Malignant Hypertension

Updated: Jan 13, 2017
  • Author: John D Bisognano, MD, PhD, FACP, FACC; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Overview

Background

A hypertensive emergency is a condition in which elevated blood pressure (BP) results in target organ damage. [1]  The systems primarily involved include the central nervous system (CNS), the cardiovascular system, and the renal system. Malignant hypertension and accelerated hypertension are both hypertensive emergencies, with similar outcomes and therapies.

Accelerated hypertension is defined as a recent significant increase over baseline BP that is associated with target organ damage. This is usually seen as vascular damage on funduscopic examination, such as flame-shaped hemorrhages or soft exudates, but without papilledema.

Hypertensive urgency must be distinguished from hypertensive emergency. Urgency is defined as severely elevated BP (ie, systolic BP >220 mm Hg or diastolic BP >120 mm Hg) with no evidence of target organ damage.

In order to diagnose malignant hypertension, papilledema (see the image below) must be present. [2]  However, Cremer et al considered the presence of retinopathy as but one of various potential presentations for acute hypertension with multiorgan damage. [1]  Accordingly, they proposed a "more modern" definition for malignant hypertension, in which hypertensive emergencies, in the absence of retinopathy, would be based on the criteria of acute elevated BP accompanied by damage to a minimum of three different target organs.

Papilledema. Note the swelling of the optic disc, Papilledema. Note the swelling of the optic disc, with blurred margins.

Hypertensive emergencies necessitate immediate therapy to decrease BP within minutes to hours. [3]  In contrast, no evidence suggests a benefit from rapidly reducing BP in patients with hypertensive urgency. In fact, such aggressive therapy may harm the patient, resulting in cardiac, renal, or cerebral hypoperfusion. This article discusses hypertensive emergency, but therapy for hypertensive urgency is discussed briefly.

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Pathophysiology and Etiology

As many as 1% of patients with essential hypertension develop malignant hypertension, but the reason why some patients develop malignant hypertension whereas others do not is unknown. The characteristic vascular lesion is fibrinoid necrosis of arterioles and small arteries, which causes the clinical manifestations of end-organ damage. Red blood cells are damaged as they flow through vessels obstructed by fibrin deposition, resulting in microangiopathic hemolytic anemia.

In a retrospective study that evaluated hospital admissions data from the Nationwide Inpatient Sample for malignant hypertension, hypertensive encephalopathy, and essential hypertension, Polgreen et al found an increasing trend for malignant hypertension and hypertensive encephalopathy from 2000 to 2011, with a dramatic increase after 2007. [4]  However, no corresponding dramatic increase was seen in morbidity for both conditions, which the investigators believed might have resulted from coding changes in diagnostic-related groups in 2007. Mortality declined significantly for patients with malignant hypertension but not for those with hypertensive encephalopathy. [4]

Another pathologic process is the dilatation of cerebral arteries following a breakthrough of the normal autoregulation of cerebral blood flow. Under normal conditions, cerebral blood flow is kept constant by cerebral vasoconstriction in response to increases in BP. In patients without hypertension, flow is kept constant over a mean pressure of 60-120 mm Hg. In patients with hypertension, flow is constant over a mean pressure of 110-180 mm Hg because of arteriolar thickening. When BP is raised above the upper limit of autoregulation, arterioles dilate. This results in hyperperfusion and cerebral edema, which cause the clinical manifestations of hypertensive encephalopathy.

Other causes of malignant hypertension include any form of secondary hypertension; complications of pregnancy; use of cocaine, monoamine oxidase inhibitors (MAOIs), or oral contraceptives; and the withdrawal of alcohol, beta blockers, or alpha stimulants. Renal artery stenosis, pheochromocytoma (most pheochromocytomas can be localized by using computed tomography [CT] of the adrenals), aortic coarctation, and hyperaldosteronism are also secondary causes of hypertension. In addition, both hyperthyroidism and hypothyroidism can cause hypertension.

The following conditions should also be considered when making the diagnosis: stroke, intracranial mass, head injury, epilepsy or postictal state, connective-tissue disease (especially lupus with cerebral vasculitis), drug overdose or withdrawal, cocaine or amphetamine ingestion, acute anxiety, and thrombotic thrombocytopenic purpura. [5, 6]

Because malignant hypertension-induced thrombotic microangiopathy may mimic thrombocytopenic purpura, the possibility exists that plasma exchange rather than antihypertensive agents might initially be administered to patients. In a literature review, Khanal et al reported that factors more likely to be present in malignant hypertension-induced thrombotic microangiopathy are (1) a previous history of hypertension, (2) high mean arterial pressure, (3) significant renal impairment but relatively modest thrombocytopenia, and (4) lack of severe ADAMTS-13 gene deficiency (activity <10%) at diagnosis. [6]

For more information, see Hypertension.

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Prognosis

In a retrospective analysis of 197 patients with malignant hypertension diagnosed between 1974 and 2007, Gonzalez et al found that at 5 and 10 years after presentation, the chances of renal survival were 84% and 72%, respectively. [7]  Reported predictors of renal outcome included whether the patient was diagnosed between 1974 and 1985, previous chronic renal impairment, the degree of proteinuria and the amount of renal function at baseline, the presence of microhematuria, systolic and diastolic BP, and proteinuria during follow-up. After multivariate analysis, the only significant risk factor was the mean proteinuria value during follow-up. The chances of renal survival in patients with a mean proteinuria value lower than 0.5 g/24 hr were 100% at 5 years and 95% at 10 years.

Before the advent of effective therapy, the life expectancy of those affected by malignant hypertension was less than 2 years, with most deaths resulting from stroke, renal failure, or heart failure. The survival rate at 1 year was less than 25%, and at 5 years, it was less than 1%. However, with current therapy, including dialysis, the survival rate at 1 year is greater than 90%, and at 5 years, it is 80%. The most common cause of death is cardiovascular, with stroke and renal failure also common.

A British study that examined survival statistics over the course of 40 years in 446 patients with malignant hypertension found an even higher 5-year survival rate. [8]  The authors determined that before 1977, the 5-year survival rate was 32%, whereas for patients who were diagnosed between 1997 and 2006, the 5-year rate was 91%. The investigators suggested that the change was associated with lower targets for and tighter control of BP, along with the availability of additional classes of antihypertensive medications. The authors also found age, baseline creatinine level, and follow-up systolic BP to be independent predictors of survival.

A study by Amraoui et al found a higher all-cause mortality in patients with malignant hypertension (n=120) than in persons who were normotensive  (n=120) or hypertensive (n=120), even though the cardiovascular risk profile for the malignant hypertension patients was more favorable than that for the hypertensive control subjects. [9] The malignant hypertension patients had lower total cholesterol, low-density lipoprotein cholesterol, and body mass index values than did the hypertensive controls. However, the median estimated glomerular filtration rate was higher in the two control groups than in the malignant hypertension group. Annual all-cause mortality per 100 patient-years was 2.6 for the  malignant hypertension group, compared with 0.2 for the normotensive group and 0.5 for the hypertensive group.

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Patient Education

Patients must be taught an appropriate diet for long-term management, and upon discharge, patients should not only know the signs and symptoms that should prompt immediate notification of a physician but also know the proper dosing and adverse effects of their medications.

For patient education resources, see the Diabetes Center as well as High Blood Pressure.

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