Diabetes

Pregnancy-Induced Hypertension

In women with pregnancy-induced hypertension (PIH) the density of mineralocorticoid receptors (MR) in human mononuclear leukocytes (HML) is reduced compared with healthy pregnant women. The same applies to plasma levels of aldosterone and 18-hydroxycorticosterone. In this study, we investigated whether alterations of these parameters preceded the development of clinical symptoms and, therefore, might be potential predictors of PIH involved in the pathogenesis.

In eighty-four women belonging to the risk-group for PIH but not showing any symptoms neither of PIH nor preeclampsia (PE) we characterized prospectively before the onset of disease in the second trimester of pregnancy mineralocorticoid receptor status in HML and steroid plasma levels of aldosterone and its precursors as well as cortisol through radioimmunoassay.

15 women developed PIH, three of which developed PE. Neither in the density of MR nor in the affinity had the women that developed PIH showed any difference from healthy women. Steroid plasma levels were identical as well.

We conclude that a reduction of mineralocorticoid receptors does not precede PIH within the peripheral blood. But still one can assume that the RAAS may be involved in the pathogenesis of PIH, possibly on a local level within the placenta or as a secondary change, initiated by still unknown factors.

The aims of this study were to examine whether the combined approach of 1) establishing tolerance intervals for the circadian variability of blood pressure as a function of gestational age, and 2) computing the hyperbaric index by comparison of any patient’s blood pressure profile (obtained by ambulatory monitoring) with the tolerance limits, provides a new highly sensitive test for the early detection of gestational hypertension and preeclampsia. We analyzed a total of 745 blood pressure series sampled by ambulatory monitoring for about 48 hours in each of several occasions in 189 women with uncomplicated pregnancies, 71 with gestational hypertension, and 29 with preeclampsia. After synchronization of all data by expressing times of sampling in hours from bed-time, circadian tolerance limits were first computed from the normotensive subjects as a function of trimester of pregnancy. The hyperbaric index and the percentage time of excess were then computed for each individual blood pressure series. The maximum hyperbaric index was below 15 mmHg X hour for normotensive pregnant women in all trimesters of pregnancy, and mostly above that value for women who subsequently developed gestational hypertension or preeclampsia. Sensitivity of the test based on the maximum hyperbaric index was 97% for women sampled during the first trimester of gestation, and increased up to 100% in the third trimester. The positive predictive value was 100% in all trimesters. Moreover, the computation of the hyperbaric index provided, on the average, an early identification of gestational hypertension or preeclampsia 20 weeks prior to the clinical confirmation of the disease.

Ambulatory monitoring of blood pressure during gestation provides sensitive endpoints for use in early risk assessment and as a guide for establishing preventive interventions. The approach presented here represents a simple, reproducible, non-invasive, and highly sensitive test for the very early identification of gestational hypertension and preeclampsia.

Characteristics of a 24-hour blood pressure monitoring and its usefulness in the diagnosis of early hypertension have been discussed. Measurements of ambulatory blood pressure in normotensive individuals are lower than those achieved with continuous monitoring at daytime whereas the situation in hypertensive subjects is reverse. Office blood pressure measurements produce higher values already in borderline hypertension and may use as differentiating diagnostic parameter. Continuous blood pressure monitoring enables to detect “white coat hypertension” estimated to occur in 7% of the general population and in 21% of patients with mild hypertension. Even a few hours of the continuous blood pressure monitoring identifies subjects with “white coat hypertension” and office hypertension and consequently avoidance of the unnecessary pharmacologic treatment. Ambulatory blood pressure monitoring is also useful in the diagnosis of early hypertension in adolescents provided that the tests will be carried out during school hours. Some investigators believe that the proportion of abnormal measurements (over 140/90 mm Hg), i.e. so-called blood pressure load, is more important at early stages of the disease because there closer correlation between blood pressure and organ damage than mean values of blood pressure. However, it was not established yet what is a percentage of abnormal blood pressure measurements in normotensive and hypertensive subjects. Blood pressure circadian rhythm in various groups but the highest changes are found in borderline hypertension. Blood pressure variability expressed as standard deviations from the mean values calculated from the ambulatory blood pressure monitoring is an individual feature considered also as a predictor of hypertension development with all its sequelae.

Renovascular hypertension is more common in hypertensive children than in hypertensive adults, and renal artery stenosis is second only to coarctation of the thoracic aorta as a cause of surgically correctable hypertension. Three infants presented with uncontrollable hypertension secondary to renal artery thrombosis due to umbilical artery catheterization for respiratory distress in the neonatal period. They all responded to nephrectomy. A fourth infant had stenosis of a polar vessel secondary to umbilical artery catheterization and was cured by partial nephrectomy. Two infants with renal artery stenosis secondary to fibromuscular dysplasia benefited from revascularization and, at last follow-up, were normotensive and off all blood pressure medication. Ultrasonography, isotope scanning, angiography and selective renal vein renin assays should be used to identify patients with surgically correctable lesions. The use of fine suture material and microvascular surgical techniques, including ex vivo revascularization and autotransplantation, can salvage renal parenchyma and relieve hypertension. Infants with less than 10 percent renal function on the involved side should have a nephrectomy. The infant with an umbilical arterial catheterization line needs blood pressure monitoring and aggressive evaluation and treatment of persistent hypertension.

Essential arterial hypertension, malignant hypertension and renovascular hypertension were studied in 64 patients, divided into 5 groups according to creatinine clearance (Ccreat) and ophthalmic fundus. Urine N-Acetyl-b-d-glucosaminidase (NAG) was expressed in units/mg creatinine in urine. Results were; Group A: Ccreat greater than 60, ophthalmic fundus less than II (n=33), NAG 13.5 + 4.5; Group B: CCreat. greater than 60, ophthalmic fundus III-IV (n=4) NAG 42.4 +/- 12.5; Group C: Ccreat. less than 60, ophthalmic fundus less than II (n = 14) NAG 31.2 +/- 10,5; Group D: (clinically malignant arterial hypertension) Ccreat. less than 60, ophthalmic fundus III–IV (n = 8), NAG 91.1 +/- 55.7 and Group E: (renovascular hypertension) Ccreat. greater than 60, ophthalmic fundus less than II  (n = 5), NAG 35.5 +/- 12.9. Only the patients in Group A had NAG within normal limits. Differences were found between groups: A-B (p less than 0.001), A-D (p less than 0.001), A-E (p less than 0.001) and C-D (p less than 0.001). Urine NAG is considered to be an early sign of renal involvement in arterial hypertension, an indication of the severity and a sign of ischemia even when the involvement is unilateral only, and helpful in the management of renovascular hypertension.

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