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A stroke is a medical emergency. Learn what to do if you or a loved one is having a stroke.

What is a stroke?

A stroke is a life-threatening condition that happens when part of your brain doesn't have enough blood flow. This most commonly happens because of a blocked artery or bleeding in your brain. Without a steady supply of blood, the brain cells in that area start to die from a lack of oxygen.

IMPORTANT: A stroke is a life-threatening emergency condition where every second counts. If you or someone with you has symptoms of a stroke, IMMEDIATELY call 911 (or your local emergency services number). The quicker stroke is treated, the more likely you'll recover without disability.

To recognize the warning signs of a stroke, remember to think BE FAST:

B. Be watchful for a sudden loss of balance.

E. Look out for sudden loss of vision in one or both eyes. Are they experiencing double vision?

F. Ask the person to smile. Look for a droop on one or both sides of their face, which is a sign of muscle weakness or paralysis.

A. A person having a stroke often has muscle weakness on one side. Ask them to raise their arms. If they have one-sided weakness (and didn't have it before), one arm will stay higher while the other will sag and drop downward.

S. Strokes often cause a person to lose their ability to speak. They might slur their speech or have trouble choosing the right words.

T. Time is critical, so don't wait to get help! If possible, look at your watch or a clock and remember when symptoms start. Telling a healthcare provider when symptoms started can help the provider know what treatment options are best for you.

Who does it affect?

Anybody can have a stroke, from children to adults, but there are some people who have a greater risk than others. Strokes are more common later in life (about two-thirds of strokes happen in people over age 65).

There are also certain medical conditions that increase the risk of stroke, including high blood pressure (hypertension), high cholesterol (hyperlipidemia), Type 2 diabetes, and people who have a history of stroke, heart attack or irregular heart rhythms like atrial fibrillation.

How common is a stroke?

Strokes are very common. Worldwide, strokes rank second among the top causes of death. In the United States, stroke is the fifth cause of death. Strokes are also a leading cause of disability worldwide.

How does a stroke affect my body?

Strokes are to your brain what a heart attack is to your heart. When you have a stroke, part of your brain loses its blood supply, which keeps that brain area from getting oxygen. Without oxygen, the affected brain cells become oxygen-starved and stop working properly.

If your brain cells go too long without oxygen, they'll die. If enough brain cells in an area die, the damage becomes permanent, and you may lose the abilities that area once controlled. However, restoring blood flow may prevent that kind of damage or at least limit how severe it is. That's why time is critical in treating a stroke.

What are the types of stroke?

There are two main ways that strokes can happen: ischemia and hemorrhage.

Ischemic stroke

Ischemia (pronounced "iss-key-me-uh") is when cells don't get enough blood flow to supply them with oxygen. This usually happens because something blocks blood vessels in your brain, cutting off blood flow. Ischemic strokes are the most common and account for about 80% of all strokes.

Ischemic strokes usually happen in one of the following ways:

Formation of a clot in your brain (thrombosis).

A fragment of a clot that formed elsewhere in your body that breaks free and travels through your blood vessels until it gets stuck in your brain (embolism).

Small vessel blockage (lacunar stroke), which can happen when you have long-term, untreated high blood pressure (hypertension), high cholesterol (hyperlipidemia) or high blood sugar (Type 2 diabetes).

Unknown reasons (these are cryptogenic strokes; the word "cryptogenic" means "hidden origin").

Hemorrhagic stroke

Hemorrhagic (pronounced "hem-or-aj-ick") strokes cause bleeding in or around your brain. This happens in one of two ways:

Bleeding inside of your brain (intracerebral). This happens when a blood vessel inside of your brain tears or breaks open, causing bleeding that puts pressure on the surrounding brain tissue.

Bleeding into the subarachnoid space (the space between your brain and its outer covering). The arachnoid membrane, a thin layer of tissue with a spiderweb-like pattern on it, surrounds your brain. The space between it and your brain is the subarachnoid space ("sub" means "under"). Damage to blood vessels that pass through the arachnoid membrane can cause a subarachnoid hemorrhage, which is bleeding into the subarachnoid space, putting pressure on the brain tissue underneath.

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Stroke: What It Is, Causes, Symptoms, Treatment & Types

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A stroke is a medical emergency caused by a lack of blood flow to part of your brain. Lack of blood flow will eventually cause permanent brain damage or even death.

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Summary

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Ischemic stroke

About 87% of strokes are ischemic. The blockage in the brain is usually caused by a piece of or a blood clot. If the blockage occurs locally in the brain, the condition is called thrombosis. If the blood clot travels from somewhere else in the body, it is called an embolism. Ischemic strokes are classified specifically based on where in the brain the blockage occurs and where in the body an embolism developed. In some cases, the location of the original embolism is not known.

When plaque builds up on the inner walls of the arteries, it can lead to a disease called atherosclerosis. Plaque hardens and narrows the arteries, limiting blood flow to tissues and organs. Plaque can build up in any artery in the body, including arteries in the brain and neck. Carotid artery disease occurs when plaque builds up in the carotid arteries in the neck that supply blood to the brain. It is a common cause of ischemic stroke.

Plaque in an artery can also break open. Blood stick to the site of the plaque injury and clump together to form blood clots. These clots can partly or fully block an artery.

Blood clots leading to stroke can happen when there are other heart and blood conditions, such as atrial fibrillation and sickle cell disease. MRI studies show that as many as 40% of children with sickle cell disease have had a stroke, even though a medical exam does not show signs of one. The only treatment for these undetected strokes (also called silent infarcts) is to receive regular blood transfusions.

Studies have found ischemic stroke in people who have COVID-19. However, it is too early to tell whether COVID-19 can cause stroke.

Inflammation

Chronic (long-term) inflammation contributes to ischemic stroke. Researchers are still trying to understand this fully. Research shows that inflammation can damage the blood vessels and contribute to atherosclerosis. Ischemic stroke can also lead to inflammation that further damages brain cells.

Transient ischemic attack

A transient ischemic attack (TIA) is caused by a blockage in the brain just like an ischemic stroke. With a TIA, the blockage breaks up before there is any damage to your brain. It typically lasts less than an hour but can come and go. Eventually, it can become a full stroke. A TIA is also called a mini-stroke. If you are diagnosed with a TIA in an emergency room, you should follow up as soon as possible with a primary care provider and a neurologist, a doctor who specializes in treating disorders of the brain, spinal cord, and nervous system.

Hemorrhagic stroke

Sudden bleeding can cause a hemorrhagic stroke. This can happen when an artery in or on top of the brain breaks open. The leaked blood causes the brain to swell, raising pressure in the brain that can damage brain cells. There are two types of hemorrhagic stroke: intracranial hemorrhage, or bleeding within the skull, and subarachnoid hemorrhage (SAH), or bleeding between the brain and the membrane that surrounds it. Intracranial hemorrhage occurs in about 10% of stroke cases, and SAH occurs in about 3%.

Some conditions make blood vessels in the brain more likely to bleed.

Aneurysm is a balloon-like bulge in an artery that can stretch and burst.

Arteriovenous malformations (AVMs) are tangles of poorly formed arteries and veins that can break open in the brain.

High blood pressure puts pressure on the inside walls of the arteries. This pressure makes them more likely to break open, especially if they are weakened from an aneurysm or AVM.

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The causes and risk factors for both ischemic and hemorrhagic stroke are important to know. Some factors can reduce stroke risk, while others are outside a patient's control.

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Summary

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Types of Strokes and Treatment | Brigham and Women’s Hospital

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There are various types of strokes, with different causes, treatments, and possible complications. Learn about the types of stroke and how they’re treated.

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What is Ischemic and Hemorrhagic Stroke?

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What is Ischemic and Hemorrhagic Stroke?

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Summary

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Although stroke risk increases after 55, many factors play a role in who has one. Learn about risks and prevention to reduce stroke risk.

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Who Can Have a Stroke and Factors that May Cause a Stroke

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Let's Talk About Black Americans and Stroke

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Let’s Talk About Black Americans and Stroke

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Black people in the U.S. face a higher risk of stroke. Identify the risk factors and take steps to reduce them. Learn more with this printable resource.

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In 2018, non-Hispanic Black or African American adults were 50% more likely to have a stroke than non-Hispanic white adults.

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The Association Between Race and Stroke Prevalence in a Patient Cohort in Mississippi

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The risk factors for stroke, including hypertension, high cholesterol, heart disease, diabetes, heavy alcohol use, and prior history of stroke, are well known. In Mississippi, there is often a wider gulf of socioeconomic disparities between racial…

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African Americans and Cardiovascular Disease

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African Americans and Cardiovascular Disease

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Summary

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African Americans and Cardiovascular Disease

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Abstract

Stroke is the second leading cause of death and a major contributor to disability worldwide. The prevalence of stroke is highest in developing countries, with ischemic stroke being the most common type. Considerable progress has been made in our understanding of the pathophysiology of stroke and the underlying mechanisms leading to ischemic insult. Stroke therapy primarily focuses on restoring blood flow to the brain and treating stroke-induced neurological damage. Lack of success in recent clinical trials has led to significant refinement of animal models, focus-driven study design and use of new technologies in stroke research. Simultaneously, despite progress in stroke management, post-stroke care exerts a substantial impact on families, the healthcare system and the economy. Improvements in pre-clinical and clinical care are likely to underpin successful stroke treatment, recovery, rehabilitation and prevention. In this review, we focus on the pathophysiology of stroke, major advances in the identification of therapeutic targets and recent trends in stroke research.

Keywords: stroke, pathophysiology, treatment, neurological deficit, recovery, rehabilitation

1. Introduction

Stroke is a neurological disorder characterized by blockage of blood vessels. Clots form in the brain and interrupt blood flow, clogging arteries and causing blood vessels to break, leading to bleeding. Rupture of the arteries leading to the brain during stroke results in the sudden death of brain cells owing to a lack of oxygen. Stroke can also lead to depression and dementia.

Until the International Classification of Disease 11 (ICD-11) was released in 2018, stroke was classified as a disease of the blood vessels. Under the previous ICD coding rationale, clinical data generated from stroke patients were included as part of the cardiovascular diseases chapter, greatly misrepresenting the severity and specific disease burden of stroke. Due to this misclassification within the ICD, stroke patients and researchers did not benefit from government support or grant funding directed towards neurological disease. After prolonged advocacy from a group of clinicians, the true nature and significance of stroke was acknowledged in the ICD-11; stroke was re-categorized into the neurological chapter [ 1]. The reclassification of stroke as a neurological disorder has led to more accurate documentation of data and statistical analysis, supporting improvements in acute healthcare and acquisition of research funding for stroke.

2. Epidemiology of Stroke

Stroke is the second leading cause of death globally. It affects roughly 13.7 million people and kills around 5.5 million annually. Approximately 87% of strokes are ischemic infarctions, a prevalence which increased substantially between 1990 and 2016, attributed to decreased mortality and improved clinical interventions. Primary (first-time) hemorrhages comprise the majority of strokes, with secondary (second-time) hemorrhages constituting an estimated 10-25% [ 2, 3]. The incidence of stroke doubled in low-and-middle income countries over 1990-2016 but declined by 42% in high-income countries over the same period. According to the Global Burden of Disease Study (GBD), although the prevalence of stroke has decreased, the age of those affected, their sex and their geographic location mean that the socio-economic burden of stroke has increased over time [ 3].

Gender-specific stroke: The occurrence of stroke in men and women also depends on age. It is higher at younger ages in women, whereas incidence increases slightly with older age in men. The higher risk for stroke in women is due to factors related to pregnancy, such as preeclampsia, contraceptive use and hormonal therapy, as well as migraine with aura. Atrial fibrillation increases stroke risk in women over 75 years by 20%. Based on the National Institutes of Health Stroke Scale (0 = no stroke, 1-4 = minor stroke, 5-15 = moderate stroke, 15-20 = moderate/severe stroke, 21-42 = severe stroke), mean stroke severity was estimated at 10 for women and 8.2 for men. Both brain infarction and intracerebral hemorrhage (ICH) are common in men, but cardioembolic stroke, a more severe form of stroke, is more prevalent among women. The fatality rate for stroke is also higher among women [ 5, 6, 7]. Women live longer than men, which is one reason for their higher incidence of stroke; another important concern is women's delay in accepting help for ongoing symptoms [ 8]. For men, the most common causes of stroke are tobacco smoking, excessive alcohol consumption, myocardial infarction and arterial disorders [ 9].

Socioeconomic variation: There is a strong inverse relationship between stroke and socioeconomic status, attributable to inadequate hospital facilities and post-stroke care among low-income populations [ 14]. A case study conducted in the US showed that people with high financial status had better stroke treatment options than deprived individuals [ 15]. A study in China linked low income and lack of health insurance to prevention of secondary stroke attack [ 16]. Research conducted in Austria associated level of education with take-up of treatments such as echocardiography and speech therapy; however, there was no difference in administration of thrombolysis, occupational therapy, physiotherapy or stroke care for secondary attack by socioeconomic status [ 17]. Similarly, in the Scottish healthcare system, basic treatments like thrombolysis were provided irrespective of the economic status of patients [ 18].

3. Pathophysiology of Stroke

Stroke is defined as an abrupt neurological outburst caused by impaired perfusion through the blood vessels to the brain. It is important to understand the neurovascular anatomy to study the clinical manifestation of the stroke. The blood flow to the brain is managed by two internal carotids anteriorly and two vertebral arteries posteriorly (the circle of Willis). Ischemic stroke is caused by deficient blood and oxygen supply to the brain; hemorrhagic stroke is caused by bleeding or leaky blood vessels.

Ischemic occlusions contribute to around 85% of casualties in stroke patients, with the remainder due to intracerebral bleeding. Ischemic occlusion generates thrombotic and embolic conditions in the brain [ 19]. In thrombosis, the blood flow is affected by narrowing of vessels due to atherosclerosis. The build-up of plaque will eventually constrict the vascular chamber and form clots, causing thrombotic stroke. In an embolic stroke, decreased blood flow to the brain region causes an embolism; the blood flow to the brain reduces, causing severe stress and untimely cell death (necrosis). Necrosis is followed by disruption of the plasma membrane, organelle swelling and leaking of cellular contents into extracellular space [ 20], and loss of neuronal function. Other key events contributing to stroke pathology are inflammation, energy failure, loss of homeostasis, acidosis, increased intracellular calcium levels, excitotoxicity, free radical-mediated toxicity, cytokine-mediated cytotoxicity, complement activation, impairment of the blood-brain barrier, activation of glial cells, oxidative stress and infiltration of leukocytes [ 21, 22, 23, 24, 25].

Hemorrhagic stroke accounts for approximately 10-15% of all strokes and has a high mortality rate. In this condition, stress in the brain tissue and internal injury cause blood vessels to rupture. It produces toxic effects in the vascular system, resulting in infarction [ 26]. It is classified into intracerebral and subarachnoid hemorrhage. In ICH, blood vessels rupture and cause abnormal accumulation of blood within the brain. The main reasons for ICH are hypertension, disrupted vasculature, excessive use of anticoagulants and thrombolytic agents. In subarachnoid hemorrhage, blood accumulates in the subarachnoid space of the brain due to a head injury or cerebral aneurysm ( Figure 1) [ 27, 28].

Figure 1.

Molecular mechanism of stroke.

4. Risk Factors for Stroke

As noted earlier, the risk of stroke increases with age and doubles over the age of 55 years in both men and women. Risk is increased further when an individual has an existing medical condition like hypertension, coronary artery disease or hyperlipidemia. Nearly 60% of strokes are in patients with a history of transient ischemic attack (TIA). Some of the risk factors for stroke are modifiable, and some are non-modifiable ( Figure 2).

Figure 2.

Risk factors associated with stroke.

4.1. Non-Modifiable Risk Factors

These include age, sex, ethnicity, TIA and hereditary characteristics. In the US in 2005, the average age of incidence of stroke was 69.2 years [ 2, 29, 30]. Recent research has indicated that people aged 20-54 years are at increasing risk of stroke, probably due to pre-existing secondary factors [ 31]. Women are at equal or greater risk of stroke than men, irrespective of age [ 32]. US research shows that Hispanic and black populations are at higher risk of stroke than white populations; notably, the incidence of hemorrhagic stroke is significantly higher in black people than in age-matched white populations [ 33, 34, 35].

Transient ischemic attack is classified as a mini stroke; the underlying mechanism is the same as for full-blown stroke. In TIA, the blood supply to part of the brain is blocked temporarily. It acts as a warning sign before the actual event, providing an opportunity to change lifestyle and commence medications to reduce the chance of stroke [ 36, 37].

Genetics contribute to both modifiable and non-modifiable risk factors for stroke. Genetic risk is proportional to the age, sex and race of the individual [ 38, 39], but a multitude of genetic mechanisms can increase the risk of stroke. Firstly, a parental or family history of stroke increases the chance of an individual developing this neurological disorder. Secondly, a rare single gene mutation can contribute to pathophysiology in which stroke is the primary clinical manifestation, such as in cerebral autosomal dominant arteriopathy. Thirdly, stroke can be one of many after-effects of multiple syndromes caused by genetic mutation, such as sickle cell anemia. Fourthly, some common genetic variants are associated with increased stroke risk, such as genetic polymorphism in 9p21 [ 40]. A genome-wide association study of stroke showed high heritability (around 40%) for large blood vessel disease, and low heritability (16.7%) for small vessel disorders. Recent evidence suggests that studying heritability will improve the understanding of stroke sub-types, improve patient management and enable earlier and more efficient prognosis [ 5, 41].

4.2. Modifiable Risk Factors

These are of paramount importance, because timely and appropriate medical intervention can reduce the risk of stroke in susceptible individuals. The major modifiable risk factors for stroke are hypertension, diabetes, lack of physical exercise, alcohol and drug abuse, cholesterol, diet management and genetics.

Hypertension: It is one of the predominant risk factors for stroke. In one study, a blood pressure (BP) of at least 160/90 mmHg and a history of hypertension were considered equally important predispositions for stroke, with 54% of the stroke-affected population having these characteristics [ 42, 43]. BP and prevalence of stroke are correlated in both hypertensive and normal individuals. A study reported that a 5-6 mm Hg reduction in BP lowered the relative risk of stroke by 42% [ 44]. Randomized trials of interventions to reduce hypertension in people aged 60+ have shown similar results, lowering the incidences of symptoms of stroke by 36% and 42%, respectively [ 45, 46].

Diabetes: It doubles the risk of ischemic stroke and confers an approximately 20% higher mortality rate. Moreover, the prognosis for diabetic individuals after a stroke is worse than for non-diabetic patients, including higher rates of severe disability and slower recovery [ 47, 48]. Tight regulation of glycemic levels alone is ineffective; medical intervention plus behavioral modifications could help decrease the severity of stroke for diabetic individuals [ 49].

Alcohol and drug abuse: The relationship between stroke risk and alcohol intake follows a curvilinear pattern, with the risk related to the amount of alcohol consumed daily. Low to moderate consumption of alcohol (≤2 standard drinks daily for men and ≤1 for women) reduces stroke risk, whereas high intake increases it. In contrast, even low consumption of alcohol escalates the risk of hemorrhagic stroke [ 57, 58, 59]. Regular use of illegitimate substances such as cocaine, heroin, phencyclidine (PCP), lysergic acid diethylamide (LSD), cannabis/marijuana or amphetamines is related to increased risk of all subtypes of strokes [ 60]. Illicit drug use is a common predisposing factor for stroke among individuals aged below 35 years. US research showed that the proportion of illicit drug users among stroke patients aged 15-44 years was six times higher than among age-matched patients admitted with other serious conditions [ 61]. However, there is no strong evidence to confirm these findings, and the relationship between these drugs and stroke is anecdotal [ 62].

Smoking: Tobacco smoking is directly linked to increased risk of stroke. An average smoker has twice the chance of suffering from a stroke of a non-smoker. Smoking contributes to 15% of stroke-related mortality. Research suggests that an individual who stops smoking reduces the relative risk of stroke, while prolonged second-hand smoking confers a 30% elevation in the risk of stroke [ 63, 64, 65].

Insufficient physical inactivity and poor diet are associated with increased risk for stroke. Lack of exercise increases the chances of stroke attack in an individual. Insufficient physical activity is also linked to other health issues like high BP, obesity and diabetes, all conditions related to high stroke incidence [ 66, 67]. Poor diet influences the risk of stroke, contributing to hypertension, hyperlipidemia, obesity and diabetes. Certain dietary components are well known to heighten risk; for example, excessive salt intake is linked to high hypertension and stroke. Conversely, a diet high in fruit and vegetables (notably, the Mediterranean diet) has been shown to decrease the risk of stroke [ 68, 69, 70, 71, 72].

5. Animal Models of Stroke

Animal models usually used for research include induced, spontaneous, negative and orphan models. In the induced model, a disease condition is induced in the animal with a view to studying the effects, whereas in the spontaneous model, an animal is selected with a similar disease state naturally present in the model. Negative animal models are used to study the resistance mechanisms underlying a particular disease condition. Orphan models are deployed to understand the pathology of a newly characterized disease in human subjects [ 73, 74].

Many animal models have been developed to study the pathophysiology associated with stroke; they offer several advantages over studying stroke in humans or in vitro. The nature of stroke in humans is unpredictable, with diverse clinical manifestation and localization, whereas animal models are highly predictable and reproducible. Pathophysiological investigation often requires direct access to brain tissue, which is possible with animal models but not in humans. Moreover, current imaging techniques are unable to characterize events occurring within the first few minutes of a stroke. Finally, some aspects of stroke, such as vasculature and perfusion, cannot be studied in in vitro models [ 75]. Different stroke models used in animals are described in the session below ( Table 1).

Table 1.

Stroke Models

Advantages

Disadvantages

Intraluminal suture MCAo model

Mimics human ischemic stroke,
Exhibits a penumbra,
Highly reproducible,
No craniectomy

Hyper-/hypothermia,
Increased haemorrhage,
Not suitable for thrombolysis studies

Craniotomy model

High long-term survival rates,
Visual confirmation of successful MCAo

Highly invasive and procedural complications,
Requires surgical skills

Photo-thrombosis model

Enables well-defined localization of an ischemic lesion,
Highly reproducible,
Less invasive

Causes early vasogenic edema,
Not suitable for investigating neuroprotective agents

Endothelin-1 model

Less invasive,
Induction of ischemic lesion in cortical regions,
Low mortality

Duration of ischemia not controllable, Induction of astrocytosis and axonal sprouting

Embolic stroke model

Mimics the pathogenesis of human stroke

Low reproducibility of infarcts, Spontaneous recanalization

Neurorehabilitation

Rapid establishment of independence in activities of daily living
Improves outcomes for cognitive, language, and motor skills

Develop cost-effective rehabilitative services
Lack of in-depth studies on efficacy related to neurorehabilitation

Biomaterial testing

Reduction in lesion volume
Bridge the lesion with neural tissue for neural reorganization
Reduce secondary damage
Improve neurological behaviour

Long-term experiments with the same biomaterial are challenging because of the degradation of material which might affect the treatment

Photo-thrombosis model: This model is based on photo-oxidation of the vasculature leading to lesion formation in the cortex and striatum. In this method, the skull is irradiated with a photoactive dye that causes endothelial damage, intraparenchymal vessel aggregation and platelet stimulation in the affected area. It is injected intraperitoneally in mice and intravenously in rats [ 91]. This model is highly reproducible, with a low mortality rate and no surgery. The pathophysiology of this method is slightly different to that seen in human stroke due to little collateral blood flow or formation of ischemic penumbra. However, recent researchers modified the photothrombotic ischemia model to include hypoperfusion in an attempt to mimic penumbra. It has also been deployed in freely moving mice to evaluate the development of motor cortex ischemia and motor deficits. This model permits assessment of the ongoing infarction and improves our understanding of the neuronal insult and repair process [ 92, 93].

Neurorehabilitation in animal models: Various rehabilitative devices and forced training strategies have been deployed in stroke-affected animals to study neurological behavior. Robotic and electric devices have also been developed for training purposes in animal models to evaluate the functionality and effectiveness of the rehabilitation process. Similarly, forced exercise regimes, such as running on a treadmill or task-oriented motor training, are used to study rehabilitation scope in humans. Housing environments that provide social, motor and sensory stimuli and support cell engraftment, creating a more realistic approximation of human treatment, can be tested using animal models [ 103, 104, 105].

Animal models in biomaterial testing: Animal models have been well characterized for the study of brain tissues via brain atlases ( http://www.med.harvard.edu/AANLIB/, https://portal.brain-map.org) for the required species. Stereotaxic techniques are utilized to introduce biomaterials or cells into particular coordinates of the target tissue. Microlesions can be studied precisely, and targeted localization can be confirmed using magnetic resonance imaging (MRI)-based lesion cartography [ 106, 107, 108].

6. Prevention and Treatment Strategies for Stroke

Stroke prevention involves modifying risk factors within a population or individuals, while stroke management depends on treating its pathophysiology. Despite an enormous amount of research into stroke over the last two decades, no simple means of treating or preventing all the clinical causes of stroke has been established. The overall direction of current stroke research is to generate novel therapies that modulate factors leading to primary and secondary stroke. Recent and current strategies for stroke prevention and treatment are discussed below ( Figure 3).

Figure 3.

Stroke therapy. This represents the overall process to manage the incidence of stroke.

Excitotoxicity: Neuronal death is a key manifestation of stroke. A key reason for this phenomenon is neuronal depolarization and inability to maintain membrane potential within the cell. This process is mediated by glutamate receptors N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), which were among the first neuroprotective agents tested in stroke prevention. However, the untimely release of glutamate overpowers the system that removes glutamate from the cell and causes abnormal release of NMDA and AMPA molecules, leading to uninhibited calcium influx and protein damage. As a result, these agents have not been shown to reduce neuronal death in human subjects. Targeting the molecular pathways downstream of excitotoxicity signaling, rather than directly targeting glutamatergic signaling, might reduce the side effects of the process [ 109, 110].

Gamma aminobutyric acid (GABA) agonists: Clomethiazole is a GABA agonist that has been tested for its ability to improve stroke symptoms in patients, but failed to reduce the toxicity induced by the glutamate receptor [ 111].

Sodium (Na⁺) channel blockers: Na⁺ channel blockers have been used as neuroprotective agents in various animal models of stroke. They prevent neuronal death and reduce white matter damage. Many voltage-gated Na⁺ channel blockers have been tested in clinical trials, but most have proved to be ineffective [ 112]. Mexiletine is a neuroprotectant and Na⁺ channel blocker that proved effective in grey and white matter ischemic stroke, though further evaluation is required to confirm its role [ 113]. Lubeluzole was shown to reduce mortality in stroke in initial clinical trials, but successive trials failed to reproduce similar outcomes. Similarly, sipatrigine is a Na⁺ and Ca ²⁺channel blocker which failed in a Phase II clinical trial in stroke patients. Amiodarone was shown to aggravate brain injury due to defective transportation and accumulation of Na⁺ ions in the brain after stroke [ 114].

Calcium (Ca²⁺) channel blockers: Voltage-dependent Ca ²⁺ ion channel blockers have been shown to decrease the ischemic insult in animal models of brain injury. The Ca ²⁺ ion chelator DP-b99 proved efficient and safe in Phase I and II clinical trials when administered to stroke patients. Similarly, Phase II trials significantly improved clinical symptoms in stroke patients treated within 12 h of onset [ 115]. In another study, Ca ²⁺ channel blockers reduced the risk of stroke by 13.5% in comparison to diuretics and β-blockers [ 116].

6.1. Reperfusion

Intra-arterial thrombolysis (IAT): IAT is another approach designed to combat acute stroke. This treatment is most effective in the first six hours of onset of MCA occlusion, and requires experienced clinicians and angiographic techniques [ 115]. Prolyse in Acute Cerebral Thromboembolism II (PROACT II) and Middle Cerebral Artery Embolism Local Fibrinolytic Intervention (MELT) were randomized clinical trials (RCTs) undertaken to test the efficacy and safety of a recombinant pro-urokinase drug [ 126, 127], but did not produce any data useful for stroke treatment. Thrombolytics and glycoprotein IIb/IIIa antagonists were combined in two small clinical trials; this approach was helpful in treating atherosclerotic occlusions but less effective for cardioembolism [ 128, 129]. The Interventional Management of Stroke (IMS) III trial tested IVT and IAT together to assess the benefits of combining rapid administration of therapy (IVT) and a superior recanalization methodology for faster relief (IAT) [ 130]. The IMS III trial was fruitful with bridging therapy (combination of IVT and IAT) as compared to IVT alone. There was an increase of 69.6% in the recanalization rate using bridging therapy in stroke patients [ 131, 132].

Fibrinogen-depleting agents: Research has found a strong correlation between high fibrinogen levels in stroke patients and poor diagnosis for clinical outcomes. Fibrinogen-depleting agents decrease blood plasma levels of fibrinogen, hence reduce blood thickness and increase blood flow. They also remove the blood clot in the artery and restore blood flow in the affected regions of the brain. However, although some RCTs of defibrinogen therapy identified beneficial effects of fibrinogen-depleting agents in stroke patients, others failed to show positive effects on clinical outcomes after stroke [ 133]. Moreover, some studies reported bleeding after treatment with defibrinogen agents. Ancrod is a defibrinogenating agent derived from snake venom that has been studied for its ability to treat ischemic stroke within three hours of onset [ 134]. The European Stroke Treatment with Ancrod Trial (ESTAT) concluded that controlled administration of ancrod at 70 mg/dL fibrinogen was efficacious and safe, and achieved lower prevalence of ICH than observed at lower fibrinogen levels [ 135].

6.2. Others

Antihypertensive therapy: Hypertension is a risk factor for stroke. There are many reasons for high BP in stroke, including a history of hypertension, acute neuroendocrine stimulation, increased intracranial pressure, stress linked to hospital admission and intermittent painful spells [ 136]. Correct treatment of high BP during stroke is uncertain due to contradictory outcomes of clinical studies. Some research shows positive correlations between high BP and stroke-related mortality, hematoma expansion or intracerebral damage, suggesting that high BP should be treated. In other studies, low BP levels led to tissue perfusion and increased lesion size, thereby worsening the clinical outcome [ 137, 138]. The multi-center Acute Candesartan Cilexetil Therapy in Stroke Survivors (ACCESS) Phase II study proved that taking medication (candesartan) for BP during stroke was safe, with no orchestrated cerebrovascular events reported due to hypotension. Similar research has been performed with antihypertensive drugs, such as the Continue Or Stop post Stroke Antihypertensives Collaborative Study (COSSACS) to study the efficacy of antihypertensive therapy in stroke; the Control of Hypertension and Hypotension Immediately Post Stroke (CHHIPS) study, designed to determine the cut-off value for BP during an attack; and the Scandinavian Candesartan Acute Stroke Trial (SCAST), which aimed to measure the effectiveness of the drug candesartan on stroke and cardiovascular disease [ 115, 139]. In the COSSACS study, continuing antihypertensive drugs for a two-week period produced no extra harm as compared to stopping it and might be associated with reduced two-week mortality in patients with ischemic stroke [ 140]. The CHHIPS study demonstrated that a relatively moderate reduction in blood pressure lowered the mortality rate [ 141], whereas the SCAST study suggested that a careful BP-lowering treatment was associated with a higher risk of poor clinical outcome [ 142].

Glucose management: Hyperglycemia (elevated blood glucose) is common in stroke patients, so targeting blood glucose levels is an efficient stroke management strategy. Hyperglycemia > 6.0 mmol/L (108 mg/dL) is observed in most stroke patients; it initiates lipid peroxidation and cell lysis in compromised tissue, leading to stroke complications. An experimental study conducted in a rat model of collagenase-induced ICH found that hyperglycemia worsens edema formation and increases cell death, accelerating the course of ischemic injury. Increased blood glucose level is also associated with progression of infarction, reduced recanalization and poor clinical outcome [ 143]. Continuous glucose monitoring systems have been deployed to reduce stroke-related risks in both diabetic and non-diabetic stroke patients [ 144].

Antiplatelet therapy: This therapy is used for acute ischemic stroke management and for prevention of stroke incidence. It is also vital in controlling non-cardioembolic ischemic stroke and TIA. Antiplatelet agents like aspirin, clopidogrel and ticagrelor are the most widely used drugs administered to stroke sufferers within the first few days of attack [ 145]. Dual antiplatelet therapy, which involves a combination of clopidogrel, prasugrel or ticagrelor with aspirin, has become popular; many studies have tested the efficacy and safety of this dual therapy. It has been claimed that clopidogrel and aspirin combination therapy is most beneficial if introduced within 24 h of stroke and continued for 4-12 weeks [ 146].

Stem cell therapy: It offers promising therapeutic opportunities, safety and efficacy to stroke patients. Research on embryonic stem cells, mesenchymal cells and induced pluripotent stem cells has assessed their potential for tissue regeneration, maintenance, migration and proliferation, rewiring of neural circuitry and physical and behavioral rejuvenation [ 147]. Recently, a new type of mesenchymal stem cells (MSCs), called multilineage differentiating stress-enduring (Muse) cells, has been found in connective tissue. These cells offer great regenerative capacity and have been tested as a stroke treatment. After intravenous transplantation of Muse cells in a mouse model, they were found to engraft into the damaged host tissue and differentiate to provide functional recovery in the host [ 148]. Neovascularization is another mode of action of cell therapies in stroke; studies conducted in vitro and in vivo have shown that transplanted cells promote angiogenesis [ 149, 150]. Furthermore, multiple stroke studies have reported that MSCs stimulate neurogenesis; this was confirmed in human embryonic neural stem cells using BrdU-labelling [ 151, 152]. Stem cell therapy enhances the proliferation of neural stem cells and neuritogenesis [ 153]. Careful experimental design and clinical trials of stem cell therapies are likely to usher in a new era of treatment for stroke by promoting neurogenesis, rebuilding neural networks and boosting axonal growth and synaptogenesis.

Neural repair: This is an alternative therapy to neuroprotection. It is used to rejuvenate the tissue when the damage is already done and is therefore not time-bound but is most effective when administered 24 h after stroke attack. Many animal models have been used in attempts to stimulate neurogenesis and initiate the neuronal repair process [ 154]. Neural repair utilizes stem cell therapy to initiate repair mechanisms through cell integration into the wound or use of neurotrophic factors to block neuronal growth inhibitors. These cells may be channeled to any injured region to facilitate greater synaptic connectivity. Clinical trials using neural stem cells have proven beneficial in stroke patients. However, trials of myelin-associated glycoprotein, neurite outgrowth inhibitor (NOGO) proteins and chondroitin sulphate proteoglycans have shown these agents to be insufficiently effective; more clinical trials are required to increase treatment efficacy [ 155]. Biological intrusions may foster regeneration of newer cells, improve axonal guidance and enhance neural circuitry. Pharmacological and immunological interventions may target receptors to provide signaling cues for regeneration or block inhibitory factors in stroke-affected regions of the brain [ 156].

7. Trends in Stroke Research

The incidence of stroke-related emergencies has decreased substantially over recent years due to improved understanding of the pathophysiology of stroke and identification of new drugs designed to treat the multitude of possible targets. Technological advancements like telestroke [ 161] and mobile stroke [ 162] units have reduced mortality and morbidity. Therefore, stroke management systems should include post-stroke care facilities on top of existing primary care and access to occupational, speech or any physical therapy following hospital discharge. Hospitals should develop standardized policies to handle emergencies in a timely fashion to avoid casualties and prevent secondary stroke [ 163]. Recently, the role of physiotherapists has emerged as an important aspect of post-stroke care management. Physiotherapists have initiated clinical trials of stroke recovery processes and rehabilitation therapy sessions. One ongoing study includes a strategy to manage disability by improving mobility using treadmill exercise, electromechanical device therapy and circuit class therapy [ 164, 165]. Stroke Recovery and Rehabilitation Roundtables bring physiotherapists and other experts together to recommend research directions and produce guidance for the post-stroke healthcare system. Optimized delivery of stroke care systems and access to rehabilitation services are the future of healthcare for stroke [ 166].

Animal models used in stroke research reflect only a portion of the consequences of the condition in human subjects. Moreover, experiments conducted within a single laboratory are often constrained in terms of their research output. In vivo animal models of stroke should include aged populations to maximize their relevance, but most recent studies involve young and adult animals. Stroke studies should be conducted in both male and female subjects to exclude gender bias, and should take account of other confounders like hypertension, diabetes and obesity. All these issues make stroke research complex and expensive, and imply that it should be carried out collaboratively, across multiple labs. Ideally, an international multicenter platform for clinical trials would be established to increase the validity of research outcomes with respect to efficacy, safety, translational value, dose-response relationships and proof-of-principle. This strategy will help to overcome the current hurdles in transforming laboratory data into therapeutics for stroke.

Advancements in stem cell technologies and genomics have led to regenerative therapy to rebuild neural networks and repair damaged neurons due to ischemic insult [ 167, 168]. The WIP1 gene is a regulator of Wnt signaling and a promising target for drug development. Studies in mice models showed that knockdown of WIP1 downregulates the stroke functional recovery process after injury, and that the presence of this gene regulates neurogenesis through activation of β-Catenin/Wnt signaling [ 169]. Similarly, NB-3 (contactin-6) plays a vital role in neuroprotection, as shown by knockdown of NB-3 in mice after stroke attack. NB-3-deficient mice had increased brain damage after MCAo, which also affected neurite outgrowth and neuronal survival rate. NB-3 is believed to have therapeutic benefits for ischemic insult [ 170]. Therefore, WIP1 and NB-3 are promising candidates for future drug trials. This is a vast field, and more research must be conducted in the coming years to enable the development of therapeutic drugs.

Numerous natural compounds have proven to be beneficial for stroke prevention and treatment. They can be synthesized at a lower cost than synthetic compounds and offer competitive efficacy and safety. Honokiol is a natural product that showed neuroprotective effects in animal models, and appears to have a role in reducing oxidative stress and inhibiting inflammatory responses [ 171]. Gastrodin, a compound extracted from Gastrodia elata, is a promising candidate in stroke treatment. In a mouse model, it improved neurogenesis and activated β-Catenin-dependent Wnt signaling to provide neuroprotection after ischemic insult. It also has antioxidative effects which protects the neural progenitor cells from neuron functional impairment. Gastrodin's safety has been proved in clinical trials, hence it is an option for stroke management in the coming years [ 172].

The Utstein methodology is a process of standardizing and reporting research on out-of-hospital stroke and defining the essential elements of management tools. Its growing popularity led to the establishment of the Global Resuscitation Alliance (GRA), an organization that governs best practices. The primary aim of GRA is to facilitate stroke care from pre-hospital admission to rehabilitation and recovery. It has developed 10 guidelines to ensure smooth transitioning of services during and after attack. It has implemented a stroke registry, public awareness and educational programs, promoted techniques for early stroke recognition by first responders, sought to optimize prehospital and in-hospital stroke care, advocated the use of advanced neuroimaging techniques and promoted a culture of excellence. The Utstein community has developed comprehensive plans to improve early diagnosis and treatment of stroke patients globally [ 173].

Future clinical trials should aim not only to determine the efficacy and safety of drugs but to characterize recovery and clinical outcomes. Clinical trials of pharmacological therapies for post-stroke recovery should adhere to the following guidelines [ 174]. Patients should be enrolled within two weeks of stroke whenever possible. Studies should include sampling from a multicenter platform and include global scale criteria for data analysis. The underlying mechanism of action of the tested drugs on target molecules should be thoroughly understood. Secondary measurements like day-to-day progress of recovery, length of rehabilitation, treatment endpoint analysis and any other compounding factors should also be recorded. Overall, research on stoke management has advanced rapidly in recent years and is certain to make additional valuable discoveries through the application of new technologies in hypothesis-driven clinical trials.

8. Translational Challenges for the Current Stroke Therapeutic Strategies

Stroke research has seen fundamental advancements over recent years. The improvements in the selection of animal models, imaging techniques and methodological progress have led to immense drug targets and therapeutic interventions. In spite of this, the subsequent clinical trials failed to prove pre-clinical outcomes. Recanalization therapy showed some promising results in the clinical trials but only a small section of stroke patients benefited from this treatment [ 175]. Hence, the translational potential of stroke research is still under-investigated.

The key challenges that hinder the smooth transition of pre-clinical research into successful drugs include relevant endpoint selection, confounding diseases models like hypertension and diabetes, modelling age and gender effects in stroke patients, development of medical devices, investigating medical conditions that co-exist during stroke incidence, reproducibility of pre-clinical stroke research data and modelling functional and behavioral outcome [ 176, 177, 178]. Multiple causality of the stroke occurrence is another problem that is often over-looked. Homogeneity in stroke models to exhibit the broad spectrum of stroke pathophysiology associated with ischemic lesions or cortical or intracerebral damage is critical. Therefore, stroke animal models that target specific causes of stroke should be included. Latent interaction between comorbidities and stroke treatment should be identified to increase the safety and efficacy of the clinical outcome [ 179]. Short-term experimental trials often result in failed therapeutic development due to false-negative outcomes in the clinical settings [ 180]. Understanding the functional and behavioral output which might mislead true recovery is problematic in clinical trials wherein animal models have greater ability to mask the functional benefits [ 181]. This affects the affecting translational capability of the research. Adapting a combined approach to model recovery and rehabilitation is also important for successful transition.

One of the other problems with the clinical trials for stroke is the lack of efficient data management. The impact of large data generated from numerous clinical experiments is over-whelming and there should be a standardized system to manage such data. Moreover, these data should be deposited into a public data repository for easy access.

Industry and academic corroborations in stroke research are critical to improve the translational value [ 182]. A consensus between industry and academic interests is vital for successful transition. The industry collaborations are mostly monetary driven and have time constraints which might compromise the pre-clinical study protocol design, appropriate sample sizes and overestimation of treatment effects. IP protection and publication of research data may discord between these groups. A multicenter approach, long-term collaborations, effective project management, use of advanced methodologies and establishment of functional endpoints will probably advance the translational roadblocks in stroke research [ 183].

9. Conclusions

Stroke is the second leading cause of death and contributor to disability worldwide and has significant economic costs. Thus, more effective therapeutic interventions and improved post-stroke management are global health priorities. The last 25 years of stroke research has brought considerable progress with respect to animal experimental models, therapeutic drugs, clinical trials and post-stroke rehabilitation studies, but large gaps of knowledge about stroke treatment remain. Despite our increased understanding of stroke pathophysiology and the large number of studies targeting multiple pathways causing stroke, the inability to translate research into clinical settings has significantly hampered advances in stroke research. Most research has focused on restoring blood flow to the brain and minimizing neuronal deficits after ischemic insult. The major challenges for stroke investigators are to characterize the key mechanisms underlying therapies, generate reproducible data, perform multicenter pre-clinical trials and increase the translational value of their data before proceeding to clinical studies.

Author Contributions

Conceptualization, D.K.; writing-original draft preparation, D.K.; writing-review and editing, Z.X.; funding acquisition, Z.X. All authors have read and agreed to the published version of the manuscript.

Funding

This research and The APC was funded by Apex Biotech Research.

Conflicts of Interest

The authors declare no conflict of interest.

Footnotes

References

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Articles from International Journal of Molecular Sciences are provided here courtesy of Multidisciplinary Digital Publishing Institute (MDPI)

# data[].attributes.attachment_link.title
Pathophysiology and Treatment of Stroke: Present Status and Future Perspectives

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Stroke is the second leading cause of death and a major contributor to disability worldwide. The prevalence of stroke is highest in developing countries, with ischemic stroke being the most common type. Considerable progress has been made in our ...

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Summary

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Ischemic strokes result from events that limit or stop blood flow, such as extracranial or intracranial thrombotic embolism, thrombosis in situ, or relative hypoperfusion. As blood flow decreases, neurons cease functioning. Although a range of thresholds has been described, irreversible neuronal ischemia and injury is generally thought to begin at blood flow rates of less than 18 mL/100 g of tissue/min, with cell death occurring rapidly at rates below 10 mL/100 g of tissue/min

Risk factors

Risk factors for ischemic stroke include modifiable and nonmodifiable conditions. Identification of risk factors in each patient can uncover clues to the cause of the stroke and the most appropriate treatment and secondary prevention plan.

Nonmodifiable risk factors include the following (although there are likely many others):

In a prospective study of 27,860 women aged 45 years or older who were participating in the Women's Health Study, Kurth et al found that migraine with aura was a strong risk factor for any type of stroke. The adjusted incidence of this risk factor per 1000 women per year was similar to those of other known risk factors, including systolic blood pressure 180 mm Hg or higher, body mass index 35 kg/m2 or greater, history of diabetes, family history of myocardial infarction, and smoking.

For migraine with aura, the total incidence of stroke in the study was 4.3 per 1000 women per year, the incidence of ischemic stroke was 3.4 per 1000 per year, and the incidence of hemorrhagic stroke was 0.8 per 1000 per year.

Modifiable risk factors include the following:

Hypertension (the most important)

Cardiac disease: Atrial fibrillation, valvular disease, heart failure, mitral stenosis, structural anomalies allowing right-to-left shunting (eg, patent foramen ovale), and atrial and ventricular enlargement

Transient ischemic attacks (TIA)

Lifestyle issues: Excessive alcohol intake, tobacco use, illicit drug use, physical inactivity

Oral contraceptive use/postmenopausal hormone use

In 2014, the American Heart Association and the American Stroke Association issued guidelines for the reduction of stroke risk specifically in women. These gender-specific recommendations include the following:

Genetic and inflammatory mechanisms

Evidence continues to accumulate that inflammation and genetic factors have important roles in the development of atherosclerosis and, specifically, in stroke. According to the current paradigm, atherosclerosis is not a bland cholesterol storage disease, as previously thought, but a dynamic, chronic, inflammatory condition caused by a response to endothelial injury.

Traditional risk factors, such as oxidized low-density lipoprotein (LDL) cholesterol and smoking, contribute to this injury. It has been suggested, however, that infections may also contribute to endothelial injury and atherosclerosis.

Host genetic factors, moreover, may modify the response to these environmental challenges, although inherited risk for stroke is likely multigenic. Even so, specific single-gene disorders with stroke as a component of the phenotype demonstrate the potency of genetics in determining stroke risk.

A number of genes are known to increase susceptibility to ischemic stroke. Mutations to the F2 and F5 genes are relatively common in the general population and increase the risk of thrombosis. Mutations in the following genes also are known to increase the risk of stroke:
Hyperhomocysteinemia and homocystinuria
Hyperhomocysteinemia is implicated in the pathogenesis of ischemic stroke. The most common concern is mutations in the 5,10-methylenetetrahydrofolate reductase ( MTHFR) gene. In many populations, the mutant allele frequency reaches polymorphic proportions, and the risk factor for cerebrovascular disease is related to the serum level of homocysteine. Furthermore, in persons who are compound heterozygotes for MTHFR mutation, if elevated homocysteine is found it can be lowered with oral folic acid therapy.

In addition, hyperhomocysteinemia can be seen in cystathione beta synthetase (CBS) deficiency, which is generally referred to as homocystinuria. This disorder is inherited in an autosomal recessive manner. Symptoms usually manifest early in life. Patients have a marfanoid habitus, ectopia lentis, and myopia and generally have intellectual disability.

Thromboembolic events are the most common cause of death for patients with homocystinuria and may be of any type, including myocardial infarction. The risk of having a vascular event in homocystinuria is 50% by age 30.It was previously suggested that persons who are heterozygous for mutations in the CBS gene may have an increased risk of cerebrovascular disease as well, but several more recent studies on this subject failed to replicate this finding.
Amyloid angiopathies
Amyloid angiopathies are also known to increase risk for stroke and dementia. Mutations in the CST3 gene are causative and are inherited in an autosomal dominant manner. Sufferers will have diffuse deposition of amyloid, including in the brain. The onset of symptoms is typically in the third or fourth decade of life, with death occurring before age 60 years. These angiopathies appear to be most common in the Icelandic population.

Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy (CADASIL), is caused by mutations in the NOTCH3 gene. It affects the small arteries of the brain. Strokelike episodes typically occur at a mean age of 46 years, with an age range of 19-67 years. White-matter changes in the brain are typically evident by young adulthood and progress over time.

Migraine headaches occur in 30-40% of people with CADASIL. Approximately 60% of symptomatic individuals have cognitive deficits, which can start as early as age 35 years, and many develop multi-infarct dementia.
Other mutations
Genome-wide association studies have revealed additional loci that are commonly associated with ischemic stroke. Early onset ischemic stroke has been found to be associated with 2 single-nucleotide polymorphisms on 2q23.3.

Large-vessel stroke has been associated with variations in HDAC9, PITX2, and ZFHX3. HDAC9 is located on7p21.1, while PITX2 and ZFHX3 are located on 9p21. It is of note that the 9p21 locus has also been associated with cardiovascular disease.

A polymorphism at 2q36.3 was found in which adenosine substitution conferred a lower risk of ischemic stroke in an additive fashion.An additional study suggested an association between ischemic stroke and a locus on 12p13.

For more information, see Genetic and Inflammatory Mechanisms in Stroke. In addition, complete information on the following metabolic diseases and stroke can be found in the following main articles:

Large-artery occlusion

Large-artery occlusion typically results from embolization of atherosclerotic debris originating from the common or internal carotid arteries or from a cardiac source. A smaller number of large-artery occlusions may arise from plaque ulceration and in situ thrombosis. Large-vessel ischemic strokes more commonly affect the MCA territory, with the ACA territory affected to a lesser degree. (See the images below.)

Lacunar strokes

Lacunar strokes represent 13-20% of all ischemic strokes. They result from occlusion of the penetrating branches of the MCA, the lenticulostriate arteries, or the penetrating branches of the circle of Willis, vertebral artery, or basilar artery. The great majority of lacunar strokes are related to hypertension. (See the image below.)

Causes of lacunar infarcts include the following:

Embolic strokes

Cardiogenic emboli may account for up to 20% of acute strokes. Emboli may arise from the heart, the extracranial arteries, including the aortic arch or, rarely, the right-sided circulation (paradoxical emboli) with subsequent passage through a patent foramen ovale.Sources of cardiogenic emboli include the following:

Acute myocardial infarction is associated with a 2-3% incidence of embolic strokes, of which 85% occur in the first month after the infarction.Embolic strokes tend to have a sudden onset, and neuroimaging may demonstrate previous infarcts in several vascular territories or may show calcific emboli.

Cardioembolic strokes may be isolated, multiple and in a single hemisphere, or scattered and bilateral; the latter 2 types indicate multiple vascular distributions and are more specific for cardioembolism. Multiple and bilateral infarcts can be the result of embolic showers or recurrent emboli. Other possibilities for single and bilateral hemispheric infarctions include emboli originating from the aortic arch and diffuse thrombotic or inflammatory processes that can lead to multiple small-vessel occlusions. (See the image below.)

For more information, see Cardioembolic Stroke.

Thrombotic strokes

Thrombogenic factors may include injury to and loss of endothelial cells; this loss exposes the subendothelium and results in platelet activation by the subendothelium, activation of the clotting cascade, inhibition of fibrinolysis, and blood stasis. Thrombotic strokes are generally thought to originate on ruptured atherosclerotic plaques. Arterial stenosis can cause turbulent blood flow, which can promote thrombus formation; atherosclerosis (ie, ulcerated plaques); and platelet adherence. All cause the formation of blood clots that either embolize or occlude the artery.

Intracranial atherosclerosis may be the cause of thrombotic stroke in patients with widespread atherosclerosis. In other patients, especially younger patients, other causes should be considered, including the following:

Watershed infarcts

Vascular watershed, or border-zone, infarctions occur at the most distal areas between arterial territories. They are believed to be secondary to embolic phenomenon or to severe hypoperfusion, as occurs, for example, in carotid occlusion or prolonged hypotension. (See the image below.)

Flow disturbances

Stroke symptoms can result from inadequate cerebral blood flow because of decreased blood pressure (and specifically, decreased cerebral perfusion pressure) or as a result of hematologic hyperviscosity from sickle cell disease or other hematologic illnesses, such as multiple myeloma and polycythemia vera. In these instances, cerebral injury may occur in the presence of damage to other organ systems. For more information, see Blood Dyscrasias and Stroke.

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Acute ischemic stroke (AIS) is characterized by the sudden loss of blood circulation to an area of the brain, typically in a vascular territory, resulting in a corresponding loss of neurologic function. Also previously called cerebrovascular accident (CVA) or stroke syndrome, stroke is a nonspecific state of brain injury with neuronal dysfunc...

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Symptoms and Long Term Affects of Stroke

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Symptoms and Long Term Affects of Stroke

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Emotional and Behavioral Changes of Stroke

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Emotional and Behavioral Changes of Stroke

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Stroke commonly causes emotional and behavioral changes. Find resources to help manage mood, outlook and other changes post-stroke.

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Emotional and Personality Changes After Stroke

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Emotional and Personality Changes After Stroke

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Emotional and Personality Changes After Stroke

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Aphasia is a disorder that results from damage (usually from a stroke or traumatic brain injury) to areas of the brain that are responsible for language.

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Aphasia is a language disorder that affects your ability to communicate. Learn about the types of aphasia and find tips to help you manage its effects.

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Time is Brain: Stroke Treatment from Emergency Care to Recovery

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Download the Finances After Stroke Guide and learn about Social Security Administration benefits and programs, the Patient Advocate Foundation, and more.

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Australian Government Department of Health, Disability and Ageing

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Private health insurance provides cover for health care not covered by Medicare such as physiotherapy and glasses. Depending on the policy you take out, it might let you have treatment in hospital as a private patient.

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US Insurance Plan Coverage Ranking - Stroke

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✉Dr. Devereux may be contacted at nancy.devereuxchristianacare.org. ✉Corresponding author.

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Evaluation & Treatment of Psychological Effects of Stroke

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Strokes are a common medical condition in the United States, including in Delaware. An under-recognized effect of stroke is the impact on mood that often occurs. Many individuals develop depression, anxiety, PTSD, and other psychological sequelae.…

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Psychological and Social Challeges After Stroke

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Psychological and Social Challeges After Stroke

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Psychological and social challenges after a stroke

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The Social Worker and The Stroke Patient.

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The Social Worker and The Stroke Patient.

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✉Ms. McDermott may be contacted at amcdermottche-east.org. ✉Corresponding author.

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The Social Worker in The Care of The Stroke Patient

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As a leading cause of death and long-term disability, stroke care is a complex endeavor, requiring a coalition of healthcare professionals. As part of a multi-disciplinary team, social workers help the patient to reach individual goals and…

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Providers for psychological and social challenges after stroke

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When an area of the brain is damaged, which typically occurs with a stroke, an impairment may result. An impairment is the loss of normal function of part of the body. Sometimes, an impairment may result in a disability, or inability to perform an activity in a normal way.

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Dysphagia affects the vast majority of acute stroke patients. Although it improves within 2 weeks for most, some face longstanding swallowing problems that place them at risk for pneumonia, malnutrition, dehydration, and significantly affect quality…

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Dysphagia - Diagnosis and treatment - Mayo Clinic

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Having trouble swallowing? Learn more about what causes this common issue, along with therapies for treating the condition.

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Effects of Stroke: Physical, Cognitive and Emotional

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Effects of Stroke: Physical, Cognitive and Emotional

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Long-term effects of stroke can include physical effects, cognitive effects, personality changes, and emotional effects. Different kinds of therapy can help with recovery after a stroke.

A stroke occurs when there is a blood clot or bleeding in a blood vessel, blocking blood flow to the brain. It can affect people of any age and can cause long-term complications. Recovery is possible but depends on the stroke's severity and a person's overall health.

Read on to learn about the long-term effects of stroke and what recovery involves.

Learn more about stroke.

There are various long-term physical effects of a stroke. They include the below.

Paralysis refers to the loss of voluntary muscle movement. It usually occurs on the side of the body opposite to the side of the brain that the stroke has damaged. Therefore, a person who has experienced a left hemisphere stroke may have impaired muscle movement on the right side of their body.

In some cases, paralysis can be severe. An example of severe paralysis is locked-in syndrome, a neurological disorder that occurs when there is damage in the brainstem. It can develop following a hemorrhagic stroke, which involves brain damage from bleeding in the brain, or an ischemic stroke, when the body stops supplying blood to the brain.

People with locked-in syndrome are usually aware of what is happening around them but cannot speak, move, or show facial expressions. They can only communicate through eye movements or blinking.

Sensory loss

Those with sensory loss may no longer be sensitive to touch, pain, or temperature. They may also be unable to recognize what object they are holding. Limb numbness is also common.

Another example of sensory disturbance that occurs in people who have had a stroke is reduced bowel control. People may have difficulty controlling bowel movements and reaching the restroom on time.

Some individuals may also receive a diagnosis of chronic pain syndrome, which results from muscle weakness. This is common in people who have not moved their joints for a long time.

According to a 2018 review, persistent headaches can affect of people who have experienced an ischemic or hemorrhagic stroke. Persistent headache is more common in females and people with:

A 2020 review considers headaches after a stroke to be a type of chronic post-stroke pain.

Depression

People with post-stroke depression may experience:

Doctors may prescribe antidepressants or anti-anxiety drugs to treat post-stroke anxiety. However, there is limited research on how a person can manage anxiety after a stroke.

Long-term cognitive effects of a stroke include the below.

It can be difficult for a person to be independent with vascular dementia. However, doctors may suggest the following steps to help manage symptoms:

taking notes or creating to-do lists

consulting a speech therapist

participating in social groups with people who have the same health condition

Aphasia is a language disorder that results from damage to a specific area in the brain that controls language expression, reading, and writing. It can develop after a stroke, head injury, or due to a brain tumor.

The CDC estimates that 1 in 4 people who have had a stroke will develop another within 5 years. It highlights the importance of treating the health problems responsible for these events. These health issues include high blood pressure, diabetes, and atrial fibrillation, which refers to an irregular heart rhythm.

The CDC also states that recovery is possible after a stroke, but lingering difficulties, such as paralysis or trouble speaking, may remain.

Some people may also experience mental health conditions after a stroke. A therapist may be able to help a person adjust to the new changes in their life.

People who have had a stroke may find it helpful to join a support group to meet others who have also had a stroke.

Support from a caregiving family member, friend, or healthcare professional may also be beneficial. A caregiver can facilitate communication with the hospital team. They may also arrange for transportation and therapy and help manage medications.

A stroke can cause several long-term problems, such as memory loss, loss of movement, muscle weakness, or speech problems.

People who have had a stroke are also more likely to have another later in life.

Rehabilitation can help people regain their movements and confidence, but their progress may depend on the person and type of stroke.

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Long-term effects of stroke: Physical, emotional, cognitive, and more

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Stroke can have several long-term effects, including physical, emotional, and cognitive changes in a person. Learn more about them and life after a stroke here.

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Summary

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Diversity of approaches in assessment of executive functions in stroke: Limited evidence?

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Stroke is a leading cause of disability worldwide. Cognitive functions and, in particular, executive function, are commonly affected after stroke, leading to impairments in performance of daily activities, decrease in social participation and in…

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Summary

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Stroke Recovery and Speech Therapy Exercises

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Stroke Recovery and Speech Therapy Exercises

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10 Best Stroke Recovery Speech Therapy Exercises

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10 Best Stroke Recovery Speech Therapy Exercises

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A Comprehensive Guide to the Risks, Symptoms, & Effects of a Stroke & 10 Best Speech Therapy Exercises for Stroke Recovery. Free Phone Consultation.

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Summary

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Speech and Swallowing Therapy – IHT Rehab

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Stroke and the Speech Language Therapist (SLT)

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Stroke and the Speech Language Therapist (SLT)

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Summary

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Summary

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Regional Differences in African Americans and Risk for Stroke

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Regional Differences in African Americans and Risk for Stroke

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Regional Differences in African Americans' High Risk for Stroke: The Remarkable Burden of Stroke for Southern African Americans

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The stroke mortality rate for African Americans aged 45-64 is three to four times higher than for whites of the same age, with a decreasing black-to-white mortality ratio with increasing age. There is also a "Stroke Belt" with higher stroke ...

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Knowledge and Awareness of Stroke among the Elderly Population: Analysis of Data from a Sample of Older Adults in a Developing Country

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Background and Objectives: Stroke prevention has traditionally concentrated on research to improve knowledge and awareness of the disease in the general population. Since stroke incidents increase with age, there is a need to focus on the elderly, a…

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Why Are The Elderly and African Americans Affected by Stroke?

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Why Are The Elderly and African Americans Affected by Stroke?

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The Elderly and African Americans are disproportionately affected by stroke

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Racial- Ethnic Disparities in Stroke Care

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Racial- Ethnic Disparities in Stroke Care

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Elderly and African American and Stroke Care

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Elderly and African American and Stroke Care

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Summary

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Elderly_African Americans and Sroke Care

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You can help prevent stroke by making healthy lifestyle choices.

Talk with your doctor about steps you can take to lower your risk for stroke.

Overview

Many strokes can be prevented through healthy lifestyle changes and working with your health care team to control health conditions that raise your risk for stroke.

You can help prevent stroke by making healthy lifestyle choices.

Take Action and Get Inspired‎

Prevention steps and strategies

Choose healthy foods and drinks

Choosing healthy meal and snack options can help you prevent stroke. Be sure to eat plenty of fresh fruits and vegetables.

Eating foods low in saturated fats, trans fat, and cholesterol and high in fiber can help prevent high cholesterol. Limiting salt ( sodium) in your diet can also lower your blood pressure. High cholesterol and high blood pressure increase your chances of having a stroke.

For more information on healthy diet and nutrition, see CDC's Nutrition website.

Keep a healthy weight

Having overweight or obesity increases your risk for stroke. To determine whether your weight is in a healthy range, doctors often calculate your body mass index (BMI). If you know your weight and height, you can calculate your BMI at CDC's Assessing Your Weight website. Doctors sometimes also use waist and hip measurements to measure excess body fat.

Get regular physical activity

Physical activity can help you stay at a healthy weight and lower your cholesterol and blood pressure levels. For adults, the surgeon general recommends 2 hours and 30 minutes of moderate-intensity aerobic physical activity, such as a brisk walk, each week. Children and teens should get 1 hour of physical activity every day.

Find inspiration and tips for getting regular physical activity from the "Live to the Beat" campaign.

Don't smoke

Cigarette smoking greatly increases your chances of having a stroke. If you don't smoke, don't start. If you do smoke, quitting will lower your risk for stroke. Your doctor can suggest ways to help you quit.

For more information about tobacco use and quitting, see CDC's Smoking & Tobacco Use website.

Limit alcohol

Avoid drinking too much alcohol, which can raise your blood pressure. Men should have no more than two drinks per day, and women should have no more than one per day. For more information, visit CDC's Alcohol and Public Health website.

Control your medical conditions

Talk with your doctor about steps you can take to lower your risk for stroke.

If you have heart disease, high cholesterol, high blood pressure, or diabetes, you can take steps to lower your risk for stroke.

Check cholesterol

Your doctor should test your cholesterol levels at least once every 5 years. Talk with your health care team about this simple blood test. If you have high cholesterol, medicine and lifestyle changes can help lower your risk for stroke.

Control blood pressure

High blood pressure usually has no symptoms, so be sure to have it checked on a regular basis. Talk to your health care team about how often you should check your levels. You can check your blood pressure at home, at a doctor's office, or at a pharmacy.

If you have high blood pressure, your doctor might prescribe medicine, suggest some changes in your lifestyle, or recommend that you choose foods with lower sodium (salt).

Control diabetes

If your doctor thinks you have symptoms of diabetes, he or she may recommend that you get tested. If you have diabetes, check your blood sugar levels regularly.

Talk with your health care team about treatment options. Your doctor may recommend certain lifestyle changes, such as getting more physical activity or choosing healthier foods. These actions will help keep your blood sugar under control and help lower your risk for stroke.

Treat heart disease

If you have certain heart conditions, such as coronary artery disease or atrial fibrillation (irregular heartbeat), your health care team may recommend medical treatment or surgery. Taking care of heart problems can help prevent stroke.

Take your medicine

If you take medicine to treat heart disease, high cholesterol, high blood pressure, or diabetes, follow your doctor's instructions carefully. Always ask questions if you don't understand something. Never stop taking your medicine without first talking to your doctor or pharmacist.

Work with your health care team

You and your health care team can work together to prevent or treat the medical conditions that lead to stroke. Discuss your treatment plan regularly, and bring a list of questions to your appointments. Learn how to find the right doctor for you from the "Live to the Beat" campaign.

If you've already had a stroke or transient ischemic attack (TIA), your health care team will work with you to prevent further strokes. Your treatment plan will include medicine or surgery and lifestyle changes to lower your risk for another stroke. Be sure to take your medicine as directed and follow your doctor's instructions.

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Prevent stroke by making healthy living choices and managing your health conditions, such as high cholesterol and high blood pressure.

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Stroke Prevention Through Dietary Changes

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Summary

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Lifestyle Modification and Stroke Prevention

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Lifestyle Modification and Stroke Prevention

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Abstract

Of nearly 800 000 strokes that occur annually, 23% are recurrent events. Risk for disability and mortality is higher following a recurrent stroke than following a first-time stroke, which makes secondary stroke prevention a priority. Many risk factors for stroke are modifiable and amenable to improvement through lifestyle modification. Lifestyle modification can be difficult for people with stroke, however, in part because of stroke-related physical and cognitive deficits. Despite these challenges, risk factor management through lifestyle modification is important. This article reviews the multiple cardiovascular and metabolic benefits associated with the modification of several lifestyle behaviors: diet, physical activity, smoking cessation, and alcohol consumption. Health behavior theories and existing lifestyle intervention programs are also reviewed to identify important behavioral and cognitive skills that can be used to facilitate modification of health behaviors, and practical skills and suggestions for health care providers are provided.

Keywords: stroke, secondary prevention, diet, physical activity, smoking cessation, alcohol consumption

'Although risk factor management through pharmacological intervention is often necessary, polypharmacy can result in a high treatment burden for people with stroke and carries added risk for morbidity and mortality.'

Introduction

A history of having a prior stroke increases the risk for experiencing a future stroke and concomitant mortality and disability. Of the 795 000 strokes that occur annually, 185 000 (23%) are recurrent events. Following a first-time stroke, the estimated risk for stroke recurrence is 13% to 16% within the first year and 4% every year thereafter. This results in an elevated risk of 30% by 5 years and 43% by 10 years. In addition to these population-level risks, the impact of stroke recurrence on individuals can be severe. The risk of death in the 30 days following a recurrent stroke ranges from 23% to 41%, and the risk of new disability ranges from 39% to 53%. Such increased risk for mortality and disability should make secondary stroke prevention a priority, which can be addressed in part through risk factor management.

Risk Factors in People With Stroke

Although secondary stroke prevention through risk factor management has not been extensively studied, the evidence for primary stroke prevention is strong. It is generally accepted that risk factors for first-ever and recurrent ischemic stroke are the same ( Table 1). Many modifiable risk factors occur in people with stroke and often go unmanaged. In one sample of community-dwelling adults with stroke, 99% had 1 unmanaged risk factor, and 91% had 2 or more unmanaged risk factors. This is concerning because risk for cardiovascular mortality is 1.6 and 3.1 times higher in people with 1 and 2 unmanaged risk factors, respectively, compared with people with managed risk factors. Risk factor management is, therefore, important for people with stroke.

Table 1.

● Increasing age: risk doubles every 10 years after the age of 55 years
● Gender: women have a higher lifetime risk for stroke than men
● Race and ethnicity: incidence is higher in Blacks, Hispanics, American Indians, and Alaska natives than Whites or Asians
● Family history: possibly related to genetics and shared environmental and lifestyle influences
● Prior stroke: 10-year risk of recurrence is 43%

● Hypertension: systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg
● Hypercholesterolemia: low-density lipoprotein ≥100 mg/dL
● Obesity: body mass index ≥30 kg/m ²
● Physical inactivity: <30-60 minutes of aerobic activity 3-5 times per week
● Diabetes
● Smoking
● Heavy alcohol consumption: >2 drinks for men and >1 for women per day

Lifestyle Modification

Although risk factor management through pharmacological intervention is often necessary, polypharmacy can result in a high treatment burden for people with stroke and carries added risk for morbidity and mortality. In recent years, the American Heart Association has published numerous guidelines directed at health care professionals for the management of cardiovascular risk factors, primary stroke prevention, acute management of stroke, and secondary stroke prevention. Each of these guidelines has identified lifestyle modification as a core component of risk factor management that should be implemented as part of comprehensive poststroke care.

Lifestyle modification can lead to improvements in hypertension, hypercholesterolemia, obesity, and glucose metabolism in diabetics, which are in turn associated with decreased risk for cardiovascular disease and death. In fact, the rate of cardiovascular mortality in people with stroke over a 10-year period can be reduced by 85% to 92% by engaging in lifestyle behaviors such as eating sufficient fruits and vegetables, exercising, maintaining a body mass index between 18.5 and 29.9 kg/m ², moderate alcohol consumption, and not smoking. Clearly, modification of lifestyle behaviors is important for secondary stroke prevention. The sections below will explore how modification of individual lifestyle behaviors can affect multiple risk factors.

Diet

Consuming a healthy diet is important for cardiovascular health and stroke prevention. In 2013, the American College of Cardiology and American Heart Association published lifestyle management guidelines to reduce cardiovascular risk. The dietary recommendations are consistent with DASH- and Mediterranean-style dietary patterns, which are effective in reducing the risk of stroke. The recommendations encourage the intake of fruits, vegetables, whole grains, low-fat dairy products, poultry, fish, legumes, vegetable oils, and nuts; limited consumption of sweets, sweetened-beverages, and red meats; and reduced sodium intake.

Multiple benefits from adhering to these dietary patterns have been observed. Blood pressure and low-density lipoprotein (LDL) cholesterol can be reduced. Improved glycemic control and insulin sensitivity occurred in diabetics. Weight loss resulted in decreased rates of obesity, which is important because of the strong relationship between obesity and stroke. Another important dietary consideration is calorie intake. Reduction of daily caloric intake by 20% to 25% for 3 months or longer in obese and nonobese individuals resulted in improved blood pressure, LDL cholesterol and triglycerides, insulin resistance, and glycemic control. Selecting healthy foods and consuming appropriate amounts can positively affect risk factors for recurrent stroke.

Physical Activity

Physical inactivity is a significant risk factor for stroke. Unfortunately, people with stroke spend up to 86% to 88% of their time in sedentary activity compared with 57% to 72% in adults without stroke. One reason for decreased physical activity after stroke is diminished exercise capacity, as measured by maximal oxygen uptake (ie, VO 2max). The amount of oxygen consumed during routine walking in people with stroke is twice that of adults without stroke; and performance of self-care activities such as bathing, grooming, and dressing after stroke can require individuals to exert 66% to 75% or more of their total exercise capacity. This illustrates how once-simple tasks become challenging after stroke. Additional barriers to physical activity after stroke include deconditioning, depression, inaccessible environments (eg, wheelchair-friendly transportation and gym equipment), low motivation, poor social support, and physical impairment.

Despite these challenges, physical activity is critical. Moderate to vigorous physical activity for primary stroke prevention leads to decreased blood pressure, LDL cholesterol, and weight gain and increased weight loss. It also results in increased glucose uptake and insulin sensitivity in people with and without diabetes. For people with stroke, exercise training can improve hypertension, lipid profiles, glucose metabolism, and insulin sensitivity. These latter improvements are important because up to 80% of people with stroke experience abnormal glucose metabolism. Additional benefits of exercise training after stroke include improved balance, gait speed, and endurance and decreased disability.

Because of the challenges associated with deconditioning and physical impairment after stroke, the American Heart and American Stroke Associations have established guidelines for health care professionals that outline physical activity and exercise recommendations after stroke (summarized in Table 2). In addition to increasing physical activity, sitting and other sedentary behaviors should be reduced by performing more light-intensity, nonexercise physical activity, such as standing and walking. Important considerations for increasing physical activity after stroke include cardiac and stress testing for high-risk individuals and supervision by a trained professional when initiating a new exercise program. Physical and occupational therapists should be involved in designing physical activity programs after stroke because these professionals have the necessary training and experience to teach people with stroke how to safely increase physical activity levels.

Table 2.

● Important considerations

○ A health care professional should supervise initiation of a physical activity program

○ Individuals at risk for cardiovascular events should undergo cardiac stress testing

○ Heart rate and perceived exertion should be regularly monitored during physical activity

● Aerobic activity

○ Duration and frequency: 20- to 60-minute sessions, 3-5 d/wk

○ Target: 55%-80% of maximum heart rate or perceived exertion of "light" to "somewhat hard"

○ Multiple short sessions (eg, 10 minutes) to build tolerance and endurance are encouraged

● Strength training

○ Amount and frequency: 1-3 sets of 10-15 repetitions targeting large muscle groups, 2-3 d/wk

○ Target: 50%-80% of 1 repetition maximum

● Nonexercise physical activity

○ Reduce sedentary time by standing and walking more often

○ Examples: stand during tasks that could be completed sitting, reduce time viewing television, go for more frequent walks, use the stairs

Smoking

The risk for first ischemic stroke in smokers is nearly 4 times the risk in nonsmokers. Although information on the risk for recurrent stroke is limited, one study demonstrated that the risk of recurrent stroke in elderly smokers was double that of nonsmokers. Smoking results in acute increases in heart rate, blood pressure, and arterial stiffness, which are especially dangerous for individuals with hypertension. Furthermore, smoking is associated with insulin resistance and dyslipidemia.

Smoking cessation, however, can lessen the risk for stroke. Smokers who quit reduce their risk for ischemic stroke by half, and smokers with hypertension who quit experience a greater benefit compared with smokers without hypertension. Chronic smokers who quit smoking experience decreased blood pressure, heart rate, and arterial stiffness and increased high-density lipoprotein (HDL) cholesterol. Additionally, diabetic smokers who stop smoking experience improved glycemic control, blood pressure, LDL cholesterol, and insulin resistance. Because of the multiple risk factors that can be improved through smoking cessation, people with stroke who smoke, and especially those with hypertension, should be given encouragement and resources to stop.

Alcohol Consumption

Heavy alcohol consumption increases the risk for first-ever and recurrent stroke. Although the exact mechanisms are unknown, heavy alcohol consumption is associated with increased risk for hypertension and diabetes, which are major risk factors for stroke and cardiovascular disease.

Low to moderate alcohol consumption, defined as ≤2 drinks for men and ≤1 drink for women daily, is associated with reduced risk for first-ever stroke. Although further research is needed, it is possible that low alcohol consumption may reduce cardiovascular risk by decreasing hypertension or increasing HDL cholesterol. Reducing current levels of alcohol consumption can lead to decreases in blood pressure, with greater reductions occurring in individuals with higher pressures, which has important implications for reducing stroke risk in hypertensive individuals. Additionally, the incidence of diabetes is lower in individuals with low alcohol consumption than in those with heavy consumption. Notwithstanding these potential benefits, the American Heart and Stroke Associations do not currently recommend drinking alcohol to gain cardiovascular benefits.

As observed with other health behaviors, modifying the amount of alcohol consumed can influence multiple risk factors for cardiovascular disease. This makes alcohol consumption a potential target for secondary stroke prevention. Because of the risk for alcohol dependence, however, individuals who do not drink should not be encouraged to drink.

Lifestyle Behavior Intervention

Behavior change is challenging and often difficult to sustain because of complex personal, environmental, and social factors. Health behavior theories have been developed to explain how these factors influence the adoption and modification of specific health behaviors, and intervention programs have been developed that utilize these theories to help patients modify lifestyle behaviors across patient populations and settings.

Barriers

A common barrier to behavior change for patients is limited insight, knowledge, and awareness of how lifestyle factors contribute to risk for subsequent stroke. If patients do not perceive a need to modify lifestyle behaviors, then behavior modification is unlikely. Even when patients understand the need to modify their behavior, knowledge rarely translates into behavior change because additional barriers exist. Limited self-efficacy (ie, one's self-confidence in one's ability to carry out a specific action), social support, outcome expectations, and motivation, among other factors, must also be considered. Additionally, physical, cognitive, and emotional conditions, including depression, are common after stroke and affect a patient's ability to enact lifestyle modifications.

Health Behavior Theories

Several theories have been proposed to explain how health behaviors are acquired and how barriers to lifestyle modification can be overcome. Well-known theories include the Social Cognitive Theory and the Transtheoretical Model. Social Cognitive Theory posits that health behaviors are influenced by interactions among environmental, social, and personal (eg, cognition, affect, biology) factors. Self-efficacy is the main component of the theory and often targeted for intervention by helping patients set small, achievable goals and helping patients observe and learn from their peers. Self-regulation strategies can also be utilized to enhance self-efficacy and promote lifestyle modification. Examples of self-regulatory strategies include systematic observation of one's behaviors (ie, self-monitoring using a food or exercise log), self-reward, enlistment of social support, and modification of social and physical environments to facilitate specific behaviors.

The Transtheoretical Model, also called the Stages of Change Model, describes behavior modification in terms of 5 stages of motivational readiness to change behavior. In the first 2 stages-precontemplation and contemplation-behavior change may be absent or considered, respectively. In the 3 remaining stages-preparation, action, and maintenance-behavior change has been attempted, implemented, or maintained, respectively. Several cognitive and behavioral strategies have been developed to help individuals modify health behaviors by progressing between stages. Examples of these strategies include increasing awareness about a person's behavior with respect to a given health condition, assessing how one feels the benefits and costs of behavior change, learning to substitute healthy behaviors for unhealthy behaviors, enlisting social support, and removing stimuli of unhealthy behaviors while adding stimuli of healthy behaviors.

Lifestyle Modification Programs

Several lifestyle modification programs for managing cardiovascular risk factors have been developed and successfully implemented that utilize elements from Social Cognitive Theory and the Transtheoretical Model. The EUROACTION program for patients with coronary heart disease and their families consisted of 8 weekly instructional workshops taught by nurses. Lifestyle behaviors and risk factors were addressed, including diet, physical activity, and smoking, using strategies from the Transtheoretical Model to help patients increase self-awareness and self-regulation of lifestyle behaviors. Following the intervention, improvements in waist circumference, blood pressure, blood cholesterol, dietary targets, and physical activity targets were observed. In the GOSPEL study for secondary prevention of myocardial infarction, participants received one-on-one counseling by a cardiac nurse, physiotherapist, and cardiologist. The intervention consisted of lifestyle and risk counseling, preventive interventions, supervised exercise, and pharmacological treatment. Visits lasted 2 hours and were held once a month for the first 6 months, then every 6 months for 3 years, and family support was encouraged. At the end of the 3-year study, cardiovascular mortality and prescription of cardioprotective medications were reduced, and lifestyle behaviors (eg, exercise, diet, stress management, body weight) were improved.

A comprehensive lifestyle health coaching program (ie, INTERVENT) administered in clinical and community-based settings has also been effective in cardiovascular disease risk reduction. This program is delivered mainly over the telephone and internet and lasts for a minimum of 1 year. Trained health coaches follow a standardized program to help participants set behavior change goals, develop action plans, and implement action plans. Health coaching consists of one-on-one counseling sessions that last for 15 to 20 minutes, where participants are taught cognitive and behavioral strategies (eg, increasing knowledge, risk awareness, and self-efficacy and developing skills in self-monitoring, enlisting social support, and controlling stimuli). This program has been successfully delivered in hospitals, physician practices, work sites, and health centers and has led to improvements in blood pressure, cholesterol, weight, and cardiorespiratory function. The program has also been utilized in randomized controlled trials for primary (ie, CREST-2) and secondary (ie, SAMMPRIS) stroke prevention.

Clinical Applications

The programs described above demonstrate the importance of intensive, long-term interventions that involve family and social support and that provide participants with the necessary knowledge, skills, and strategies for successful health behavior modification. For busy clinical practices, the time required to implement intensive health behavior interventions may be a barrier. Additional barriers include limited reimbursement for preventive services, low outcome expectations that patients will comply with behavior prescriptions, and lack of provider self-efficacy in providing lifestyle intervention counseling. Even though these factors are real barriers for providers, clinical guidelines are explicit about lifestyle modification for the prevention of cardiovascular disease and stroke. Suggestions for implementing clinical guidelines in the face of provider-related barriers are given below.

Meet the Patient "Where They're At"

Although physicians and other health care providers are recognized as health experts, patients often resist being told what to do. Therefore, it is important to meet patients "where they're at" and provide them with information that is consistent with their current level of motivation. One strategy for doing so is to utilize motivational interviewing. Motivational interviewing is a patient-centered, collaborative approach to help patients become aware of their values and priorities, understand how current health behaviors act as barriers to or facilitators of values and priorities, and generate action plans for changing health behaviors. Motivational interviewing has been extensively studied in the context of diet and physical activity. In meeting patients at their current level of readiness to change behavior, patients may be less resistant and more open to discussing strategies for modifying lifestyle behaviors.

Provide Opportunities for Skills Training

Once patients are aware of the need to modify lifestyle behaviors and are willing to discuss strategies for behavior change, they must be given the opportunity to develop skills to ensure success. In addition to learning the cognitive and behavioral skills outlined in Social Cognitive Theory and the Transtheoretical Model, patients may also need to learn skills for performing specific health behaviors (eg, reading a nutrition label, preparing a meal, using gym equipment). It is unreasonable to expect that any one health care provider will be an expert in all these skills. One option, therefore, is to refer patients to commercial lifestyle behavior programs, such as those described in this article. Programs that are phone- or internet-based may be especially important for people with stroke, where stroke-related impairments may impede transportation.

Another option is to implement a multidisciplinary, team-based approach to managing health behaviors. Following an initial consultation with a physician, more intensive skills training and lifestyle counseling may be delegated to a nurse or health coach who works in a physician practice. In cases where patients require more specialized intervention, referral to a health psychologist may be appropriate. Physicians may also refer patients to physical therapy for the design and implementation of a home exercise program, a dietitian for education and training in selecting appropriate foods, and occupational therapy for skills training in meal preparation, increasing nonexercise physical activity, using adaptive equipment, and implementing compensatory strategies to overcome physical and cognitive impairments.

Patients may also learn skills from their peers, as emphasized by Social Learning Theory. Thus, participation in social groups that bring stroke survivors together may be beneficial. Stroke groups can be found using the American Stroke Association's Stroke Support Group Registry: http://www.strokeassociation.org/STROKEORG/strokegroup/public/zipFinder.jsp.

Review Progress

Reviewing progress at regular intervals with patients can be an important way to provide feedback on patients' behavior change efforts. In the same way that self-monitoring provides feedback to patients about their behavior, reviewing progress during regularly scheduled appointments allows providers to provide feedback. Follow-up appointments also give patients the opportunity to discuss challenges to behavior change with providers, which may lead to much needed interventions or referrals.

Just as when initiating a conversation about behavior change, it is important to provide feedback that is consistent with a patient's current level of readiness for behavior change. When patients are not aware of or are just beginning to think about the need to modify health behaviors, general feedback on the benefits of behavior change is appropriate. When patients are ready to make a change or are actively changing their behaviors, targeted feedback with specific information can be shared. Regardless of the feedback provided, the manner in which it is provided should be positive, genuine, and empathetic.

Opportunities for Future Research

There are many opportunities for future research on secondary stroke prevention through lifestyle modification. Few large-scale randomized controlled trials have been conducted that examine secondary stroke prevention as the primary outcome; for practical reasons, cardiovascular risk reduction has been the main outcome of interest. Small, nonrandomized studies have demonstrated an improvement in health behaviors and cardiovascular risk factors, but sample sizes have been too small to detect a reduction in stroke recurrence. Large-scale, randomized trials of lifestyle interventions for secondary stroke prevention are needed.

Effectiveness trials that examine primary care-based intervention are also needed. Because physicians are often the first point of contact for patients seeking help for chronic conditions, effective physician-based or physician-initiated interventions need to be developed and tested. It is also important that clinical and effectiveness trials examine interventions that result in long-term adherence in the form of lasting behavior change. Permanent behavior change is paramount for secondary stroke prevention, and additional research is needed to determine how lifestyle interventions can achieve this outcome.

Conclusion

Modifiable risk factors for recurrent stroke and cardiovascular disease are common in people with stroke. These risk factors often go unmanaged, which leads to increased risk for mortality and disability. Clinical guidelines recognize that lifestyle modification for risk factor management should be a priority following stroke. Improving diet, increasing physical activity, smoking cessation, and reducing alcohol consumption are specific health behaviors that should be targeted because of their effects on multiple cardiovascular risk factors.

Health behavior theories and lifestyle modification programs demonstrate that modification of health behaviors is possible through intensive, long-term interventions that elicit social support and provide individuals and families with a variety of skills. Lifestyle modification can be initiated in clinical practice environments and enhanced through referral to allied health care professionals or lifestyle intervention programs. Although behavior change is difficult, provider use of health behavior theories, implementation of cognitive and behavioral strategies, and refinement of communication skills may facilitate patients' efforts at secondary stroke prevention through lifestyle modification.

References

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59. Linke SE, Robinson CJ, Pekmezi D. Applying psychological theories to promote healthy lifestyles. Am J Lifestyle Med. 2013;8:4-14. [Google Scholar]

60. Prochaska JO, Redding CA, Evers KE. The transtheoretical model and stages of change. In: Glanz K, Rimer BK, Viswanath KK. eds. Health Behavior and Health Education: Theory, Research, and Practice. 4th ed. San Francisco, CA: John Wiley & Sons; 2008:97-121. [Google Scholar]

65. The Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Study. http://www.crest2trial.org/. Accessed January 4, 2016.

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Articles from American Journal of Lifestyle Medicine are provided here courtesy of SAGE Publications

# data[].attributes.attachment_link.title
Lifestyle Modification for Secondary Stroke Prevention

# data[].attributes.attachment_link.description
Of nearly 800 000 strokes that occur annually, 23% are recurrent events. Risk for disability and mortality is higher following a recurrent stroke than following a first-time stroke, which makes secondary stroke prevention a priority. Many risk ...

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Challenge to Lifestyle Changes to Prevent Stroke

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Challenge to Lifestyle Changes to Prevent Stroke

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Summary

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Challege to Lifestyle Changes to Prevent Stroke

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Role of Technology and Stroke Prevention

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Role of Technology and Stroke Prevention

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Signs and Symptoms

While public misconception typically says that strokes only occur in people with old age, studies say that this disease can occur at any age. While the risk for this condition goes up as individuals get older there is ample evidence which indicates that individuals can fall at risk to this condition at a very young age.

In fact, those who are diagnosed with high blood pressure, high levels of cholesterol, obesity, diabetes, and history of smoking have higher chances of stroke. In a study conducted in 2009, it showed that at least 34% of the individuals who were hospitalized with this disease fell under the age of 65.

While the world revolves around the highly advanced technological medical landscape, there are still some people who remain in the dark about this type of illnesses. The most common signs and symptoms of this condition include numbness or weakness in the facial structure or extremities on one side of the body, confusion, slurred speech, blurred vision, difficulty in walking or balancing, and severe headaches.

While knowing these warning signs serve as a great help in addressing the onset of a stroke and preventing it from further escalating, technological advancements in the field of medicine lends great help in ensuring the safety and survival of individuals suffering from this condition.

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The Role of Technology in Stroke Prevention and Recovery

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Throughout the world, highly advanced gadgets and devices are being used on a daily basis. Advancements in the field of science and technology give rise to more effective tools for disease prevention and recovery.

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Stroke Technology Devices in Prevention, Diagnosis, and Treatment

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Stroke Technology Devices in Prevention, Diagnosis, and Treatment

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Summary

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Summary

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High blood pressure (hypertension) can lead to heart disease and stroke. Learn more and explore resources on measuring and managing blood pressure.

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Summary

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Abstract

Background:

Stroke is one of the leading causes of death and disability for adult men and women worldwide, and a number of studies have explored the influences of smoking on stroke. However, few studies have discussed the relationship between stroke and smoking with consideration of the following factors: sex, the number of cigarettes smoked per day, stroke subtype, and the follow-up duration. Consequently, we aimed to extend previous work by using a systematic review to explore the relationship between stroke and cigarette smoking in reference to the above factors.

Methods:

A systematic review was conducted using the PubMed, Embase, and Cochrane Central Register databases and the following search criteria: ["stroke" (MeSH) and "smoking" (MeSH)]. All analyses were conducted with Stata, and funnel plots and Egger regression asymmetry tests were used to assess publication bias.

Results:

The meta-analysis included 14 studies involving 303134 subjects. According to the meta-analysis, smokers had an overall increased risk of stroke compared with nonsmokers, with a pooled odds ratio (OR) of 1.61 (95% confidence interval [CI]: 1.34-1.93, P < .001). A subgroup analysis conducted based on smoking status revealed ORs of 1.92 (95% CI: 1.49-2.48) for current smokers and 1.30 (95% CI: 0.93-1.81) for former smokers. In addition, the relationship between stroke of any type and smoking status was also statistically significant; current smokers had an increased risk of stoke compared with nonsmokers (OR: 1.46, 95% CI: 1.04-2.07, P < .001), which was influenced by sex (men: OR: 1.54, 95% CI: 1.11-2.13, P = .002; women: OR: 1.88, 95% CI: 1.45-2.44, P < .023). From the analysis, we also observed that passive smoking increased the overall risk of stroke by 45% (OR: 1.45, 95% CI: 1.0-2.11, P  < .05). Based on the dose-response meta-analysis, the risk of stroke increased by 12% for each increment of 5 cigarettes per day.

Keywords: meta-analysis, smoking, stroke

1. Introduction

Stroke, known as an acute cerebrovascular event closely related to brain tissue injury, is one of the leading causes of death and disability for adult men and women worldwide.[1] According to World Health Organization reports, every year, approximately 15 million people have a stroke,[2] leading to a substantial economic burden. Stroke can be divided into different subtypes: 87% are classified as ischaemic stroke (IS), 10% are classified as intracerebral hemorrhagic stroke (HS), and the remaining 3% are classified as subarachnoid HS.[3] Epidemiological studies have revealed that there are sex differences in stroke and that the burden from stroke in women was on the rise in Eastern Europe (post-socialist countries).[4]

Smoking is prevalent all over the world, especially among youth and in developing countries.[5] Although policies using different measures have successfully encouraged people to quit smoking, the absolute global number of smokers has increased because of population growth.[6] According to the Centers for Disease Control and Prevention (CDC), their most recent data indicated that 20.8% of the US adult population smokes.[4,7] Low nicotine-content cigarettes are generally believed to be relatively safe regarding the health effects.[8] However, smoking is still one of the most important risk factors for stroke, and previous studies have revealed a strong dose-dependent relationship between smoking and the risk of IS.[7,9,10] Other studies have also revealed that smoking has a close relationship with inflammatory factors, which play an important role in stroke pathogenesis.[11-13]

In recent years, a number of studies have been conducted to explore the influences of smoking on stroke;[14,15] however, few studies have been conducted to explore the relationship between stroke and smoking with consideration of the following factors: sex, the number of cigarettes per day, stroke subtype, follow-up duration, and so on. Consequently, we aimed to extend the previous work by using a systematic review to explore the relationship between stroke and cigarette smoking in reference to the above factors.

2. Methods

2.1. Ethics statement

As all analyses were based on previously published studies, and no ethical approval or patient consent was required.

2.2. Search strategy

We conducted a systematic review using the PubMed, Embase, and Cochrane Central Register databases and the following search criteria ["stroke" (MeSH) and "smoking" (MeSH)]. The search was limited to studies published between January 1, 1980, and June 1, 2018. The studies must have included human subjects and must have been published in English. Furthermore, the references of the retrieved articles were manually searched for additional studies.

2.3. Selection criteria and data extraction

To meet the inclusion criteria, the original research should meet the following criteria.

1.
The study was a case-control, cross-sectional, cohort or nested case-control design.

2.
The study analyzed the relationship between smoking and stroke, and stroke was one of the endpoints of the results.

3.
The relative risk ratios (RRs) and 95% confidence intervals (CIs) of the relationship between smoking and stroke were provided in the publication.

4.
The overall risk of stroke (all types), as well as the risk of IS or HS, were reported as the outcomes of interest.

We excluded letters, comments, reviews, meta-analyses, ecological studies, and experimental studies.

2.4. Data extraction

For the included studies, we extracted the following information: the first author's name, the publication year, the country of the study population, the average age of the participants, the sample size, the smoking status of the participants, the follow-up duration, the number of stroke events, the odds ratios (ORs) and corresponding 95% CIs of stroke based on smoking status, and the covariates adjusted for in the statistical analysis. Two investigators, XJ and BQP, extracted the data independently; any disagreements they were resolved by discussion with a third investigator (MWQ).

2.5. Statistical analysis

RRs and 95% CIs were considered measures of effect size, and ORs and hazard ratios (HRs) were considered equal to RRs in view of the low incidence rates. Pooled risk estimates were performed based on smoking status. The number of cigarettes was divided into different categories across studies, and the mean or median number of cigarettes in each category was extracted. If the mean or median was not provided, the midpoint of each category was extracted. If the upper boundary of the highest category was not provided, we considered 1.2 times its lower boundary as the midpoint. If the lower boundary of the lowest category was not provided, we considered it to be 0. Heterogeneity was evaluated by the Q-test statistic. We performed a subgroup meta-analysis stratified by age, stroke subtype, and study sample size. Funnel plots and Egger regression asymmetry tests were used to assess publication bias. All analyses were conducted by Stata (version 12.0, StataCorp, College Station, TX). The significance level in this meta-analysis was set as 0.05.

3. Results

3.1. Study selection

In the initial search, a total of 486 studies were identified. After removing the duplicates, 108 studies remained and needed to be further evaluated. Sixty-eight studies were removed after reading the abstracts and titles. We excluded 26 studies for the following reasons: 14 studies did not report the relevant data (such as ORs) on smoking and stroke; 4 studies were commentaries, letters or editorials; and 8 studies did not evaluate the relationship between stroke and smoking status. For the final meta-analysis, 14 studies met the inclusion criterion and were included (Fig. 1).

3.2. Characteristics of the selected studies

A total of 14 studies including 303134 participants met the inclusion criteria, and 4050 stroke events were identified in the included studies (Table 1). Among the included studies, 9 studies[14,16-23] were prospective cohort studies, 4 studies[9,15,24,25] were case-control studies and 1 study[26] was a cross-sectional study. The publication years of the included studies were between 1988 and 2018. The sample sizes of the selected studies ranged from 1070 to 118539 participants. The average follow-up period ranged from 2 to 18 years. Four studies[9,19,21,22] evaluated only men, 5 studies[17,20,23,24,26] evaluated only women, and 5 studies[17,20,23,24,26] included both men and women. Twelve studies defined former smokers and current smokers, and 2 studies did not refer to former smokers in the publications. In addition, among the included studies, 10 studies[14-18,21-23,25,26] evaluated the relationship between smoking and overall stroke (stroke of any type), 2 studies[19,20] evaluated only IS, and 2 studies[9,24] evaluated only HS. Most of the included studies adjusted for potential confounding factors, including age, race, education, hypertension, alcohol use, and exercise.

Table 1.

3.3. Smoking and overall risk of stroke

The pooled OR for the relationship between current smoking and the risk of stroke is shown in Figure 3. Smokers had an increased risk of overall stroke compared with nonsmokers, with a pooled OR of 1.61 (95% CI: 1.34-1.93). A subgroup analysis was conducted based on smoking status: the ORs were 1.92 (95% CI: 1.49-2.48) for current smokers and 1.30 (95% CI: 0.93-1.81) for former smokers. Significant statistical heterogeneity was noted in the studies reporting ORs for overall stroke (I ² = 88.0%, P < .001), and a random-effects model was used in this meta-analysis (Fig. 2).

3.4. Stratified analysis

To better explore the sources of heterogeneity between studies and the relationship between smoking and stroke, a stratified analysis was conducted based on effect modifiers or confounding factors. Based on the stratified analysis, the incidence rate of overall stroke increased in all the included subgroups. However, we did not find that sex significantly influenced the relationship between smoking and IS or HS. Furthermore, we found that the follow-up duration can significantly influence the observed relationship between smoking and stroke (Table 2).

Table 2.

3.5. Former smoking and overall risk of stroke

According to the stratified analysis, the relationship between stroke of any type and current smoking was statistically significant; current smokers had an increased risk of stoke compared with nonsmokers (OR: 1.46, 95% CI: 1.04-2.07, P < .001), which was influenced by sex (men: OR: 1.54, 95% CI: 1.11-2.13, P = .002; women: OR: 1.88, 95% CI: 1.45-2.44, P < .023). However, we did not obtain the same results with overall stroke in former smokers versus nonsmokers (OR: 1.38, 95% CI: 0.99-1.92, P < .001), which did not change with sex. In former smokers, the ORs were 0.97 (95% CI: 0.68-1.39, P = .025) and 1.18 (95% CI: 0.72-1.92) for men and women, respectively (Fig. 3).

3.6. A dose-dependent relationship between current smoking and stroke

Among the included studies, 7 reported the details of the relationship between the number of cigarettes smoked and the incidence of stroke. In the dose-response meta-analysis, the non-linear association between cigarette smoking and stroke was non-significant ( P for nonlinearity = .729). A linear elevation in stroke incidence was observed when cigarette consumption increased, and the risk of stroke was increased by 12% for each increment of 5 cigarettes per day (95% CI: 0.01, 0.02, P < .001) (Fig. 4).

3.7. Passive smoking and risk of stroke

From the analysis, we also observed that passive smoking can increase the overall risk of stroke by 45% (OR: 1.45, 95% CI: 1.0-2.11) compared with no current exposure to passive smoking, and this difference in risk was statistically significant ( P  < .05).

3.8. Publication bias

To evaluate the publication bias, funnel plots and Egger regression asymmetry tests were used. A funnel diagram did not show symmetry, which meant that publication bias existed in this meta-analysis. Consequently, a trim-and-fill method was conducted to evaluate the sensitivity, which hypothetically imputed 8 negative and unpublished studies that were missing from the initial analysis (Fig. 5).

4. Discussion

In this meta-analysis, we found an increased risk of stroke in smokers compared with nonsmokers, which was consistent with previous studies. An increased risk of stroke associated with current smoking was observed in most subgroups. In addition, there was a dose-dependent relationship between current smoking status and the overall risk of stroke, and the risk was increased by 12% for each increment of 5 cigarettes per day. However, we did not obtain the same results for the relationship between overall stroke and former smokers (OR: 1.38, 95% CI: 0.99-1.92, P  < .001). According to the stratified analysis, there was a relationship between overall stroke and current smoking status regardless of sex, follow-up duration or study sample size. However, we did not obtain the same results with the HS and IS subgroups. The above factors investigated in this study significantly influenced the results.

Although several meta-analyses have evaluated the relationship between smoking and stroke,[27-29] our meta-analysis provides new information and implications. Compared with the meta-analysis published in 1989, our meta-analysis updated the included studies and performed subgroup analysis based on smoking status.[27] Another meta-analysis published in 2011 only discussed the association between second-hand smoke exposure and stroke,[28] and the meta-analysis published in 2018 mainly discussed the association of low cigarette consumption and the risk of coronary heart disease and stroke.[29] For the previous cohort studies, most of the studies only considered 1 confounding factor.[9,15,24,30] In our meta-analysis, we performed subgroup analysis with consideration of the following factors sex, the number of cigarettes smoked per day, stroke subtype, follow-up duration, and smoking status. We also performed a dose-response analysis between the number of cigarettes per day and the risk of stroke. According to the results of the meta-analysis, we can conclude that current smokers have a relationship with the risk of stroke, which was consistent with finding from previous studies. However, in this meta-analysis, we did not find an association between former smokers and the incidence of stroke, indicating that quitting smoking has a positive effect on the incidence of stroke. This result highlights the benefits of smoking cessation on stoke outcomes.

In this meta-analysis, minor differences were observed between sexes. In the subgroup analysis, we found that there was a greater risk of stroke for women. Earlier studies also revealed a strong dose-dependent relationship between smoking and stroke among women.[23,24] Current use of oral contraceptives and a higher dose of harmful chemicals per unit of body mass may contribute to these results. In addition, we observed that current smoking is related to the occurrence of stroke of any type. The idea that there is a population of ex-smokers who started smoking again and are actually current smokers cannot be neglected. Moreover, passive smoking can also increase the risk of stroke; consequently, people living in an environment with smokers should also be considered.

The mechanism by which passive smoking can increase the risk of stroke has been reported in many studies. Passive smoking can lead to carotid atherosclerosis,[31] and the levels of homocysteine, fibrinogen, and oxidized low-density lipoprotein cholesterol can also be elevated by smoking.[29,32] Epidemiological studies have concluded that smoking can increase the risk of sudden cardiac death.[33] A meta-analysis also revealed that smoking was associated with an increased risk of atrial fibrillation in a dose-dependent manner.[34] Additionally, smoking has also proven to be related to diabetes, high blood pressure, and elevated resting heart rate, which are all risk factors for stroke.[35,30] Furthermore, smoking plays a possible role in some genetic diseases, such as Fabry disease, which can impair the central nervous system and lead to cerebral infarction and transient ischaemic attack.[36,37] The key strength of the present study is that it explored the relationship between stroke and smoking from different aspects. From this meta-analysis, we can conclude that passive smokers and ex-smokers have a higher risk of stroke than nonsmokers do. In addition, the relationship between smoking and stroke can also be influenced by sex.

4.1. Limitations

Limitations also exist in this study. First, heterogeneity was observed in this meta-analysis, resulting from different characteristics of the participants and inconsistent definitions of outcome measures. To decrease the publication bias, stratified analyses were conducted. Second, the trim-and-fill method was used, which can estimate the number of unpublished and grey literature studies and suggested that the association was not affected by unpublished negative studies. Third, stroke can be divided into different subtypes. In this meta-analysis, however, we discussed only IS and HS. HS can be further subdivided into intracerebral HS and subarachnoid HS; however, because of limited information, we did not perform further analyses on the HS subtypes.

4.2. Future directions

Stroke can be divided into subtypes; however, most of the included studies discussed only IS and HS. HS can be subdivided into intracerebral HS and subarachnoid HS, and further analysis may be performed between the subtypes of HS in future studies. In addition, this meta-analysis indicated that former smokers did not show a higher risk of stroke; however, further studies should be conducted among former smokers to determine whether the duration of smoking cessation affects the current risk of stroke.

5. Conclusion

From this meta-analysis, we can conclude that stroke has a dose-dependent relationship with smoking, regardless of status as a current smoker or passive smoker. In addition, there was a relationship between stroke of any type and current smoking status regardless of sex, follow-up duration or study sample size. However, in this meta-analysis, we did not find an association between former smokers and the incidence of stroke, indicating that quitting smoking has a positive effect on the incidence of stroke.

Additionally, there are still some potential confounders due to lack of information; consequently, additional studies with larger sample sizes and more detailed information are needed for further clarification.

Author contributions

Conceptualization: Qiuping Zheng.

Data curation: Xiao Jin, Shaohong Qiu.

Formal analysis: Xiao Jin, Shaohong Qiu.

Funding acquisition: Mingwo Pan.

Methodology: Biqi Pan, Liu Jun, Qiuping Zheng, Mingwo Pan.

Project administration: Biqi Pan.

Resources: Biqi Pan.

Software: Shaohong Qiu.

Writing - original draft: Xiao Jin, Qiuping Zheng, Mingwo Pan.

Writing - review & editing: Liu Jun, Qiuping Zheng, Mingwo Pan.

Footnotes

Abbreviations: CI = confidence interval, HS = hemorrhagic stroke, IS = ischaemic stroke, OR = odds ratio, RR = risk ratio.

BP and XJ contributed equally to this work.

This project was funded by the Project of Guangdong Provincial Department of Finance (No. [2014]157, No. [2018]8), Science and Technology Research Project of Guangdong Provincial Hospital of Chinese Medicine (No. YK2013B2N19, YN2015MS15).

The authors have no conflicts of interest to disclose.

References

Articles from Medicine are provided here courtesy of Wolters Kluwer Health

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The relationship between smoking and stroke: A meta-analysis

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Stroke is one of the leading causes of death and disability for adult men and women worldwide, and a number of studies have explored the influences of smoking on stroke. However, few studies have discussed the relationship between stroke and smoking ...

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Summary

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Public Health and Promoting Quality Improvement in Stroke

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Public Health and Promoting Quality Improvement in Stroke

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The Role of Public Health in Promoting Quality Improvement in Care for Stroke and Heart Disease

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Public Health Measures and Stroke Prevention

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Public Health Measures and Stroke Prevention

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Summary

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Public Health Measures to Prevent Stroke

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Public Health Promotion of Healthy Lifestyles 

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Public Health Promotion of Healthy Lifestyles 

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When heart experts talk about prevention, they usually refer to one of three types: secondary, primary and primordial prevention. [1] All three have similar elements, but different starting times and different effects.

1. Secondary prevention. These efforts are started after someone has a heart attack or stroke, undergoes angioplasty or bypass surgery, or develops some other form of heart disease. It involves taking medications like aspirin and/or a cholesterol-lowering statin, quitting smoking and losing weight if needed, exercising more, and following a healthy diet. Although secondary prevention may sound like "closing the barn door after the horse has gone," it isn't. These steps can prevent a second heart attack or stroke, halt the progression of heart disease, and prevent early death. It may be obvious, but the number one killer of individuals who survive a first heart attack is a second heart attack.

2. Primary prevention. Primary prevention aims to keep an individual at risk of heart disease from having a first heart attack or stroke, needing angioplasty or surgery, or developing some other form of heart disease. Primary prevention is usually aimed at people who already have developed cardiovascular risk factors, such as high blood pressure or high cholesterol. As with secondary prevention, primary prevention focuses on controlling these risk factors by making healthy lifestyle changes and, if needed, taking medications. That said, the appearance of worrisome cardiovascular risk factors means that inflammation, atherosclerosis, and/or endothelial dysfunction are already at work and, in most cases, aren't reversible.

3. Primordial prevention. The word "primordial" means existing from the beginning. Primordial prevention involves working to prevent inflammation, atherosclerosis, and endothelial dysfunction from taking hold, and thus prevent risk factors such as high blood pressure, high cholesterol, excess weight, and ultimately cardiovascular events. Once rarely discussed, primordial prevention is now the cornerstone of the American Heart Association's definition of ideal heart health and efforts to help people achieve it. [1] As its name implies, the sooner you can start practicing primordial prevention-ideally from childhood on-the more likely you are to achieve it and protect yourself from heart disease.

Steps for the Primordial Prevention of Heart Disease

Five key lifestyle steps can dramatically reduce your chances of developing cardiovascular risk factors and ultimately heart disease:
1. Not smoking

One of the best things you can do for your health is to not use tobacco in any form. Tobacco use is a hard-to-break habit that can slow you down, make you sick, and shorten your life. One way it does this is by contributing to heart disease.

In fact, researchers examining the relationship between cigarette smoking and smoking cessation on mortality during a decades-long perspective study of over 100,000 women found that approximately 64% of deaths among current smokers and 28% of deaths among former smokers were attributable to cigarette smoking. [2]

This study also reported that much of the excess risk due to smoking may be drastically lowered after quitting. Additionally, the excess risk for all-cause mortality-that is, death from any cause-decreases to the level of a "never-smoker" 20 years after quitting.

The nicotine that tobacco products deliver is one of the most addictive substances around. That makes tobacco use one of the toughest unhealthy habits to break. But don't get discouraged; many smokers do quit! In fact, in the United States today there are more ex-smokers than smokers. [3] Learn more about the hazards of smoking, the benefits of quitting, and tips for quitting from the Centers for Disease Control and Prevention.
2. Maintaining a healthy weight

Excess weight and an extra-large waist size both contribute to heart disease, as well as a host of other health problems. [4-6]

In a study of over one million women, body-mass index (BMI) was a strong risk factor for coronary heart disease. The incidence of coronary heart disease increases progressively with BMI. [7]

In the Nurses' Health Study and the Health Professionals Follow-Up Study, middle-aged women and men who gained 11 to 22 pounds after age 20 were up to three times more likely to develop heart disease, high blood pressure, type 2 diabetes, and gallstones than those who gained five pounds or fewer.

Those who gained more than 22 pounds had an even greater risk of developing these diseases. [4,8-11]

Weight and height go hand-in-hand. The taller you are, the more you weigh. That's why researchers have devised several measures that account for both weight and height. The one most commonly used is BMI.

You can calculate your BMI by dividing your weight in kilograms by your height in meters squared (kg/m²). You can also use an online BMI calculator or BMI table.

A healthy BMI is under 25 kg/m². Overweight is defined as a BMI of 25 to 29.9 kg/m², and obesity is defined as a BMI of 30 kg/m²

Waist size matters, too. In people who are not overweight, waist size may be an even more telling warning sign of increased health risks than BMI. [12] An expert panel convened by the National Institutes of Health identified these useful benchmarks: Men should aim for a waist size below 40 inches (102 cm) and women should aim for a waist size below 35 inches (88 cm). [13]

3. Exercising

Exercise and physical activity are excellent ways to prevent heart disease and many other diseases and conditions, [14-16] but many of us get less activity as we get older.

Getting regular physical activity is one of the best things you can do for your health. It lowers the risk of heart disease, diabetes, stroke, high blood pressure, osteoporosis, and certain cancers, and it can also help control stress, improve sleep, boost mood, keep weight in check, and reduce the risk of falling and improve cognitive function in older adults.

It doesn't take marathon training to see real health gains. A 30-minute brisk walk five days of the week will provide important benefits for most people. Getting any amount of exercise is better than none.

Exercise and physical activity benefit the body, while a sedentary lifestyle does the opposite-increasing the chances of becoming overweight and developing a number of chronic diseases.

Research shows that people who spend more time each day watching television, sitting, or riding in cars have a greater chance of dying early than people who are more active. [17-19] A 2013 study showed that, among women ages 50-79 with no cardiovascular disease at the start of study, prolonged sitting time was associated with increased heart disease risk regardless of the amount of time spent in leisure-time physical activity. [16]

4. Following a healthy diet

For years, research into connections between diet and heart disease focused on individual nutrients like cholesterol (and foods high in dietary cholesterol, like eggs), types of fats, and specific vitamins and minerals. This work has been revealing, but it has also generated some dead ends, along with myths and confusion about what constitutes a heart-healthy diet. That's because people eat food, not nutrients.

The best diet for preventing heart disease is one that is full of fruits and vegetables, whole grains, nuts, fish, poultry, and vegetable oils; includes alcohol in moderation, if at all; and goes easy on red and processed meats, refined carbohydrates, foods and beverages with added sugar, sodium, and foods with trans fat.

People with diets consistent with this dietary pattern had a 31% lower risk of heart disease, a 33% lower risk of diabetes, and a 20% lower risk of stroke. [20]

A randomized controlled trial found that a Mediterranean diet supplemented with extra-virgin olive oil or nuts, both rich sources of unsaturated fat, reduced the incidence of major cardiovascular events amongst patients with cardiovascular disease over a 4.8-year follow-up period.

This study highlighted that low-fat diets are not beneficial to heart health, and that incorporating healthy fats - such as those included in the Mediterranean diet - can improve heart health and weight loss.

There isn't one exact Mediterranean diet, as this eating style takes into account the different foods, eating patterns, and lifestyles in multiple countries that border the Mediterranean Sea. However, there are similarities that define a Mediterranean eating pattern, including: high intake of olive oil, nuts, vegetables, fruits, and cereals; moderate intake of fish and poultry; low intake of dairy products, red meat, processed meats, and sweets; and wine in moderation, consumed with meals. [21]

A 2020 study focused on dietary scores for 4 healthy eating patterns: Healthy Eating Index-2015 ; Alternate Mediterranean Diet Score; Healthful Plant-Based Diet Index; and Alternate Healthy Eating Index. Despite different scoring methods, each of these patterns emphasizes higher intake of whole grains, vegetables, fruits, legumes, and nuts, and lower intakes of red and processed meats and sugar-sweetened beverages.
The study found that those who adhered most to healthy eating patterns had a 14% to 21% lower risk of cardiovascular disease when compared with those who adhered least. The findings also showed that these different healthy eating patterns were similarly effective at lowering risk across racial and ethnic groups and other subgroups studied, and that they were statistically significantly associated with lower risk of both coronary heart disease and stroke. [22]

Sodium and potassium are two interrelated minerals that play major roles in regulating blood pressure and a healthy heart. Eating less salty foods and more potassium-rich foods may significantly lower the risk of cardiovascular disease. [29] Potassium is found in many foods, especially fruits, vegetables, legumes, and low-fat dairy. But the reverse of eating a lot of sodium-rich foods especially from processed breads, packaged snacks, canned goods, and fast-food meals while skimping on potassium can increase cardiovascular disease risk.

5. Improving sleep health

Research has shown that sleep is an essential component of cardiovascular health.

Sleeping for too short or too long a stretch is associated with heart disease and can negatively affect other heart-related risk factors like dietary intake, exercise, weight, blood pressure, and inflammation. [30]

There are various reasons causing poor sleep, including clinical sleep disorders, working overnight shifts, or poor sleep hygiene. Talk with your doctor if you have frequent restless nights or do not feel adequately rested during the day. Improving sleep habits can make a difference. Examples include setting a sleep schedule and sticking to it, having a calming bedtime ritual like doing stretches or meditating, getting regular exercise, stopping use of electronic devices an hour before bedtime, and avoiding heavy meals, caffeine, and alcohol several hours before bed.

Other factors to consider
Along with these five practices, the American Heart Association recommends controlling cholesterol, managing blood sugar, and managing blood pressure as additional factors for improving and maintaining cardiovascular health. Learn more at the American Heart Association's "Life's Essential 8."

Reprinted from Journal of the American College of Cardiology, Vol 72, Issue 8, E Yu, VS Malik, FB Hu, Cardiovascular Disease Prevention by Diet Modification: JACC Health Promotion Series, 914-926, 2018, with permission from Elsevier.

Putting It All Together

You can help prevent heart disease by doing five key things and making them into habits:

Strong studies make it possible to link reductions in risk to these habits. Following a healthy lifestyle may prevent over 80% of cases of coronary artery disease, [24, 25] 50% of ischemic strokes, [26] 80% of sudden cardiac deaths, [27] and 72% of premature deaths related to heart disease. [28] In other words, a healthy lifestyle is a good investment in a longer, healthier life.

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Last reviewed August 2022

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When heart experts talk about prevention, they usually refer to one of three types: secondary, primary and primordial prevention. [1] All three have similar elements, but different starting ti...

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Summary