Search

Scleroderma renal crisis (SRC) is a rare but life-threatening complication of systemic sclerosis (SSc) characterized by malignant hypertension and acute kidney injury. Historically, SRC was the leading cause of death in SSc. However, with the advent of angiotensin converting enzyme (ACE) inhibitors, mortality rates have decreased significantly. Nevertheless, one-year outcomes remain poor, with over 30% mortality and 25% of patients remaining dialysis-dependent. There is an urgent need to improve early recognition and treatment, and to identify novel treatments to improve outcomes of SRC. In this chapter, the clinical features, classification, pathophysiology, differential diagnosis, management and outcomes of SRC are presented. Specific issues relating to pregnancy, prophylactic ACE inhibition and management of essential hypertension are also discussed., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Objective: Malignant hypertension represents a high-risk condition and there are scarce data on current clinical patterns of this condition. The aim of the study is to identify the clinical and demographic factors associated with poor outcome., Methods: The data collected from 1958 to May 2016 included a total of 351 patients whose 5-year survival status was known: 221 white Caucasians (63%, age 51 ± 13 years, 64% male), 83 African-Caribbeans (24%, 45 ± 11 years, 61% male), and 47 South Asians (13%, 42 ± 11 years, 74% male)., Results: During the 5-year follow-up 119 (34%) patients suffered a primary outcome, defined as the composite endpoint of death or dialysis. The 5-year mortality ranged from 76% in patients diagnosed before 1967 to 7% in patients diagnosed between 1997 and 2006. The independent predictors of outcome were advanced age (vs. a reference group of < 40-year-old; P = 0.01 for age at presentation 51-60 years, P < 0.001 for age > 60 years), prior use of antihypertensive medications (P = 0.002), higher serum creatinine (P = 0.006), and proteinuria (P < 0.01). Also, white Caucasian (odds ratio12.02, 95% confidence interval 1.64-88.15, P = 0.01) and African-Caribbean (odds ratio 15.55, 95% confidence interval 2.06-117.29, P = 0.008) origins were associated with higher mortality vs. South Asians. The years of the diagnosis after 1977 were significantly associated with lower composite endpoint of death or dialysis, all P < 0.01., Conclusion: There has been a major improvement in 5-year survival in patients with malignant hypertension over recent decades. Abnormal renal function at presentation still predicts worse outcome. South Asian ethnicity is also associated with better outcome, although mechanisms involved are yet to be established.

Hypertensive emergency (HE) is a life-threatening condition that requires immediate blood pressure (BP) reduction. Although it has been on the decline, the incidence of HE has recently increased in a few countries. The aim of the present retrospective study was to evaluate the incidence, aetiology and 1-year mortality of HE in a large medical centre over a 20-year period (1991-2010). The electronic medical records of all patient files who were hospitalized in the Chaim Sheba Medical Center in Israel from 1991 to 2010 with a primary diagnosis (at admission or discharge) of Malignant Hypertension, Hypertensive Emergency or Accelerated Hypertension were retrieved and analysed. The study interval was divided into four periods of 5 years each. Among 306 files reviewed, only 142 patients had a true HE. Average age at presentation was 63.3±16.5 years. Men were younger than women (59±16 vs 68±16 years; P<0.001). At presentation, most patients (80.3%) had been diagnosed with essential hypertension previously and were undertreated. Average maximum mean arterial pressure (MAP) was higher in men (169±22 mm Hg) than in women (161±17 mm Hg; P=0.026). The rate of HE decreased over the course of the study, from 12.7/100 000 admissions during 1991-1995 to 6.2/100 000 admissions (2006-2010). Similarly, 1-year mortality decreased from 16.7 to 3.6%. The rate of HE has decreased and the prognosis has improved over the last two decades. Appropriate BP control of patients with essential hypertension may further decrease the risk of HE.

The survival of patients with malignant hypertension (MHT) has considerably improved over the past decades. Data regarding the excess risk of mortality and the contribution of conventional cardiovascular risk factors are lacking. The authors retrospectively assessed cardiovascular risk factors and all-cause mortality in 120 patients with a history of MHT and compared them with 120 normotensive and 120 hypertensive age-, sex-, and ethnicity-matched controls. Total cholesterol, low-density lipoprotein cholesterol, and body mass index were lower in MHT patients compared with hypertensive controls, whereas blood pressure, high-density lipoprotein cholesterol, and smoking habit were similar. Median estimated glomerular filtration rate was lower in MHT patients compared with normotensive and hypertensive controls (both P<.01). The annual incidence of all-cause mortality per 100 patient-years was higher in MHT patients (2.6) compared with normotensive (0.2) and hypertensive (0.5) controls (both P<.01). Mortality of patients with a history of MHT remains high compared with normotensive and hypertensive controls. Patients with MHT had a more favorable cardiovascular risk profile compared with hypertensive controls but a higher prevalence of renal insufficiency., (©2013 Wiley Periodicals, Inc.)

Objective: The prognosis of patients with hypertensive emergencies has recently improved dramatically owing to the development of effective antihypertensive therapy. We examined the histological and clinical features of patients with hypertensive emergency-related nephropathy., Methods: Twelve patients (11 men and one woman) were diagnosed as having hypertensive emergencies with acute renal failure according to the Joint National Committee-7 classification of blood pressure for adults and underwent renal biopsies at our hospital between 1995 and 2008. These patients were enrolled in this retrospective study., Results: The age of the subjects was 40.1±9.8 years. At presentation, the mean systolic/diastolic blood pressure was 232±32/146±12 mmHg and none of the patients were being treated with antihypertensive drugs, although 10 patients had histories of hypertension. The mean serum creatinine level was 6.1±4.7 mg/dL. All 12 patients showed left ventricular hypertrophy on echocardiography. On light microscopy of the renal biopsy specimens, all 12 patients showed onion skin patterns of the arterioles; however, no fibrinoid necrosis of the small arteries was found. Electron microscopy revealed electron-lucent widening of the subendothelial zone of the glomerular capillary walls in seven patients. One of the 12 patients did not respond to medical therapy and required regular dialysis. The other 11 patients responded to treatment., Conclusion: An onion skin pattern of the arterioles is the most frequent histological finding in patients with hypertensive emergency-related nephropathy. Long-standing hypertension might contribute to this arteriolar change, since left ventricular hypertrophy was also seen in these patients. With strict control of hypertension using antihypertensive medications, the prognosis of patients with hypertensive emergency-related nephropathy can be improved.

Background: Malignant hypertension is frequently complicated by renal insufficiency. Although the survival of this hypertensive emergency has improved, recent data on renal outcome and its predictors are lacking. We assessed renal outcome and its predictors in patients with malignant hypertension., Methods: Retrospective analysis of patients admitted with malignant hypertension in Amsterdam, the Netherlands between August 1992-January 2010. Follow-up data on vital status, renal function and blood pressure (BP) were obtained from the outpatient department and from general practitioners. The primary composite endpoint was end-stage renal disease (ESRD) defined as the start of kidney replacement therapy (KRT) or ≥ 50% decline of estimated glomerular filtration rate (eGFR). The secondary endpoint was all cause mortality., Results: A total of 120 patients admitted with malignant hypertension were included. After a median follow-up period of 67 months (IQR 28 to 108 months) the primary endpoint was reached by 37 (31%) patients, whereas 18 patients (15%) reached the secondary endpoint. Twenty-nine (24%) patients started KRT and 8 patients (7%) had an eGFR decline ≥ 50%. After the acute phase (> 3 months after admission), initial serum creatinine and follow-up BP were the main predictors of future ESRD with hazard ratios of 6.1 (95% CI, 2.2-17) for patients with initial serum creatinine ≥ 175 μmol /L and 4.3 (95% CI, 1.4-14) for patients with uncontrolled hypertension., Conclusions: Progressive renal function decline leading to ESRD remains a major threat to patients with malignant hypertension. BP control during follow-up was an important modifiable predictor of renal outcome.

Object: Recent randomized trials have demonstrated a positive role (improved survival) in patients treated with cranial decompression for malignant cerebral infarction. However, many variables regarding operative decompression in this setting remain to be determined. Hinge craniotomy is an alternative to decompressive craniectomy, but its role in space-occupying cerebral infarctions has not been delineated. The objective of this study was to compare the authors' experiences with these 2 procedures in the management of space-occupying cerebral infarctions to determine the efficacy of each., Methods: The authors conducted a retrospective review of 28 cases involving patients who underwent cranial decompression (hinge craniotomy in 9 cases, decompressive craniectomy in 19) for treatment of malignant intracranial hypertension after ischemic cerebral infarction., Results: No significant differences were identified in baseline demographics, neurological examination, or Rotterdam score between the hinge craniotomy and decompressive craniectomy groups. Both treatments resulted in adequate control of intracranial pressure (ICP). The need for reoperation for persistent intracranial hypertension and duration of mechanical ventilation and intensive care unit stay were similar. Hospital survival was significantly higher in the decompressive craniectomy group (89% vs 56%), whereas long-term functional outcome was better in the hinge craniotomy group. Cranial defect size was comparable in the 2 groups. Postoperative imaging revealed a higher rate of subarachnoid hemorrhage, contusion/hematoma progression, and subdural effusions/hygromas after decompressive craniectomy. The requirement for cranial revision in survivors was higher for patients undergoing decompressive craniectomy (100%) than those undergoing hinge craniotomy (20%)., Conclusions: Hinge craniotomy appears to be at least as good as decompressive craniectomy in providing postoperative ICP control at a similar therapeutic index. Although the in-hospital mortality was higher in patients treated with hinge craniotomy, that procedure resulted in superior long-term functional outcomes and may help limit postoperative complications.

Background: Some studies have shown an improvement in the prognosis of patients with essential malignant hypertension (MHT), but data about long-term outcome and prognostic factors of these patients are scarce., Methods: We performed a single-centre retrospective analysis of 197 patients with MHT, diagnosed in the period 1974-2007., Results: Incidence of MHT remained stable along the different periods of the study. Renal damage at presentation was common (63% of patients) but renal function improved or remained stable after diagnosis in a majority of patients. The probability of renal survival was 84 and 72% after 5 and 10 years, respectively. Diagnosis during the first period (1974-85) of the study, previous chronic renal impairment, baseline renal function and proteinuria, presence of microhaematuria, systolic and diastolic blood pressure and proteinuria during follow-up were associated with an unfavourable outcome. By multivariate analysis, mean proteinuria during follow-up remained as the only significant risk factor (OR, 2.72; 95% CI, 1.59-4.64). Renal survival for patients with mean proteinuria <0.5 g/24 h was 100 and 95% after 5 and 10 years, respectively. The number of patients who improved or stabilized their renal function significantly increased in the second and third periods of the study (1987-2007)., Conclusions: Renal survival in MHT has improved in recent years. Mean proteinuria during follow-up is a fundamental prognostic factor for renal survival.

Background: To examine changing demography and survival of patients with malignant phase hypertension (MHT) over 40 years., Methods: Patients from our MHT registry whose survival status on 31 December 2006 was known were included, with analyses conducted based on decade of MHT diagnosis., Results: Four-hundred and forty-six patients with MHT (overall mean (s.d.) age 48.2 (12.9), years; 65.5% male; 64.7% white-European; 20.4% African Caribbean, and 14.8% South-Asian) were included. No significant demographic differences at diagnosis were evident over the 40 years, with the exception of a significant increase (P = 0.001) in the proportion of MHT among ethnic minorities (South-Asian and Afro-Caribbeans). There were no significant differences in mean systolic blood pressure (SBP) at presentation but baseline diastolic BP (DBP) was significantly lower after 1976 (P < 0.0001). The total number of person-years of observation was 5,725.5 years, with a median (interquartile range (IQR)) length of follow-up of 103.8 (31.3-251.2) months. Overall 203 patients (55.6%) died, 125 (32.0%) within 5 years of diagnosis. There was a significant improvement in 5-year survival from 32.0% prior to 1977 to 91.0% for patients diagnosed between 1997 and 2006. SBP and DBP improved significantly during follow-up (P < 0.0001). Multivariate analyses revealed that age, decade of MHT diagnosis, baseline creatinine, and follow-up SBP were independent predictors of survival (all P < 0.0001)., Conclusions: Demography and number of new cases of MHT have not changed dramatically over the past 40 years. Five-year post-MHT survival has improved significantly, possibly related to lower BP targets, tighter BP control, and availability of new classes of antihypertensive drugs.

In patients with malignant hypertension, immediate blood pressure reduction is indicated to prevent further organ damage. Because cerebral autoregulatory capacity is impaired in these patients, a pharmacologically induced decline of blood pressure reduces cerebral blood flow with the danger of cerebral hypoperfusion. We compared the reduction in transcranial Doppler-determined middle cerebral artery blood velocity during blood pressure lowering with sodium nitroprusside with that of labetalol. Therefore, in 15 patients, fulfilling World Health Organization criteria for malignant hypertension, beat-to-beat mean arterial pressure, systemic vascular resistance (Modelflow), mean middle cerebral artery blood velocity, and cerebrovascular resistance index (mean blood pressure:mean middle cerebral artery blood flow velocity ratio), were monitored during treatment with sodium nitroprusside (n=8) or labetalol (n=7). The reduction in mean arterial blood pressure with sodium nitroprusside (-28+/-3%; mean+/-SEM) and labetalol (-28+/-4%) was comparable. With labetalol, both systemic and cerebral vascular resistance decreased proportionally (-13+/-10% and -17+/-5%), whereas with sodium nitroprusside, the decline in systemic vascular resistance was larger than that in cerebral vascular resistance (-53+/-4% and -7+/-4%). The rate of reduction in middle cerebral artery blood velocity was smaller with labetalol than with sodium nitroprusside (0.45+/-0.05% versus 0.78+/-0.04% cm.s(-1).%mm Hg(-1); P<0.05). In conclusion, sodium nitroprusside reduced systemic vascular resistance rather than cerebral vascular resistance with a larger rate of reduction in middle cerebral artery blood velocity, suggesting a preferential blood flow to the low resistance systemic vascular bed rather than the cerebral vascular bed.

Hypertensive crisis is a serious condition that is associated with end-organ damage or may result in end-organ damage if left untreated. Causes of acute rises in blood pressure include medications,noncompliance, and poorly controlled chronic hypertension. Treatment of a hypertensive crisis should be tailored to each individual based on the extent of end-organ injury and comorbid conditions. Prompt and rapid reduction of blood pressure under continuous surveillance is essential in patients who have acute end-organ damage.

Background: Idiopathic IgA nephropathy is one of the main causes of secondary malignant hypertension, especially in Chinese population. But little information has been available about malignant hypertension secondary to IgA nephropathy (IgANMHT). The purpose of this study is to evaluate the clinico-pathological features and outcomes of IgANMHT patients., Methods: A case control retrospective study was carried out in 45 cases of IgANMHT and 26 cases of primary malignant hypertension (PMHT) diagnosed by renal biopsy. Their clinical features and pathological findings were investigated. Their average follow-up time was 37.4 months. Univariate analysis and multivariate Cox regression analysis were performed to select variables to predict renal survival., Results: In the study, 1.2% of all the IgA nephropathy patients presented malignant hypertension. The amounts of urine protein excretion and red blood cells in IgANMHT patients were significantly higher, while the levels of serum creatinine were significantly lower than those in PMHT patients. The glomerular injury in IgANMHT patients was more severe than that in PMHT patients. The two characteristic vascular lesions of primary malignant hypertension, proliferative endoarteritis and fibrinoid necrosis were also found in IgANMHT patients but with less severity. Renal survival of IgANMHT patients was significantly higher than that of PMHT patients (p = 0.0043). However, log-rank test showed no significant difference in the renal survival between IgANMHT and PMHT patients with similar SCr levels at admission. Multivariate Cox regression analysis revealed that a high amount of urine protein excretion(> or =1.5 g/24 h), mesangial proliferation and elevated serum creatinine (> or =2 mg/dl) were statistically independent risk factors for renal prognosis (RR = 1.90, 2.72, 2.84, respectively). Conversely, strict blood pressure control had a favorable effect on renal prognosis., Conclusion: The clinico-pathological features and outcomes of IgANMHT patients were different from those of PMHT patients. The renal survival of IgANMHT patients was poor, which was determined by many factors. Early control of proteinuria, early monitoring and strictly controlling blood pressure may contribute to the renal survival.

Previous studies have demonstrated that adrenomedullin has inhibitory effects on the proliferation and DNA synthesis of mesangial cells and vascular smooth muscle cells in vitro and that plasma adrenomedullin levels are markedly elevated in malignant hypertension. This study was designed to examine whether chronic adrenomedullin infusion has renoprotective effects in malignant hypertensive rats. We studied the following 3 groups: control Wistar Kyoto rats, deoxycorticosterone acetate-salt spontaneously hypertensive rats, and adrenomedullin-treated deoxycorticosterone acetate-salt spontaneously hypertensive rats. Chronic adrenomedullin infusion using an osmotic minipump was started simultaneously with deoxycorticosterone acetate-salt treatment. After 3 weeks of the treatment, malignant hypertensive rats were characterized by higher blood pressure, kidney weight, urinary protein excretion, glomerular injury score, plasma renin concentration, aldosterone level, endogenous rat plasma adrenomedullin level, renal cortical tissue angiotensin II level, angiotensin-converting enzyme mRNA level, and transforming growth factor-beta1 mRNA level in the renal cortex, and by lower creatinine clearance, compared with the control rats. Chronic adrenomedullin infusion significantly improved these parameters (kidney weight -6.5%, urinary protein excretion -63.8%, glomerular injury score -38.3%, plasma renin concentration -52.4%, aldosterone -23.2%, rat adrenomedullin -28.6%, renal angiotensin II -28.1%, renal angiotensin-converting enzyme mRNA -38.3%, renal transforming growth factor-beta1 mRNA -56.2%, and creatinine clearance +20.5%) without significant reduction of mean arterial pressure (-4%). Kaplan-Meier survival analysis showed that adrenomedullin infusion significantly prolonged survival time. These results suggest that subdepressor dose of chronic adrenomedullin infusion has renoprotective effects in this malignant hypertension model, at least in part, via inhibition of the circulating and intrarenal renin-angiotensin system.

The aim of the present study is to investigate the pathophysiological characteristics of a number of recent cases of malignant hypertension (MHT) and to compare them to the characteristics of earlier cases. Patients with MHT (age 25-76, mean 44+/-2 years) who were admitted to our hospital from 1984-1999 were retrospectively studied. All of the patients had either grade III or IV retinopathy and diastolic blood pressure levels higher than 120 mmHg. The observations in this study were compared to previously reported findings regarding 59 MHT patients who were admitted from 1971-1983. Of the 37 recent MHT patients, 20 had essential hypertension (EHT) as the underlying disease, 13 had chronic glomerulonephritis (CGN), and the remaining 4 presented with other diseases including pyelonephritis and renovascular hypertension. A positive family history of hypertension was more prevalent in the EHT patients than in other patients, and persistent proteinuria, microhematuria, and anemia were more prevalent in the CGN patients. These characteristics were similar between the recent and previous cases. Within 4 weeks after admission, hemodialysis was initiated in 3 of the 13 patients (23%) with CGN and 2 of the 20 (10%) patients with EHT. The prevalence of renal death at 1 year after admission was 30%, which was lower than the prevalence in the previous cases (42%). Grade IV retinopathy was seen in 45% of the patients admitted from 1984-1999, significantly less than in the patients admitted from 1971-1983 (66%, p<0.05). In addition, left ventricular hypertrophy was less frequently observed on electrocardiogram in the recent cases (67%) than in the previous cases (88%, p<0.05). Our results suggest that the recent cases of MHT demonstrate less severe organ damage.

Background: There has been speculation whether serum uric acid levels are an independent prognostic factor in patients with hypertension., Objective: To investigate the clinical associations and prognostic value of serum urate in patients with malignant phase hypertension (MHT), by comparing clinical features in patients with serum urate levels above and below the median levels for this population, and secondly, by performing a survival analysis in these patients., Patients and Methods: Review of the data on 153 patients (98 males; mean age 50.3 years, SD 13.5) with MHT on the west Birmingham MHT register. Median uric acid levels in this population was 0.41 mmol/l (6.9 mg/dl), with an interquartile range of 0.34-0.50 mmol/l (5.7-8.4 mg/dl). Clinical characteristics of patients with a serum urate <0.41mmol/1 (group 1) were compared to those with levels above the median (0.41 mmol/l, group 2)., Results: Mean duration of follow-up was similar in both groups. The mean diastolic blood pressure at presentation and both mean systolic and diastolic blood pressures at follow-up were significantly higher in group 2 (that is, those with high serum urate levels) (unpaired t test, P= 0.039). There was also more renal dysfunction in group 2 patients with MHT, with higher mean serum urea and creatinine levels, both at presentation and at follow-up (unpaired t test, P< 0.01). The commonest causes of death were myocardial infarction (n = 7), heart failure (n = 4), stroke (n = 10) and renal failure (n = 5). There was no difference in mean survival duration between groups 1 and 2 (Kaplan-Meier, 64.6 versus 66.8 months; log-rank test, P= 0.519). Serum urate levels also did not predict the rise in serum creatinine levels (log-rank test, P= 0.84) or urea (P= 0.4033) amongst these patients. Using a multivariate Cox proportional hazards analysis, the only independent predictors of outcomes (death or the need for dialysis) were age (P = 0.007) and serum creatinine levels at presentation (P = 0.0046)., Conclusion: Our analysis of a large series of patients with MHT shows that those with high urate levels had higher diastolic blood pressures and greater renal impairment at baseline. At follow-up, patients with median serum urate >0.41 mmol/l showed a greater deterioration in renal function and higher blood pressures, but no significant difference in survival. Serum urate levels also do not appear to be predictive of the deterioration in renal function or overall survival in patients with MHT.

Malignant hypertension is associated with high mortality and morbidity usually caused by cardiovascular events. The course and prognosis of malignant hypertension patients treated with renal replacement therapy has not been thoroughly investigated. In the present work, we compared the clinical evolution and survival of 24 end-stage renal failure malignant hypertension patients with that of a group of individually matched renal failure patients admitted to the same dialysis center during a period of 21 years. Survival rates at 1, 5 and 8 years were 87, 82 and 50% for malignant hypertension patients and 87, 75 and 65% for controls, respectively (p = 0.766, NS). Nonfatal cardiovascular complications occurred in 2 individuals of each group. The most important cause of death in both groups was cardiovascular. The frequency of fatal cardiovascular events was similar in the two groups: 64% of deaths for malignant hypertension and 71% for controls (NS). In conclusion, previous malignant hypertension did not increase the risk of patients in long-term hemodialysis in our series., (Copyright 2000 S. Karger AG, Basel)

We report a series of seven patients who had scleroderma renal crisis. Their primary clinical and laboratory features along with the details of their management were compared with those of similar cases from the literature. The seven patients died within one to four months of the diagnosis with a pattern of acute renal failure, left ventricular failure and malignant hypertension. Histopathologic examination was performed in four of the patients, in two of whom it revealed thickening of the wall of the interlobular arteries related to the scleroderma, and in the other two patients nonspecific lesions of malignant hypertension. This histopathologic particularity led us to propose, on the basis of multiple renal biopsies performed in patients with scleroderma, a lesion chronology of the kidney in patients with scleroderma. Nevertheless, the triggering factors and pathophysiologic mechanisms of scleroderma renal crisis remain unclear and its prognosis is severe. Early treatment with angiotensin-converting enzyme inhibitors and other vasodilatators administered intravenously can prevent death and dialysis.

Previous studies have suggested that one-third of women of childbearing age who develop malignant phase hypertension (MHT) are likely to be taking oral contraceptives (OC). We surveyed 104 women with a history of MHT. None of the 65 aged > 45 years were taking OC or other sex hormones. Thirty-nine (mean age 34.9 years, SD 8.0) were aged 15-44 years at presentation: 22 Caucasian, 10 Black/Afro-Caribbean and seven Indo-Asian. Of these 39, 22 had a history of hypertension in pregnancy (group 1), and 17 did not (group 2). Three of group 1 also had a history of OC-induced hypertension. None were pregnant, but one was taking an OC at presentation with MHT. Blood pressures at presentation and follow-up, and mean serum urea and creatinine at presentation were similar between groups, as was median survival (96 vs. 47 months, Lee-Desu statistic 0.75, p = 0.38). There was a trend towards poorer renal function at follow-up in group 1 patients, with higher mean serum urea and creatinine levels. The causes of death were renal failure (5), stroke (4) and heart disease (2). The OC was not a common cause of MHT-amongst our sample of women of childbearing age, but a past history of hypertension in pregnancy was important. Such patients also had a longer duration of hypertension and poorer renal function at follow-up.

Patients with severe hypertension with retinoscopic bilateral papilloedema only are not classically regarded as having malignant hypertension (MHT). We have encountered 23 such patients between 1965-1993, whilst over a similar period we have seen 315 patients who fulfilled the conventional criteria for MHT with bilateral retinal haemorrhages, exudates with or without papilloedema. We hypothesised that patients with "lone" papilloedema and severe hypertension were suffering from a disease which was identical in aetiology and outcome to conventional MHT. There were no significant differences in age, mean blood pressure, proteinuria or renal function at presentation, ethnic composition, smoking status and followup blood pressure control between the papilloedema group and those presenting with conventional MHT. Clinical features at presentation in the papilloedema only group included strokes in 4, visual disturbance in 2, headaches in 3 and heart failure in 1 patient. Many patients however had no complications at presentation. After a mean followup of 59.8 months, of the "lone" papilloedema group, 7 patients (30.4%) were still alive, 1 patient was on renal dialysis therapy, 13 were dead (56.5%) and 2 (8.7%) were lost to followup. The commonest causes of death were stroke in 4 patients, renal failure in 4 and heart disease in 2. This was a similar pattern of mortality to those patients with "conventional" MHT. Lifetable analyses showed a median survival of 35.9 months for the papilloedema group which was significantly worse than the 108.7 months for the conventional MHT group (Lee-Desu statistic 4.04, p = 0.045). We suggest that patients with high blood pressure and lone bilateral papilloedema may comprise a hitherto unrecognised subgroup of patients with MHT. Once intracerebral pathology has been excluded, these patients need to be treated as aggressively as those with MHT.

To investigate age-related differences in malignant hypertension (MHT), we studied 38 elderly patients (18 males, 20 females; mean age 70.6 years, SD 4.6 years, range 65 to 84) and 277 younger patients (193 males, 84 females; mean age 46.4 years, SD 10.5, range 15 to 64) with MHT presenting 1965-93. Mean duration of known hypertension before presentation was greater in the elderly group (43.8 months vs. 23.1 months). The elderly group included 18 (47.4%) newly diagnosed hypertensives, compared to 160 (55.8%) in the younger group. At presentation, 19 (50.0%) elderly patients were receiving no antihypertensive drug therapy, whilst 18 (47.4%) were taking one or more drugs for hypertension. Presenting clinical features in elderly MHT patients included visual disturbance (9), headaches (2), headaches with visual disturbance (2), stroke (3), and heart failure (2). Six patients were asymptomatic. The commonest clinical complications were ischaemic heart disease (angina and myocardial infarction) (5), heart failure (4) and stroke (4). The majority (58%) of patients, however, had no vascular complications at presentation. Comparing elderly and younger MHT groups, there was no significant difference in presenting systolic blood pressures, although mean diastolic blood pressure was significantly greater in the younger group (mean 143.7 mmHg +/- 19.3 vs. 130.0 mmHg +/- 15.2; p < 0.0001). After a mean follow-up of 30.9 months (SD 37.1; range 1 to 123 months), 17 (44.7%) of the elderly patients were still alive, 15 were dead (39.5%) and six were lost to follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To investigate the factors affecting survival in patients with malignant hypertension by analysing the prognosis of all of the patients referred to the City Hospital, Birmingham, with malignant hypertension since 1965., Results: We identified 315 patients with malignant hypertension (211 men, 104 women; mean age +/- SD 49.4 +/- 12.7 years). Of those patients, 219 were Caucasian, 55 were black and 41 were Asian. Black patients had greater renal impairment and higher blood pressures at presentation. After a median follow-up period of 33 months (range 1-389), 126 patients (40.0%) were still alive, 126 patients (40.0%) were dead, 10 patients (3.2%) were receiving chronic haemodialysis and 53 patients (16.8%) were lost to follow-up. Mean follow-up blood pressures in the patients who died were significantly higher than in those who lived. Median survival times for Caucasian, black and Asian patients were 121.0, 30.4 and 107.5 months, respectively, with the lowest survival time being that of black patients. There was a lower median survival time among patients with proteinuria and high serum urea (> 10 mmol/l) and creatinine (> 200 mumol/l) levels at presentation and if left ventricular hypertrophy was detected on the electrocardiogram, but there was no difference in median survival time between those with and without haematuria, nor between non-smokers and current or former smokers. The most common causes of death were renal failure (39.7%), stroke (23.8%), myocardial infarction (11.1%) and heart failure (10.3%). Median survival times for the patients who presented before 1970, during 1970-1979 and during 1980-1989 were 39.2, 68.6 and 144.0+ months, respectively, demonstrating an improved survival time for the patients who were diagnosed after 1980. Using multivariate Cox's proportional hazards analyses, the duration of known hypertension and serum urea level at presentation were found to be the main predictors of survival., Conclusion: Malignant hypertension remains a disease with a poor overall prognosis, namely progression to death or chronic renal haemodialysis. The prognosis has improved with recent advances in therapy, with a 5-year survival of 74% of patients. The poor outlook for black patients could be explained by their late presentation with severe hypertension and the higher prevalence of renal impairment in this group.

A female patient who underwent a carotid endarterectomy, died following a hypertensive crisis which may have been due to an unknown phaeochromocytoma.

One hundred and thirty-five patients with malignant hypertension seen over a period of 11 years (1979 to 1989) at a referral hospital were analyzed to characterize the clinical features and etiology of this disease. Ninety male and 45 female patients with an average age of 38.2 +/- 1.4 years were studied. Malignant hypertension was the presenting feature in 68 patients. The etiology included essential hypertension in 88 patients and a secondary cause in 47 patients. Secondary causes included a renovascular etiology in 20 patients, renal parenchymal disease in 19, pheochromocytoma in 6 and Conn's syndrome and adrenal carcinoma in one patient each. Among the 20 patients with renovascular hypertension, Takayasu's arteritis was seen in 15 (75%). The mean age of patients with essential hypertension was 41.7 + 1.14 years while the mean age in patients with secondary hypertension was 33.2 + 1.96 years. Duration of preexisting hypertension was longer in essential hypertensives (2.42 + 0.45 years) than in patients with secondary hypertension (1.27 + 0.41 years, p < 0.05). Raised serum creatinine was seen in 93 patients. Seventy-seven patients had left ventricular hypertrophy on ECG. Ninety-six patients were followed for a period ranging from 18 months to 10 years (mean 32 months). Sixteen patients died during hospital stay while 6 patients died during the follow-up period. The deaths were related to the effects of uncontrolled hypertension including, renal failure (11), stroke (6), congestive cardiac failure (3) and myocardial infarction (1).(ABSTRACT TRUNCATED AT 250 WORDS)

Life table analysis was used to compare survival rates in 168 whites, 39 blacks and 26 Asians with malignant phase hypertension. Amongst men, survival until death or the requirement of chronic renal dialysis was significantly worse in blacks, who initially presented with higher blood pressures and more renal impairment. There were no differences in survival in women in the three ethnic groups. Malignant hypertension remains common in Britain and still carries a poor prognosis.

This study determines the prognostic factors involved in both patient and kidney survival rates in 97 consecutive patients admitted for malignant hypertension (diastolic blood pressure > or =130 mmHg and stage 3 or 4 retinopathy according to Keith-Wegener classification) between January 1976 and December 1987. For this we used the Cox's proportional hazards regression model to specify the independent covariates linked to the patient and renal survival rates. Renal death referred to endstage renal disease treated with dialysis or transplantation (i.e., probability of surviving without dialysis or transplantation). The following covariates were entered into the Cox's model: sex, duration of hypertension before malignant phase, age, serum creatinine, stages 3 and 4 fundi, diastolic blood pressure, cardiac and neurological involvements, extrarenal atheromatous disease, aetiology of the malignant hypertension (primary, secondary to parenchymal nephropathy, and secondary to renovascular abnormalities), all these covariates being recorded during the initial admission; and mean diastolic blood pressure during the period the patients were observed. At the final follow-up, we had no record of five patients. At 5 years the cumulative survival rates were 75% in the case of patients and 65% for the renal function. Age, mean diastolic blood pressure during the observation period, and serum creatinine increase independently and significantly the risk of patient death. On the other hand the risk of renal death is decreased by neurological involvement.

In 51 consecutive patients with malignant hypertension collected from 1976 to 1981 we have analysed patient and kidney survival at 5 years and at last follow-up. The patients were 41 men, 10 women, mean age 53 years, with a stage III (63%) or stage IV (27%) fundi and a diastolic blood pressure (BP) greater than 130 mmHg. The hypertension was primary in 26, renovascular in 17 and secondary to bilateral nephropathy in eight. At 5-years follow-up, the patient and kidney survival rates were respectively 72.5% and 47%. At last follow-up, 18 patients had died (35%) and 18 additional patients require dialysis (renal death = 70%). The principal causes of death related to terminal renal failure and/or dialysis. Initial involvement of heart (27%) and brain (35%) led to a few more deaths. Blood pressure control reduced consequences for the heart and brain but not for the kidney. Patients at higher risk are those with serum creatinine greater than 200 mumol/l on admission.

A diagnosis of malignant hypertension was recorded for 165 patients in the national morbidity study between 1970 and 1973. Three patients with benign hypertension were selected as age- and sex-matched controls for each case. The general practitioners in the study were asked to complete a further questionnaire about the patients and 66% of the practices agreed to take part. Information about the retinal findings for the patients was requested and less than half of those in the national morbidity study proved to have a strict diagnosis of accelerated or malignant hypertension although they were originally recorded as patients with malignant hypertension. Of those patients originally classified as having benign hypertension 5% had the retinal appearance of accelerated or malignant hypertension.Patients had been diagnosed as having hypertension for a mean of more than five years prior to entry into the national morbidity study and the survival of patients with both benign and accelerated or malignant hypertension was good. Thirtyfour per cent of those with confirmed benign hypertension and 62% of those with definite accelerated or malignant hypertension died in the follow-up period which was on average 10 years from entry into the national morbidity study.The survival of patients registered with doctors who did not collaborate and of patients whose clinical details were missing was similar to the survival of patients for whom full details were provided.Blood pressure control was only fair with a mean of 172/101 mmHg for the group with benign hypertension and 177/107 mmHg for the group with accelerated or malignant hypertension. Blood pressure control was the poorest for those who died from a stroke. A high proportion (78%) of deaths in association with accelerated or malignant hypertension were from cardiovascular or renal causes.

A long-term prognosis was studied in 69 patients with malignant hypertension, followed for an average of 56 months. Overall survival rate was 90% for a 5-year period, although the prognosis was different between two major underlying diseases, namely the 5-year survival was 79% for 33 essential hypertension (EHT) and 100% for 26 chronic glomerulonephritis (CGN); the difference is significant (p less than 0.01). In contrast, the 5-year rate for renal survival, defined as the probability of surviving without hemodialysis, was 37% in all cases. However, there was significant difference in the renal survival between EHT (60% for a 5-year period) and CGN (4% for a 18-month period). Multivariate analyses of the Cox's proportional hazards model revealed that the long-term change in renal function was different between the two groups, namely more rapid deterioration in the CGN group. These results indicate that a long-term prognosis of malignant hypertension is influenced by the underlying diseases and hemodialysis besides antihypertensive treatment may increase survival in malignant hypertension associated with severely damaged renal function.

1 The 5 year survival of hypertensive patients in several studies was reviewed to demonstrate the adverse effects of increasing age, being male, having a higher untreated blood pressure of severe retinal changes. 2 The decrease in survival with increase in diastolic blood pressure was not linear, mortality being relatively constant below 90 mmHg. 3 The adverse effect of severe retinal changes was independent of the untreated blood pressure. 4 In patients selected with mild hypertension, 5 year survival can exceed 97% even when untreated. 5 Owing to the lack of suitable data we cannot conclude that treatment was more effective in prolonging life in the 1970s than in previous decades. 6 In the United States non-white patients with hypertension fared worse than white patients. 7 The serum cholesterol was not positively related to mortality in treated hypertension patients. 8 Treated hypertensive patients who smoked had at least a two-fold increase in mortality over those who did not. 9 Treated patients under the age of 50 years had a four-fold increase in mortality compared with the general population. This was greater than any excess mortality observed in the elderly.

140 cases of malignant hypertension were diagnosed in our clinic from January 1966 to December 1982. On admission the mean blood pressure was 183 +/- 17 mm Hg, and all patients had grade III to IV retinopathy according to the Keith and Wagener classification; 84% of the patients had renal failure (10% of acute origin). 43% of the patients presented with clinical signs of left heart failure. Hypertension was associated with various renal diseases in 48%, was essential in 41%, and renovascular lesions were found in 9% of the cases. Headaches, asthenia and visual disorders were the 3 main symptoms of malignant hypertension, as classically described. Severe cerebral damage (including all the neurological manifestations present on admission) was found in 27% of the patients. Among the 122 patients available to follow-up, half died during the study period. The survival rate, calculated on a 5-year basis, has doubled compared with a similar patient population 17 years ago, increasing from 35% (period 1966 to 1970) to 72% (period 1977-1982). This remarkable achievement in survival rate is due to more intensive research and therapeutic progress (including, more recently, extrarenal epuration) reaching an increasingly large hypertensive population.

Eleven of 34 women aged 15-44 with malignant phase hypertension were taking oral contraceptives at presentation. All had had normal blood pressure before starting to take the pill. In four the interval between the start of oral contraception and the diagnosis of malignant hypertension was less than four months, and in eight no other cause for the hypertension was found. Underlying renal disease and renal failure were less common among pill users than among non-users with malignant hypertension who were of similar age. No pill user became normotensive after withdrawal of the pill, but blood pressure was well controlled (diastolic less than 90 mm Hg) in three patients taking only one drug. By contrast, all 23 non-users needed two or more antihypertensive drugs to control blood pressure. Ten year survival was 90% among pill users and 50% among non-users. These results suggest that oral contraceptives may be a common cause of malignant hypertension in women of child-bearing age. If the pill is stopped and underlying renal disease excluded the long term prognosis for such patients is excellent.

To assess the diagnostic and prognostic importance of papilloedema in malignant hypertension a two part study was undertaken. Four observers reviewed 56 photographs of fundi from patients with grade 3 or 4 hypertensive retinopathy. Complete agreement on the presence or absence of haemorrhages was recorded in 52 cases and on exudates in 53 cases. Opinion on papilloedema, however, was divided, all four observers agreeing in only 34 cases. In the second part of the study survival in 139 consecutive hypertensive patients with bilateral retinal haemorrhages and exudates was examined by life tables. Ten year survival was 46% in patients with bilateral haemorrhages and exudates alone (n = 43) and 48% when papilloedema was also present (n = 96). Multivariate analysis confirmed that papilloedema was not related to survival. These results suggest that papilloedema is an unreliable physical sign and does not adversely influence prognosis in hypertensive patients who already have bilateral retinal haemorrhages and exudates when effective treatment is available. Papilloedema should no longer be regarded as a necessary feature of malignant hypertension.

Hypertension-induced morbidity and mortality can be positively affected by antihypertensive treatment. This was first shown in malignant phase hypertension and it is now clearly established that not only total mortality but also morbidity from stroke, left ventricular failure, and progressive renal failure can be positively affected by pharmacological lowering of arterial pressure. Benefits of treatment for coronary artery disease are less obvious. In spite of the positive effects of antihypertensive therapy briefly mentioned here, recent data from several centers show that hypertension-induced risks in treated hypertensive patients are not reduced down to the level seen in comparable normotensive subjects. There could be several reasons for this. Some of the hypertension-induced cardiovascular changes are irreversible, or that antihypertensive pharmacological agents may have some adverse effects that would partially offset the advantages obtained through a reduction in blood pressure, or that treated arterial blood pressure usually has not been brought down to strictly normotensive levels. Therefore, the risks associated with hypertension have not been lowered to those seen in normotensive subjects. This latter point assumes particular significance in view of some recent suggestions that a too drastic lowering of blood pressure in hypertensive subjects may be associated with an increased risk, particularly for coronary artery disease mortality.

Hypertension has been found to imply a disease entity since the beginning of this century. Effective treatment available in the last two decades has changed the outlook remarkably, especially in malignant hypertension. There are more and more evidence that less severe forms of hypertension will benefit from keeping the blood pressure under control.

The clinical features and survival rates of 200 consecutive patients with malignant and accelerated hypertension admitted to a district hospital were investigated. Ninety five patients had bilateral haemorrhages and exudates and papilloedema (grade IV retinopathy) and 31 had bilateral haemorrhages and exudates with no papilloedema (grade III). A further 74 patients had bilateral retinopathy but failed to meet the criteria for grade IV or III and were investigated separately. No overall differences were found in survival when comparing the various grades of retinopathy. Cigarette smoking was significantly commoner only in grade IV patients compared with those with non-malignant hypertension matched for age, sex, and race. In patients with grade III retinopathy excess smoking was not statistically significant. In conclusion, the clinical features and survival rate showed that malignant and accelerated hypertension are one and the same disease.

Five patients with malignant nephrosclerosis (MNSC) and severe renal failure (mean plasma creatinine 926 micromoles/L) were followed for 52 to 83 months. Blood pressure was controlled by a minoxidil-nadolol-diuretic combination. Combined renal length (CRL) on presentation was greater than 18 cm in four patients and 15.3 cm in one patient. Plasma creatinine values declined into the second year, and improved function persisted into the third and fourth years after presentation. The patient with least renal mass on presentation had evidence of declining renal function at 60 months. The data suggest that CRL and sustained blood pressure control are critical determinants of both short- and long-term recovery and preservation of self-sustaining renal function in patients with MNSC.

In a study designed primarily to assess mortality, 139 consecutive patients presenting with malignant hypertension (MHT) in Glasgow between 1968 and 1983 were matched individually for age, sex and initial blood pressure with 139 non-malignant hypertensives attending the Glasgow Blood Pressure Clinic. Fifty-four patients with MHT and 34 controls died before 1 April 1984. Multivariate analysis showed that initial serum creatinine and blood pressure achieved during treatment were significantly and independently related to outcome among the patients with MHT, but that age, smoking habit, presence of papilloedema, underlying diagnosis, initial blood pressure and year of presentation were not. Overall survival among patients with MHT was 63% at 5 years and 47% at 10 years. Although this was better than in earlier studies patients with MHT were still twice as likely to die as non-malignant controls. The excess mortality was confined largely to patients with underlying renal disease and/or renal failure at presentation. Moreover, renal failure contributed to four times more deaths among patients with MHT than controls. Thus, despite an improvement in survival compared with previous years, renal failure remains the most serious manifestation of patients with this disease.

A follow-up was made of 69 patients diagnosed as having malignant hypertension during 1969--76, essential in 26, secondary in 39 and unclassified in 4. A clear male dominance was seen (41 men, 28 women), particularly in the group with essential hypertension (18 men, 8 women). The mortality in this series was less than in previously published series. Thus, the 5-year survival rate was 75% in the patients with essential and 72% in those with secondary hypertension. In part this was due to haemodialysis and renal transplantation. The importance of renal function at the time of diagnosis was evident in this study. In most patients with essential hypertension and serum creatinine levels below 300 mumol/l, renal function could be maintained or improved when antihypertensive treatment was instituted, whereas progression of the renal damage was seen in those with serum creatinine levels above 300 mumol/l in spite of antihypertensive treatment with 3 or more drugs. The incidence of new cases of malignant hypertension tended to decrease during the observation period, particularly as regards essential hypertension.