Malignant Hypertension – Causes, Symptoms, Diagnosis, Treatment

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Malignant hypertension is a term that has been used to describe patients with elevated blood pressure (BP) and multiple complications with poor prognoses. Today, the term hypertensive crisis is used to describe patients who present with severe BP elevations as follows Systolic blood pressure and (SBP) greater than 180 mm Hg and Diastolic blood pressure (DBP) greater than 120 mm Hg). The diagnosis can be further classified as a hypertensive emergency when severe elevation in BP is associated with end-organ damage, or hypertensive urgency when severe hypertension occurs without it. This activity reviews the cause of malignant hypertension, its pathophysiology and highlights the role of the interprofessional team in its management.

Malignant hypertension is a term that has been used to describe patients with elevated blood pressure (BP) and multiple complications (End organ damage) with a poor prognosis. Today, the term hypertensive crisis is used to describe patients who present with severe BP elevations as follow:

  • Systolic blood pressure (SBP) greater than 180 mm Hg
  • Diastolic blood pressure (DBP) greater than 120 mm Hg)

The diagnosis can be further classified as a hypertensive emergency when severe elevation in BP is associated with end-organ damage, or hypertensive urgency when severe hypertension occurs without it. Prompt treatment of BP can prevent a hypertensive emergency and consequently, serious life-threatening complications.

In order to make a diagnosis of malignant hypertension, papilledema has to be present. In malignant hypertension, the key is to lower the blood pressure within a few hours.

Causes of Malignant Hypertension

There are multiple causes of malignant hypertension (hypertensive crisis) including the following:

  • Medication noncompliance
  • Renovascular diseases, such as renal artery stenosis, polyarteritis nodosa, and Takayasu arteritis
  • Renal parenchymal disease including glomerulonephritis, tubulointerstitial nephritis, systemic sclerosis, hemolytic-uremic syndrome, systemic lupus erythematosus
  • Endocrine dysfunction, such as pheochromocytoma, Cushing disease, primary hyperaldosteronism, renin-secreting tumor
  • Coarctation of aorta; drugs or other exposures, including cocaine, phencyclidine, sympathomimetics, erythropoietin, cyclosporine
  • Antihypertensive medication withdrawal
  • Amphetamines
  • Central nervous system disorders, such as head injury, cerebral infarction, and cerebral hemorrhage
  • Hypertensive emergencies occur when a relatively rapid elevation of BP develops in a short period.
  • An increase in systemic vascular resistance by an increase in vasoconstriction mechanisms through renin-angiotensin activation, pressure natriuresis, hypoperfusion, and ischemia are the most common culprits of end-organ damage.
  • The classic vascular feature is fibrinoid necrosis of the small vessels. In addition, red cell destruction is common as they pass through these obstructed vessels leading to microangiopathic hemolytic anemia. Another feature of a hypertensive emergency is the loss of autoregulation in the brain, which can present as hypertensive encephalopathy.

Symptoms of Malignant Hypertension

The main symptoms of malignant hypertension are rapidly increasing blood pressure of 180/120 or higher and signs of organ damage. Usually, the damage happens to the kidneys or the eyes.

Other symptoms depend on how the rise in blood pressure affects your organs. A common symptom is bleeding and swelling in the tiny blood vessels in the retina. The retina is the layer of nerves that line the back of the eye. It senses light and sends signals to the brain through the optic nerve, which can also be affected by malignant hypertension. When the eye is involved, malignant hypertension can cause changes in vision.

Other symptoms of malignant hypertension include:

  • Change in mental status, such as anxiety, confusion, decreased alertness, decreased ability to concentrate, fatigue, restlessness, sleepiness, or stupor
  • Chest pain (feeling of crushing or pressure)
  • Cough
  • Headache
  • Nausea or vomiting
  • Numbness of the arms, legs, face, or other areas
  • Reduced urine output
  • Seizure
  • Shortness of breath
  • Weakness of the arms, legs, face, or other areas
  • Blurred vision
  • Chest pain (angina)
  • Difficulty breathing
  • Dizziness
  • Numbness in the arms, legs, and face
  • Severe headache
  • Shortness of breath

In rare cases, malignant hypertension can cause brain swelling, which leads to a dangerous condition called hypertensive encephalopathy. Symptoms include:

  • Blindness
  • Changes in mental status
  • Coma
  • Confusion
  • Drowsiness
  • Headache that continues to get worse
  • Nausea and vomiting
  • Seizures

High blood pressure, in general, makes it difficult for kidneys to filter wastes and toxins from the blood. It is a leading cause of kidney failure. Malignant hypertension can cause your kidneys to suddenly stop working properly.

Diagnosis of Malignant Hypertension

Most patients have persistently elevated BP for years before presenting with a hypertensive emergency. Initial questioning should focus on finding indicators related to end-organ damage including a headache, nausea or vomiting, visual disturbances, chest or back pain, dyspnea, orthopnea, or visual disturbances. Review all prescription and nonprescription medications, adherence, and time from the last dose. Ask about recreational drug use, such as amphetamines, cocaine, phencyclidine.

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Physical Examination

On physical exam, confirm BP on both arms using an appropriately-sized blood pressure cuff. Funduscopic exam findings may include hemorrhages, exudates or papilledema. Assess for murmurs and gallops or other signs of heart failure. Look for evidence of pulmonary edema, abdominal bruits. Neurological findings can include stupor, seizures, delirium, agitation.

Accurate Blood Pressure Measurement

  • Reassess normal blood pressure yearly.
  • Take blood pressure after the patient rests for 5 minutes.
  • The patient should sit in a chair with both feet flat on the ground and the back straight.
  • The patient’s arm should be placed on a flat surface at the level of the chest or heart.
  • Choosing the right cuff size is important.
  • SBP is the first Korotkoff sound.
  • DBP is the fifth Korotkoff sound.
  • Obtain an average of 2 to 3 blood pressure measurements on 2 or 3 separate occasions to confirm a hypertension diagnosis.

General Appearance

  • Body mass index calculation
  • Signs of Cushing syndrome such as buffalo hump, moon face, thinning of the skin, and red or purple striae.
  • Restlessness
  • Sweating
  • Flushing
  • Neurofibromatosis

Neck

  • Thyroid enlargement
  • Carotid bruits

Fundoscopy

  • Papilledema
  • Cotton wool spots
  • Arteriolar narrowing
  • Arteriovenous nicking
  • Hemorrhage

Heart

  • Gallop rhythm, S4
  • Heave
  • Jugular venous distension

Lungs

  • Rales
  • Rhonchi

Abdomen

  • Enlarged kidneys
  • Aorta or renal bruits

Neurologic

  • Visual changes
  • Confusion
  • focal weakness

Extremities

  • Peripheral pulses
  • Pedal edema
  • Cold peripheral limbs

An eye exam will reveal changes that indicate high blood pressure, including

  • Bleeding of the retina (back part of the eye)
  • Narrowing of the blood vessels in the retina
  • Swelling of the optic nerve
  • Other problems with the retina

Lab Test And Imaging

The history and physical examination are really important in patients presenting with a very elevated BP, or an acute rise over a previously normal baseline, even if the presenting BP is less than 180/120 mm Hg. Furthermore, the following evaluation should be performed to find the presence of end-organ damage in association with targeted clinical symptoms or signs:

  • Electrocardiography
  • Chest x-Ray
  • Urinalysis
  • Electrolytes and creatinine
  • Cardiac biomarkers, when the acute coronary syndrome is suspected
  • Toxicology screen
  • CT/MRI of the brain, when head injury, neurologic symptoms, hypertensive retinopathy, nausea, or vomiting are present
  • Contrast CT/MRI of the chest or TEE, if aortic dissection is suspected

It is often easiest to categorize hypertensive emergencies by the organ that is being damaged. The evaluation above can usually identify the at-risk target organ and can direct both, the target BP and the promptness with which the target is achieved.

The cardiac exam may reveal the presence of an MI, CHF or pulmonary edema. Concentric left ventricular hypertrophy is often present, including the 4th heart sound. Always check the blood pressure in both arms to rule out aortic dissection. Patients may also have bruit in the neck and groin

CNS exam may reveal a headache, visual changes, vomiting, confusion, and seizures. The eye exam may reveal soft exudates, flame-shaped hemorrhages, and papilledema

The renal exam may present with oliguria and the GI symptoms may include nausea, vomiting and vague abdominal pain.

Treatment of Malignant Hypertension

Adequate therapy, including the choice of the medication and the BP target, changes depending on the specific hypertensive emergency and the affected organ.

It is not recommended to decrease the BP too fast or too much, as ischemic damage can occur in vascular territories that have become habituated with the elevated level of BP. For the majority of hypertensive emergencies, mean arterial pressure (MAP) should be reduced by approximately 10 to 20% within the first hour and by another 5% to 15% over the next 24 hours. This often results in a target BP of less than 180/120 mm Hg for the first hour and less than 160/110 mm Hg for the next 24 hours, but rarely less than 130/80 mm Hg during that time frame.

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Nonpharmacologic Therapy

  • Recommended for all patients, regardless of the reading of the blood pressure.
  • Restrict dietary salt (aim for 1.5 g or less per day). Randomized controlled trials have shown that moderate sodium reduction can result in an average blood pressure reduction of 4.8/2.5 mmHg).
  • Weight loss (every 1 pound of weight loss will result in a reduction of 1 mmHg blood pressure).
  • Start a Dietary Approaches to Stop Hypertension (DASH) diet (rich in fruits, vegetables, whole grains, fish, and low-fat dairy products). A clinical trial has shown that the DASH diet helps to reduce blood pressure by an average of 6/4 mmHg.
  • Increase physical activity. Aerobic and resistance training can reduce blood pressure by an average of 4/3 to 6/3 mmHg, irrespective of body weight.
  • Limit alcohol intake to no more than one alcoholic drink per day for women and two for men.
  • Take a potassium supplement (unless contraindicated in chronic kidney disease patients).
  • Quit smoking.
  • Use stress management.

Pharmacologic Therapy

Common intravenous (IV) medications and doses used to treat hypertensive emergencies include

  • Nicardipine, initial infusion rate 5 mg per hour, increasing by 2.5 mg per hour every 5 minutes to a maximum of 15 mg per hour
  • Sodium nitroprusside, 0.3 to 0.5 mcg/kg/minute, increase by 0.5 mcg/kg per minute every few minutes as needed to a maximum dose of 10 mcg/kg per minute
  • Labetalol 10 to 20 mg IV followed by bolus doses of 20 to 80 mg at 10-minute intervals until a target blood pressure is reached to a maximum 300-mg cumulative dose
  • Esmolol, initial loading dose 500 mcg/kg/minute over 1 minute, then 50 to 100 mcg/kg/minute to a maximum dose of 300 mcg/kg per minute.

If there is any possibility of over or underestimation of BP using frequent noninvasive cuff measurements or if the end-organ damage is life-threatening, consider arterial catheterization for precise, second-to-second measurements allowing for more careful medication titration.

  • In general, start off with a single-agent oral antihypertensive drug therapy, especially in the elderly because of the risk of orthostatic hypotension.
  • An exception to the above is when the initial SBP is above 160 or blood pressure is > 20/10 mmHg above the goal of blood pressure, which often needs the initiation of two oral antihypertensive agents.
  • The four major classes of oral antihypertensive agents include thiazide-like diuretics (chlorthalidone and indapamide), dihydropyridine calcium channel blockers (CCBs: amlodipine, nifedipine, nitrendipine), angiotensin-converting enzyme inhibitors (ACEi: lisinopril, ramipril), and angiotensin receptor blockers (ARBs: losartan, valsartan).
  • Randomized controlled trials have shown that thiazide-like diuretics and CCBs are the preferred first-line agents in reducing the risk of stroke and other morbidities in patients with isolated systolic hypertension.
  • The dose of the single oral antihypertensive agent should be titrated to the maximum before initiating a second oral antihypertensive agent.
  • In patients who require two oral antihypertensive agents, a combination of thiazide-like diuretic and CCB is the preferred strategy.
  • ACEi or ARB is often used in the patient with compelling indications such as heart failure reduced ejection, post-myocardial infarction, diabetes, or chronic kidney disease.
  • A combination of either ACEi or ARB with CCB or a thiazide-like diuretic can be considered.
  • It is important to note that ACEi should never be used concomitantly with ARB under any circumstances.
  • Patients with secondary causes of hypertension should have their respective diseases addressed concurrently.
  • Studies have shown that the use of beta-blockers in the management of hypertension is inferior compared with ARB, ACEi or CCB for cardiovascular and stroke risk reduction.

The major exceptions to gradual BP lowering over the first day are

  • Acute Phase of an Ischemic CVA – The BP is usually not treated unless it is greater than 185/110 mmHg in patients whose reperfusion therapy could be an option or greater than 220/120 mm Hg in patients who might not qualify for it. Consider labetalol or nicardipine infusion.
  • Acute Aortic Dissection – The SBP should be lowered to 120 mm Hg within 20 minutes, and a target heart rate around 60 beats per minute, to reduce aortic shearing forces. Treatment usually requires a beta-blocker and a vasodilator. Options include esmolol, nicardipine, or nitroprusside.
  • An Intracerebral Hemorrhage – The goals of therapy are different and depend on the location and surgical approach.
  • Acute Myocardial Ischemia – Nitroglycerin is the drug of choice; do not use if the patient has taken phosphodiesterase inhibitors, including sildenafil or tadalafil, within the past 48 hours.

After a suitable period, often 8 to 24 hours, of BP control at a target, oral medications are usually given, and the initial intravenous therapy is tapered and discontinued.

Blood Pressure Goals

  • SHEP and HYVET trials have shown significant benefits of antihypertensive treatment in patients with the goal of SBP <150 mmHg.
  • The VALsartan in Elderly Isolated Systolic Hypertension (VALISH) trial showed no significant difference in the primary outcome of sudden death, fatal or nonfatal myocardial infarction and stroke, heart failure death, or other cardiovascular death among patients with strict (< 140 mmHg) and moderate (140 to 150 mmHg) SBP control.
  • However, the VALISH trial was underpowered due to the low number of events.
  • Hence, the optimal SBP in patients with hypertensive disorder remained a controversial topic.
  • The most recent Systolic Blood Pressure Intervention Trial (SPRINT) has shown that intensive SBP target of < 120 mmHg improved the cardiovascular outcomes and the overall survival compared to the standard SBP target of 135 to 139 mmHg.
  • However, aggressive SBP lowering may be harmful in the elderly and incite more adverse effects such as hypotension, end-organ hypoperfusion (causing acute kidney injury, and intracranial hypoperfusion which may link to cognitive decline), and polypharmacy.
  • It is suggested that a goal blood pressure of < 130/80 mmHg is appropriate as long as the patient tolerates it.
  • Otherwise, < 140/90 mmHg is considered reasonable in patients who are in the elderly population and patients with labile blood pressure or polypharmacy.
  • Management strategies should always be patient-centered, with the aim of optimizing blood pressure control and avoiding polypharmacy, especially in the elderly.

J-curve Phenomenon

  • Various studies have shown a J-curve association between blood pressure with risk of myocardial infarction and death.
  • Patients with isolated systolic hypertension who receive antihypertensive treatment may precipitously drop their DBP as well.
  • As myocardial perfusion occurs mainly during diastole, an excessive drop in DBP may increase the risk of cardiovascular disease and death.

Lifestyle changes

You may also need to make some lifestyle changes as part of your ISH treatment plan. These can include:

  • Losing weight. This can help lower your blood pressure. In fact, for every two pounds you lose, you could lower your blood pressure by about 1 mm Hg.
  • Eating a heart-healthy diet. You should also aim to reduce the amount of sodium in your diet. Consider the DASH diet, which emphasizes eating:
    • vegetables
    • whole grains
    • low-fat dairy products
    • fruits
  • Exercising. Not only can exercise help you lower your blood pressure, but it can help you control your weight and stress levels. Aim to perform some sort of aerobic exercise for at least 30 minutes most days of the week.
  • Decreasing alcohol consumption. Healthy alcohol intake is one drink per day for women and two per day for men.
  • Quitting smoking. Smoking can raise your blood pressure and also contribute to a variety of other health problems.
  • Managing stress. Stress can raise your blood pressure, so finding ways to relieve it are important. Examples of techniques to help lower stress are meditation and deep breathing exercises.
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References

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