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Resume Une hypertension arterielle (HTA) survient dans 6 a 8 % des grossesses, une preeclampsie (PE) dans 2 % (elle est dite grave dans 0,6 %). La preeclampsie reste une cause majeure de mortalite fœtale, voire maternelle. Il en existe deux aspects differents : la preeclampsie « maternelle » est due a des anomalies vasculaires preexistantes chez la mere, la preeclampsie « placentaire » est due a un defaut primaire de la placentation precoce. L’anomalie premiere semble etre une « maladaptation immune » maternofœtale, avec defaut de la cooperation entre les antigenes trophoblastiques et les cellules NK maternelles, moteur primordial de l’invasion trophoblastique. Une inhibition de l’angiogenese intervient egalement et la production anormale de recepteurs solubles en a ete recemment rendue responsable. L’ischemie placentaire qui en resulte entraine la liberation accrue de debris trophoblastiques dans le sang maternel, un syndrome inflammatoire, et une dysfonction endotheliale generalisee qui explique les symptomes maternels. Les tableaux cliniques vont de l’hypertension simple et benigne a la gravissime preeclampsie severe comportant un risque majeur de complications maternelles et de mort fœtale. Le traitement antihypertenseur n’ameliore en rien ce pronostic. Des traitements preventifs tres precoces representent une voie plus fructueuse et la recherche est active dans ce domaine. Les femmes qui ont eu une preeclampsie sont plus exposees que d’autres a l’apparition ulterieure d’une hypertension arterielle, d’un diabete de type 2 ou d’une maladie coronaire.

Menopause coincides with an increase in the incidence of hypertension in women. A direct role of estrogen deprivation in this increased blood pressure remains a topic of debate. Menopause probably accelerates the arterial changes related to aging. Hormone replacement therapy does not influence blood pressure significantly and is not contraindicated in hypertensive women. The effect of hormone replacement treatment on cardiovascular risk was recently the object of controversy. It does not increase risk except in cases of late treatment in older women who already have atherosclerosis. Hypertension management in women is otherwise similar to management in men.

Objectives: Randomized trials with low-dose aspirin to prevent preeclampsia and intrauterine growth restriction have yielded conflicting results. In particular, 3 recent large trials were not conclusive. Study designs, however, varied greatly regarding selection of patients, dose of aspirin, and timing of treatment, all of which can be determinants of the results. Retrospectively analyzing the conditions associated with failure or success of aspirin may therefore help to draw up new hypotheses and prepare for more specific randomized trials. Study Design: We studied a historical cohort of 187 pregnant women who were considered at high risk for preeclampsia, intrauterine growth restriction, or both and were therefore treated with low-dose aspirin between 1989 and 1994. Various epidemiologic, clinical, and laboratory data were extracted from the files. Univariate and multivariate analyses were performed to search for independent parameters associated with the outcome of pregnancy. Results: Age, parity, weight, height, and race had no influence on the outcome. The success rate was higher when treatment was given because of previous poor pregnancy outcomes than when it was given for other indications, and the patients with successful therapy had started aspirin earlier than had those with therapy failure (17.7 vs 20.0 weeks' gestation, P = .04). After multivariate analysis an increase in Ivy bleeding time after 10 days of treatment by >2 minutes was an independent predictor of a better outcome (odds ratio 0.22, 95% confidence interval 0.09-0.51). Borderline statistical significance was observed for aspirin initiation before 17 weeks' gestation (odds ratio 0.44, 95% confidence interval 0.18-1.08). Abnormal uterine artery Doppler velocimetric scan at 20-24 weeks' gestation (odds ratio 3.31, 95% confidence interval 1.41-7.7), abnormal umbilical artery Doppler velocimetric scan after 26 weeks' gestation (odds ratio 37.6, 95% confidence interval 3.96-357), and use of antihypertensive therapy (odds ratio 6.06, 95% confidence interval 2.45-15) were independent predictors of poor outcome. Conclusions: Efficacy of aspirin seems optimal when bleeding time increases ≥2 minutes with treatment, indicating a more powerful antiplatelet effect. This suggests that the dose of aspirin should be adjusted according to a biologic marker of the antiplatelet effect. A prospective trial is warranted to test this hypothesis. (Am J Obstet Gynecol 1999;180:135-40.)

Cardiovascular risk factor management by French vs US primary care physicians was studied. A survey was conducted that found that French physicians spend >20 minutes while US physicians spend five to 10 minutes (P

Hypertension occurs in 6-8% of pregnancies, preeclampsia in 2%, found to be "severe" in 0.6%. Preeclampsia remains a major cause of foetal, and even maternal, mortality. Two different aspects are described: "maternal" preeclampsia is related to pre-existent vascular lesions in the mother, "placental" preeclampsia is due to a primary defect in early placentation. The earliest disorder seems to be a "materno-foetal immune maladaptation", characterized by a defective cooperation between uterine NK cells and foetal HLA-C. Defective angiogenesis is also involved, which has been accounted for by an abnormal production of soluble receptors for angiogenic factors and TGF-beta. The resulting placental ischemia is responsible for an increased shedding of trophoblastic debris in the maternal circulation, an inflammatory syndrome, and finally generalized endothelial dysfunction, which is the clue to maternal symptoms. Clinical presentations range from benign isolated hypertension to life-threatening severe preeclampsia, which entails a major risk of maternal complications and foetal death. Antihypertensive treatment does not improve the foetal or maternal prognosis, in spite of blood pressure lowering. Very early preventive treatments have been developed, which seem largely more promising. Research is very active in this field. Finally, women who had preeclampsia are more prone to future hypertension, type 2 diabetes, or coronary disease.

Measurement of urinary albumin excretion (UAE) may be done on a morning urinary sample or on a 24 hours-urine sample. Values defining microalbuminuria are: 24 hour-urine sample: 30-300 mg/24 hours; morning urine sample: 20-200 mg/ml or 30-300 mg/g creatinine or 2.5-25 mg/mmol creatinine (men) or 3.5-35 mg/mol (women). Timed urine sample: 20-200 microg/min. The optimal use of semi-quantitative urine test-strip is not clearly defined. It is generally believed that microalbuminuria reflects a generalized impairment of the endothelium; however, no definite proof has been shown in humans.Microalbuminuria is a marker of increased risk of cardiovascular (CV) and renal morbidity and mortality in type 1 and type 2 diabetic subjects. The increase in UAE during follow-up is also a marker of CV and renal risk in type 1 and type 2 diabetic subjects; its decrease during follow-up is associated with lower risks.Microalbuminuria is a marker of increased risk for diabetes mellitus, deterioration of the renal function, CV morbidity and all-cause mortality. It is a marker of increased risk for the development of hypertension in normotensive subjects, and is associated with unfavorable outcome in patients with cancer and lymphoma. Persistence or elevation of UAE overtime is associated with deleterious outcome in some hypertensive subjects. Measurement of UAE may be recommended in hypertensive subjects with one or two CV risk factors in whom CV risk remains difficult to assess, and in those with refractory hypertension: microalbuminuria indicates a high CV risk and must lead to strict control of arterial pressure. Studies focused on microalbuminuria in non-diabetic non-hypertensive subjects are limited; most of them suggest that microalbuminuria predicts CV complications and deleterious outcome as it is in diabetic or hypertensive subjects. Subjects with a history of CV or cerebrovascular disease have an even greater CV risk if microalbuminuria is present than if it is not; however, in all cases, therapeutic intervention must be aggressive regardless of whether microalbuminuria is present or not. It is not recommended to measure UAE in non-diabetic non-hypertensive subjects in the absence of history of renal disease. Monitoring of renal function (UAE, serum creatinine and estimation of GFR) is annually recommended in all subjects with microalbuminuria.In patients with microalbuminuria, weight reduction, sodium restriction (6 g/day), smoking cessation, strict glucose control in diabetic subjects, strict arterial pressure control are necessary; in diabetic subjects: use of maximal doses of ACEI or ARB are recommended; ACEI/ARB and thiazides have synergistic actions on arterial pressure and reduction of UAE; in non diabetic subjects, any of the five classes of antihypertensive medications (ACEI, ARB, thiazides, calcium channel blockers or betablockers) can be used.

Menopause coincides with an increase in the incidence of hypertension in women. A direct role of estrogen deprivation in this increased blood pressure remains a topic of debate. Menopause probably accelerates the arterial changes related to aging. Hormone replacement therapy does not influence blood pressure significantly and is not contraindicated in hypertensive women. The effect of hormone replacement treatment on cardiovascular risk was recently the object of controversy. It does not increase risk except in cases of late treatment in older women who already have atherosclerosis. Hypertension management in women is otherwise similar to management in men.

Hypertension is the most common medical complication of pregnancy. Isolated and moderate hypertensions most often have an uneventful course. On the contrary, preeclampsia is a severe condition, that threatens the fetal survival, and even maternal prognosis. Recent knowledge demonstrates that preeclampsia is related to a very early defect in placentation, with late maternal systemic effects. This has important practical counterparts. Any manifestation of placental dysfunction should be detected as early as possible. Antihypertensive treatment should be used with great caution, to preserve an appropriate blood flow through a placenta whose hemodynamic resistance is high. Finally, the most appropriate therapeutic way is a preventive one. Cardiovascular risk of those young women should be later monitored.

The phenomenon of implantation anchors the embryo into the uterine wall and produces a hemochorial placenta that maintains the pregnancy and fetal growth. Implantation and placentation are intimately linked and cannot be dissociated either in time or in space. Preeclampsia is characterized by hypertension and proteinuria. It is secondary to an anomaly of the invasion of the uterine spiral arteries by extra-villous cytotrophoblast cells, associated with local disruptions of vascular tone, of immunological balance and inflammatory status, and sometimes with genetic predispositions. Preeclampsia is a disease of early pregnancy, a form of incomplete spontaneous abortion, but is expressed late in pregnancy. Aspirin may play a favorable role in implantation which is related to the genesis of preeclampsia and some cases of intra-uterine growth restriction. The most important points in obtaining a preventive effect from low-dose aspirin during the pregnancy are early treatment (before 13 weeks of gestation) and the prescription of a sufficient dose (more than 100 mg per day).

A multicentric randomized double-blind trial was realized in order to determine whether a treatment with a low-dose aspirin (150 mg/day) with or without dipyridamole (225 mg/day) was able to prevent the perinatal consequences of pre-eclampsia. This study demonstrated a significant difference in birthweight and incidence of fetal growth retardation between treatment and placebo groups. No difference was demonstrated between aspirin and aspirin + dipyridamole patients.

Accessible online at: http://BioMedNet.com/karger Several recent studies have called into question the interest of aspirin in preventing some complications of pregnancy, preeclampsia in particular. One of these studies concerned a population at high risk [1], and the other two low-risk populations [2, 3]. Among the explanations evoked by the authors of these studies to explain the absence of any difference between the placebo and aspirin groups, a statistical bias has been suggested. In particular, the authors suggest that the trials that have demonstrated an effect from aspirin were those with only a few subjects, and that larger trials have found no difference. The authors add that, generally, small trials without any significant results might not be published, which would explain the apparent distortion. We think that these arguments are simplistic, reductive, and (involuntarily) ignore other differences between the trials that found aspirin ineffective and those observing a positive effect. What are these differences? What reflections might they nourish? Our group’s first publications [4, 5] involved patients at high risk of preeclampsia and especially of intrauterine growth retardation (IUGR), with vascular aspects. Two points must be mentioned. (1) The risk level is important: when the EPREDA trial analyses stratified patients with an obstetric history, that is, severe IUGR (3rd percentile), death in utero or abruptio placentae associated with high blood pressure, by the number of such previous incidents (one, or two or more), the efficacy of aspirin was more marked for the patients with two incidents (risk of recurrence: 25–30%) than for those with only one (risk of recurrence: 10–15%). (2) The population was relatively homogeneous, and it is possible that a high risk level in a heterogeneous population would not lead to the same results. One example involves the degree of growth retardation (or even fetal weight), which was the principal end-point in our trial (which included more than 300 patients). It appears difficult to induce changes in this end-point in a population with inclusion criteria as diverse as insulin-dependent

Objective: Study of maternal and fetal consequences of lone hyperuricemia during pregnancy and demonstration that lone hyperuricemia is not a risk factor regarding the onset of preeclampsia. Study design: Retrospective study of two groups of women, one found to have lone hyperuricemia during pregnancy (n=102) and the others with normal serum uric acid levels (n=100). Results: The only consequence identified of the lone hyperuricemia was a lower birth weight of children born to mothers found to have lone hyperuricemia for more than 2 weeks (P

Renal hemodynamics in essential hypertensives is characterized by an increase in renal vascular resistance (RVR) and a decrease in renal plasma flow (RPF), while glomerular filtration rate (GFR) is either normal or slightly decreased. Filtration fraction (FF) is increased, indicating that vasoconstriction predominantly affects postglomerular arteries. This increase in FF, called hyperfiltration, can be regarded as a successful maintenance of a normal glomerular filtration but can be deleterious for long-term renal function by favoring the development of glomerulosclerosis. Administration of some beta-blockers (especially propranolol) to hypertensive patients still reduces RPF and GFR, and increases FF. Conversely, in short-term studies, tertatolol has been shown to reduce RVR and increase RPF, without altering FF in hypertensive patients. These effects correspond to a normalization of the renal hemodynamic profile. Their practical interest is however strongly dependent on their persistence in long-term treatment. The beneficial effects of tertatolol were confirmed in 3 long-term studies, lasting for one year. These three studies yielded remarkably similar results: there was a modest overall decrease in serum creatinine, and a more pronounced drop in patients whose pretreatment renal function was altered. These data suggest that tertatolol may preserve the long-term autoregulation of renal hemodynamics. The possibility is raised that in patients with minimal renal dysfunction, tertatolol may also slow down the progression of renal failure.

Perinatal outcome and various indicators of perinatal risk were analyzed in a prospective study of 268 pregnant women with hypertension. Poor perinatal outcome was defined by stillbirth (n = 13), neonatal death (n = 2), and in surviving babies, by birth before 32 weeks or a birthweight below 1500 g (n = 13). In multivariate analysis, proteinuria and onset of hypertension between the 27th and 36th weeks of amenorrhea were the only two independent indicators of poor outcome (relative risks of 4.0 and 3.7, p less than 0.001 and p less than 0.01 respectively). Both these indicators were more frequent in mothers with no history of pre-pregnancy hypertension.

Renal hemodynamics of hypertensive patients are characterized by an increased renal vascular resistance (RVR), resulting in low renal plasma flow (RPF). Normal glomerular filtration rate (GFR) is maintained through an increased filtration fraction (FF). This pattern may have long term harmful consequences for the kidneys. Propranolol, given in the short- or long-term, lowers both RPF and GFR. Pindolol, as well as so called cardioselective beta-blockers and labetalol, alter renal hemodynamics only slightly, if not at all. In some studies, nadolol has been shown to increase RPF, leaving GFR unchanged. A new beta-blocker, tertatolol, seems to consistently increase RPF and GFR. These different renal actions of various beta-blockers are poorly explained. They may be, however, of clinical significance, in the short term for patients with already impaired renal function, and possibly over the long term for other hypertensive patients.