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Carotid plaque components and other carotid artery features associated with risk of stroke: A systematic review and meta-analysis

Open AccessPublished:November 03, 2022DOI:https://doi.org/10.1016/j.jstrokecerebrovasdis.2022.106857

      Abstract

      Objective

      To compare the difference in the risk of stroke for four kinds of carotid artery plaque and carotid artery stenosis.

      Methods

      Literature was collected by searching the PubMed, Embase, Cochrane library and Ovid databases up to June 2022, using the free search terms "carotid plaque" and "stroke". Meta-analysis was performed on the selected articles using Stata16 to analyse the relationship of stroke risk factors.

      Results

      A total of 11 studies including 6661 participants were included. Meta-analysis results showed that the incidence of stroke was statistically significantly different between IPH (intraplaque haemorrhage) plaques and LRNC (lipid-rich necrotic core) plaques (RR: 1.27, 95% CI: 1.04–1.55, P < 0.05) and IPH plaques and calcification plaques (RR: 2.99, 95% CI: 1.74–5.14, P < 0.0001). Furthermore, there was a statistically significant difference between TRFC (thinned or ruptured fibrous caps) plaques and carotid artery stenosis (RR: 10.84, 95% CI: 5.60–20.98, P < 0.0001) and calcification plaques and carotid artery stenosis (RR: 0.83, 95% CI: 0.75–0.92, P < 0.0001). However, there was no statistically significant difference between the IPH and carotid artery stenosis (RR: 1.55, 95% CI: 0.68–3.52, P > 0.05), LRNC and TRFC (RR: 0.80, 95% CI: 0.11–5.82, P > 0.05), LRNC and calcification (RR: 1.81, 95% CI: 0.90–3.66, P > 0.05) and LRNC and carotid artery stenosis (RR: 1.40, 95% CI: 0.69–2.81, P > 0.05).

      Conclusion

      IPH was associated with a higher incidence of stroke compared to LRNC and calcification plaques and TRFC has a higher risk of stroke than calcification plaques and carotid stenosis. This evidence suggests that IPH and TRFC may play an important role in predicting stroke.

      Keywords

      Introduction

      Stroke is a leading cause of death and disability globally,
      • Katan M
      • L A.
      Global burden of stroke.
      obviously placing a heavy health burden on the public.
      • Benjamin EJ
      • B M.
      • Chiuve SE
      • Cushman M
      • Das SR
      • Deo R
      • et al.
      Heart disease and stroke statistics-2017 Update: a report from the American Heart Association.
      The World Health Organisation defines it as a vascular disorder, portraying rapid focal or global disturbances in cerebral functions continuing for more than 24 h or leading to death.
      • Xu W
      • G L
      • Zheng J
      • Li T
      • Shao A
      • Reis C
      • et al.
      The roles of microRNAs in stroke: possible therapeutic targets.
      Pathophysiologically, it is an emergency state within a cerebral infarct or the sudden death of neural cells in a localised area due to a blocked or ruptured artery, resulting in inadequate blood flow and a subsequent lack of oxygen and nutrients.
      Intracranial atherosclerotic disease (ICAD) represents one of the most common causes of ischemic stroke worldwide.
      • Holmstedt CA
      • T T.
      • Chimowitz MI
      Atherosclerotic intracranial arterial stenosis: risk factors, diagnosis, and treatment.
      Atherosclerotic disease is characterised by plaque formation within the arterial wall. The presence of unstable atherosclerotic plaques in the carotid artery is a known aetiological factor causing cerebrovascular events, such as an ischemic stroke (IS), transient ischemic attack, or amaurosis fugax.
      • Lee RT
      • L P.
      The unstable atheroma.
      Thus, carotid atherosclerotic plaques represent an important disease burden.

      PHAo., C., Tracking heart disease and stroke in Canada. 2009.

      In brief, carotid atherosclerosis may result in a stroke through rupture of a carotid atherosclerotic plaque, which leads to the embolisation of plaque material and thrombi into distal arteries.
      Plaques are generally located between the intima and the middle membrane; that is, they are almost located in the lumen of the blood vessel. The gradual increase in plaques will lead to carotid stenosis or even occlusion, resulting in blocked blood flow in the carotid artery and insufficient brain blood supply, which may lead to stroke. Those plaques, which are more prone to rupture and are associated with a higher risk of ischemic stroke, are known as vulnerable plaques. Important characteristics of these vulnerable plaques are the presence of intraplaque haemorrhage (IPH)
      • Gupta A
      • B H.
      • Schweitzer AD
      • Kamel H
      • Pandya A
      • Delgado D
      • et al.
      Carotid plaque MRI and stroke risk: a systematic review and meta-analysis.
      , a lipid-rich necrotic core (LRNC), a thin-or-ruptured fibrous cap (TRFC) and plaque ulceration.
      • Schindler A
      • S R.
      • Altaf N
      • Hosseini AA
      • Simpson RJ
      • Esposito-Bauer L
      • et al.
      Prediction of stroke risk by detection of hemorrhage in carotid plaques: meta-analysis of individual patient data.
      ,
      • Homburg PJ
      • R S.
      • van Gils MJ
      • Jansen T
      • de Weert TT
      • Dippel DW
      • et al.
      Atherosclerotic plaque ulceration in the symptomatic internal carotid artery is associated with nonlacunar ischemic stroke.
      Many cross-sectional and prospective studies have shown that the main morphological characteristics of high-risk carotid plaques are IPH, fibrous cap rupture (FCR) and large LRNC, which are closely related to the risk of stroke. More importantly, the occurrence of IPH and FCR in carotid atherosclerosis is significantly higher in patients with cerebrovascular symptoms (transient ischemic attack or stroke) than in asymptomatic patients.
      • Saam T
      • C J.
      • Ma L
      • Cai YQ
      • Ferguson MS
      • Polissar NL
      • et al.
      Comparison of symptomatic and asymptomatic atherosclerotic carotid plaque features with in vivo MR imaging.
      A prospective study showed that the characteristics of vulnerable plaques such as IPH, FCR and large LRNC were important predictors of cerebrovascular events.
      • Takaya N
      • Y C.
      • Chu B
      • Saam T
      • Underhill H
      • Cai J
      • et al.
      Association between carotid plaque characteristics and subsequent ischemic cerebrovascular events: a prospective assessment with MRI–initial results.
      The brain's blood is supplied by four blood vessels: two carotid arteries and two vertebral arteries. A lesion in any one of these four arteries can lead to cerebral ischemia, causing a stroke. Carotid artery stenosis (CAS) accounts for about 80% of ischemic stroke. CAS is a well-established risk factor of ischemic stroke, contributing to up to 10–20% of strokes or transient ischemic attacks.
      • Brinjikji W
      • H J.r.
      • Rabinstein AA
      • Kim GM
      • Lerman A
      • et al.
      Contemporary carotid imaging: from degree of stenosis to plaque vulnerability.
      CAS, typically resulting from atherosclerotic progression, is more common than intracranial atherosclerotic disease in patients with cerebrovascular disease and is one of the major causes of stroke and transient ischemic attack (TIA).
      • Lovrencic-Huzjan A
      • R T.
      • Katsnelson M
      Recommendations for management of patients with carotid stenosis.
      ,
      • Flaherty ML
      • K B
      • Khoury JC
      • Alwell K
      • Moomaw CJ
      • Woo D
      • Khatri P
      • Ferioli S
      • Adeoye O
      • Broderick JP
      • Kleindorfer D.
      Carotid artery stenosis as a cause of stroke.
      The presence of plaques in the carotid artery and CAS are usually asymptomatic, but high-risk plaques are associated with the possibility of stroke; therefore, it is important to clear the stroke incidence risk difference between four domains kinds of plaque components. The aim of this systematic review and meta-analysis is to investigate the relative risk of stroke for carotid plaques.

      Methods

      Search strategy

      We adhered to the meta-analysis in the preferred reporting items for systematic reviews and meta-analyses (PRISMA)Guidelines.
      • Page MJ
      • M J.
      • Bossuyt PM
      • Boutron I
      • Hoffmann TC
      • Mulrow CD
      • et al.
      The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.
      Three reviewers (ZY, BY, XJ) independently searched all relevant publications published in the PubMed, Embase, Cochrane library and Ovid databases. The deadline for searching the self-built database was June 2022. The free words used in the search strategy were “stroke,” "carotid plaque" and "carotid artery", regardless of date, language, region, or publication type. The search was limited to published clinical studies.

      Inclusion and exclusion criteria

      If the following conditions were met at the same time, the study was included: (1) The following plaque components were detected: IPH, LRNC, TRFC or carotid artery stenosis degree(the degree of carotid stenosis>25%); (2) there were outcome indicators (stroke); and (3) no history of stroke. Exclusion criteria: (1) unable to apply and convert the data in the original literature; (2) unable to obtain the full text of the literature; and (3) review, expert opinion, or case report, etc.

      Data extraction

      Three reviewers (ZY, BY, XJ) independently extracted the general characteristics of the research data, including the first author's last name, year, region, baseline characteristics (total sample size, average age and gender distribution), research design (prospective or cross control study), risk factors for stroke (IPH, LRNC, TRFC, calcification, carotid artery stenosis), follow-up information (with the average or maximum follow-up), outcome indicators (stroke) and the number of strokes.

      Study quality assessment

      The Newcastle Ottawa Scale (NOS) was used to assess the quantity of literature. Quality was classified according to the final score: 0–3 as low quality, 4–6 as medium quality and 7–9 as high quality.

      Data analysis

      Microsoft Excel 2016 software was used to establish the database. Stata16 software was used for analysis, while the RR (risk ratio) and 95% confidence interval were used for analysis. The relationship between IPH, LRNC, TRLC, calcification plaques, carotid artery stenosis and stroke was analysed. The heterogeneity was assessed by Cochrane's Q statistics (Chi-square), or inverse variance (I2). If I2<50% and P > 0.1, it indicated that these studies could be considered as homogeneous by using a fixed-effect model; alternatively, if I2≥50%, P < 0.10, the random effect model was used for meta-analysis.

      Ethics approval

      It was not required, because the study type of our article is systematic review and meta-analysis .

      Results

      Flow chart and study quality assessment

      A total of 3736 articles were retrieved from the databases. After eight duplicate records were deleted, the remaining 3728 full text studies were screened. Of these studies, 621 were excluded due to the articles being reviews or meta-analyses, while 3033 studies did not have related titles and abstracts. The full text of the remaining 74 studies was screened. Three studies were deleted due to incomplete data, 14 were deleted as the study subjects were stroke patients and 40 were deleted due to the presence of risk data for only one plaque. The remaining 11 papers underwent data extraction in accordance with the requirements of data extraction. The literature screening process is shown in Fig. 1. The basic characteristics of the included studies are shown in Table 1. The quality assessment of the included literatures according to the Ottawa scale is shown in Table 2 and the included articles were of medium and high quality.
      Fig 1
      Fig. 1The literature screening process of the meta-analysis
      Tabel 1Basic characteristics of enrolled studies.
      AuthorStudyYearRegionSampleAge (mean±sd/range)Sex (female, n)Risk factor
      Daniel Bos, MD, PHDprospective2021Netherlands134972.3±9.3668IPH, LRNC, Cal
      Mariana Selwanessprospective2016Netherlands173172.4±9.1795IPH, LRNC, Cal
      Marie-Luise Monoprospective2012Switzerland6268.7±8.610LRNC, TRFC, Stenosis
      Mingming Luprospective2018China6366.5±10.09IPH, LRNC, TRFC, Cal, Stenosis
      Clothilde Isabelprospective2014France6567.4 (40–88)17IPH Stenosis
      Rémy Pascotprospective2018France14170.5±8.034IPH,Cal,Stenosis
      Lorena Esposito-Bauerprospective2013Germany7772.8 (54–88)35IPH,LRNC,Cal,Stenosis
      Navneet Singhprospective2009Canada9174.8±7.930IPH,Stenosis
      Willem E. Hellingsprospective2010Netherlands81868.1±8.7247IPH,Stenosis
      Nishath Altafprospective2007United Kingdom6669.5 (65.0–77.8)10IPH,Stenosis
      B Lernfeltcase control study2002Sweden142——76Cal,Stenosis
      note:IPH: intraplaque hemorrhage; LRNC: lipid-rich necrotic core; TRFC: thinned or ruptured fifibrous caps;Cal:calcification;Stenosis:the degree of carotid stenosis
      Tabel 2The quality assessment of the included literatures.
      StudyStudy designNEWCASTLE-OTTAWA SCALE
      SelectionComparabilityExposure
      Bos D 2021Prospective☆☆☆☆☆☆☆☆☆
      Selwaness M 2016Prospective☆☆☆☆☆☆☆☆
      Mono ML2012Prospective☆☆☆☆☆
      Lu M 2018Prospective☆☆☆☆☆
      Isabel C 2014Prospective☆☆
      Pascot R 2018Prospective
      Esposito-Bauer L 2013Prospective☆☆☆☆☆
      Singh N 2009Prospective☆☆☆☆☆
      Hellings WE 2010Prospective☆☆☆☆☆
      Altaf N 2007Prospective☆☆☆☆☆
      B Lernfelt 2002Prospective☆☆☆☆☆☆☆☆☆

      IPH against LRNC

      In total, 4 articles including 2450 patients were analysed. The heterogeneity test results showed P > 0.1 and I2<50%, indicating that the heterogeneity was acceptable. The fixed effect model was used for analysis and calculate the combined statistics (RR: 1.27, 95% CI: 1.04–1.55, P = 0.018), indicating the incidence of stroke in IPH was 1.27 times higher than that in LRNC, as shown in Fig. 2.
      Fig 2
      Fig. 2Results of meta-analyses of stroke risk in IPH and LRNC

      IPH against calcification

      A total of 5 articles on stroke, including IPH and calcification (Cal) composition, included 3717 patients. The heterogeneity test results show P < 0.1 and I2>50%, indicating that several studies have heterogeneity, so the random effects model analysis was used. Meta-analysis results showed that the incidence of stroke was statistically significant different between IPH and calcification plaques (RR: 2.99, 95% CI: 1.74–5.14, P = 0.000), as shown in Fig. 3.
      Fig 3
      Fig. 3Results of meta-analyses of stroke risk in IPH and Cal

      IPH against stenosis

      Seven articles including 1861 patients were analysed. The random-effect model (P < 0.1 and I2>50%) was used to analyse the combined statistics (RR: 1.55, 95% CI: 0.68–3.52, P = 0.503), indicating that there was no statistically significant difference between IPH and carotid stenosis regarding stroke risk, as shown in Fig. 4.
      Fig 4
      Fig. 4Results of meta-analyses of stroke risk in IPH and Stenosis

      LRNC against TRFC

      The heterogeneity test results showed P < 0.1 and I2>50%. It could be considered that studies had heterogeneity, so the random-effect model was used for analysis and to calculate the combined statistics. There was no statistically significant difference in the incidence of stroke between LRNC and TRFC (RR: 0.80, 95% CI: 0.11–5.82, P = 0.829), as shown in Fig. 5.
      Fig 5
      Fig. 5Results of meta-analyses of stroke risk in TRFC and LRNC

      LRNC against cal

      A total of 4 articles on stroke, including LRNC and Cal, included 3957 patients. The heterogeneity test results showed P < 0.1 and I2>50%, so the random-effect model was used. No statistically significant difference regarding the incidence of stroke was found between LRNC and TRFC (RR: 1.81, 95% CI: 0.90–3.66, P = 0.099), as shown in Fig. 6.
      Fig 6
      Fig. 6Results of meta-analyses of stroke risk in Cal and LRNC

      LRNC against stenosis

      The fixed effect model (P > 0.1 and I2 < 50%) was used to analyse and calculate the combined statistics. There was no statistically significant difference for stroke risk between LRNC and carotid stenosis (RR: 1.40, 95% CI: 0.69–2.81, P = 0.351), as shown in Fig. 7.
      Fig 7
      Fig. 7Results of meta-analyses of stroke risk in Stenosis and LRNC

      TRFC against stenosis

      There were 4 articles on stroke, including TRFC and carotid stenosis, which included 95 patients. The heterogeneity test results showed P > 0.1 and I2<50%, indicating that the heterogeneity was acceptable. The fixed effect model was used to analyse and calculate the combined statistics (RR:10.84, 95% CI: 5.60–20.98, P = 0.000), indicating that the incidence of stroke in the TRFC was 10.84 times higher than stenosis, as shown in Fig. 8.
      Fig 8
      Fig. 8Results of meta-analyses of stroke risk in Stenosis and TRFC

      Cal against stenosis

      A total of 4 articles on stroke including Cal and carotid stenosis were analysed. There was a statistically significant difference between Cal and Stenosis regarding stroke risk; the Cal was higher than stenosis (RR: 0.83, 95% CI: 0.75–0.92, P = 0.000), as shown in Fig. 9.
      Fig 9
      Fig. 9Results of meta-analyses of stroke risk in Stenosis and Cal

      Publication bias

      Publication bias was evaluated by symmetry of the funnel plot. The effect estimates of the large number of small sample studies with low accuracy are widely distributed at the bottom of the plot and arranged symmetrically. The effect estimates of small and high precision large samples are distributed at the top of the figure and the distribution range is narrow and gradually concentrated to the position centred on the combined effect size. The IPH against LRNC funnel plot distribution of the literature was concentrated to the position centred on the combined effect size and has no publication bias, as shown in Fig. 10a. The IPH against the Cal funnel plot, IPH against the stenosis funnel plot, LRNC against TRFC funnel plot, LRNC against Cal funnel plot, LRNC against stenosis funnel plot, TRFC against stenosis funnel plot and Cal against stenosis funnel plot distribution of the literature was asymmetric and has publication bias, as shown in Fig. 10b-h.

      Discussion

      Stroke is the leading cause of disability in the United States and the leading cause of death worldwide
      • Esenwa C
      • G J.
      Secondary stroke prevention: challenges and solutions.
      ; however, according to the latest data, 85% of strokes are preventable.
      • Sarikaya H
      • F J.
      • Arnold M
      Stroke prevention–medical and lifestyle measures.
      Stroke is associated with many factors. Elevated total high cholesterol levels are a risk factor for stroke,
      • Silverman MG
      • F B.
      • Im K
      • Wiviott SD
      • Giugliano RP
      • Grundy SM
      • Braunwald E
      • Sabatine MS.
      Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis.
      while obesity, a lack of physical activity and poor diet have also been proven to be risk factors for stroke, as have hypertension, diabetes, carotid artery stenosis and plaque rupture, among others.
      • Caprio FZ
      • S F.
      Cerebrovascular disease: primary and secondary stroke prevention.
      Some studies suggested that asymptomatic carotid stenosis patients with unstable plaques, such as intraplaque haemorrhage, a lipid-rich necrotic core and thinned or ruptured fibrous caps in carotid plaque components, are more likely to have an associated stroke than stable plaques.
      • Esposito-Bauer L
      • S T.
      • Ghodrati I
      • Pelisek J
      • Heider P
      • Bauer M
      • Wolf P
      • Bockelbrink A
      • Feurer R
      • Sepp D
      • Winkler C
      • Zepper P
      • Boeckh-Behrens T
      • Riemenschneider M
      • Hemmer B
      • Poppert H.
      MRI plaque imaging detects carotid plaques with a high risk for future cerebrovascular events in asymptomatic patients.
      ,
      • Gupta A
      • B H.
      • Schweitzer AD
      • Kamel H
      • Pandya A
      • Delgado D
      • et al.
      Carotid plaque MRI and stroke risk: a systematic review and meta-analysis.
      Mauro Silvestrini et al. suggested that stenosis progression and severity should be considered as risk factors for cerebrovascular events in asymptomatic subjects with severe ICA stenosis.
      • Silvestrini M
      • A C.
      • Cerqua R
      • Pasqualetti P
      • Viticchi G
      • Provinciali L
      • et al.
      Ultrasonographic markers of vascular risk in patients with asymptomatic carotid stenosis.
      Meanwhile, several studies suggested
      • Bos D
      • A B.
      • van den Bouwhuijsen QJA
      • Ikram MK
      • Selwaness M
      • Vernooij MW
      • Kavousi M
      • van der Lugt A.
      Atherosclerotic Carotid Plaque Composition and Incident Stroke and Coronary Events.
      that IPH was promising as a marker of plaque vulnerability in healthy people with subclinical atherosclerosis.
      • Singh N
      • M A.
      • Gladstone DJ
      • Leung G
      • Ravikumar R
      • Zhan J
      • et al.
      Moderate carotid artery stenosis: MR imaging-depicted intraplaque hemorrhage predicts risk of cerebrovascular ischemic events in asymptomatic men.
      ,
      • Altaf N
      • M S.
      • Gladman J
      • Auer DP
      Carotid intraplaque hemorrhage predicts recurrent symptoms in patients with high-grade carotid stenosis.
      Also, Marie-Luise Mono et al. indicated that LRNC was a predictor of cerebrovascular events.
      • Mono ML
      • K A.
      • Slotboom J
      • Remonda L
      • Galimanis A
      • Jung S
      • Findling O
      • De Marchis GM
      • Luedi R
      • Kiefer C
      • Stuker C
      • Mattle HP
      • Schroth G
      • Arnold M
      • Nedeltchev K
      • El-Koussy M.
      Plaque characteristics of asymptomatic carotid stenosis and risk of stroke.
      However, there was no systematic evidence of which plaque component is more strongly associated with stroke; therefore, it was necessary to conduct a meta-analysis to present systematic evidence.
      Here, we illustrated the difference in risk for four kinds of carotid artery plaques which cause stroke. Our study found that IPH plaques were more dangerous than LRNC plaques and had a higher associated risk than calcification plaques. Andreas Schindler et al. indicated that IPH was common in patients with symptomatic and asymptomatic carotid stenosis and was a stronger predictor of stroke than any known clinical risk factors. Meanwhile, the results suggested that stroke was more likely to occur in LRNC plaques than calcification plaques, which was consistent with the results of Lorena Esposito-Bauer.
      • Esposito-Bauer L
      • S T.
      • Ghodrati I
      • Pelisek J
      • Heider P
      • Bauer M
      • Wolf P
      • Bockelbrink A
      • Feurer R
      • Sepp D
      • Winkler C
      • Zepper P
      • Boeckh-Behrens T
      • Riemenschneider M
      • Hemmer B
      • Poppert H.
      MRI plaque imaging detects carotid plaques with a high risk for future cerebrovascular events in asymptomatic patients.
      Compared with carotid artery stenosis and calcification plaques, TRFC plaques contributed more to stroke. Mingming Lu et al. suggested that IPH and TRFC have additional predictive value for recurrent ischemic cerebrovascular events,
      • Lu M
      • P P.
      • Cui Y
      • Qiao H
      • Li D
      • Cai J
      Association of progression of carotid artery wall volume and recurrent transient ischemic attack or stroke: a magnetic resonance imaging study.
      which was consistent with our results.
      It is possible to reduce blood pressure and possibly reduce the risk of stroke by changing poor diets, lowering sodium intake, increasing potassium intake and recommending a diet of fruits, vegetables and low-fat dairy products.
      • Meschia JF
      • B C.
      • Boden-Albala B
      • Braun LT
      • Bravata DM
      • Chaturvedi S
      • et al.
      Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association.
      Unstable carotid plaques are associated with an increased risk of future cerebrovascular accident. Meanwhile, there is sufficient evidence from our systematic review and meta-analysis to conclude that MRI characterisation of the specific plaque elements of IPH, LRNC and TRFC can provide additional measures of stroke risk that are not provided by simple measurements of luminal stenosis. The early prevention of risk factors was expected to reduce the incidence of stroke.

      Conclusion

      IPH was associated with a higher incidence of stroke compared to LRNC and calcification plaques, while TRFC has a higher risk of stroke than calcification plaques and carotid stenosis. This evidence shows that IPH and TRFC may play an important role in predicting stroke. Early intervention can avoid unnecessary surgery and stroke events.

      Limitations

      This meta-analysis has several limitations: First, the literature for comparison between some groups was small. More relevant studies should be included in the future. Second, despite the study's large sample and rigorous methods, there was substantial heterogeneity in the prevalence of high-risk features among the studies included in the meta-analysis, which may be explained by differences across studies regarding the definition criteria and the imaging modalities used. Consensus imaging recommendations are needed to help to decrease the heterogeneity of carotid imaging data across studies.

      Author contributions

      ZY and BY designed and wrote the manuscript for XF. ZY, BY and XJ screened the references and extracted the data from the literature. ZY and XF analysed and interpreted the data. BY evaluated the quality of studies. XF and HM proofread the manuscript.

      Ethics statement

      Not available.

      Declaration of Competing Interest

      The authors declare that they have no conflicts of interest.

      Funding

      This study was supported by the Chengdu Science and Technology Bureau focus on research and development support plan ( 2019-YF09-00097-SN ).

      Acknowledgment

      We thank the postgraduate candidates Wang Meng and Zhang Yan who performed numerous clinical examinations on the prediction of stroke in community hospitals and provided valuable suggestions for this study.

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