eMedicine Specialties > Nephrology > Hypertension and the Kidney

Hypertension, Malignant

Author: John D Bisognano, MD, PhD, FACP, FACC, Associate Professor, Director of Outpatient Cardiology, Department of Medicine, Cardiology Division, University of Rochester Medical Center
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Updated: Sep 15, 2009

Introduction

Background

A hypertensive emergency is a condition in which elevated blood pressure results in target organ damage. The systems primarily involved include the central nervous system, the cardiovascular system, and the kidneys. Malignant hypertension and accelerated hypertension are both hypertensive emergencies, with similar outcomes and therapies. In order to diagnose malignant hypertension, papilledema must be present. Accelerated hypertension is defined as a recent significant increase over baseline blood pressure that is associated with target organ damage. This is usually vascular damage on funduscopic examination, such as flame-shaped hemorrhages or soft exudates, but without papilledema. (See image below and Image 1.)

Hypertensive emergencies require immediate therapy to decrease blood pressure within minutes to hours.¹ In contrast, no evidence suggests a benefit from rapidly reducing blood pressure 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.

Pathophysiology

The pathogenesis of malignant hypertension is not fully understood. 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.

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 blood pressure. 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 blood pressure 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.

Why some patients with severe hypertension develop end-organ damage while others do not is unclear.

Frequency

United States

Up to 1% of patients with essential hypertension develop malignant hypertension. The average age at diagnosis is 40 years, and men are affected more often than women. People who smoke cigarettes, black people, and patients with secondary hypertension are at higher risk than the general population.

Mortality/Morbidity

Prior to effective therapy, life expectancy 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 was less than 1%. With current therapy, including dialysis, the survival rate at 1 year is greater than 90% and at 5 years is 80%.

A British study that examined survival statistics over the course of 40 years in patients with malignant hypertension found an even higher 5-year survival rate.² Reviewing information from 446 patients with malignant hypertension, the authors determined that prior to 1977, the 5-year survival rate was 32%, while 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 patients' blood pressure, along with the availability of additional classes of antihypertensive medications.

The authors also found age, baseline creatinine level, and follow-up systolic blood pressure to be independent predictors of survival.

The most common cause of death in cases of malignant hypertension is cardiac, with stroke and renal failure also being common. Gastrointestinal symptoms are nausea and vomiting. Diffuse arteriolar damage can result in microangiopathic hemolytic anemia.

• The heart's initial response to systemic hypertension is to develop concentric left ventricular hypertrophy. Eventually, the left ventricle becomes dilatated. This is reflected on physical examination by a fourth heart sound initially, followed by the typical changes of dilated cardiomyopathy. In the earliest stages, electrocardiogram (ECG) and echocardiogram reveal left atrial enlargement and left ventricular hypertrophy. The cardiac presentation of malignant hypertension is angina and/or myocardial infarction or congestive heart failure.
• The funduscopic changes are flame-shaped retinal hemorrhages, soft exudates, and papilledema. Neurological presentations are occipital headaches, cerebral infarct, cerebral hemorrhage, or hypertensive encephalopathy. Hypertensive encephalopathy is a symptom complex of severe hypertension, headache, vomiting, visual disturbance, mental status changes, seizure, and retinopathy with papilledema. Focal signs and symptoms are uncommon and may indicate another process, such as cerebral infarct or hemorrhage. (See image below and Image 2.)
• Renal disease presents as proteinuria, microscopic hematuria, red blood cell casts, and azotemic oliguric renal failure. Diffuse intrarenal ischemia results in increased levels of plasma renin, angiotensin II, and aldosterone, with resulting hypovolemia and hypokalemia. Sodium depletion is common and may be severe.³

Race

Black people are at higher risk of developing hypertensive emergencies than the general population.

Sex

Men are affected more often than women.

Age

The average age at diagnosis is 40 years, but a wide range of ages is observed.

Clinical

History

The history should screen for symptoms of malignant hypertension, focusing on the cardiac, renal, and central nervous systems. Underlying medical disorders should be reviewed, including the possibility of eclampsia. The patient's medications and other drugs should be thoroughly reviewed.⁴

• In one review, the most common presentations of hypertensive emergencies at an emergency department were chest pain (27%), dyspnea (22%), and neurologic deficit (21%).
• The primary cardiac symptoms are angina, myocardial infarction, and pulmonary edema. Orthostatic symptoms may be prominent.
• Neurologic presentations are occipital headache, cerebral infarction or hemorrhage, visual disturbance, or hypertensive encephalopathy (a symptom complex of severe hypertension, headache, vomiting, visual disturbance, mental status changes, seizure, and retinopathy with papilledema).
• Medications or drugs that may cause a hypertensive emergency include cocaine, monoamine oxidase inhibitors (MAOIs), and oral contraceptives; the withdrawal of beta-blockers, alpha-stimulants (eg, clonidine), or alcohol also may cause hypertensive emergency.
• Renal disease may present as oliguria or any of the typical features of renal failure. 
• Gastrointestinal symptoms are nausea and vomiting.

Physical

The initial evaluation begins with a thorough physical examination. Once again, the focus is on the cardiovascular and central nervous systems and on the retinal examination.

• Cardiovascular system
  • Blood pressure must be checked in both arms to screen for aortic dissection or coarctation. If coarctation is suspected, blood pressure also should be measured in the legs.
  • Screen for carotid or renal bruits.
  • Palpate the precordium, looking for sustained left ventricular lift.
  • Auscultate for a third or fourth heart sound or murmurs.
  • Volume status must be assessed, with orthostatic vital signs, examination of jugular veins, assessment of liver size, and investigation for peripheral edema and pulmonary rales.
• Central nervous system
  • A complete neurologic examination is needed to screen for localizing signs.
  • Focal neurologic signs might not be attributable to encephalopathy. Focal signs mandate screening for cerebral hemorrhage, infarct, or the presence of a mass.
• Retinal examination: A funduscopic examination may reveal flame-shaped retinal hemorrhages, soft exudates, or papilledema.

Causes

The pathogenesis is not fully understood.

Up to 1% of patients with essential hypertension develop malignant hypertension, and the reason some patients develop malignant hypertension while others do not is unknown.

Other causes include any form of secondary hypertension; complications of pregnancy; use of cocaine, MAOIs, or oral contraceptives; and the withdrawal of alcohol, beta-blockers, or alpha-stimulants. Renal artery stenosis, pheochromocytoma (most pheochromocytomas can be localized using CT scan of the adrenals), aortic coarctation, and hyperaldosteronism are secondary causes of hypertension. Both hyperthyroidism and hypothyroidism can cause hypertension.

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