Impaired vascular dilatation in women with a history of pre-eclampsia.

OBJECTIVE: The mechanisms underlying increased cardiovascular risk among women with a history of pre-eclampsia remain unclear. Impaired endothelial function has been observed in both pre-eclampsia and atherosclerosis, and provides a plausible link between the two conditions. We studied endothelial function and arterial compliance in non-pregnant, previously pre-eclamptic women. DESIGN: A study of 30 women with a history of pre-eclampsia and 21 women with a previous normotensive, uncomplicated pregnancy was carried out. METHODS: Changes in brachial artery blood flow, induced by intra-arterial infusions of an endothelium-independent (sodium nitroprusside) and an endothelium-dependent (acetylcholine) vasodilator, were measured by venous occlusion plethysmography. Arterial stiffness was assessed by pulse-wave analysis. RESULTS: Vasodilatation was impaired in women with previous pre-eclampsia; at low and high concentrations of endothelium-independent (P = 0.004 and P = 0.057, respectively) and endothelium-dependent (P = 0.045 and P = 0.02) vasodilators, respectively. There was no difference in arterial stiffness between the groups (P = 0.45). In multiple regression analyses both endothelium-independent and endothelium-dependent vasodilatations were independently associated with a history of pre-eclampsia and parity. There was no correlation with blood pressure, body mass index (BMI), smoking or age. CONCLUSIONS: The finding of impaired vascular dilatation several years after a pre-eclamptic pregnancy could contribute to the higher risk of cardiovascular disease in these women.

Pulse wave reflection in currently and previously preeclamptic women.

OBJECTIVE: Disturbed maternal endothelial function is believed to be central in the pathogenesis of preeclampsia and has been observed to persist for several years following the preeclamptic pregnancy. Endothelial dysfunction has been reported to cause increased pulse wave reflection, a measure of systemic arterial stiffness. This study tested the hypothesis that preeclampsia and a history of preeclampsia are associated with increased pulse wave reflection. DESIGN AND METHODS: We carried out a cross-sectional case-control study of 26 pregnant women with preeclampsia, 26 pregnant controls, 22 normotensive nonpregnant previously preeclamptic women, and 22 nonpregnant controls. Pulse wave reflection was assessed by applanation tonometry on the radial artery. RESULTS: Pregnant preeclamptic women had a significantly higher heart rate-adjusted augmentation index than did pregnant controls (23 +/- 1 vs. 8 +/- 1%, P < 0.001). The augmentation index of women with a history of preeclampsia was similar to that of the nonpregnant controls (9 +/- 2 vs. 9 +/- 2%, P = 0.78). In a multiple linear regression analysis (R2 = 0.76) the augmentation index of pregnant women was independently associated with a diagnosis of preeclampsia (P < 0.001) and heart rate (P < 0.001), but not with mean arterial blood pressure (P = 0.59). CONCLUSIONS: This study demonstrates that pulse wave reflection and, thus, systemic arterial stiffness are increased in pregnant women with preeclampsia, but not in normotensive nonpregnant women with a history of preeclampsia. The results support the concept of generalized vascular dysfunction in preeclampsia.

Thromboprophylaxis for recurrent miscarriage in women with or without thrombophilia. HABENOX: a randomised multicentre trial.

Recurrent miscarriage affects 1-2% of women. In more than half of all recurrent miscarriage the cause still remains uncertain. Thrombophilia has been identified in about 50% of women with recurrent miscarriage and thromboprophylaxis has been suggested as an option of treatment. A randomised double-blind (for aspirin) multicentre trial was performed among 207 women with three or more consecutive first trimester (<13 weeks) miscarriages, two or more second trimester (13-24 weeks) miscarriages or one third trimester fetal loss combined with one first trimester miscarriage. Women were analysed for thrombophilia. After complete work-up, women were randomly allocated before seven weeks' gestation to either enoxaparin 40 mg and placebo (n=68), enoxaparin 40 mg and aspirin 100 mg (n=63) or aspirin 100 mg (n=76). The primary outcome was live-birth rate. Secondary outcomes were pregnancy complications, neonatal outcome and adverse effects. The trial was ended prematurely because of slow recruitment. A live birth rate of 71% [relative risk (RR) 1.17, 95% confidence interval (CI) 0.92-1.48] was found for enoxaparin and placebo and 65% [RR 1.08, 95% CI 0.83-1.39] for enoxaparin and aspirin when compared to aspirin alone (61%, reference group). In the whole study group the live birth rate was 65% (95% CI 58.66-71.74) for women with three or more miscarriages (n=204). No difference in pregnancy complications, neonatal outcome or adverse effects was observed. No significant difference in live birth rate was found with enoxaparin treatment versus aspirin or a combination of both versus aspirin in women with recurrent miscarriage.

A relationship between insulin sensitivity and vasodilation in women with a history of preeclamptic pregnancy.

Women with a history of preeclampsia are characterized by vascular dysfunction and an increased risk of cardiovascular disease. In the present study we investigated whether insulin sensitivity is decreased in women with previous preeclampsia and whether it is associated with endothelium-dependent and/or -independent vasodilation and/or features of metabolic syndrome. Twenty-eight nonobese women with previous severe preeclampsia and 20 women with a previous normotensive pregnancy were studied 5 to 6 years after the index pregnancy. Vasodilation was measured by venous occlusion plethysmography after intra-arterial infusions of sodium nitroprusside and acetylcholine and insulin sensitivity by the intravenous glucose tolerance test using the minimal model technique. The women were tested for lipid profile, inflammatory status and endothelial activation. Insulin sensitivity did not differ between the groups (P=0.24). Insulin sensitivity correlated positively to endothelium-dependent vasodilation only in the patient group in both low (beta=0.59; P=0.04) and high (beta=0.53; P=0.04) concentrations of acetylcholine and in a high concentration of sodium nitroprusside (beta=0.0007; P=0.006). In multivariate analysis, the waist/hip ratio (P=0.04) and serum triglycerides (P=0.04) had the most effect on insulin sensitivity in the patient group. Gestational weeks at the onset of preeclamptic hypertension (P=0.02) and proteinuria (P=0.02) associated positively with insulin sensitivity together with first-trimester body mass index (P=0.008) and maximum diastolic blood pressure during preeclampsia (P=0.005). The present study indicates a relation between insulin sensitivity with vascular dilatory function in women with previous preeclampsia. Furthermore, early onset preeclampsia correlates with impaired insulin sensitivity later in life.

Treatment of postpartum thrombotic microangiopathy with plasma exchange using cryosupernatant as replacement.

Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are rare but acknowledged problems of pregnancy and the postpartum period. These diseases together with thrombotic angiopathy are associated with high maternal and fetal mortality and severe long-term morbidity. We describe four women with postpartum HUS/TTP treated with plasma exchange cryosupernatant fraction of plasma (CFP) as replacement fluid. Anuria or oliguria at the beginning of treatment and thrombocytopenia [thromb- (29-68) x 109/L] were common features. Two of the patients developed a prolonged and more difficult clinical condition affecting the central nervous system and the liver and their platelet counts remained low despite the plasma exchange. The renal and hepatic function of all of the patients recovered fully. This small analysis lends weight to early plasma exchange with cryosupernatant as part of the treatment of postpartum HUS/TTP and suggests that persistent thrombocytopenia is a signal of more serious disease.