There are risk factors that make some people more likely to have a stroke, and there are underlying causes and pre-existing conditions that could actually trigger a stroke.
Sometimes, the line between a risk factor and a cause is blurred. A risk factor like high blood pressure, for example, turns into a cause. The pressure against an arterial wall causes the blood vessel to break, depriving brain cells from getting their supply of oxygen.
Some risk factors or causes can be controlled; others can’t. You can’t do anything about age or family history, but you can stop smoking or lose weight to lower the risk of a cerebrovascular event (see “Cerebrovascular Disease Defined”).
The purpose of this chapter is to make you more aware of the major risk factors for stroke. The number one cause of stroke in the U.S., according to the National Stroke Association, is hypertension.
New Definition of Hypertension
Almost half of Americans have hypertension (high blood pressure), and according to the Centers for Disease Control and Prevention, three out of 10 who have high blood pressure don’t control their condition with medications.
Chronic high blood pressure creates more resistance to the flow of blood through the arteries and greatly increases the risk of stroke. It also increases the risk of second stroke among stroke survivors. Widely fluctuating blood pressure may be an even greater danger.
Based on American College of Cardiology guidelines, high blood pressure should be treated with lifestyle changes and in some patients, with medication, at 130/80 rather than 140/90.
The guidelines lower the definition of high blood pressure to account for complications that can occur at lower numbers and to allow for earlier intervention. The new definition has resulted in nearly half of the U.S. adult population described as having high blood pressure.
Most people with hypertension have essential, or primary, hypertension, meaning there is no known underlying cause. High blood pressure can progress for years without causing symptoms, yet is easy to identify at a regular checkup.
Hypertension is dangerous because increased pressure and stress on the blood vessels cause arteries to age faster, making them more likely to rupture and cause hemorrhagic stroke or develop fatty plaques, which increases the risk of ischemic stroke. Hypertension appears to increase the risk of “silent strokes” deep in the brain by as much as 60 percent.
Most hypertension-related hemorrhages in the brain are spontaneous and occur most commonly in the small arteries located deep in the brain. A hemorrhage in another part of the brain is likely due to a different cause, although hypertension may play a role.
Age Increases Risk
As it relates to stroke, the age factor can’t be overlooked. The Centers for Disease Control and Prevention confirms that the older a person is, the greater the likelihood of having a stroke. The chance of suffering a stroke approximately doubles every 10 years after age 55.
Although stroke is common among older adults, people under 65 are not immune to strokes. About one in seven strokes occur in adolescents and young adults ages 15 to 49. Younger people are thought to be having more strokes because they are increasingly obese, and have high blood pressure
and diabetes.
Although age is not controllable, awareness of age as a risk factor and acting on that information lowers the risk.
Women at Greater Risk. Women appear to be at greater risk for stroke than men. Each year, about 55,000 more women than men suffer a stroke, although a 2017 study in the journal Neurology suggested that the rates may be more evenly distributed than previously thought.
Women share many risk factors with men, but are at greater risk of stroke if they have diabetes, metabolic syndrome, hypertension, atrial fibrillation, or migraine. Much of the increased risk of stroke is due to factors unique
to women.
Black People at Higher Risk. Black people are at particularly high risk for stroke. According to the American Heart Association’s Heart Disease and Stroke Statistical Fact Sheet Update, black men and women have a significantly higher risk of a first stroke than whites. The reasons are not clear. Some of the increased incidence may be explained by untreated risk factors, such as high blood pressure
or diabetes.
The Genetic Role. If a parent, grandparent, sister, or brother has had a stroke—especially before reaching age 65—you may be at greater risk, according to the American Stroke Association.
The CDC explains that genetic factors are likely to play a role in stroke and other cardiovascular conditions. People with a family history of stroke are likely to share environments and factors that increase the risk of stroke. The odds of a stroke increase even more when heredity is combined with unhealthy lifestyle choices such as tobacco use and an unhealthy diet.
High Rates in Southeast
The risk for stroke varies by geographic region, with the highest rates of stroke in the southeastern United States, an area known as the “stroke belt.” It includes Kentucky, Indiana, Virginia, North Carolina, South Carolina, Georgia, Tennessee, Mississippi, Alabama, Louisiana, and Arkansas. The risk of dying from stroke in the stroke belt is about 20 percent higher than in the rest of the country.
At least part of the difference is explained by the fact that people living in the Southeast have higher rates of high blood pressure and diabetes. The Southern-style diet of foods rich in grease (think fried chicken, fish, and potatoes), salt (bacon, ham), and sugar (desserts) also may increase the risk of stroke. People who eat a Southern-style diet six times a week have a 41 percent greater chance of having a stroke than someone who indulges once a month.
Alcohol Moderation for Protection
Although alcohol has been shown to have cardiovascular benefits, the key is moderation. Heavy consumption is associated with increased risk of both hemorrhagic and ischemic stroke. Binge drinking also may increase the risk of hemorrhagic stroke.
Sedentary Lifestyle, Increased Inflammation
An inactive lifestyle can be a cause of many chronic diseases and can raise the risk of stroke, according to the U.S. National Library of Medicine. Among the inactivity-related problems that may lead to a stroke are poor circulation, more inflammation, and impaired immune system. The age for lifestyle diseases, including stroke, has dropped from the 40s to people in their 30s.
NSAIDs Warning
In 2017, the Food and Drug Administration (FDA) strengthened its warning that nonsteroidal anti-inflammatory drugs (NSAIDs) like naproxen (Aleve) and ibuprofen (Motrin, Advil) increase a person’s risk of heart attack and stroke. The warning was based on a comprehensive review of studies and the recommendation of an advisory committee. Among their findings:
- The risk of heart attack or stroke may begin within a few weeks of starting to take an NSAID.
- The risk increases with higher doses taken for longer periods of time.
- The risk is greater for patients with heart disease.
- The evidence is not strong enough to suggest that one type of NSAID is safer than others.
The FDA says that it is important to take the lowest effective dose for the shortest possible length of time.
Smoking Damages Blood Vessels
Smoking can damage blood vessels and raise blood pressure, according to the National Heart, Lung, and Blood Institute. It may also reduce the amount of oxygen that reaches tissues. Exposure to secondhand smoke also can damage the blood vessels.
Smoking makes you twice as likely to die if you have a stroke, and the more you smoke, the greater your risk of stroke, says the U.K.’s Stroke Association. If you smoke 20 cigarettes a day, you are six times more likely to have a stroke compared to a non-smoker.
Infections May Trigger Strokes
Several studies have identified an increased risk of stroke among individuals recently exposed to common viruses and bacteria. It is not yet known whether aggressive treatment to eradicate these pathogens lowers the risk of stroke. These infections may increase the risk or “trigger” strokes by causing chronic low-level inflammation in the blood vessels.
While we all get sick from viral and bacterial infections from time to time, and usually recover in a few days, these pathogens can cause lasting damage. Cumulative exposure to five common pathogens increases the risk of stroke: the viruses herpes simplex 1 and 2 and cytomegalovirus, and the bacteria chlamydia pneumoniae and helicobacter pylori.
Ocular shingles (shingles in and around the eyes) caused by the herpes zoster virus, the same virus that causes chickenpox, more than quadrupled the risk of stroke in one study.
Although the risk of stroke in children is low—about five in 100,000—a significant percentage of children who have a stroke had an infection in the days leading up to the event. The risk was highest within a few days of developing an infection and essentially disappeared a month after the infection.
Progressive Atherosclerosis
Atherosclerosis is a progressive disease in which plaque builds up inside arteries. In some cases, these plaques become so large they may restrict or block the flow of blood. They can also erupt or break apart.
Plaque formation is likely to start at a young age and may take years—even decades—to grow. Most people are unaware they have growing plaques, because symptoms do not appear until 70 percent or more of the artery’s interior channel (lumen) is blocked.
Cholesterol impacts plaque development. Cholesterol molecules are wrapped in protein-covered particles that move easily through the bloodstream. They are called lipoproteins, and there are four types:
- Low-density lipoproteins (LDL)
- High-density lipoproteins (HDL)
- Very-low-density lipoproteins (VLDL)
- Chylomicrons primarily containing triglycerides
Low-density and high-density lipoproteins contain high concentrations of cholesterol. When the different lipoproteins exist in proper proportion, they are not a health risk. However, when total cholesterol or LDL-cholesterol levels rise, or the amount of HDL-cholesterol drops, the body starts depositing cholesterol in the arteries. Abnormally high levels of triglycerides also are associated with an increased risk of stroke or heart attack.
In the latter stage of development, certain cells in the slowly developing plaque deposit calcium inside the plaque—a process most people describe as “hardening of the arteries.” By the time a plaque develops to this point, it contains many different types of cells, both living and dead, lots of cholesterol and lipoproteins, pieces of old blood clots, and calcium.
Atherosclerosis can affect almost any artery in the body. Symptoms vary, depending on the organ fed by that artery. When atherosclerosis affects arteries supplying blood to the brain or inside the brain, a stroke can occur. When atherosclerosis affects the arteries supplying blood to the heart muscle (coronary artery disease, or CAD), a heart attack can occur. The same disease process can affect the arms and legs (peripheral arterial disease, or PAD) or the kidneys (renovascular disease).
Patients with atherosclerosis in one site are at increased risk of having atherosclerosis elsewhere. If you have had an ischemic stroke or have experienced symptoms of a transient ischemic attack (TIA), you have a 20 to 40 percent chance of having CAD.
In fact, 2 to 5 percent of ischemic stroke survivors have a fatal heart attack less than 90 days after their stroke. If you are under the age of 60 and have a TIA, your risk of having a heart attack is 15 times that of a healthy person your age.
Similarly, CAD is a risk factor for stroke, since patients with CAD also may have cerebrovascular disease. In addition, they are at increased risk for strokes caused by blood clots forming in the heart and traveling to the brain. While about 47 percent of all deaths from cardiovascular disease are due to CAD, about 16 percent are due to stroke.
Researchers in the U.S. and Spain have uncovered an unexpected risk factor for developing atherosclerosis. The medical records of approximately 4,000 subjects showed that poor sleep quality is associated with the condition (see “Poor Sleep Quality and Duration Linked to Atherosclerosis”).
Aortic Arch Atheroma, Older Patients
In patients with atherosclerosis, the aortic arch can be a source of blood clots. This is known as aortic arch atheroma, and it tends to affect older patients with high blood pressure. Although the arch itself is large and not likely to become blocked with plaque, atherosclerotic plaques that form in this region are prone to breaking off and traveling toward the brain.
Plaques in the aortic arch should be treated medically. However, the optimal medical regimen is unclear. Antiplatelet therapy and statin therapy are recommended. Most patients are not candidates for surgical treatment, due to a greatly increased risk of a stroke occurring during the operation.
Lowering blood pressure, lowering cholesterol, and stopping smoking are most important in preventing these plaques from growing.
Aneurysms, Weakened Walls
Aneurysms form in weakened areas of an artery wall. As the wall weakens, even normal blood pressure can cause it to balloon out. They most often form in arteries located at the base of the brain, particularly where the arteries divide, such as in the circle of Willis. Many aneurysms are thought to begin early in life and enlarge slowly until they suddenly rupture many years later. Other aneurysm facts:
- Smoking and hypertension increase the risk of rupture.
- About 20 percent of people with one aneurysm have several aneurysms.
- A person with a parent or sibling who has had an aneurysm is at increased risk.
Aneurysms also may form in smaller arteries of the brain. These microaneurysms usually cannot be seen on imaging. Hypertension and smoking may contribute to the development of microaneurysms.
A burst aneurysm is the most common cause of a hemorrhagic stroke. If the pressure builds up rapidly and compresses parts of the brain, it may cause loss of consciousness or death. About half of all subarachnoid hemorrhage patients who arrive at the hospital alive die within 30 days. More than half of those who survive suffer major neurologic deficits or other complications.
Non-ruptured aneurysms are typically discovered incidentally on brain imaging performed for another condition. It is difficult to predict which aneurysms are prone to rupture.
Physicians consider factors such as the size and location of the aneurysm, family history, and use of tobacco products in their decision to offer preventive treatment. This is often weighed against the risk of surgical treatment. As aneurysms grow, they may press on certain nerves or areas of the brain, disrupting their normal function.
Atrial Fibrillation, Heart Rhythm Disturbance
Atrial fibrillation (A-fib) is a heart rhythm disturbance originating in the upper chambers of the heart. When atrial fibrillation lasts for more than several days, it is said to be persistent. It also may last for a short time and revert to normal spontaneously, without any treatment. A-fib increases ischemic stroke risk.
Atrial fibrillation affects 9 percent of people ages 65 and older, and its incidence increases with age. One-third of people ages 85 and older with atrial fibrillation will have a stroke, compared with only 16.7 percent of people in this age group without the arrhythmia. Atrial fibrillation most often occurs in people with high blood pressure, coronary artery disease, heart valve disease, or cardiomyopathy.
When the cause of stroke is not immediately clear, the doctor may recommend a 30-day heart-rhythm monitor or an insertable cardiac monitor. The latter device is implanted under the chest skin, where it can monitor the heart’s electrical signals for as long
as necessary.
Information downloaded from the device will reveal whether the patient is having intermittent or paroxysmal atrial fibrillation. If so, a blood thinner such as warfarin, factor Xa inhibitor, or direct thrombin inhibitor can be prescribed to prevent another stroke.
A catheter-based procedure called ablation may be performed to help control atrial fibrillation. Ablation stops atrial fibrillation by creating scar tissue that blocks the rogue electrical signals from causing the chaotic rhythm. It is generally reserved for patients whose arrhythmia persists, despite antiarrhythmic medications. Ablation reduces the long-term risk of stroke close to that of people without atrial fibrillation.
Untreated atrial fibrillation increases the risk for ischemic stroke by five times because uncoordinated, poor pumping action of the heart may cause blood to pool in some areas and form a clot. Most of these clots form in a sac called the atrial appendage. From there, the clot may become dislodged and flow to areas where it lodges, causing an ischemic stroke.
Heart Valve Disease, Three Conditions
Diseases of the mitral valve, which separates the left atrium and left ventricle, are associated with increased risk of ischemic stroke. Mitral stenosis and mitral regurgitation account for most of these strokes.
Mitral Valve Stenosis. The mitral valve has two flaps, which open inward when pressure is higher in the left atrium than in the left ventricle. As pressure builds in the contracting ventricle, the leaflets snap shut, preventing blood from being pumped backward into the atrium. In mitral stenosis, the calcified leaflets become rigid, preventing them from opening well. The edges of the leaflets also can fuse, reducing the size of the opening through which blood flows.
As stenosis begins to impede the emptying of blood from the left atrium into the left ventricle, blood backs up. The lungs become fluid-filled and congested, causing shortness of breath. After several years of mitral stenosis, it’s also common for atrial fibrillation or other atrial arrhythmia to develop.
Mitral Regurgitation. In mitral regurgitation, the leaves of the mitral valve fail to form a tight seal when the ventricle contracts, allowing blood to flow backward into the atrium. The symptoms are similar to those of mitral stenosis.
About two-thirds of all cases of mitral stenosis and one-third of all cases of mitral regurgitation are caused by rheumatic or scarlet fever (Streptococcal infection).
Mitral regurgitation also may occur after a heart attack, particularly if the muscles attached to the mitral and tricuspid valves are affected. Mitral regurgitation may occur as well in heart failure, particularly when the left ventricle enlarges.
Infective Endocarditis. A bacterial infection known as infective endocarditis can cause plaque and other debris to slough off, resulting in an embolic stroke.
Obesity, 69 Percent of Americans
Sixty-nine percent of U.S. adults are overweight or obese, and the percentage is steadily rising, according to the American Heart Association. This is a serious problem, because obesity is a risk factor for cardiovascular disease, including stroke. It also is a risk factor for death from stroke.
The more overweight you are, the greater your risk of stroke. One study found the risk of ischemic stroke was 22 percent higher among people who were overweight and 64 percent higher among those who were obese, compared with people of normal weight.
One way to determine whether you are overweight or obese is to calculate your body mass index (see “What’s Your Body Mass Index?”). If you are in the overweight or obese category, you should seriously consider changing how you eat and start to exercise. If you are a man and 100 pounds over your ideal weight, or a woman carrying an extra 80 pounds, you are considered morbidly obese. This means your obesity is highly likely to cause medical problems. Your doctor may prescribe a weight-loss drug for you or recommend bariatric surgery.
PFO, Hole in the Heart
A patent foramen ovale (PFO) is a hole between the right and left atria. Before birth, the hole enables blood from the umbilical cord to flow from the right atrium to the left atrium, bypassing the lungs, which have not yet begun to work.
At birth, the hole usually closes permanently, but in about 20 to 25 percent of people it remains open. PFO often is associated with stroke in people younger than age 50 and is found in about 40 percent of patients who die from ischemic stroke at a young age.
A PFO is not simply a hole, but a hole with a flap. After the umbilical cord is cut, the flap normally closes and fuses to the edge of the opening to form a solid wall. When the flap remains open, blood flows from the right into the left atrium when the pressure on the right side is greater than on the left. This can occur as easily as when a person coughs, sneezes, or strains on the toilet.
The danger is that an embolus on the right side of the heart will pass to the left side, where it is eventually pumped to the brain and causes a stroke. The source of these emboli is thought to be blood clots in leg or pelvic veins. Older patients with PFO and deep vein thrombosis (DVT) are at increased risk of stroke.
Most people with a PFO never notice any symptoms or suffer a stroke. Despite the increased risk of stroke conferred by PFO in some patients, closing these holes in patients without stroke symptoms is not recommended.
However, several major clinical trials reported that PFO closure significantly reduced the rate of recurrent stroke in certain patients the Amplatzer PFO Occluder is the only device currently approved by the FDA to treat the condition (see “The Amplatzer PFO Occluder”).
Other Causes
Among the many other potential causes of stroke are obstructive sleep apnea, certain medications, diet drinks, cerebral amyloid angiopathy, and arteriovenous malformations. Blood diseases and blood-clotting deficiencies, brain tumors, head trauma, and hyperthyroidism are other examples.
Obstructive Sleep Apnea
When you sleep, the muscles in your neck relax. In some people, this causes their throat to collapse, slowing or temporarily halting their breathing. When this happens repeatedly throughout the night, it is called obstructive sleep apnea (OSA).
People with OSA may be unaware they stop breathing, but other people are very aware. That’s because OSA causes heavy snoring interrupted by periods of silence that end with a gasp. Poor quality sleep may cause the person to feel excessively sleepy during the day.
OSA increases the risk of a fatal or nonfatal stroke and heart attack. Some patients with OSA are overweight and have excess fat in the neck. In these people, losing weight may cause OSA and its associated risks to disappear. In other patients, OSA appears to be associated with nasal obstruction and the shape of the tongue, airway, palate, or jaw.
Medications
Certain medications, including ranibizumab (Lucentis) for macular degeneration and COX-2 inhibitors (Celebrex) for arthritis pain, may raise the risk of stroke.
A study presented in 2018 found the two classes of blood pressure drugs were linked to the risk of stroke. The two were alpha blockers and alpha-2 agonists. Alpha blockers (doxazosin and prazosin hydrochloride) dilate blood vessels. Alpha-2 agonists (methyldopa) reduce blood vessel constriction.
Your physician will weigh the benefits of these drugs against the possible risk before prescribing them.
Diet Drinks
A large study found that women who reported drinking more than one diet soda or other artificially sweetened drink a day had a higher risk of stroke caused by a blood clot (see “Diet Drinks Associated with Increased Risk of Stroke in Women”).
Cerebral Amyloid Angiopathy
In some people, a protein called beta-amyloid accumulates in the small arteries throughout the brain, causing the condition known as cerebral amyloid angiopathy. It is the same protein seen in Alzheimer’s disease. Affected arteries become weaker and more brittle, making them more likely to rupture. It is not known why beta-amyloid accumulations cause hemorrhage in some individuals and Alzheimer’s disease in others.
Some patients may have multiple hemorrhages over a period of months or years. Small ones may be asymptomatic.
Cerebral amyloid angiopathy may occur in more than one-third of people ages 60 and older. Unfortunately, there is no treatment for it. The risk of spontaneous hemorrhage can be reduced by managing hypertension and avoiding drugs that prevent blood from clotting.
Arteriovenous Malformations (AVM)
Arteriovenous malformations are congenitally abnormal blood vessels that grow between arteries and veins in the brain. A direct shunt between an external carotid artery branch and a vein is called an intracranial dural arteriovenous fistula (AVF). Both are prone to rupture and spill blood into the brain.
AVMs and AVFs can be tiny or large. Some AVMs never cause symptoms, while others may cause headaches, seizures, and if they burst, hemorrhagic stroke. These vascular malformations are rare in the general population and often go undetected unless a patient develops symptoms or undergoes brain imaging for another reason.
Blood Diseases/Deficiencies
Blood diseases and blood-clotting deficiencies that increase the risk of a hemorrhagic stroke include leukemia, aplastic anemia, and thrombotic thrombocytopenic purpura.
Certain inherited disorders that cause abnormally long bleeding times, such as hemophilia, also are associated with increased risk of brain hemorrhage. Drugs that inhibit blood clotting also increase the risk.
Brain Tumors
Brain tumors, which either originate in the brain or metastasize from tumors located elsewhere in the body, may cause an intracerebral hemorrhage. Sometimes a hemorrhage is the first indication a brain tumor is present.
As tumors grow, they stimulate the growth of new arteries and veins to reinforce their blood supply. These new arteries may not be fully formed, and may be weaker and prone to rupture from ordinary blood pressure fluctuations or hypertension.
Head Trauma
A serious injury to the head may cause an artery in the brain to rupture. Any time a person exhibits unexplained neurologic deficits following an accident or sports injury, an intracerebral hemorrhage may be responsible.
Hyperthyroidism
An overactive thyroid has been shown to increase the risk of stroke by 44 percent in adults under age 45. Although hyperthyroidism may not be directly responsible, various mechanisms associated with hyperthyroidism—hypercoagulability (abnormality of blood that makes it clot too much), hypofibrinolysis (abnormality of blood clots to resist breaking down), endothelial dysfunction, and atrial fibrillation—make hyperthyroidism a risk factor.
Other Risk Factors
Restless legs syndrome, psychological distress, and inflammation are examples of other risk factors.
Restless Legs Syndrome
People with restless legs syndrome are twice as likely to have a stroke as people without the disorder. The worse the condition, the greater the risk of stroke.
Psychological Distress
Depression and other types of psychological distress increase the risk of stroke. The risk appears to increase in proportion to the extent of the distress. Depression is associated with a two-fold increased risk of a first stroke and 34 percent higher risk of a second stroke. The reason for the link between depression and stroke is unknown.
Inflammation
Tests for two indicators of increased inflammation (high-sensitivity C-reactive protein [hs-CRP] and lipoprotein-associated phospholipase A2 [PLA2]) can improve the ability to predict five-year risk of stroke when added to traditional risk factor assessment. Patients with inflammatory conditions, such as rheumatoid arthritis and lupus, are at increased risk for stroke and should take extra precautions to lower their risk.
Rare Causes
Less than 5 percent of ischemic strokes are caused by unusual or rare conditions/diseases. These include dissections, hypercoagulable states, vasculitis, and systemic hypotension.
Dissections
Arteries are comprised of several different types of cells that allow them to stretch, contract, and relax. These include layers of muscle cells and elastic tissues. An arterial dissection occurs when a tear in the innermost layer allows blood to flow between these layers, separating them.
A dissection is usually confined to a small area of an artery, but since the blood has no place to go it stagnates and comes in contact with surfaces that stimulate blood clotting, and it clots. When a dissection occurs in an artery leading to the brain, a stroke may happen. Dissections are most often caused by blunt trauma to the head and neck, or chiropractic manipulations of the neck.
Because younger people are more active in sports, about 5 to 20 percent of ischemic strokes in patients under 45 years of age are caused by dissections, compared to about 1 to 2.5 percent of all ischemic strokes in the general population.
Hypercoagulable States
Under normal conditions, blood is fluid and unlikely to clot. Certain diseases, however, cause blood to clot when ordinarily it would not. When this happens, the blood is said to be hypercoagulable.
Inherited deficiencies in certain blood proteins involved in blood clotting can be responsible, as can pregnancy. Other possible risks include
1) oral contraceptive use in women who have high blood pressure, smoke, or have migraines; 2) obesity, 3) cancer; 4) chemotherapy, 5) lupus erythematosus, and 6) certain kidney diseases.
In a hypercoagulable state, blood clots may form spontaneously, and if they flow into an artery of the brain, cause a stroke.
Vasculitis
This condition is characterized by inflammation of the blood vessels. Many forms of vasculitis are treatable. A common feature, however, is the tendency for blood to clot as it flows through an affected artery. When vasculitis affects arteries in the brain or arteries leading to the brain, a stroke may occur.
Systemic Hypotension
This sudden, significant drop in blood pressure can be caused by life-threatening heart rhythm disturbances that cause blood flow to stop.
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