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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., (Copyright 2010 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.)

The kidney has a key role in blood pressure control, and an abnormal regulation of sodium balance is involved in essential hypertension. It has been suggested that a reduced nephron number at birth could be one possible mechanism. Indeed various strains of hypertensive animals exhibit a reduced nephron number. In human beings, two autopsy studies have clearly shown a lower (about 50%) nephron number in hypertensive subjects. The glomeruli are also enlarged, indicating hyperfiltration. This could be the cause of both high blood pressure and later nephrosclerosis. A low number of nephrons is part of the perinatal programming which occurs together with fetal growth retardation, and this has been reproduced experimentally. There is a negative correlation between birth weight and glomerular number. Such a situation is associated with a largely increased risk of cardiovascular complications in adulthood.

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.

Purpose: Hypertension occurs in 10 to 15 p cent of pregnancies. Among them, 10 to 20% also have proteinuria. This situation defines preeclampsia, and involves a serious threat on fetal and even maternal prognosis. Presence of the hepatic (HELLP) syndrome still severely worsens the prognosis., Current Knowledge and Key Points: Pathophysiology of preeclampsia is based on a very early abnormality of placentation, leading to insufficient blood supply to the feto-placental unit. At the maternal level, the main consequence of placental ischemia is generalized endothelial dysfunction, responsible for systemic vasoconstriction and clotting abnormalities. In such a context, lowering blood pressure with drugs is quite inefficient, or even harmful. The prognosis of this disease is mainly related to the pertinence of obstetrical management., Future Prospects and Projects: An early preventive strategy is the most logical approach of preeclampsia, its modalities remain under discussion.

Hypertension occurs in 10 to 15 p cent of pregnancies. Among them, 10 to 20% also have proteinuria. This situation defines preeclampsia, and involves a serious threat on foetal and even maternal prognosis. Presence of the hepatic (HELLP) syndrome still severely worsens the prognosis. Pathophysiology of preeclampsia is based on a very early abnormality of placentation, leading to insufficient blood supply to the foeto-placental unit. At the maternal level, the main consequence of placental ischemia is diffuse endothelial dysfunction, responsible for systemic vasoconstriction and clotting abnormalities. In such a context, merely lowering blood pressure with drugs is quite inefficient, or even harmful. The prognosis of this disease is mainly related to the pertinence of obstetrical management. An early preventive strategy is the most logical approach of preeclampsia, its modalities remain under discussion. Hypertension has a high recurrence rate on subsequent pregnancies. It is most often linked to a high global vascular risk level, therefore many of those patients will become permanent hypertensives in the near future.

There are three circumstances where hypertension develops specifically in women: oral contraception, pregnancy, and menopause. Oral contraception usually shifts the blood pressure moderately upwards, but hypertension appears in less than 5% of women. Still it may (rarely) be very severe. Hypertension is poorly related to the dosage of the estrogenic compound, but rather to the nature and dosage of the progestive part. This hypertension does not significantly increase the cardiovascular risk of these women. The role of menopause itself in the trigging of hypertension remains uncertain. It seems however that confounding factors such as age, body weight, sodium balance and so on explain the increased incidence of hypertension after menopause. The latter is also associated with an increase of cardiovascular risk, which requires adequate treatment. Hormone replacement therapy is not contra-indicated, even in hypertensive patients.

The aim of the treatment of hypertensive disease is to reduce its associated cardiovascular morbidity and mortality. Simply reducing blood pressure levels is clearly not adequate since its impact on coronary heart disease is particularly unsatisfactory. Moreover, the beneficial effects of antihypertensive treatment seem to plateau for several years, and the incidence of cardiac and renal failure is even increasing. Therefore, recommendations by groups of national or international experts are periodically updated on the basis of current epidemiological data. Two such recommendations appeared in 1997, one from the Agence Nationale d'Accréditation et d'Evaluation en Santé (ANAES) in France and the other from the Joint National Committee (JNC) on Prevention, Detection, Evaluation and Treatment of High Blood Pressure, in the United States. Both advocate the use of lifestyle modifications in all patients. The threshold blood pressure level at which pharmacological therapy is introduced largely depends on associated cardiovascular risk factors and/or involvement of target organs. The JNC recommends a particularly low threshold in patients with diabetes. Pharmacological treatment is usually initiated with a single drug. The choice of any one drug depends on the patient profile and takes into consideration such characteristics as age and associated risk factors or comorbidity. Some represent a contraindication for certain therapeutic classes (for example, asthma for beta-blockers, renovascular hypertension for ACE inhibitors), while others are a specific or even 'compelling' indication (heart failure, angina, renal disease, peripheral vascular disease etc.). This patient profiling is very precisely described in the new recommendations. However, any such single drug therapy provides adequate blood pressure control in no more than about 50 to 60% of patients. When the patient does not respond to the drug used or experiences side effects, substitution of a drug from another pharmacological class is recommended. In contrast, if the patient is a responder but blood pressure remains above the target level, it is preferable to add a second drug from a class offering complementary action. The use of a combination therapy allows blood pressure control in more than 80% of patients. More authors are suggesting that combination therapy as first-line treatment may increase the number of responders and reduce the impact of counter-regulatory effects occurring with single drug therapy (e.g. sodium retention, or sympathetic activation). This alternative strategy is now acknowledged in the recommendations.

Hypertension is observed in 10 to 15% of pregnancies, but only 10% of affected women will suffer preeclampsia. The pathophysiology of preeclampsia is based on an early anomaly of placental implantation, leading to a cascade of events (secretion of vasopressive prostaglandins, anomalies of hemostatis) which can cause disseminated intravascular coagulation. The diagnosis of preeclampsia is based on hypertension and significant proteinuria (above 0.5 g/24 h), and paraclinical maternal and fetal examinations to follow the evolution and detect the appearance of maternal complications (retroplacental haematoma, Hellp syndrome and eclampsia) and (or) fetal complications (delayed growth, in utero fetal death, perinatal death). The aim of hypertensive treatment is to normalise blood pressure and to avoid maternal complications. Preventive treatment with aspirin reduces the frequency of recurrent preeclampsia and delayed growth of the fetus.

Our understanding of the pathophysiology underlying the hypertensive diseases of pregnancy has clearly progressed during the past ten years. The key phenomenon is an early defect of placentation occurring at the end of the first trimester and associated with a more widespread endothelial disorder. This results in early activation of the coagulation cascade and imbalance between prostacyclin and thromboxanes. Hypertension and proteinuria only occur after several weeks or months of placental dysfunction. This explains why antihypertensive treatments are ineffective in improving the prognosis of such pregnancies. In contrast, early preventive treatments, such as antiplatelet therapy, seem to be very promising for these patients. In this respect, early prediction of the risk associated with pregnancy has become a key goal.

Pathophysiologic understanding of the hypertensive diseases of pregnancy has largely progressed in the past 10 years. The key phenomenon is an early defect of placentation, occurring at the end of first trimester. It is associated with a more global endothelial disorder. This results in early activation of coagulation, and an imbalance between prostacyclin and thromboxanes. Hypertension and proteinuria only occur after several weeks or months of placental dysfunction. This explains why antihypertensive treatments are ineffective in improving the prognosis of such pregnancies. On the contrary, early preventive treatments, such as antiplatelet therapy, seem very promising for those patients.

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.

Hypertension and diabetes mellitus are strongly associated conditions from epidemiologic, genetic, and pathophysiologic points of view. The prevalence of hypertension is high in patients with diabetes, and, conversely, many patients with essential hypertension are glucose intolerant. Proteinuria appears in 40-50% of patients with insulin-dependent diabetes mellitus and 20-30% of patients with non-insulin-dependent diabetes mellitus. Progressive renal failure occurs in 30-40 and 3-8% of patients, respectively, hypertension being a leading factor in its rate of progression. In various animal experiments, ACE inhibitors are able to prevent proteinuria and glomerular sclerosis, presumably by lowering transglomerular capillary pressure. In the diabetic human, ACE inhibitors are powerful antihypertensive drugs, devoid of metabolic side effects. Clinical studies indicate that ACE inhibitors reduce proteinuria and possibly slow the rate of decline in renal function. Such an effect is not observed with beta-blockers. Large-scale studies are needed to confirm this very important hypothesis.

Gravidic hypertension remains one of the most frequent causes of perinatal mortality and morbidity. There are two aims when investigating this disease: evaluate the gravity, try to find early signs of a risk of pre-eclampsia. This last point has become particularly important over the past few years because of the development of preventive treatment (platelet anti-agregates). Mother and fetal blood velocimetry play a more and more important role. Three measurement sites appear to have different and complementary importance: for long-term prediction, measuring the velocimetric index of the uterin artery seems the most interesting because it schematically explores the type of placentations; for mid-term, measuring the ombilical artery evaluates placenta resistance, an essential factor in chronic fetal suffering; at short-term, measuring the fetal cerebral and carotid vessels explores the hemodynamic reactions of fetal adaptation to fetal suffering.

High blood pressure occurs in many pregnant diabetic patients (30 to 40 p cent), and it is associated with significant impairement of fetal prognosis. Hypertension is no doubt a marker of the vascular diabetic disease, which obviates an adequate placentation. Proper antihypertensive management is necessary in those patients, but its prognostic importance is far less than is that of a perfect glycemic control. Antihypertensive therapy differs in some aspects from what is should be in non-pregnant patients: first, compounds such as angiotensin converting enzyme inhibitors, or calcium-channel blockers are not considered safe in pregnant women, whereas they are the first choice in non-pregnant diabetics. Second, over-control of blood pressure is very harmful to fetal growth, and should be carefully avoided. Finally, present literature lacks proper controlled studies, which could help in designing the best antihypertensive therapeutic strategy in pregnant diabetic patients.

Chronic renal failure (CRF) is often associated with hypertension, as a cause or a consequence. We studied the changes in blood pressure (BP), heart rate (HR), renal function (as measured by creatinine clearance), and plasma renin activity (PRA) in 19 hypertensive patients with CRF before, during and after oral administration once a day for at least 30 days of 5 mg tertatolol, a new beta-blocker. All patients were free of any antihypertensive medication for at least 1 month before administration of tertatolol. The dose of tertatolol given in this study was the same as that commonly used in patients with normal renal function. From day 0 to day 30 of tertatolol, measurements in the supine position were as follows: systolic BP (SBP) decreased from 168.4 +/- 4.6 to 145.3 +/- 4.3 mm Hg (p less than 0.01); diastolic BP (DBP) decreased from 106.1 +/- 2.4 to 87.1 +/- 2.0 mm Hg (p less than 0.01); HR decreased from 77.9 +/- 1.6 to 63.2 +/- 1.7 b.p.m. (p less than 0.01); PRA decreased from 1.816 +/- 0.521 to 1.052 +/- 0.323 ng/ml/h (p less than 0.01). Creatinine clearance remained stable: 37.1 +/- 4.1 versus 37.1 +/- 4.7 ml/min/1.73 m2 (not significant). Similar results (for SBP, DBP, HR and PRA) were obtained in the erect position. It is concluded that tertatolol in hypertensive patients with CRF: significantly lowers BP and HR without excessive bradycardia, significantly lowers PRA, the most important decrease being observed for the highest initial PRA, does not alter renal function, and has a good clinical acceptability.

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.

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.

Plasma antidiuretic hormone (ADH) was measured before and after furosemide administration in hypertensive patients (essential benign hypertensions with low plasma renin activity) and in normal subjects. Furosemide-induced reduction of plasma volume was about 10% after 2 hours. In normal subjects, plasma ADH rose progressively till the end of the study (1.5 pg/ml per hour corresponding to about 3 pg/ml per liter of plasma water lost) whereas it remained unchanged in hypertensive patients. There was an early increase of plasma renin activity (PRA) in normal subjects followed by a progressive fall. PRA response was blunted in hypertensive patients. These results show that volume-dependent ADH secretion is inhibited in patients with essential benign hypertension.

We studied retrospectively the case records of 442 women who were followed because of hypertension during a pregnancy. Pregnancy hypertension was more frequent in white european than in black or arabic women. It occurred more frequently in women with an important professional activity than it did in housewives. 58% of patients had a familial history of high blood pressure, 35% were obese, 12% had glucose intolerance and 18% had hypercholesterolemia. Those frequencies were out of proportion with those in the control population. Finally, 32% of patients remained hypertensive after pregnancy. It is concluded that pregnancy hypertension occurs mainly in women whose genetic and metabolic background is that of essential hypertension.