history of preeclampsia skin autofluorescence as marker of tissue AGEs accumulation is increased, supporting a common causal metabolic or vascular link between preeclampsia and cardiovascular diseases. Objective. To investigate whether skin autofluorescence (AF), as marker of tissue accumulation of advanced glycation end-products (AGEs), is elevated in women with a 4-year history of severe preeclampsia. Methods. About 17 formerly preeclamptic women and 16 controls were included. Skin AF and several traditional cardiovascular risk factors were recorded. Results. In comparison to controls, formerly preeclamptic women had higher skin AF of the legs, body mass index (BMI), blood pressure, and high-sensitivity C-reactive protein (hsCRP), HbA1C, and triglycerides in serum. Conclusion. Skin AF as well as cardiovascular risk factors is elevated in formerly preeclamptic women. These results suggest a common causal vascular link between preeclampsia and cardiovascular diseases.

Time Development Models for Perfusion Provocations Studied with Laser-Doppler Flowmetry, Applied to Iontophoresis and PORH

Objective: Clinical acceptance of laser‐Doppler perfusion monitoring (LDPM) of microcirculation suffers from lack of quantitatively reliable signal data, due to varying tissue constitution, temperature, hydration, etc. In this article, we show that a novel approach using physiological models for response upon provocations provides quantitatively and clinically relevant time constants.