Ischemic Stroke of Cardioembolic Origin - Systematic Review

Introduction: Ischemic stroke corresponds to 80% of cases in Brazil, which demonstrates the epidemiological importance in Brazil. The magnitude of this fact reflects the reason why stroke is considered the second cause of death in the world, and the first cause of death in Brazil, in addition to being the second cause of cognitive losses. The main causes that favor the occurrence of ischemic stroke determine the situation of risk groups. Such factors can be classified as modifiable, non-modifiable and potential risk group.

Objective: The aim of the present study was to systematically review the literature on public health Ischemic Cerebral Vascular Accident of Cardioembolic Origin.

Methods: Systematized literature review performed by searching the US National Library of Medicine (Pub Med), Scientific Online Electronic Library (SCIELO), Latin American Caribbean Health Sciences Information System (LILACS), Science Direct and Embase, using the descriptors: stroke, ischemic stroke and cardioembolic stroke in Portuguese and Stroke, ischemic stroke and cardioembolic stroke in the English language. A total of 852 articles were found, of which 11 were selected for the review by six evaluators independently. The articles searched are from the last 5 years.

Results: The Strategic Action Plan for Combating Chronic Non-Communicable Diseases (NCDs) showed a reduction in deaths in the two that kill the most in the country, stroke and ischemic heart disease. Conclusion: This work contributes to the realization of new studies, since it analyzed the studies that deal with ischemic stroke in Brazil, gathering the available information.

Ischemic stroke (CVA) results from the obstruction of a cerebral artery, resulting from the accumulation of fat leading to atherosclerosis and/or blood clot [1] Circulation is blocked in a certain brain area, causing ischemia by decreasing neurological function. Due to lack of blood supply to the obstructed area, these events promote the death of nervous tissue [2,3].

Stroke is classified as embolic, lacunar and thrombotic. The embolic is derived from small portions of matter that are released into the bloodstream and move to the cerebral arteries, the lacunar occurs by small infarctions where perforating arterioles branch directly from the large vessels and the thrombotic occurs through a clot or thrombus in the interior of the cerebral arteries or their branches [4,5].

Stroke is classified as of ischemic or hemorrhagic origin and about 87% of strokes are ischemic. Ischemic stroke is a disease of heterogeneous causes, including occlusive disease of small arteries, cardioembolism, microatheroma, in addition to other risk factors such as undiagnosed transient ischemic attacks, hypertension, diabetes, dyslipidemia and smoking [6-8].

In Brazil, 80% of stroke cases are classified as ischemic, demonstrating that it is of paramount epidemiological importance in the country, resulting in the first cause of death in the country, in addition to being the second cause of cognitive losses [9].

Many studies show that the most affected individuals are elderly, in general black and male. On the other hand, studies show that more severe cases occur in female patients with a higher fatality rate than in males. Some other studies have also shown that stroke incidence and hospitalization rates emerge among young people, becoming a serious public health problem [10-12].

The main associated risk factors that increase the occurrence of ischemic stroke can be classified into modifiable, non-modifiable and potential risk groups. In the first classification, the greatest relationship stems from habits such as smoking and control of pre-existing diseases, such as arterial hypertension and diabetes mellitus. The second classification, non-modifiable risk factors, presents characteristics such as advanced age, gender and ethnicity. The potential risk group lists factors resulting from poor lifestyle habits, such as sedentary lifestyle, obesity and alcoholism. It is believed that obesity is a triggering factor for cardiovascular diseases, transfiguring it as one of the key points for risk classification models [13].

The extent and establishment of collateral flow are determined by the affected site, severity, signs and symptoms. The main indicative signs can be listed as loss of strength, sudden headache, loss of speech, imbalance, visual changes, immediate changes in sensitivity, instability, vertigo, nausea or vomiting, fatigue and changes in personality and mood [14].

Ischemic stroke is confirmed by imaging tests that allow the identification of the affected area of the brain, and some tests have a high degree of accuracy for confirming the mechanisms of the stroke, such as Computed Tomography (CT), Magnetic Resonance (RM), electrocardiogram, echocardiogram and Doppler ultrasound of the carotid arteries [15,16].

Accounting for approximately 15-30% of cases, cardiac embolism is the second leading cause of stroke [17].

The aim of the present study was to systematically review the literature in public health on Ischemic Cerebral Vascular Accident of Cardioembolic Origin.

This study constitutes a systematic review, classified as exploratory and descriptive. The elaboration of the research was bibliographical research in electronic databases on methods associated with RSL (Systematic Literature Review) and SMARTER applications (Simple Multi-Attribute Rating Technique using Exploiting Rankings). The work carried out is qualitative and quantitative. The qualitative analysis of the data is carried out intuitively and inductively during the survey of the theoretical framework. It is also quantitative by using the multicriteria method. In addition, there is also a numerical experimental study in order to simulate an article selection situation based on the observed criteria. From bibliographical research, located in the databases: US National Library of Medicine (PubMed), Scientific Online Electronic Library (SCIELO), Latin American Caribbean Health Sciences Information System (LILACS), Science Direct (Elsevier) and Embase.

The search in the databases was carried out using the terminologies registered in the Health Sciences Descriptors created by the Virtual Health Library developed from the Medical Subject Headings of the US National Library of Medicine, which allows the use of common terminology in Portuguese, English and Spanish. The keywords used in Portuguese for the search in the databases were: Cerebral vascular accident, ischemic vascular accident and cardioembolic vascular accident. As a tool to support decision in the selection and prioritization of articles, were considered a set of criteria as essential to represent the state of the art of the subject object of the research. This method has the following characteristics: (i) rigorous logic allows acceptance of the method as a decision support tool; (ii) simple to understand and apply with easily interpreted results. After all, the result obtained totaled 11 articles that contemplated the desired characteristics for the study.

According to the World Health Organization, diseases classified as non-communicable are responsible for 74% of deaths in Brazil and 71% worldwide. These diseases include chronic respiratory diseases, cancers, diabetes, mental conditions and diseases of the circulatory system also known as Cardiovascular Diseases (CVD). In Brazil, CVDs cause 28% of deaths, of which ischemic heart diseases stand out as main cause, followed by stroke. These categories together represent 1/3 of global deaths [18].

Brazilian Society of Cerebrovascular Diseases, the Cerebral Vascular Accident (CVA) presents high morbidity and mortality, being the main cause of death of Brazilians. Worldwide, it is a disabling disease because, due to its consequences, approximately 70% of people do not return to work and 50% are dependent on other people the day they leave. Despite more frequently reaching individuals over 60 years of age, stroke can occur at any age, including children. Stroke is increasing among young people, occurring in 10% of patients under 55 years of age and the World Stroke Organization ( World Stroke Organization ) predicts that one in every six people in the world will have a stroke during their lifetime [19].

The stroke classifications are: anoxic-ischemic (result of vasogenic failure to adequately supply brain tissue with oxygen and substrates) and hemorrhagic (result of extravasation of blood into or around the structures of the central nervous system) [20]. Ischemic subtypes are lacunar, atherosclerotic, and embolic, and hemorrhagic subtypes are intraparenchymal and subarachnoid [21,22].

Cardiac embolism is the second leading cause of stroke, accounting for approximately 15-30% of cases [17]. A large number of heart diseases are considered potential sources of embolism, in which we can mention atrial fibrillation, recent myocardial infarction, artificial mechanical valves, mitral valve stenosis, atrial or left ventricular thrombus and atrial myxoma, dilated cardiomyopathy, non-bacterial infectious and thrombotic endocarditis and ventricular aneurysm [23,24].

Cardioembolic stroke caused by atrial fibrillation often requires the administration of oral anticoagulants such as warfarin, which are necessary to reduce the risk of recurrence [25,26]. The recurrence rate is common in 6% to 12% of patients and can occur within two weeks of the first event. However, in many cases, echocardiographic techniques are not sufficient to detect abnormalities, because these may not be present when the patient is examined. This makes adequate treatment with anticoagulant therapy difficult. In this case, there is a clear need for biomarkers that can identify this stroke subtype in time to prevent recurrence [27,28].

Eight hundred and fifty-six articles were identified in the databases referring to ischemic stroke and were found. From this, the SMARTER method (Simple Multi-Attribute Rating Technique using Exploiting Rankings). Of the 856 articles found by combining descriptors, 102 were selected for abstract reading, 21 were selected for full text reading, and only 11 articles were included for descriptive data analysis. In figure 1, we describe the strategy for selecting articles on the topic in question (Table 1).

Figure 1: Descriptive data analysis.

Ichemic stroke is a neurological syndrome with high morbidity and mortality worldwide, being the second cause of death in the world and the leading cause of disability in Brazil, with approximately 17 million victims per year. Compared with other diseases, stroke had the highest total in-hospital mortality and odds ratio, which is consistent with the severity of the disease described in the Brazilian study. Regarding the comorbidity index, the probability of death was higher when the CHF score (Congestive Heart Failure) was equal to or greater than 2, indicating a greater degree of severity, which was similar to previous studies [39-41].

At the hospital level, total hospital mortality was higher in public hospitals (16.7%) than in non-profit private hospitals (11.6%) and in for-profit private hospitals (10.0%). Adjusting this indicator decreased the TMHA only in public hospitals, highlighting the importance of risk adjustment. There is great variability in total hospital mortality between hospitals, which raises the hypothesis of possible problems related to the quality of hospital care [42].

Separating the variation due to the severity of the case, the care process and the clinical performance of professionals and the organization is an even more complex task in elderly patients, in which these elements can be more intertwined. However, this type of approach is understood as a screening tool, that is, a warning sign that requires subsequent analysis in order to improve the effectiveness of care and, consequently, its quality [4].

In addition to the analysis of factors associated with the outcome of hospital care for elderly patients, it can be used as an indicator of the effectiveness of care. Despite the limits, due to the lack of information, the risk adjustment model showed a reasonable ability to discriminate. In addition, the analysis indicated that the length of hospital stay predicted the risk of death. There was a clear improvement in comparing the predictive ability of the models with the inclusion of length of stay. A protective effect was observed for hospitalizations lasting more than one day, possibly related to the severity of the case at the time of admission or the inadequacy of emergency care, which strictly requires timely and adequate actions [43,44].

The use of these indices, along with the other variables, could reasonably predict in-hospital death in the elderly, and could be improved in the future to monitor the quality of care provided. On the other hand, despite the contribution made, the development of new research is essential to increase knowledge about the profile of hospital interventions performed in elderly patients in Brazil and their effectiveness [45-47].

We found that in Brazil the number of overweight patients with their first stroke was greater than the number with normal BMI and stroke. Most of the former had less than eight years of schooling, belonged to social class C and were significantly more physically inactive, often associated with obesity, which affects about 41 million people (25.9%) [48,49].

Between the years 2014 and 2019, stroke mortality rates in women, aged 30 to 69 years, decreased by 11%. This data was verified by the Saúde Brasil 2018 study, carried out by the Ministry of Health. In this same period, the stroke rate decreased from 39.5 to 35.2 deaths per 100,000 female inhabitants, while Heart Diseases decreased from 55 to 51.6 deaths per 100,000 [50].

In a previous population study conducted in Joinville, it was found that 16% (95%CI 14-19) of 601 patients with a first ischemic stroke were obese in the period 2005-2006. Six years later (period 2012 to 2013), the prevalence of obesity in 786 patients with ischemic stroke jumped significantly to 23% (95% CI, 20-27). This proportion is similar to our finding of 26% (CI95%, 24-29) in this study in five Brazilian cities [51].

The most frequent comorbidities were arterial hypertension (84.6%) and diabetes mellitus (51.9%), with similar distribution between the studied groups and both comorbidities are also included in the CHADS2 and CHA2DS2-VASc scores. Although these scores provide simple methods for predicting an individual's risk of ischemic stroke, the risk estimated by these instruments represents only part of the overall risk (statistical agreement 0.5). A recent meta-analysis showed that smoking is associated with a modest increase in AF and that quitting smoking reduces, but does not eliminate, the risk associated with the disease [52,53]. However, adding smoking to the score does not improve stroke or TIA risk prediction [54,55].

The causality between obesity and stroke is debatable. Factors such as diabetes, hypertension, age, among others, would be involved in myocardial damage. In this sample, more than 80% of the patients had arterial hypertension and more than 50% were diabetic. However, other studies demonstrated that the association with obesity was substantially attenuated after controlling for the variables hypertension and diabetes, contributing to the decrease in obesity and the associated risk of stroke [56-58].

The main findings in another study on ischemic stroke were high prevalence of arterial hypertension and diabetes mellitus, some connectivity problems and problems related to the recording of PoIP signs (Ambulatory Monitoring System) and similar profile of cardiac arrhythmias between the study groups [59].

Studies looking at stroke onset may help to distinguish cardioembolic from atherothrombotic infarcts. Sudden onset to maximal deficit were significant predictors of embolic stroke, whereas subacute onset or early neurologic deterioration were independent predictors of atherothrombotic stroke [8].

The deterioration of brain and cognitive functions can contribute to depression, which may be associated with the worsening of ischemic stroke. Depression is also an important factor for the development of stroke, which contributes to the worsening of the patient's condition. The prevalence of depression at any time after stroke is about 29%. Anxiety disorders are also common after stroke. Between 25% and 50% of patients develop GAD (Generalized Anxiety Disorder) in the first few months after stroke, with a small reduction in incidence over the next three years. Phobic disorders and GAD are the most common types of anxiety disorders after a stroke [60-62].

The relationship between depression after stroke and functional impairment is complex. Depressed patients have a significantly greater disability in activities of daily living than euthymic individuals with equivalent neurological diseases [63].

In Brazil, mental disorders associated with social vulnerability negatively influence the recovery of patients after stroke. Often, patients do not have resources for post- stroke rehabilitation treatments, or still do not have access, as such treatments are only available in medium-complexity services, requiring displacement. All of these factors contribute to the high frequency of depression and anxiety disorders, which draws attention to the possible consequences that can result if patients are not identified and treated appropriately, even when the functional impact of stroke in patients is mild [62,64].

It is known today that stroke is one of the major causes of morbidity and mortality among patients, mostly in the elderly. It is associated with NCDs, among which we mention hypertension, diabetes and dyslipidemia. This disease is more common in men, black and with low education, but in women it is more lethal, according to preexisting data.

The survey showed that, in the population aged between 30 and 69 years and over 70 years, ischemic heart disease had the highest mortality rates, both in women and in men. Stroke, on the other hand, occupied the second place of the main causes of death among women, aged between 30 and 69 years.

Our data shed light on important information, from causes, both motor and emotional sequelae, and the lack of information about quality of care (both clinical and diagnostic) and hospitalization of these stroke patients. This shows the importance of this systematic review, and of new studies that can elucidate and bring more data about this gap within stroke studies.

The main limitations found while carrying out this review is the correct correlation between stroke and cardioembolic diseases, due to the multifactorial characteristic of both diseases, which makes it difficult to standardize control and study methods in different locations. Still, it is not possible to make a correlation by segmenting the study into subgroups grouped by diseases, in addition to statistical data being more complete in countries with adequate monitoring, and lacking indicators in countries with lower purchasing and economic power.

Thus, new methodologies and analyzes need to be elaborated on the effects of the multiplicity of chronic diseases, which affect the elderly more intensely. Considering this context, this work contributes to the production of studies, since it analyzed the studies that deal with ischemic stroke, gathering the available information.

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