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The risk factors for recurrent stroke are multi-factorial. It is important to identify risk factors contributing to recurrent stroke in order to produce effective preventive measurement. This study aims to find non-modifiable and modifiable factors contributing to recurrent stroke.
Methods
A Systematic review of studies on non-modifiable and modifiable factors contributing to recurrent stroke in the PubMed, ProQuest, and EBSCO were employed to search related articles published from January 2010 to January 2021. The Pooled Hazard Ratio (PHR) of the risk factors were calculated by using fixed and random-effect models. The heterogeneity was computed by calculation of I2. Publication bias was assessed using Egger's test. All data processing and analysis were performed using STATA 16.0.
Results
Modifiable risk factors contributing to recurrent stroke included ischemic heart disease (PHR = 2.78 [95% CI 1.91–6.47]), atrial fibrillation (PHR = 1.87 [95% CI 1.23–2.52]), hypertension (PHR = 1.66 [95% CI] 1.15–2.17]), and obesity (PHR = 0.85 [95% CI] 0.78–0.92]). Non-modifiable risk factor associated to recurrent stroke was older age (PHR = 1.03 [95% CI 1.02–1.04]). The heterogeneity calculation showed homogenous among studies in hypertension, obesity and older age (I2 ≤ 50%).
Conclusion
Ischemic heart disease, atrial fibrillation, hypertension, obesity and older age contribute to recurrent stroke. Thus, prevention measurements for recurrent stroke are suggested in patients with these conditions.
Low awareness of identifying risk factors and symptoms of stroke, inadequate stroke care and low adherence to therapy programs for the prevention of recurrent stroke are problems that arise in stroke management nowadays. This has led to an increase in first stroke and recurrent stroke incidence, as well as mortality.
Basically, after the first stroke, recurrent strokes are still very likely to occur within 6 months after the first accident. Recurrent stroke is more likely to cause severe disability or death.
Thus, in order to prevent as well as to decrease the incidence of recurrent strokes, identifying the risk factors carefully, and subsequently taking preventive measures, are serious concerns. The preventive measurements should include both modifying the lifestyle factors and undergoing the necessary therapy as preventive medication. More importantly, another preventive action is to educate and promote the patient about factors identified as risk factors of recurrent stroke, especially when the risk factors found in the patient.
Therefore, it is important to identify risk factors contributing to recurrent stroke in order to produce effective preventive measurement. The identification of risk factors enables both professional health workers as well as patients to recognize the risk of recurrent stroke immediately.
South London Stroke Register. Cause of stroke recurrence is multifactorial: patterns, risk factors, and outcomes of stroke recurrence in the South London Stroke Register.
The risk factors include modifiable and non-modifiable risk factors. Firstly, the non-modifiable risk factors include age, gender, family history of stroke, and ethnicity. Secondly, the modifiable risk factors for stroke include hypertension, heart disease, diabetes mellitus, hypercholesterolemia, obesity, smoking, alcohol consumption, unhealthy lifestyle, and stress.
However, to the best of our knowledge, although there have been numerous studies identifying factors related to recurrent stroke, study summarizing the factors with significant effect increasing risk of recurrent stroke is currently unavailable.
We should avoid recurrent strokes because they pose a serious risk and may be fatal. Recurrent stroke prevention is a worthwhile endeavor, and data must be readily available to support attempts to reduce the incident that could prevent high treatment, rehabilitation, and mortality. Particularly, this study provides input or information as well as an evaluation of the current scientific evidence regarding the non-modifiable and modifiable factors that contributing to recurrent stroke by combining and analysing the results of studies in several countries through a systematic review and meta-analysis approach. This study aims to determine non-modifiable and modifiable factors contributing to recurrent stroke.
2. Materials and methods
2.1 Study design and sample
A systematic review and meta-analysis studies were performed to assess non-modifiable and modifiable factors contributing to recurrent stroke. This study followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guideline.
Three databases, i.e. The PubMed, Proquest, and EBSCO, were employed to search related articles published from January 2010 to January 2021.
2.2 Operational definitions
In this study, recurrent stroke was the dependent variable. The independent variables were the risk factors of recurrent stroke, including non-modifiable risk factors, i.e., age, gender, family history of stroke, and ethnicity, and modifiable risk factors, i.e., hypertension, heart disease, atrial fibrillation, diabetes mellitus, hypercholesterolemia, obesity, smoking history, alcohol consumption, unhealthy lifestyle, and stress.
2.3 Data extraction
The keywords used to search related articles in PubMed, ProQuest and EBSCO between January 2010 and January 2021 were: “((recurrence) AND (stroke OR ischemic stroke OR transient ischemic attack OR embolic stroke OR atherothrombotic stroke OR cerebral infarction) AND (risk factors)).
The included articles limited to original or research articles, with English texts and with human as study subjects. The inclusion criteria included study on risk factors for recurrent stroke with study design of cohort. The study exclusion criteria included full-text version is unavailable, irrelevant topic or subjects, and the data in articles could not be extracted or used for further analysis. The data obtained from the articles were presented in tabulated form by presenting author's name and year of publication, study location, study design, total participants, type of stroke, follow-up duration, risk factors and the effect size. The titles and abstracts of all possibly relevant articles were independently reviewed by two writers (RDN and AH). In order to conduct this systematic review and meta-analysis, we finally determined which articles satisfied the eligibility requirements mentioned above and obtained the full texts of those studies. Differences were resolved through discussion.
2.4 Study quality assesment
Data were separately extracted by two authors (RDN and AH) from each study, and discrepancies were cleared up by discussion with a third author. If more information was required, the authors of these studies were contacted. The Newcastle-Ottawa Quality Assessment Scale (NOS) was used in the assessment of the quality of the articles. The NOS assessed on nine questions: 1) Is the case definition sufficient? 2) the cases' representativeness; 3) controls selection; 4) controls definition; 5) study controls for the most significant factor; 6) study controls for any significant factor; 7) exposure measurement; 8) identical measurement procedure (cases and controls); 9) non response rate. Articles were classified into poor, medium and high quality as the following categories, i.e., score from 0 to 3, 4–6 and 7–9.
The Pooled Hazard Ratio (PHR) with a 95% Confidence Interval (CI) of each risk factors from the extracted data were calculated for further data analysis. I2> 50% showed heterogeneity among studies. After that, the random effect model was used if the result was heterogenous, while the fixed effect model was used if the result was homogenous. Furthermore, the results were presented as forest plots, and then Egger's test was performed to analysed publication bias. The results of p-value >0.05 from the two tests showed no publication bias among the studies. All data processing and analysis were performed using STATA 16.0 software.
3. Results
This systematic review study included eleven recent studies from 2012 to 2022 on non-modifiable and modifiable factors contributing to recurrent stroke (Table 1). The total sample from the included studies was 135,614 patients.
Gender differences and risk factors of recurrent stroke in type 2 diabetic Malaysian population with history of stroke: the observation from Malaysian National Neurology Registry.
Predictors of stroke recurrence in patients with recent lacunar stroke and response to interventions according to risk status: secondary prevention of small subcortical strokes trial.
Gender differences and risk factors of recurrent stroke in type 2 diabetic Malaysian population with history of stroke: the observation from Malaysian National Neurology Registry.
Predictors of stroke recurrence in patients with recent lacunar stroke and response to interventions according to risk status: secondary prevention of small subcortical strokes trial.
Table 1 is based on a synthesis of studies related to risk factors for recurrent stroke, including 11 cohort studies. This study found modifiable factors contributing to recurrent stroke included diabetes mellitus, hypertension, obesity, ischemic heart disease, and atrial fibrillation. Furthermore, non-modifiable factors contributing to recurrent stroke included older age.
Meta-estimate of non-modifiable factors contributing to recurrent stroke was presented on Fig. 2. Fig. 2 showed an association between older age with recurrent stroke (PHR = 1.03 [95% CI 1.02–1.04]). The heterogeneity calculation showed an evidence homogenous among studies in older age (I2 ≤ 50%).
Fig. 2Meta-estimate of non-modifiable factors contributing to recurrent stroke.
Meta-estimate of modifiable factors contributing to recurrent stroke was presented on Fig. 3. Fig. 3 showed modifiable risk factors contributing to recurrent stroke were ischemic heart disease (PHR = 2.78 [95% CI 1.91–6.47]), atrial fibrillation (PHR = 1.87 [95% CI 1.23–2.52]), hypertension (PHR = 1.66 [95% CI] 1.15–2.17]), and obesity (PHR = 0.85 [95% CI] 0.78–0.92]). The heterogeneity calculation showed an evidence homogenous among studies in hypertension, and obesity (I2 ≤ 50%). But,heterogeneity analysis results show heterogeneous variation among studies included in ischemic heart disease, and atrial fibrillation.
Fig. 3Meta-estimate of modifiable factor contributing to recurrent stroke.
The assessment of the publication bias result was verified using Egger's test (Table 2). Table 2 showed that based on Egger's test result (p > 0.05), determinant factors of diabetes mellitus, hypertension, obesity, ischemic heart disease, atrial fibrillation, and older age had no publication bias among studies combined with recurrent stroke. Our analysis also showing the symmetries among the studies combined for each risk factors of recurrent stroke (Fig. 4). Fig. 4 showed each chart consisted of plots separated by vertical lines. In general, the funnel plots in this study described symmetrical plots separated by vertical lines. Overall, in this study there was no publication bias in the study.
Table 2The results of Egger's test to assess bias among studies included.
In this study, our findings showed modifiable factors contributing to recurrent strokes from the highest to the lowest risk were ischemic heart disease, atrial fibrillation, hypertension, and obesity. Non-modifiable factor contributing to recurrent stroke in our study was older age. Current challenges in stroke management include limited awareness of recognizing stroke risk factors and symptoms, insufficient stroke care, and low adherence to therapeutic programs for the prevention of recurrent stroke. As a result, the incidence of first strokes and recurrent strokes has increased, along with death.
Given the continuous improvements in acute diagnosis as well as medical and surgical therapies for stroke patients led by enhanced neuroimaging techniques, the seemingly unchanging rates of stroke recurrence over the previous 20 years are surprising.
In order to develop effective preventative measures, it is crucial to understand the risk factors for recurrent stroke. Knowing the risk factors makes it possible for patients and trained healthcare professionals to recognize the possibility of a recurrent stroke right away.
Previous studies found that the risk for recurrent strokes increased in stroke survivors with heart diseases.
Gender differences and risk factors of recurrent stroke in type 2 diabetic Malaysian population with history of stroke: the observation from Malaysian National Neurology Registry.
Association between atrial fibrillation and the risk of cardiovascular mortality among elderly adults with ischemic stroke in Northeast China: a community-based prospective study.
Another study confirmed that stroke survivors with heart defects, in particular atrial fibrillation, increased risk of recurrent stroke incidence by 1.9 times for the same age and sex.
All these studies supported the results of previous studies which state that atrial fibrillation increased the risk of recurrent stroke incidence about twice higher. The role of atrial fibrillation on recurrent stroke is explained by the embolic mechanism which blocks blood flow, causing hypoxia to the neurons it supplies. This blockage will cause the stroke to recur in the patient.
Gender differences and risk factors of recurrent stroke in type 2 diabetic Malaysian population with history of stroke: the observation from Malaysian National Neurology Registry.
The results of previous studies demonstrated that history of ischemic heart disease as a predictor for recurrent stroke. Another study affirmed a previous history of ischemic heart disease as a determinant factor for recurrent stroke.
This previous study was in line with our findings through a meta-analysis method, with pooled hazard ratio of the risk of ischemic heart disease was more 2 times.
Hypertension causes dysregulation on brain blood vessels. Furthermore, high blood pressure in hypertension increases the risk of atherosclerotic plaque to rupture, as well as the rupture of the vessel in the brain, and thus, causing stroke.
In patients with history of hypertension, recurrent stroke was more likely to occur if there is an increase in diastolic pressure after the first stroke.
Patients who underwent a diastolic blood pressure control twice a year, 4 years and started 1 month after initial stroke, to achieve diastolic <80 mmHg, had a lower risk of recurrent stroke compared to patients who had diastolic 80–90 mmHg.
Furthermore, the incidence of recurrent stroke associated with obesity. Obesity increases the risk of atherosclerosis blood vessels throughout the body including in the brain.
Another determinant factor found in this study is older age. The older age is related to higher systolic blood pressure until the age of 80, while the higher diastolic blood pressure peak at age of 50 and thereafter shows a decrease.
Thus, showing the recurrent stroke distribution on mostly elderly. A previous study with two groups of old age, i.e., 40–64 years and> 65 years, demonstrated that in the duration of the observation >2 years the incidence of recurrent stroke that occurred in the 40–64-year age group was 3.8% and increased in the group> 65 years with 12.7%.
Moreover, with the older age, the greater the risk of recurrent stroke. In the elderly the blood vessels are stiffer due to the presence of plaque. This is related to natural process of degeneration.
Because of etiological presumptions, previously unrecognized risk factors for stroke recurrence may be related. The recurrence patterns of the various stroke subtypes and pertinent risk variables for stroke recurrence might be thoroughly mapped. By determining the risk factors and therapies that should be addressed to decrease stroke recurrence, this mapping could enhance the diagnostic work-up for strokes and preventative initiatives.
The combined study results found high heterogeneity for the risk of diabetes mellitus on stroke recurrence. This happened because the results of several studies that we found in this study varied quite varied, thus affecting the combining effect. The combined study results found high heterogeneity for the risk of diabetes mellitus on stroke recurrence. This happened because the results of several studies were quite varied, thus affecting the combining effect. Furthermore, due to variations in the study population, duration of follow-up, selection of covariates, and diagnostic methods for diabetes and recurrent stroke outcomes, findings on its impact on outcomes after stroke have been contradictory.
Large-scale randomized controlled trials or epidemiological research are still required to prove this association.
The strengths of this study revealed the PHR for modifiable and non-modifiable risk factors with recurrent stroke identified from a diverse range of studies with large sample size and different demographic characteristics in the country. Thus, the limitations of this study found the analysis could provide a basis for concluding risk factors statistically associated with the incidence of recurrent stroke. However, risk factors were estimated by hazard ratio and it may be affected by other confounding variables. The other limitation is that the search strategy restricted articles published in the selected databases and only in English language. There might be articles published in other databases using another language that was not included.
Thus, the implications of this study emphasizes the important of recurrent stroke prevention by identifying the risk factors. Efforts to detect the risk of atrial fibrillation and ischemic heart disease after the onset of an initial stroke are important to reduce the risk of recurrent strokes, supporting the recommendation of heart disease management in stroke patients. Additionally, this study supporting the blood pressure as well as blood glucose level control as an important measurement to prevent recurrent stroke. Lastly, since the older age is a non-modifiable factor contributing to recurrent stroke, a secondary preventive measurement, e.g., healthy lifestyle and regular control for other modifiable risk factors may help to decrease the risk of recurrent stroke. Furthermore, future prospective research will be needed to determine whether or not these risk factors may be effectively treated, closely monitored, and educated about in order to reduce or prevent the chance of stroke recurrence.
The implementation of recurrent stroke prevention programs, which seek to change relevant factors associated and take into consideration each person's non-modifiable characteristics, may lower the incidence of recurrent stroke in the population at risk. Next studies must investigate novel therapeutic targets to lower the risk of stroke recurrence and maximize understanding of the impact of non-medical preventive measures, such as diet consumption, body weight control, physical activity, lifestyle modification, and patient compliance, on stroke recurrence. The findings of this investigation suggest to the necessity for larger prospective studies in the future, along with consistent definitions of diabetes and stroke recurrence assessments, in order to give strong data to management guidelines.
5. Conclusion
Our findings affirm that based on non-modifiable and modifiable factors contributing to recurrent stroke include atrial fibrillation, ischemic heart disease, hypertension, obesity, and older age. The development of recurrent stroke prevention initiatives, which aim to modify relevant risk factors and to consider each individual's non-modifiable factors, may result in a reduction of recurrent stroke incidence in the population at risk. Furthermore, Future studies must investigate novel therapeutic targets to lower the risk of stroke recurrence and maximize understanding of the impact of non-medical preventive measures, such as diet consumption, body weight control, physical activity, lifestyle modification, and patient compliance on stroke recurrence.
Souce of funding
Nil.
Declaration of competing interest
There are no conflicts of interest.
Acknowledgments
The authors would like to thank Riyani Betri Novialita, MA for collecting data.
South London Stroke Register. Cause of stroke recurrence is multifactorial: patterns, risk factors, and outcomes of stroke recurrence in the South London Stroke Register.
Gender differences and risk factors of recurrent stroke in type 2 diabetic Malaysian population with history of stroke: the observation from Malaysian National Neurology Registry.
Predictors of stroke recurrence in patients with recent lacunar stroke and response to interventions according to risk status: secondary prevention of small subcortical strokes trial.
Association between atrial fibrillation and the risk of cardiovascular mortality among elderly adults with ischemic stroke in Northeast China: a community-based prospective study.
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