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Malignant hypertension

not quite an obsolete diagnosis yet

Shantsila, Alenaa; Lip, Gregory Y.H.a,b

doi: 10.1097/HJH.0000000000001974

aInstitute of Cardiovascular Sciences, University of Birmingham, Birmingham

bLiverpool Centre of Cardiovascular Science, University of Liverpool, Liverpool, UK

Correspondence to Gregory Y.H. Lip, Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK. Tel: +44 121 507 5080; e-mail:

Received 21 September, 2018

Accepted 24 September, 2018

Malignant hypertension (MHT) has traditionally been clinically diagnosed as the presence of severe blood pressure (BP) in association with hypertensive retinopathy changes of haemorrhages and exudates with or without papilledema. The pathophysiological hallmark in MHT is the presence of fibrinoid necrosis, which can involve multiple target organs. Thus, there is the view that the term MHT is obsolete and should be replaced by alternative terms, including hypertension with multi-organ damage [1]. A recent position document on hypertensive emergencies from the European Society of Cardiology (ESC) Council on Hypertension reflects this view [2].

In the current issue of the Journal of Hypertension, Rubin et al.[3] report a detailed evaluation of the target organs damage found in patients with MHT at the time of clinical presentation. The authors also report updated data on the 5-year survival status in these patients. The main novelty of the study was perhaps the inclusion of a systematic evaluation of brain target organ damage, using MRI scanning, in all patients, irrespective of their neurological symptoms. They found that target organ damage in the brain was very highly prevalent, in 93% of all examined patients. Second, the group used a universal treatment protocol, for BP lowering during the acute phase, on all their MHT patients from the Bordeaux cohort.

A major increase in systemic and cerebral perfusion pressure, as occur in MHT, disturbs the autoregulation of the cerebral circulation, leading to the failure of autoregulatory cerebral vasoconstriction with focal or generalized dilatation of small arteries and arterioles [4]. This results in cerebral blood volume overload, impairment of blood–brain barrier function and, in extreme cases, development of brain oedema. Of importance, these cerebral abnormalities occur in parallel to the systemic impairment of macrovascular and microvascular function [5], thus limiting the ability to provide appropriate adjustment in peripheral vascular tone. The first signs and symptoms of the brain involvement are usually sudden onset of headache, nausea and vomiting. This may be followed by development of different visual signs and visual field loss, which in some cases may be accompanied by fluctuating neurological symptoms (restlessness, confusion and, in extreme, seizures and coma) [4,6].

In the MHT cohort from Bordeaux [3] only 20% of patients were admitted to the hospital due to high BP, and 10% due to the heart failure. The majority (70%) required hospital admission due to some degree of neurological problems. Although a substantial proportion of these patients had presented with headache and dizziness, but without obvious neurological damage, a quarter of the assessed population was found to have visual impairment and one in five developed a stroke. These data highlight the fact that despite the availability of various antihypertensive treatments symptomatic patients in acute phase of MHT are at risk of hypertensive encephalopathy, a life-threatening condition that requires hospital admission.

The Bordeaux cohort [3] suggests that brain imaging can be helpful in the assessment of MHT patients. MRI usually shows evidence of white matter lesions, more often located in the posteriors brain regions [4,7]. Computed tomography or MRI scanning is also advisable to exclude cerebral haemorrhage, or infarction. In cases of hypertensive encephalopathy alone, white matter lesions are completely reversible after patient stabilization. Indeed, the study by Rubin et al.[3], following systematic evaluation of the brain by MRI, found that the white matter lesions were more prevalent in the posterior regions, with 51% of included patients affected. Other locations of white matter lesions were found in 27% of the tested population from the Bordeaux region.

Analysis of the US data from the largest all-payer Nationwide Inpatient Sample database of national discharges found an increasing trend for hospital admissions of patients with either hypertensive encephalopathy or MHT over the last decade despite no increase in overall morbidity [8]. Also, increasing awareness of hypertension, changes in coding practices and subsequent increase in the costs from insurance, were suggested as reasons for these trends. White matter lesions, in the posterior part of the brain, are also evident in other conditions with microvascular dysfunction (e.g. antiphospholipid antibody syndrome, thrombotic thrombocytopenic purpura, haemolytic uraemic syndrome) and this mandates a holistic approach to patient assessment.

MHT is a hypertensive emergency and the ESC position document on the management of hypertensive emergencies recommends use of intravenous BP lowering medications in patients with acute presentations [2]. However, the position document acknowledges that any recommendations are made based on consensus from clinical experience, given the lack of randomized controlled trials on different treatment strategies. Use of the angiotensin-converting enzyme (ACE) inhibitors at the acute phase must be commenced at a very much lower dose, as they could result in a rapid and dangerous fall in BP in some patients. One of the reasons for profound BP drop is volume depletion, secondary to pressure natriuresis. Intravenous saline infusion is recommended to be started together with the oral low-dose ACE inhibitors to correct the circulating volume.

In the current report by Rubin et al.[3], very low oral dose of renin–angiotensin system blockers was carefully titrated over 48 h. The treatment was well tolerated and efficient in all patients, with no complications reported. Nevertheless, one of the study limitations was the use of a changed MHT definition during the data collection period. But it only applies to 15 patients who did not show signs of MHT retinopathy, although in others, three target organs were affected. The main cardiovascular risk factors at the time of the MHT diagnosis were not different in these patients compared with the rest of the cohort.

In conclusion, MHT is the most severe and one of most challenging forms of the hypertension, affecting multiple organs, including the brain. MHT is not quite an obsolete diagnosis yet, but perhaps evolution of the definition may be needed in the twenty-first century reflecting contemporary practice [2]. Otherwise the principles of early diagnosis, detailed systematic evaluation (including modern brain imaging) and effective treatment remain key factors for a longer event free survival. Further data are clearly needed to assess the clinical significance of brain damage and the relation to patient survival and optimal long-term management.

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Conflicts of interest

There are no conflicts of interest.

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