Pathophysiology of deoxycorticosterone-secreting adrenal tumors.

Two patients with hypermineralocorticoidism due to deoxycorticosterone (DOC) excess are described. The plasma 17-deoxysteroids of the zona fasciculata (ZF), namely DOC, corticosterone, 18-hydroxydeoxycorticosterone, and 18-hydroxycorticosterone, were elevated. Plasma androgen concentrations were normal, and plasma aldosterone and renin levels were low. One patient, who had benign adrenocortical adenoma, had normal plasma cortisol levels. The other patient, who had metastatic adrenocortical carcinoma, had low plasma cortisol, presumably due to elevated plasma corticosterone levels. While tumors producing only 17-deoxysteroids are rare, they have provided new insights into the regulation of 17-deoxysteroid secretion by the ZF. Presumptive suppression of a non-ACTH factor by adenoma-produced DOC transiently impaired the early postoperative responses to ACTH of the ZF 17-deoxysteroids of the contralateral adrenal. The dissociation of 17-deoxysteroids from cortisol in normal subjects given either dexamethasone or DOC acetate provides additional evidence for such a factor.

Hypertension and pregnancy-related hypertension.

Pregnant women with hypertension can be divided into two groups: normotensive women who develop the uniquely pregnancy-related syndrome of preeclampsia, which is characterized by hypertension, proteinuria, and edema; and women with chronic hypertension who become pregnant and are at increased risk for developing superimposed preeclampsia. Preeclampsia is a syndrome of generalized endothelial dysfunction initiated by abnormal placentation and consequent placental under-perfusion, release of cytokines and other toxins, and vasoconstriction and platelet activation. Preeclampsia is the major cause of both maternal and fetal morbidity and mortality and may be complicated by eclampsia (seizures) and hepatic and renal failure. The process is completely reversible by delivery of the fetus and placenta, but intrauterine growth retardation and premature delivery pose major threats to the fetus and may require care in tertiary care center. Treatment of preexisting or pregnancy-induced hypertension does not prevent or reverse the process, but is justified to prevent maternal cardiovascular complications, especially during labor and delivery.

Ambulatory blood pressure measurements, prognostic implications.

Repeated measurements of the arterial pressure made in free ranging non-hospitalized individuals, termed "ambulatory blood pressures", have been shown to provide useful additional information to that obtained from measurements made in a physician's office or hospital. In general, the average of measurements made throughout the day (and night) correlates better with the severity of hypertensive target organ involvement than does the office pressure. This may be so because the ambulatory pressure is more representative of the individual's overall pressure load, and avoids the potential pressor effect of the artificial circumstances of the medical environment. We hypothesized that ambulatory pressure measurements would also provide additional prognostic information to that obtained from measurements made in the office. To test this hypothesis we have reviewed the clinical course of 1076 hypertensive patients for whom we had adequate baseline clinical information, including both office and ambulatory blood pressure readings, and at least one year of follow up. These patients were treated with standard antihypertensive therapy aimed lowering the office pressure below 140/90 mmHg, and were followed regularly in the clinic or by their primary physicians with periodic reassessment of their cardiovascular status. After a maximum of 10 years of follow up we found that individuals with higher office pressures, had a greater cardiovascular morbidity than did those with lower office pressures. Morbidity was further increased in older patients and in those who had evidence of target organ involvement or had had a prior clinical cardiovascular event.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory blood pressure: the San Francisco experience.

Results obtained at the University of California in San Francisco with the Remler M-2000, patient-activated, semi-automatic portable blood pressure recorder were reviewed. The automated recordings were accurate and reproducible in comparison with simultaneous readings obtained with a conventional sphygmomanometer. Daytime pressures in ambulatory patients were correlated reasonably well with office blood pressures (r = 0.63-0.69), but in 80% of the patients ambulatory blood pressures were lower than office blood pressures, and the disparity between the two tended to increase as office blood pressures rose. Average ambulatory blood pressure was better correlated than office blood pressure with the degree of target-organ damage and the presence of cardiovascular complications. Among patients with an equivalent office blood pressure, those with a large office-ambulatory blood pressure disparity or a relatively low ambulatory blood pressure had less target-organ damage than those with a high ambulatory blood pressure or a small ambulatory-office blood pressure disparity. Beyond the well known and powerful effect of age on prognosis, the office blood pressure level and the presence of target-organ damage, such as left ventricular hypertrophy, the ambulatory blood pressure level provided additional prognostic information. Thus patients with a low ambulatory blood pressure, in relation to the level predicted from the office blood pressure, had a better prognosis, and were less likely to develop clinical events over a 10-year period, than patients with higher ambulatory blood pressure levels. This was confirmed in patients with both uncomplicated and complicated hypertension.

Ambulatory blood pressure: mortality and morbidity.

Our data justify the conclusion that ambulatory blood pressures are useful in combination with office pressures and standard measures of target organ abnormalities in quantifying the severity of the hypertension in the individual patient. Ambulatory pressures are also useful for stratifying risk in predicting short-term prognosis; they may be markers for tracking the severity of disease and height of the pressure, but should not be used to determine long-term outcome independently of information on subsequent blood pressure control and other risk factors.

The prognostic value of ambulatory blood pressure monitoring in treated hypertensive patients.

The clinical course of 459 treated hypertensive patients who wore the Remler M-2000 patient-activated, semi-automatic, portable blood pressure recorder was reviewed in order to determine whether the average awake ambulatory blood pressure was better able than office blood pressure and standard risk prognosticators to predict the development of cardiovascular morbid events. The patients who developed events were older, had higher office blood pressures and more evidence of target-organ damage, and were more likely to have suffered a clinical cardiovascular event before entry into the study. Ambulatory pressures were lower than office blood pressure in 78% of patients; the correlation coefficients were 0.67 for systolic pressure and 0.60 for diastolic pressure. Each patient was classified according to whether his observed ambulatory blood pressure was greater than or equal to 10/6 mmHg above, within 9/5 mmHg or greater than or equal to 10/6 mmHg below the level derived from his or her office blood pressure and the regression line derived from the scatter plot of ambulatory blood pressure on office blood pressure for the entire sample. Using life-table analyses to record the rate of development of a first cardiovascular event, and log rank tests to compare curves, significant differences in outcome were found between patients whose observed ambulatory blood pressure was above the regression line compared with those whose ambulatory blood pressure was below the regression line. We conclude that ambulatory blood pressure measurements can provide additional prognostic information to that available from office blood pressure and from the standard prognostic indicators, age and severity of disease.

Prognostic value of ambulatory blood pressure measurements: further analyses.

The value of ambulatory systolic blood pressure as a predictor of the development of cardiovascular complications was investigated in a sample of 761 hypertensive patients who had undergone ambulatory blood pressure monitoring and who were followed for an average of 5.5 years. Of the 695 patients without prior cardiovascular events at entry into the study, 11% subsequently experienced an event during the follow-up period (up to 10 years) compared to 48% of the 102 patients with a prior cardiovascular event. For each patient, a 'predicted' ambulatory systolic blood pressure was calculated, using the patient's office systolic blood pressure and the equation derived from regressing ambulatory on office blood pressure for the entire sample. By subtracting the predicted from the observed ambulatory pressure, a 'residual' ambulatory systolic blood pressure was derived for each patient, as a measure of that portion of the ambulatory pressure that could not be predicted from the office pressure. We used a Cox proportional hazards model to analyse the independent effect of each of the following patient characteristics at entry on the occurrence of subsequent cardiovascular events: sex, age, ECG evidence of left ventricular hypertrophy, hypertensive retinopathy, ambulatory systolic blood pressure, office systolic blood pressure, residual ambulatory systolic blood pressure and subsequent drug therapy. In both groups, with and without a prior cardiovascular event, women, younger patients and those with lower residual ambulatory systolic blood pressure tended to have longer periods of survival without new cardiovascular events. In the group without prior cardiovascular events, a lower office systolic blood pressure and the absence of advanced ECG evidence of left ventricular hypertrophy were also independently predictive of longer event-free survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Retrospective and prospective research on hypertension-related end-organ damage.

Persistent inappropriate blood pressure elevation leads to the development of left ventricular hypertrophy, progressive atherosclerosis, and structural changes in the arterial tree. These changes result in clinical manifestations such as ischemic cardiac and cerebral events, congestive heart failure, renal failure, and peripheral vascular insufficiency. This article reviews the 5-year course of 439 patients with primary hypertension who were seen at a time (1946-1953) when potent antihypertensive therapy was not widely used. At the end of 5 years, 55% of the men (78 of 143) and 28% of the women (83 of 296) were dead. The principal causes of death were coronary insufficiency, congestive heart failure, cerebral infarction and hemorrhage, accelerated hypertension, renal failure, and dissecting aneurysm of the aorta. Coronary insufficiency and accelerated hypertension predominated in men, whereas women died principally of cerebral events and congestive heart failure. The 439 patients were stratified according to the level of their office blood pressure on the first visit, the severity of the changes in the optic fundi, the degree of left ventricular hypertrophy determined by electrocardiogram, cardiac enlargement determined by roentgenogram and their renal function, as measures of end-organ damage. Patients who had higher initial blood pressures showed more evidence of end-organ damage than patients with lower initial pressures. The higher the initial blood pressure or the more advanced the evidence of end-organ damage, the greater was the 5-year mortality. The mortality was particularly high in patients who had already sustained a clinical cardiovascular event before entry into the study and in those with malignant hypertension or gross cardiomegaly.(ABSTRACT TRUNCATED AT 250 WORDS)

Conduct of therapeutic trials.

Monitoring the blood pressure of individuals throughout the day and night has p;rovided information concerning the variability of blood pressure, the diurnal fluctuation of blood pressure levels, and the often exaggerated response of some individuals to the medical environment, the 'white-coat' effect. The average of multiple pressures obtained during the waking hours has been shown to correlate better with the degree of target-organ damage from hyhpertension than does the average of a few readings performed over a brief period of time in a physician's office. Thus it is generally agreed that the average ambulatory blood pressure (ABP) is more representative of the blood pressure of a subject than is the casual, clinic or office blood pressure (OBP). With the mounting evidence that lowering blood pressure in hyertensive individuals is beneficial by reducing cardiovascular complications and prolonging life, there has been a proliferation of new antihypertensive agents. Before these drugs can be released for general use, they need to be tested both for their short-term effects, peak and trough effects and duration of action, and for their long-term safety and effectiveness in reducing the number of cardiovascular events. ABP monitoring (ABPM), using the currently available portable, automatic equipment seems to be a simple, theoretically reproducible and reliable method for conducting such therapeutic trials. Yet the use of ABPM has raised a host of new questions concerning the reliability and need for standardized testing of the equipment, the definitions of hypertension and normotension, and the precise methods for quantifying the blood pressure-reducing effect of a drug and the effect of this reduction on clinical outcome. This session addressed some of these concerns.

The prognostic value of ambulatory blood pressures.

We reviewed the course of 1,076 patients with essential hypertension whose condition had been initially evaluated with both ambulatory BP (ABP) and office BP (OBP) measurements. During the period of follow-up (mean, five years), fatal cardiovascular events occurred in 75 patients, and nonfatal events occurred in 153. Each patient was classified according to the difference between the mean observed ABP at entry and that predicted from the mean OBP at entry by means of an equation for the linear regression of ABP on OBP. Life-table analyses demonstrated a significantly greater estimated cumulative ten-year incidence of both fatal and nonfatal events among patients with higher than predicted ABPs than among those with lower than predicted ABPs. Because OBPs were comparable in the two groups, we conclude that ABP was an important determinant of clinical outcome.

Hypertension and the obstetrician-gynecologist.

Hypertension is a major risk factor for cardiovascular-related morbidity and death. Antihypertensive therapy markedly reduces the risk caused by elevated blood pressure. Earlier treatment of hypertensive patients should reduce deaths and morbidity even further. The obstetrician-gynecologist has the opportunity and responsibility to identify hypertensive patients early in the course of their disease. He must also confront the problem of elevated blood pressure associated with the use of oral contraceptives. In addition to its impact on the general population, chronic hypertension presents special problems during pregnancy. Pregnant women with elevated blood pressure have an increased fetal mortality rate and develop pre-eclampsia more frequently and earlier than nonhypertensive women. Antihypertensive treatment possibly increases fetal survival; when used appropriately, it definitely does not decrease fetal salvage. The appropriate use of antihypertensive therapy during pregnancy requires an understanding of the mechanism of action of these agents and recognition of side effects, especially those important during pregnancy.

Clinical relevance of ambulatory blood pressure measurements.

The development of vascular complications in patients with hypertension is related to the level of blood pressure. A more representative measure of blood pressure is obtained by repeatedly measuring pressure after a period of rest or activity, and on several occasions. Really satisfactory values are, however, only obtained by multiple measurements throughout the day during a patient's normal activities. This is achieved with the Remler equipment (Model M-100-1 and M 2000). The working of the apparatus is described and its accuracy investigated. The findings of 675 untreated patients with essential hypertension are reviewed, and a few individual cases described which have been followed up to 10 years.

Blood pressure variability and its implications for antihypertensive therapy.

Although it is clear that antihypertensive treatment is beneficial in reducing stroke morbidity and mortality, the results of the major outcome studies show less impact on coronary heart disease. Studies utilizing 24-h blood pressure (BP) monitoring show a positive association between target organ damage and the level of 24-h BP, and with variability in BP, which is an independent determinant of target organ damage. Current understanding of the pathogenesis and pathophysiology of coronary heart disease suggests that optimal antihypertensive treatment should ensure the following: effective 24-h BP control, smooth antihypertensive effect with reduced variability; attenuation of the early morning surge in BP; maintenance of the normal circadian pattern of BP; effective therapeutic coverage in the face of suboptimal compliance; and lack of reflex activation of the sympathetic nervous system. On the basis of our current understanding, this optimum is most likely to be achieved by the use of antihypertensive agents with a long duration of action.

Renal arteriography in the evaluation of unexplained hypertension in children and adolescents.

Arteriography demonstrated renal artery stenosis in 24% of 101 selected patients whose hypertension was first diagnosed before the age of 20 years. Arteriographic findings were normal in 58%. The prevalence of RAS was greater in the younger than in the older age groups. An abdominal bruit and urographic abnormalities were frequently observed in association with RAS. Adequate follow-up information was available for 16 patients who underwent vascular repair or nephrectomy for RAS. In 14 of the 16, the hypertension was eliminated (81%) or definitely reduced (6%).