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94-480: The hospital is home to the Hickman Cancer Center, an emergency department, primary stroke center, and adult inpatient psychiatry services. The emergency department has 25 beds and serves approximately 30,000 patients each year. In memory of his late wife, Ellen, Stevens Warren Flower took up the task of building Flower Hospital in 1910. It was originally built near his home in downtown Toledo, Ohio , but it

188-425: A broken bone ), air, cancer cells or clumps of bacteria (usually from infectious endocarditis ). Because an embolus arises from elsewhere, local therapy solves the problem only temporarily. Thus, the source of the embolus must be identified. Because the embolic blockage is sudden in onset, symptoms are usually maximal at the start. Also, symptoms may be transient as the embolus is partially resorbed and moves to

282-895: A class of medications that lower cholesterol . They are prescribed typically to people who are at high risk of cardiovascular disease . Low-density lipoprotein (LDL) carriers of cholesterol play a key role in the development of atherosclerosis and coronary heart disease via the mechanisms described by the lipid hypothesis . As lipid-lowering medications , statins are effective in lowering LDL cholesterol; they are widely used for primary prevention in people at high risk of cardiovascular disease, as well as in secondary prevention for those who have developed cardiovascular disease. Side effects of statins include muscle pain , increased risk of diabetes , and abnormal blood levels of certain liver enzymes . Additionally, they have rare but severe adverse effects, particularly muscle damage, and very rarely rhabdomyolysis . They act by inhibiting

376-459: A physical exam and supported by medical imaging such as a CT scan or MRI scan . A CT scan can rule out bleeding, but may not necessarily rule out ischemia, which early on typically does not show up on a CT scan. Other tests such as an electrocardiogram (ECG) and blood tests are done to determine risk factors and possible causes. Low blood sugar may cause similar symptoms. Prevention includes decreasing risk factors, surgery to open up

470-431: A 10% 10-year risk of heart disease, as calculated by the 2013 ACC/AHA Pooled Cohort algorithm. Risk factors for coronary heart disease included abnormal lipid levels in the blood , diabetes mellitus , high blood pressure , and smoking . They recommended selective use of low-to-moderate doses statins in the same adults who have a calculated 10-year cardiovascular disease event risk of 7.5–10% or greater. In people over

564-751: A 17% reduced risk of stroke after long-term treatment. A greater benefit is observed with high-intensity statin therapy. They have less effect than the fibrates or niacin in reducing triglycerides and raising HDL-cholesterol ("good cholesterol"). No studies have examined the effect of statins on cognition in patients with prior stroke. However, two large studies (HPS and PROSPER) that included people with vascular diseases reported that simvastatin and pravastatin did not impact cognition. Statins have been studied for improving operative outcomes in cardiac and vascular surgery. Mortality and adverse cardiovascular events were reduced in statin groups. Older adults who receive statin therapy at time of discharge from

658-569: A 2012 review found benefits in both women and men. A 2010 review concluded that treatment without history of cardiovascular disease reduces cardiovascular events in men but not women, and provides no mortality benefit in either sex. Two other meta-analyses published that year, one of which used data obtained exclusively from women, found no mortality benefit in primary prevention. The National Institute for Health and Clinical Excellence (NICE) recommends statin treatment for adults with an estimated 10 year risk of developing cardiovascular disease that

752-444: A complete blockage of one of the carotid arteries, the risk of stroke on that side is about one percent per year. A special form of embolic stroke is the embolic stroke of undetermined source (ESUS). This subset of cryptogenic stroke is defined as a non-lacunar brain infarct without proximal arterial stenosis or cardioembolic sources. About one out of six cases of ischemic stroke could be classified as ESUS. Cerebral hypoperfusion

846-405: A connection. Lovastatin induces the expression of gene atrogin-1 , which is believed to be responsible in promoting muscle fiber damage. Tendon rupture does not appear to occur. The relationship between statin use and risk of developing diabetes remains unclear and the results of reviews are mixed. Higher doses have a greater effect, but the decrease in cardiovascular disease outweighs

940-441: A different location or dissipates altogether. Emboli most commonly arise from the heart (especially in atrial fibrillation ) but may originate from elsewhere in the arterial tree. In paradoxical embolism , a deep vein thrombosis embolizes through an atrial or ventricular septal defect in the heart into the brain. Causes of stroke related to the heart can be distinguished between high- and low-risk: Among those who have

1034-400: A high risk for ischemic stroke. There are two main types of hemorrhagic stroke: The above two main types of hemorrhagic stroke are also two different forms of intracranial hemorrhage , which is the accumulation of blood anywhere within the cranial vault ; but the other forms of intracranial hemorrhage, such as epidural hematoma (bleeding between the skull and the dura mater , which is

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1128-586: A net effect of less LDL circulating in blood. Statins, by inhibiting the HMG CoA reductase pathway, inhibit downstream synthesis of isoprenoids, such as farnesyl pyrophosphate and geranylgeranyl pyrophosphate . Inhibition of protein prenylation for proteins such as RhoA (and subsequent inhibition of Rho-associated protein kinase ) may be involved, at least partially, in the improvement of endothelial function, modulation of immune function, and other pleiotropic cardiovascular benefits of statins, as well as in

1222-441: A person, when asked to raise both arms, involuntarily lets one arm drift downward) and abnormal speech are the findings most likely to lead to the correct identification of a case of stroke, increasing the likelihood by 5.5 when at least one of these is present. Similarly, when all three of these are absent, the likelihood of stroke is decreased (– likelihood ratio of 0.39). While these findings are not perfect for diagnosing stroke,

1316-404: A previous TIA , end-stage kidney disease , and atrial fibrillation . Ischemic stroke is typically caused by blockage of a blood vessel, though there are also less common causes. Hemorrhagic stroke is caused by either bleeding directly into the brain or into the space between the brain's membranes . Bleeding may occur due to a ruptured brain aneurysm . Diagnosis is typically based on

1410-453: A prior heart attack, stroke, stable or unstable angina , aortic aneurysm , or other arterial ischemic disease, in the presence of atherosclerosis. They are also advocated for use in people at high risk of developing coronary heart disease. On average, statins can lower LDL cholesterol by 1.8 mmol/L (70 mg/dL), which translates into an estimated 60% decrease in the number of cardiac events (heart attack, sudden cardiac death ) and

1504-452: A problem. Its appearance makes it advisable to seek medical review and to consider prevention against stroke . In thrombotic stroke, a thrombus (blood clot) usually forms around atherosclerotic plaques. Since blockage of the artery is gradual, onset of symptomatic thrombotic stroke is slower than that of hemorrhagic stroke. A thrombus itself (even if it does not completely block the blood vessel) can lead to an embolic stroke (see below) if

1598-540: A severe headache known as a thunderclap headache ) or reveal evidence of a previous head injury . Stroke may be preceded by premonitory symptoms, which may indicate a stroke is imminent. These symptoms may include dizziness, dysarthria (speech disorder), exhaustion, hemiparesis (weakness on one side of the body), paresthesia (tingling, pricking, chilling, burning, numbness of the skin), pathological laughter, seizure that turns into paralysis, "thunderclap" headache, or vomiting. Premonitory symptoms are not diagnostic of

1692-461: A statin. This is known as statin intolerance. A 2021 double-blind multiple crossover randomized controlled trial (RCT) in statin-intolerant patients found that adverse effects, including muscle pain, were similar between atorvastatin and placebo. A smaller double-blind RCT obtained similar results. The results of these studies help explain why statin symptom rates in observational studies are so much higher than in double-blind RCTs and support

1786-432: A stroke, and may be a sign of other illness. Assessing onset (gradual or sudden), duration, and the presence of other associated symptoms are important, and premonitory symptoms may not appear at all or may vary depending on the type of stroke. Stroke symptoms typically start suddenly, over seconds to minutes, and in most cases do not progress further. The symptoms depend on the area of the brain affected. The more extensive

1880-415: A subarachnoid hemorrhage or an embolic stroke. If the area of the brain affected includes one of the three prominent central nervous system pathways —the spinothalamic tract , corticospinal tract , and the dorsal column–medial lemniscus pathway , symptoms may include: In most cases, the symptoms affect only one side of the body (unilateral). The defect in the brain is usually on the opposite side of

1974-472: A warning about the potential for non-serious and reversible cognitive side effects with the medication (memory loss, confusion). In observational studies 10–15% of people who take statins experience muscle problems; in most cases these consist of muscle pain . These rates, which are much higher than those seen in randomized clinical trials have been the topic of extensive debate and discussion. Muscle and other symptoms often cause patients to stop taking

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2068-399: Is a major inhibitor of only lovastatin, simvastatin, and to a lesser degree, atorvastatin) and some other medications (flavonoids (i.e. naringin ) were thought to be responsible). This increases the levels of the statin, increasing the risk of dose-related adverse effects (including myopathy / rhabdomyolysis ). The absolute prohibition of grapefruit juice consumption for users of some statins

2162-501: Is a medical condition in which poor blood flow to a part of the brain causes cell death . There are two main types of stroke: ischemic , due to lack of blood flow, and hemorrhagic , due to bleeding . Both cause parts of the brain to stop functioning properly. Signs and symptoms of stroke may include an inability to move or feel on one side of the body , problems understanding or speaking , dizziness , or loss of vision to one side . Signs and symptoms often appear soon after

2256-400: Is a related syndrome of stroke symptoms that resolve completely within 24 hours. With the availability of treatments that can reduce stroke severity when given early, many now prefer alternative terminology, such as "brain attack" and "acute ischemic cerebrovascular syndrome" (modeled after heart attack and acute coronary syndrome , respectively), to reflect the urgency of stroke symptoms and

2350-409: Is an irritant which could potentially destroy cells since it is an acid and disrupts the normal acid-base balance in the brain. The ischemia area is referred to as the "ischemic penumbra ". After the initial ischemic event the penumbra transitions from a tissue remodeling characterized by damage to a remodeling characterized by repair. As oxygen or glucose becomes depleted in ischemic brain tissue,

2444-574: Is an underlying history of cardiovascular disease, it has a significant impact on the effects of statin. This can be used to divide medication usage into broad categories of primary and secondary prevention. For the primary prevention of cardiovascular disease, the United States Preventive Services Task Force (USPSTF) 2016 guidelines recommend statins for those who have at least one risk factor for coronary heart disease , are between 40 and 75 years old, and have at least

2538-418: Is called stroke rehabilitation , and ideally takes place in a stroke unit; however, these are not available in much of the world. In 2023, 15 million people worldwide had a stroke. In 2021, stroke was the third biggest cause of death, responsible for approximately 10% of total deaths. In 2015, there were about 42.4 million people who had previously had stroke and were still alive. Between 1990 and 2010

2632-428: Is caused by interruption of the blood supply to the brain, while hemorrhagic stroke results from the rupture of a blood vessel or an abnormal vascular structure . About 87% of stroke is ischemic, with the rest being hemorrhagic. Bleeding can develop inside areas of ischemia, a condition known as " hemorrhagic transformation ." It is unknown how many cases of hemorrhagic stroke actually start as ischemic stroke. In

2726-422: Is controversial. The U.S. Food and Drug Administration (FDA) notified healthcare professionals of updates to the prescribing information concerning interactions between protease inhibitors and certain statin drugs. Protease inhibitors and statins taken together may increase the blood levels of statins and increase the risk for muscle injury (myopathy). The most serious form of myopathy, rhabdomyolysis, can damage

2820-590: Is greater than 10%. Guidelines by the American College of Cardiology and the American Heart Association recommend statin treatment for primary prevention of cardiovascular disease in adults with LDL cholesterol ≥ 190 mg/dL (4.9 mmol/L) or those with diabetes, age 40–75 with LDL-C 70–190 mg/dL (1.8–4.9 mmol/dL); or in those with a 10-year risk of developing heart attack or stroke of 7.5% or more. In this latter group, statin assignment

2914-527: Is lacking as of 2017 . The gene SLCO1B1 ( Solute carrier organic anion transporter family member 1B1 ) codes for an organic anion-transporting polypeptide that is involved in the regulation of the absorption of statins. A common variation in this gene was found in 2008 to significantly increase the risk of myopathy. Records exist of over 250,000 people treated from 1998 to 2001 with the statin drugs atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, and simvastatin. The incidence of rhabdomyolysis

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3008-442: Is less reliable in the recognition of posterior circulation stroke. The revised mnemonic BE FAST , which adds balance (sudden trouble keeping balance while walking or standing) and eyesight (new onset of blurry or double vision or sudden, painless loss of sight) to the assessment, has been proposed to address this shortcoming and improve early detection of stroke even further. Other scales for prehospital detection of stroke include

3102-550: Is on the World Health Organization's List of Essential Medicines with simvastatin being the listed medicine. In 2005, sales were estimated at US$ 18.7 billion in the United States. The best-selling statin is atorvastatin, also known as Lipitor, which in 2003 became the best-selling pharmaceutical in history. The manufacturer Pfizer reported sales of US$ 12.4 billion in 2008. Patient compliance with statin usage

3196-692: Is problematic despite robust evidence of the benefits. Statins are usually used to lower blood cholesterol levels and reduce risk for illnesses related to atherosclerosis, with a varying degree of effect depending on underlying risk factors and history of cardiovascular disease. Clinical practice guidelines generally recommend people start with lifestyle modification through a cholesterol-lowering diet and physical exercise . For those unable to meet their lipid-lowering goals through such methods, statins can be helpful. The medication appears to work equally well regardless of sex, although some sex-related differences in treatment response were described. If there

3290-409: Is the reduction of blood flow to all parts of the brain. The reduction could be to a particular part of the brain depending on the cause. It is most commonly due to heart failure from cardiac arrest or arrhythmias , or from reduced cardiac output as a result of myocardial infarction , pulmonary embolism , pericardial effusion , or bleeding. Hypoxemia (low blood oxygen content) may precipitate

3384-447: Is the second leading cause of death in people under 20 with sickle-cell anemia. Air pollution may also increase stroke risk. An embolic stroke refers to an arterial embolism (a blockage of an artery) by an embolus , a traveling particle or debris in the arterial bloodstream originating from elsewhere. An embolus is most frequently a thrombus, but it can also be a number of other substances including fat (e.g., from bone marrow in

3478-422: The cerebral cortex is involved, the central nervous system pathways can again be affected, but can also produce the following symptoms: If the cerebellum is involved, ataxia might be present and this includes: In the days before a stroke (generally in the previous 7 days, even the previous one), a considerable proportion of patients have a "sentinel headache": a severe and unusual headache that indicates

3572-617: The JUPITER trial showed statins provided benefit in those who had no history of high cholesterol or heart disease, but only in those with elevated high-sensitivity C-reactive protein (hsCRP) levels, an indicator for inflammation. The study has been criticized due to perceived flaws in the study design, although Paul M. Ridker , lead investigator of the JUPITER trial, has responded to these criticisms at length. Click on genes, proteins and metabolites below to link to respective articles. As

3666-509: The LDL receptor or apolipoprotein B genes, both of which are responsible for LDL clearance from the blood. Statins remain a first-line treatment in familial hypercholesterolemia, although other cholesterol-reducing measures may be required. In people with homozygous deficiencies, statins may still prove helpful, albeit at high doses and in combination with other cholesterol-reducing medications. A 2014 meta-analysis found that statins could reduce

3760-617: The Los Angeles Prehospital Stroke Screen (LAPSS) and the Cincinnati Prehospital Stroke Scale (CPSS), on which the FAST method was based. Use of these scales is recommended by professional guidelines. For people referred to the emergency room , early recognition of stroke is deemed important as this can expedite diagnostic tests and treatments. A scoring system called ROSIER (recognition of stroke in

3854-545: The hormone insulin . One way this is thought to occur is by interfering with cholesterol synthesis which is necessary for the production of certain proteins responsible for glucose uptake into cells such as GLUT1 . Several meta-analyses have found no increased risk of cancer, and some meta-analyses have found a reduced risk. Specifically, statins may reduce the risk of esophageal cancer , colorectal cancer , gastric cancer , hepatocellular carcinoma , and possibly prostate cancer . They appear to have no effect on

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3948-421: The nucleus and bind to the sterol response elements. The sterol response elements then facilitate increased transcription of various other proteins, most notably, LDL receptor . The LDL receptor is transported to the liver cell membrane and binds to passing LDL and VLDL particles, mediating their uptake into the liver, where the cholesterol is reprocessed into bile salts and other byproducts. This results in

4042-487: The ventricular system , CSF or the pial surface. A third of intracerebral bleed is into the brain's ventricles. ICH has a mortality rate of 44 percent after 30 days, higher than ischemic stroke or subarachnoid hemorrhage (which technically may also be classified as a type of stroke ). Other causes may include spasm of an artery. This may occur due to cocaine . Cancer is also another well recognized potential cause of stroke. Although, malignancy in general can increase

4136-470: The 1970s the World Health Organization defined "stroke" as a "neurological deficit of cerebrovascular cause that persists beyond 24 hours or is interrupted by death within 24 hours", although the word "stroke" is centuries old. This definition was supposed to reflect the reversibility of tissue damage and was devised for the purpose, with the time frame of 24 hours being chosen arbitrarily. The 24-hour limit divides stroke from transient ischemic attack , which

4230-602: The 2015 Cochrane systematic review, atorvastatin showed greater cholesterol-lowering effect in women than in men compared to rosuvastatin. In children, statins are effective at reducing cholesterol levels in those with familial hypercholesterolemia . Their long term safety is, however, unclear. Some recommend that if lifestyle changes are not enough statins should be started at 8 years old. Statins may be less effective in reducing LDL cholesterol in people with familial hypercholesterolemia, especially those with homozygous deficiencies. These people have defects usually in either

4324-456: The Bamford or Oxford classification) relies primarily on the initial symptoms; based on the extent of the symptoms, the stroke episode is classified as total anterior circulation infarct (TACI), partial anterior circulation infarct (PACI), lacunar infarct (LACI) or posterior circulation infarct (POCI). These four entities predict the extent of the stroke, the area of the brain that is affected,

4418-577: The Patient-Centered Research into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) study and the Health Protection Study (HPS) demonstrated that simvastatin and pravastatin did not affect cognition for patients with risk factors for, or a history of, vascular diseases. There are reports of reversible cognitive impairment with statins. The U.S. Food and Drug Administration (FDA) package insert on statins includes

4512-586: The age of 70, statins decrease the risk of cardiovascular disease but only in those with a history of heavy cholesterol blockage in their arteries. Most evidence suggests that statins are also effective in preventing heart disease in those with high cholesterol but no history of heart disease. A 2013 Cochrane review found a decrease in risk of death and other poor outcomes without any evidence of harm. For every 138 people treated for 5 years, one fewer dies; for every 49 treated, one fewer has an episode of heart disease. A 2011 review reached similar conclusions, and

4606-649: The annual incidence of stroke decreased by approximately 10% in the developed world , but increased by 10% in the developing world. In 2015, stroke was the second most frequent cause of death after coronary artery disease , accounting for 6.3 million deaths (11% of the total). About 3.0 million deaths resulted from ischemic stroke while 3.3 million deaths resulted from hemorrhagic stroke. About half of people who have had stroke live less than one year. Overall, two thirds of cases of stroke occurred in those over 65 years old. Stroke can be classified into two major categories: ischemic and hemorrhagic . Ischemic stroke

4700-501: The area of the brain affected, the more functions that are likely to be lost. Some forms of stroke can cause additional symptoms. For example, in intracranial hemorrhage, the affected area may compress other structures. Most forms of stroke are not associated with a headache , apart from subarachnoid hemorrhage and cerebral venous thrombosis and occasionally intracerebral hemorrhage. Systems have been proposed to increase recognition of stroke. Sudden-onset face weakness, arm drift (i.e., if

4794-493: The arteries to the brain in those with problematic carotid narrowing , and anticoagulant medication in people with atrial fibrillation . Aspirin or statins may be recommended by physicians for prevention. Stroke is a medical emergency. Ischemic strokes, if detected within three to four-and-a-half hours, may be treatable with medication that can break down the clot , while hemorrhagic strokes sometimes benefit from surgery . Treatment to attempt recovery of lost function

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4888-629: The blood due to liver damage . Over 5 years of treatment statins result in 75 cases of diabetes, 7.5 cases of bleeding stroke , and 5 cases of muscle damage per 10,000 people treated. This could be due to the statins inhibiting the enzyme (HMG-CoA reductase), which is necessary to make cholesterol, but also for other processes, such as CoQ 10 production, which is important for muscle function and sugar regulation. Other possible adverse effects include neuropathy , pancreatic and liver dysfunction, and sexual dysfunction . The rate at which such events occur has been widely debated, in part because

4982-401: The blood supply by narrowing the lumen of blood vessels leading to a reduction of blood flow by causing the formation of blood clots within the vessel or by releasing showers of small emboli through the disintegration of atherosclerotic plaques. Embolic infarction occurs when emboli formed elsewhere in the circulatory system, typically in the heart as a consequence of atrial fibrillation, or in

5076-471: The body. However, since these pathways also travel in the spinal cord and any lesion there can also produce these symptoms, the presence of any one of these symptoms does not necessarily indicate stroke. In addition to the above central nervous system pathways, the brainstem gives rise to most of the twelve cranial nerves . A brainstem stroke affecting the brainstem and brain, therefore, can produce symptoms relating to deficits in these cranial nerves: If

5170-504: The brain and places the person at increased risk for both transient ischemic attack and major stroke in the future. Conversely, those who have had major stroke are also at risk of having silent stroke. In a broad study in 1998, more than 11 million people were estimated to have experienced stroke in the United States. Approximately 770,000 of these were symptomatic and 11 million were first-ever silent MRI infarcts or hemorrhages . Silent stroke typically causes lesions which are detected via

5264-426: The carotid arteries, break off, enter the cerebral circulation, then lodge in and block brain blood vessels. Since blood vessels in the brain are now blocked, the brain becomes low in energy, and thus it resorts to using anaerobic metabolism within the region of brain tissue affected by ischemia. Anaerobic metabolism produces less adenosine triphosphate (ATP) but releases a by-product called lactic acid . Lactic acid

5358-411: The case of muscle cramps or of deterioration in kidney function . Consumption of grapefruit or grapefruit juice inhibits the metabolism of certain statins, and bitter oranges may have a similar effect. Furanocoumarins in grapefruit juice (i.e. bergamottin and dihydroxybergamottin ) inhibit the cytochrome P450 enzyme CYP3A4 , which is involved in the metabolism of most statins (however, it

5452-424: The cells of the nervous system is normally kept low by so-called uptake carriers, which are powered by the concentration gradients of ions (mainly Na ) across the cell membrane. However, stroke cuts off the supply of oxygen and glucose which powers the ion pumps maintaining these gradients. As a result, the transmembrane ion gradients run down, and glutamate transporters reverse their direction, releasing glutamate into

5546-411: The emergency room) is recommended for this purpose; it is based on features from the medical history and physical examination. Loss of consciousness , headache , and vomiting usually occur more often in hemorrhagic stroke than in thrombosis because of the increased intracranial pressure from the leaking blood compressing the brain. If symptoms are maximal at onset, the cause is more likely to be

5640-460: The enzyme HMG-CoA reductase , which plays a central role in the production of cholesterol. High cholesterol levels have been associated with cardiovascular disease. There are various forms of statins, some of which include atorvastatin , fluvastatin , lovastatin , pitavastatin , pravastatin , rosuvastatin , and simvastatin . Combination preparations of a statin and another agent, such as ezetimibe/simvastatin , are also available. The class

5734-499: The extracellular space. Glutamate acts on receptors in nerve cells (especially NMDA receptors), producing an influx of calcium which activates enzymes that digest the cells' proteins, lipids, and nuclear material. Calcium influx can also lead to the failure of mitochondria , which can lead further toward energy depletion and may trigger cell death due to programmed cell death . Statin Statins (or HMG-CoA reductase inhibitors ) are

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5828-503: The fact that a number of other drugs that lower LDL have not shown the same cardiovascular risk benefits in studies as statins, and may also account for some of the benefits seen in cancer reduction with statins. In addition, the inhibitory effect on protein prenylation may also be involved in a number of unwanted side effects associated with statins, including muscle pain (myopathy) and elevated blood sugar (diabetes). As noted above, statins exhibit action beyond lipid-lowering activity in

5922-685: The fact that they can be evaluated relatively rapidly and easily make them very valuable in the acute setting. A mnemonic to remember the warning signs of stroke is FAST (facial droop, arm weakness, speech difficulty, and time to call emergency services), as advocated by the Department of Health (United Kingdom) and the Stroke Association , the American Stroke Association , and the National Stroke Association (US). FAST

6016-477: The guidelines. The European Society of Cardiology and the European Atherosclerosis Society recommend the use of statins for primary prevention, depending on baseline estimated cardiovascular score and LDL thresholds. Statins are effective in decreasing mortality in people with pre-existing cardiovascular disease . Pre-existing disease can have many manifestations. Defining illnesses include

6110-679: The hidden benefits of statin use. The statins are divided into two groups: fermentation -derived and synthetic . Some specific types are listed in the table below. Note that the associated brand names may vary between countries. LDL-lowering potency varies between agents. Cerivastatin is the most potent (withdrawn from the market in August 2001 due to risk of serious rhabdomyolysis), followed by (in order of decreasing potency) rosuvastatin, atorvastatin, simvastatin, lovastatin, pravastatin, and fluvastatin. The relative potency of pitavastatin has not yet been fully established, but preliminary studies indicate

6204-436: The hospital after an inpatient stay have been studied. People with cardiac ischemia not previously on statins at the time of admission have a lower risk of major cardiac adverse events and hospital readmission two years post-hospitalization. All statins appear effective regardless of potency or degree of cholesterol reduction. Simvastatin and pravastatin appear to have a reduced incidence of side-effects. According to

6298-535: The hypoperfusion. Because the reduction in blood flow is global, all parts of the brain may be affected, especially vulnerable "watershed" areas—border zone regions supplied by the major cerebral arteries. A watershed stroke refers to the condition when the blood supply to these areas is compromised. Blood flow to these areas does not necessarily stop, but instead it may lessen to the point where brain damage can occur. Cerebral venous sinus thrombosis leads to stroke due to locally increased venous pressure, which exceeds

6392-597: The incidence of major cardiac events by up to 20% and are not that likely to increase the risk of stroke or kidney failure. Asthma Statins have been identified as having a possible adjunct role in the treatment of asthma through anti-inflammatory pathways. There is low quality evidence for the use of statins in treating asthma, however further research is required to determine the effectiveness and safety of this therapy in those with asthma. The most important adverse side effects are muscle problems, an increased risk of diabetes mellitus , and increased liver enzymes in

6486-422: The kidneys and lead to kidney failure, which can be fatal. Studies have found that the use of statins may protect against getting osteoporosis and fractures or may induce osteoporosis and fractures. A cross-sectional retrospective analysis of the entire Austrian population found that the risk of getting osteoporosis is dependent on the dose used. Statins act by competitively inhibiting HMG-CoA reductase ,

6580-482: The need to act swiftly. During ischemic stroke, blood supply to part of the brain is decreased, leading to dysfunction of the brain tissue in that area. There are four reasons why this might happen: Stroke without an obvious explanation is termed cryptogenic stroke ( idiopathic ); this constitutes 30–40% of all cases of ischemic stroke. There are classification systems for acute ischemic stroke. The Oxford Community Stroke Project classification (OCSP, also known as

6674-1164: The notion that the difference results from the nocebo effect ; that the symptoms are caused by expectations of harm. Media reporting on statins is often negative, and patient leaflets inform patients that rare but potentially serious muscle problems can occur during statin treatment. These create expectations of harm. Nocebo symptoms are real and bothersome and are a major barrier to treatment. Because of this, many people stop taking statins, which have been proven in numerous large-scale RCTs to reduce heart attacks, stroke, and deaths – as long as people continue to take them. Serious muscle problems such as rhabdomyolysis (destruction of muscle cells) and statin-associated autoimmune myopathy occur in less than 0.1% of treated people. Rhabdomyolysis can in turn result in life-threatening kidney injury . The risk of statin-induced rhabdomyolysis increases with older age, use of interacting medications such as fibrates , and hypothyroidism . Coenzyme Q10 (ubiquinone) levels are decreased in statin use; CoQ10 supplements are sometimes used to treat statin-associated myopathy, though evidence of their efficacy

6768-721: The pressure generated by the arteries. Infarcts are more likely to undergo hemorrhagic transformation (leaking of blood into the damaged area) than other types of ischemic stroke. It generally occurs in small arteries or arterioles and is commonly due to hypertension, intracranial vascular malformations (including cavernous angiomas or arteriovenous malformations ), cerebral amyloid angiopathy , or infarcts into which secondary hemorrhage has occurred. Other potential causes are trauma, bleeding disorders , amyloid angiopathy , illicit drug use (e.g., amphetamines or cocaine ). The hematoma enlarges until pressure from surrounding tissue limits its growth, or until it decompresses by emptying into

6862-416: The prevention of atherosclerosis through so-called "pleiotropic effects of statins". The pleiotropic effects of statins remain controversial. The ASTEROID trial showed direct ultrasound evidence of atheroma regression during statin therapy. Researchers hypothesize that statins prevent cardiovascular disease via four proposed mechanisms (all subjects of a large body of biomedical research): In 2008,

6956-537: The producer. By inhibiting HMG-CoA reductase, statins block the pathway for synthesizing cholesterol in the liver. This is significant because most circulating cholesterol comes from internal manufacture rather than the diet. When the liver can no longer produce cholesterol, levels of cholesterol in the blood will fall. Cholesterol synthesis appears to occur mostly at night, so statins with short half-lives are usually taken at night to maximize their effect. Studies have shown greater LDL and total cholesterol reductions in

7050-423: The production of high energy phosphate compounds such as adenosine triphosphate (ATP) fails, leading to failure of energy-dependent processes (such as ion pumping) necessary for tissue cell survival. This sets off a series of interrelated events that result in cellular injury and death. A major cause of neuronal injury is the release of the excitatory neurotransmitter glutamate. The concentration of glutamate outside

7144-606: The rate of muscle pain associated with statin use, the rates of rhabdomyolysis are still "reassuringly low" and similar to those seen in clinical trials (about 1–2 per 10,000 person years). Another systematic review from the International Centre for Circulatory Health of the National Heart and Lung Institute in London concluded that only a small fraction of side effects reported by people on statins are actually attributable to

7238-625: The rate-limiting enzyme of the mevalonate pathway . Because statins are similar in structure to HMG-CoA on a molecular level, they will fit into the enzyme's active site and compete with the native substrate (HMG-CoA). This competition reduces the rate by which HMG-CoA reductase is able to produce mevalonate , the next molecule in the cascade that eventually produces cholesterol . A variety of natural statins are produced by Penicillium and Aspergillus fungi as secondary metabolites . These natural statins probably function to inhibit HMG-CoA reductase enzymes in bacteria and fungi that compete with

7332-452: The risk decision. Additional factors that could be used were an LDL-C ≥ 160 mg/dL (4.14 mmol/L) or a very high lifetime risk. However, critics such as Steven E. Nissen say that the AHA/ACC guidelines were not properly validated, overestimate the risk by at least 50%, and recommend statins for people who will not benefit, based on populations whose observed risk is lower than predicted by

7426-533: The risk of contrast-induced nephropathy by 53% in people undergoing coronary angiography /percutaneous interventions. The effect was found to be stronger among those with preexisting kidney dysfunction or diabetes mellitus. The risk of cardiovascular disease is similar in people with chronic kidney disease and coronary artery disease and statins are often suggested. There is some evidence that appropriate use of statin medications in people with chronic kidney disease who do not require dialysis may reduce mortality and

7520-441: The risk of lung cancer , kidney cancer , breast cancer , pancreatic cancer , or bladder cancer . Combining any statin with a fibrate or niacin (other categories of lipid-lowering drugs) increases the risks for rhabdomyolysis to almost 6.0 per 10,000 person-years. Monitoring liver enzymes and creatine kinase is especially prudent in those on high-dose statins or in those on statin/fibrate combinations, and mandatory in

7614-420: The risk of developing diabetes. Use in postmenopausal women is associated with an increased risk for diabetes. The exact mechanism responsible for the possible increased risk of diabetes mellitus associated with statin use is unclear. However, recent findings have indicated the inhibition of HMGCoAR as a key mechanism. Statins are thought to decrease cells' uptake of glucose from the bloodstream in response to

7708-462: The risk of stroke, certain types of cancer such as pancreatic, lung and gastric are typically associated with a higher thromboembolism risk. The mechanism with which cancer increases stroke risk is thought to be secondary to an acquired hypercoagulability . Silent stroke is stroke that does not have any outward symptoms, and people are typically unaware they had experienced stroke. Despite not causing identifiable symptoms, silent stroke still damages

7802-662: The risk/benefit ratio of statins in low-risk populations is highly dependent on the rate of adverse events. A Cochrane meta-analysis of statin clinical trials in primary prevention found no evidence of excess adverse events among those treated with statins compared to placebo. Another meta-analysis found a 39% increase in adverse events in statin treated people relative to those receiving placebo, but no increase in serious adverse events. The author of one study argued that adverse events are more common in clinical practice than in randomized clinical trials . A systematic review concluded that while clinical trial meta-analyses underestimate

7896-443: The short-acting simvastatin taken at night rather than the morning, but have shown no difference in the long-acting atorvastatin . In rabbits, liver cells sense the reduced levels of liver cholesterol and seek to compensate by synthesizing LDL receptors to draw cholesterol out of the circulation. This is accomplished via proteases that cleave membrane-bound sterol regulatory element binding proteins , which then migrate to

7990-399: The statin. Multiple systematic reviews and meta-analyses have concluded that the available evidence does not support an association between statin use and cognitive decline. A 2010 meta-review of medical trials involving over 65,000 people concluded that Statins decreased the risk of dementia, Alzheimer's disease, and even improved cognitive impairment in some cases. Additionally, both

8084-504: The stroke has occurred. If symptoms last less than 24 hours, the stroke is a transient ischemic attack (TIA), also called a mini-stroke. Hemorrhagic stroke may also be associated with a severe headache . The symptoms of stroke can be permanent. Long-term complications may include pneumonia and loss of bladder control . The biggest risk factor for stroke is high blood pressure . Other risk factors include high blood cholesterol , tobacco smoking , obesity , diabetes mellitus ,

8178-507: The target of statins, the HMG-CoA reductase, is highly similar between eukaryota and archaea , statins also act as antibiotics against archaea by inhibiting archaeal mevalonate biosynthesis. This has been shown in vivo and in vitro. Since patients with a constipation phenotype present with higher abundance of methanogenic archaea in the gut, the use of statins for management of irritable bowel syndrome has been proposed and may actually be one of

8272-592: The thick outermost layer of the meninges that surround the brain) and subdural hematoma (bleeding in the subdural space ), are not considered "hemorrhagic stroke". Hemorrhagic stroke may occur on the background of alterations to the blood vessels in the brain, such as cerebral amyloid angiopathy , cerebral arteriovenous malformation and an intracranial aneurysm , which can cause intraparenchymal or subarachnoid hemorrhage. In addition to neurological impairment, hemorrhagic stroke usually causes specific symptoms (for instance, subarachnoid hemorrhage classically causes

8366-479: The thrombus breaks off and travels in the bloodstream, at which point it is called an embolus . Two types of thrombosis can cause stroke: Anemia causes increase blood flow in the blood circulatory system. This causes the endothelial cells of the blood vessels to express adhesion factors which encourages the clotting of blood and formation of thrombus. Sickle-cell anemia , which can cause blood cells to clump up and block blood vessels, can also lead to stroke. Stroke

8460-681: The underlying cause, and the prognosis. The TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification is based on clinical symptoms as well as results of further investigations; on this basis, stroke is classified as being due to (1) thrombosis or embolism due to atherosclerosis of a large artery, (2) an embolism originating in the heart , (3) complete blockage of a small blood vessel, (4) other determined cause, (5) undetermined cause (two possible causes, no cause identified, or incomplete investigation). Users of stimulants such as cocaine and methamphetamine are at

8554-407: The use of neuroimaging such as MRI . Silent stroke is estimated to occur at five times the rate of symptomatic stroke. The risk of silent stroke increases with age, but they may also affect younger adults and children, especially those with acute anemia . Ischemic stroke occurs because of a loss of blood supply to part of the brain, initiating the ischemic cascade . Atherosclerosis may disrupt

8648-602: Was 0.44 per 10,000 patients treated with statins other than cerivastatin. However, the risk was over 10-fold greater if cerivastatin was used, or if the standard statins (atorvastatin, fluvastatin, lovastatin, pravastatin, or simvastatin) were combined with a fibrate ( fenofibrate or gemfibrozil ) treatment. Cerivastatin was withdrawn by its manufacturer in 2001. Some researchers have suggested hydrophilic statins, such as fluvastatin, rosuvastatin, and pravastatin, are less toxic than lipophilic statins, such as atorvastatin, lovastatin, and simvastatin, but other studies have not found

8742-476: Was later relocated to Sylvania, Ohio , in 1975. The hospital has a cafeteria with a Subway restaurant , two gift shops , internet access , a library, and pastoral services. 41°42′32″N 83°41′28″W  /  41.70878°N 83.690974°W  / 41.70878; -83.690974 This article relating to a hospital in Ohio is a stub . You can help Misplaced Pages by expanding it . Stroke Stroke

8836-536: Was not automatic, but was recommended to occur only after a clinician-patient risk discussion with shared decision making where other risk factors and lifestyle are addressed, the potential for benefit from a statin is weighed against the potential for adverse effects or drug interactions and informed patient preference is elicited. Moreover, if a risk decision was uncertain, factors such as family history, coronary calcium score, ankle-brachial index , and an inflammation test ( hs-CRP ≥ 2.0 mg/L) were suggested to inform

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