Skip to main content
Top
Published in:

Open Access 01-12-2024 | Systematic Review

Risk of stroke in patients with congenital heart disease: a systematic review and meta-analysis

Authors: Ramez M. Odat, Muhammad Idrees, Hritvik Jain, Sakhr Alshwayyat, Husam Aldean H. Hussain, Basma Badrawy Khalefa, Ali O. Aldamen, Abdel Rahman K. Bani Yaseen, Bassel Alrabadi, Mohammad-Amer A. Tamimi, Ayham Mohammad Hussein, Hamdah Hanifa, Osama Aloudat

Published in: BMC Neurology | Issue 1/2024

Login to get access

Abstract

Background

Patients with congenital heart disease (CHD) are more likely to experience ischemic and hemorrhagic stroke due to factors such as arrhythmias, residual shunts and related cardiovascular complications. However, guidelines for identifying CHD patients at the highest risk of stroke remain unclear. In this study, we aimed to evaluate the risk of developing stroke in patients with CHD.

Methods

A systematic literature search was performed on PubMed, Scopus, Cochrane, and Embase databases to retrieve studies that evaluated stroke risk in patients with CHD. Random effects model was used to pool the hazard ratios (HR) with 95% confidence intervals (CI). Subgroup analysis was conducted on age, type of stroke, type of study and region. Publication bias was assessed by Egger’s regression test. Statistical significance was set at p < 0.05. All the analysis was performed using R studio V4.3.1.

Results

Eleven studies (5,490,412 participants) were included in this systematic review and meta-analysis. Patients with CHD were at a higher risk of stroke [Pooled HR: 3.25; 95% CI: 2.25, 4.68; p < 0.01; I2: 100%] than the control group. In subgroup analysis, patients with CHD were at a higher risk of ischemic stroke [Pooled HR: 4.45; 95% CI: 2.24, 8.85; p < 0.01; I2: 100%] and hemorrhagic stroke [Pooled HR: 4.70; 95% CI: 1.70, 12.96; p < 0.01; I2: 99%] than the control group.

Conclusion

Our meta-analysis indicates a significantly increased stroke risk in patients with CHD. Subgroup analyses showed higher stroke risk in European regions compared to Asia and USA, and among adults compared to pediatric populations. Future studies should focus on addressing regional and data limitations to better inform clinical strategies for managing stroke risk in CHD patients.

Graphical Abstract

Appendix
Available only for authorised users
Literature
1.
go back to reference Guzik A, Bushnell C. Stroke epidemiology and risk factor management. CONTINUUM: Lifelong Learn Neurol. 2017;23(1):15–39. Guzik A, Bushnell C. Stroke epidemiology and risk factor management. CONTINUUM: Lifelong Learn Neurol. 2017;23(1):15–39.
2.
go back to reference Ravandi F, Haj Mohamad Ebrahim Ketabforoush A, Azedi F, Hoshyarkhani M, Fayyaz F, Abbasi Khoshsirat N. Heart failure status among Acute ischemic stroke patients: a hospital-based study. Neurol Res Int. 2022;2022:1–6.CrossRef Ravandi F, Haj Mohamad Ebrahim Ketabforoush A, Azedi F, Hoshyarkhani M, Fayyaz F, Abbasi Khoshsirat N. Heart failure status among Acute ischemic stroke patients: a hospital-based study. Neurol Res Int. 2022;2022:1–6.CrossRef
3.
go back to reference Ashiq S, Ashiq K. Genetic perspective of the congenital heart disease. Pakistan Heart J. 2020;53(3). Ashiq S, Ashiq K. Genetic perspective of the congenital heart disease. Pakistan Heart J. 2020;53(3).
4.
go back to reference Liu Y, Chen S, Zühlke L, Black GC, Choy MK, Li N et al. Global birth prevalence of congenital heart defects 1970–2017: updated systematic review and meta-analysis of 260 studies. Int J Epidemiol. 2019;48(2). Liu Y, Chen S, Zühlke L, Black GC, Choy MK, Li N et al. Global birth prevalence of congenital heart defects 1970–2017: updated systematic review and meta-analysis of 260 studies. Int J Epidemiol. 2019;48(2).
5.
go back to reference Araujo JJ, Araujo JJ. Adults with congenital heart disease in the Americas - where we are today and where we are heading: a General View of the inter-american adult congenital heart Disease Council. J Integr Cardiol Open Access. 2020;1–5. Araujo JJ, Araujo JJ. Adults with congenital heart disease in the Americas - where we are today and where we are heading: a General View of the inter-american adult congenital heart Disease Council. J Integr Cardiol Open Access. 2020;1–5.
6.
go back to reference Dellborg M, Giang KW, Eriksson P, Liden H, Fedchenko M, Ahnfelt A et al. Adults with congenital heart disease: Trends in Event-Free Survival Past Middle Age. Circulation. 2023;147(12). Dellborg M, Giang KW, Eriksson P, Liden H, Fedchenko M, Ahnfelt A et al. Adults with congenital heart disease: Trends in Event-Free Survival Past Middle Age. Circulation. 2023;147(12).
7.
go back to reference Brida M, Gatzoulis MA. Adult congenital heart disease: Past, present and future. Vol. 108, Acta Paediatrica, International Journal of Paediatrics. 2019. Brida M, Gatzoulis MA. Adult congenital heart disease: Past, present and future. Vol. 108, Acta Paediatrica, International Journal of Paediatrics. 2019.
8.
go back to reference Lotto R, Thomet C. Emerging adulthood: The ageing problem of congenital heart disease. Vol. 27, Nursing in Critical Care. 2022. Lotto R, Thomet C. Emerging adulthood: The ageing problem of congenital heart disease. Vol. 27, Nursing in Critical Care. 2022.
9.
go back to reference Portal D, Hirsch R, Benderly M. Increased prevalence of cardiac and non-cardiac chronic morbidity among adults with congenital heart disease. Int J Cardiol Congenital Heart Disease. 2022;7. Portal D, Hirsch R, Benderly M. Increased prevalence of cardiac and non-cardiac chronic morbidity among adults with congenital heart disease. Int J Cardiol Congenital Heart Disease. 2022;7.
10.
go back to reference Cocomello L, Taylor K, Caputo M, Cornish RP, Lawlor DA. Health and Well-being in surviving congenital Heart Disease patients: an Umbrella Review with synthesis of best evidence. In: Frontiers in Cardiovascular Medicine. Vol 9. Switzerland; 2022. p. 870474. Cocomello L, Taylor K, Caputo M, Cornish RP, Lawlor DA. Health and Well-being in surviving congenital Heart Disease patients: an Umbrella Review with synthesis of best evidence. In: Frontiers in Cardiovascular Medicine. Vol 9. Switzerland; 2022. p. 870474.
12.
go back to reference Tsui C, Wan D, Grewal J, Kiess M, Barlow A, Human D et al. Increasing age and atrial arrhythmias are associated with increased thromboembolic events in a young cohort of adults with repaired tetralogy of Fallot. J Arrhythm. 2021;37(6). Tsui C, Wan D, Grewal J, Kiess M, Barlow A, Human D et al. Increasing age and atrial arrhythmias are associated with increased thromboembolic events in a young cohort of adults with repaired tetralogy of Fallot. J Arrhythm. 2021;37(6).
13.
go back to reference Poisson SN, Hills NK, Sidney S, Fullerton HJ. Prevalence of atherosclerotic risk factors among children and young adults with arterial ischemic stroke. JAMA Neurol. 2022;79(9). Poisson SN, Hills NK, Sidney S, Fullerton HJ. Prevalence of atherosclerotic risk factors among children and young adults with arterial ischemic stroke. JAMA Neurol. 2022;79(9).
14.
go back to reference Yang H, Kuijpers JM, de Groot JR, Konings TC, van Dijk A, Sieswerda GT et al. Impact of atrial arrhythmias on outcome in adults with congenital heart disease. Int J Cardiol. 2017;248. Yang H, Kuijpers JM, de Groot JR, Konings TC, van Dijk A, Sieswerda GT et al. Impact of atrial arrhythmias on outcome in adults with congenital heart disease. Int J Cardiol. 2017;248.
15.
go back to reference Lin YS, Liu PH, Wu LS, Chen YM, Chang CJ, Chu PH. Major adverse cardiovascular events in adult congenital heart disease: a population-based follow-up study from Taiwan. BMC Cardiovasc Disord. 2014;14. Lin YS, Liu PH, Wu LS, Chen YM, Chang CJ, Chu PH. Major adverse cardiovascular events in adult congenital heart disease: a population-based follow-up study from Taiwan. BMC Cardiovasc Disord. 2014;14.
16.
go back to reference Hoffmann A, Chockalingam P, Balint OH, Dadashev A, Dimopoulos K, Engel R et al. Cerebrovascular accidents in adult patients with congenital heart disease. Heart. 2010;96(15). Hoffmann A, Chockalingam P, Balint OH, Dadashev A, Dimopoulos K, Engel R et al. Cerebrovascular accidents in adult patients with congenital heart disease. Heart. 2010;96(15).
17.
go back to reference Jain H, Odat RM, Goyal A, Jain J, Dey D, Ahmed M, et al. Association between psoriasis and atrial fibrillation: a systematic review and meta-analysis. Curr Probl Cardiol. 2024;49(6):102538.CrossRefPubMed Jain H, Odat RM, Goyal A, Jain J, Dey D, Ahmed M, et al. Association between psoriasis and atrial fibrillation: a systematic review and meta-analysis. Curr Probl Cardiol. 2024;49(6):102538.CrossRefPubMed
18.
go back to reference Goyal A, Jain H, Maheshwari S, Jain J, Odat RM, Saeed H, et al. Association between inflammatory bowel disease and atrial fibrillation: a systematic review and meta-analysis. IJC Heart Vasculature. 2024;53:101456.CrossRefPubMedPubMedCentral Goyal A, Jain H, Maheshwari S, Jain J, Odat RM, Saeed H, et al. Association between inflammatory bowel disease and atrial fibrillation: a systematic review and meta-analysis. IJC Heart Vasculature. 2024;53:101456.CrossRefPubMedPubMedCentral
19.
go back to reference Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.CrossRefPubMedPubMedCentral Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.CrossRefPubMedPubMedCentral
20.
go back to reference Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–5.CrossRefPubMed Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–5.CrossRefPubMed
21.
go back to reference Balduzzi S, Rücker G, Schwarzer G. How to perform a meta-analysis with R: a practical tutorial. Evid Based Mental Health. 2019;22(4):153–60.CrossRef Balduzzi S, Rücker G, Schwarzer G. How to perform a meta-analysis with R: a practical tutorial. Evid Based Mental Health. 2019;22(4):153–60.CrossRef
23.
go back to reference Nolte IM. Metasubtract: an R-package to analytically produce leave-one-out meta-analysis GWAS summary statistics. Bioinformatics. 2020;36(16):4521–2.CrossRefPubMedPubMedCentral Nolte IM. Metasubtract: an R-package to analytically produce leave-one-out meta-analysis GWAS summary statistics. Bioinformatics. 2020;36(16):4521–2.CrossRefPubMedPubMedCentral
24.
25.
go back to reference Giang KW, Mandalenakis Z, Dellborg M, Lappas G, Eriksson P, Hansson PO, et al. Long-term risk of hemorrhagic stroke in young patients with congenital heart disease. Stroke. 2018;49(5):1155–62.CrossRefPubMedPubMedCentral Giang KW, Mandalenakis Z, Dellborg M, Lappas G, Eriksson P, Hansson PO, et al. Long-term risk of hemorrhagic stroke in young patients with congenital heart disease. Stroke. 2018;49(5):1155–62.CrossRefPubMedPubMedCentral
26.
go back to reference Maxwell BG, Wong JK, Kin C, Lobato RL. Perioperative outcomes of major noncardiac surgery in adults with congenital heart disease. Anesthesiology. 2013;119(4):762–9.CrossRefPubMed Maxwell BG, Wong JK, Kin C, Lobato RL. Perioperative outcomes of major noncardiac surgery in adults with congenital heart disease. Anesthesiology. 2013;119(4):762–9.CrossRefPubMed
27.
go back to reference Giang KW, Fedchenko M, Dellborg M, Eriksson P, Mandalenakis Z. Burden of ischemic stroke in patients with congenital heart disease: a Nationwide, Case-Control Study. J Am Heart Assoc. 2021;10(13):e020939.CrossRefPubMedPubMedCentral Giang KW, Fedchenko M, Dellborg M, Eriksson P, Mandalenakis Z. Burden of ischemic stroke in patients with congenital heart disease: a Nationwide, Case-Control Study. J Am Heart Assoc. 2021;10(13):e020939.CrossRefPubMedPubMedCentral
28.
go back to reference Pedersen MGB, Olsen MS, Schmidt M, Johnsen SP, Learn C, Laursen HB, et al. Ischemic stroke in adults with congenital heart disease: a Population-based Cohort Study. J Am Heart Assoc. 2019;8(15):e011870.CrossRefPubMedPubMedCentral Pedersen MGB, Olsen MS, Schmidt M, Johnsen SP, Learn C, Laursen HB, et al. Ischemic stroke in adults with congenital heart disease: a Population-based Cohort Study. J Am Heart Assoc. 2019;8(15):e011870.CrossRefPubMedPubMedCentral
29.
go back to reference Mandalenakis Z, Rosengren A, Lappas G, Eriksson P, Hansson PO, Dellborg M. Ischemic stroke in children and young adults with congenital heart disease. J Am Heart Assoc. 2016;5(2). Mandalenakis Z, Rosengren A, Lappas G, Eriksson P, Hansson PO, Dellborg M. Ischemic stroke in children and young adults with congenital heart disease. J Am Heart Assoc. 2016;5(2).
30.
go back to reference Billett J, Cowie MR, Gatzoulis MA, Vonder Muhll IF, Majeed A. Comorbidity, healthcare utilisation and process of care measures in patients with congenital heart disease in the UK: cross-sectional, population-based study with case-control analysis. Heart. 2008;94(9):1194–9.CrossRefPubMed Billett J, Cowie MR, Gatzoulis MA, Vonder Muhll IF, Majeed A. Comorbidity, healthcare utilisation and process of care measures in patients with congenital heart disease in the UK: cross-sectional, population-based study with case-control analysis. Heart. 2008;94(9):1194–9.CrossRefPubMed
31.
go back to reference Yelton SEG, Flores S, Sun LR, Nelson-McMillan K, Loomba RS. Association between Congenital Heart Disease and stroke: insights from a National Database. Pediatr Cardiol. 2024;45(1):1–7.CrossRefPubMed Yelton SEG, Flores S, Sun LR, Nelson-McMillan K, Loomba RS. Association between Congenital Heart Disease and stroke: insights from a National Database. Pediatr Cardiol. 2024;45(1):1–7.CrossRefPubMed
32.
go back to reference Lin YS, Liu PH, Wu LS, Chen YM, Chang CJ, Chu PH. Major adverse cardiovascular events in adult congenital heart disease: a population-based follow-up study from Taiwan. BMC Cardiovasc Disord. 2014;14:38.CrossRefPubMedPubMedCentral Lin YS, Liu PH, Wu LS, Chen YM, Chang CJ, Chu PH. Major adverse cardiovascular events in adult congenital heart disease: a population-based follow-up study from Taiwan. BMC Cardiovasc Disord. 2014;14:38.CrossRefPubMedPubMedCentral
33.
go back to reference Dellborg M, Björk A, Pirouzi Fard MN, Ambring A, Eriksson P, Svensson AM, et al. High mortality and morbidity among adults with congenital heart disease and type 2 diabetes. Scand Cardiovasc J. 2015;49(6):344–50.PubMed Dellborg M, Björk A, Pirouzi Fard MN, Ambring A, Eriksson P, Svensson AM, et al. High mortality and morbidity among adults with congenital heart disease and type 2 diabetes. Scand Cardiovasc J. 2015;49(6):344–50.PubMed
34.
go back to reference Videbæk J, Laursen HB, Olsen M, Høfsten DE, Johnsen SP. Long-Term Nationwide Follow-Up study of simple congenital heart Disease diagnosed in otherwise healthy children. Circulation. 2016;133(5):474–83.CrossRefPubMed Videbæk J, Laursen HB, Olsen M, Høfsten DE, Johnsen SP. Long-Term Nationwide Follow-Up study of simple congenital heart Disease diagnosed in otherwise healthy children. Circulation. 2016;133(5):474–83.CrossRefPubMed
35.
go back to reference Lee JS, Choi J, Shin HJ, Jung JM, Seo WK. Incidence and risk of stroke in Korean patients with congenital heart disease. J Stroke Cerebrovasc Dis. 2023;32(12):107408.CrossRefPubMed Lee JS, Choi J, Shin HJ, Jung JM, Seo WK. Incidence and risk of stroke in Korean patients with congenital heart disease. J Stroke Cerebrovasc Dis. 2023;32(12):107408.CrossRefPubMed
37.
go back to reference El-Chouli M, Meddis A, Christensen DM, Gerds TA, Sehested T, Malmborg M et al. Lifetime risk of comorbidity in patients with simple congenital heart disease: a Danish nationwide study. Eur Heart J. 2023;44(9). El-Chouli M, Meddis A, Christensen DM, Gerds TA, Sehested T, Malmborg M et al. Lifetime risk of comorbidity in patients with simple congenital heart disease: a Danish nationwide study. Eur Heart J. 2023;44(9).
38.
go back to reference Bokma JP, Zegstroo I, Kuijpers JM, Konings TC, Van Kimmenade RRJ, Van Melle JP et al. Factors associated with coronary artery disease and stroke in adults with congenital heart disease. Heart. 2018;104(7). Bokma JP, Zegstroo I, Kuijpers JM, Konings TC, Van Kimmenade RRJ, Van Melle JP et al. Factors associated with coronary artery disease and stroke in adults with congenital heart disease. Heart. 2018;104(7).
39.
go back to reference Fox CK, Sidney S, Fullerton HJ. Community-based case-control study of childhood stroke risk associated with congenital heart disease. Stroke. 2015;46(2). Fox CK, Sidney S, Fullerton HJ. Community-based case-control study of childhood stroke risk associated with congenital heart disease. Stroke. 2015;46(2).
40.
go back to reference Fox CK, Kamel H. Congenital heart Disease, Atrial Fibrillation, and ischemic stroke risk. J Am Heart Assoc. 2024;13(17). Fox CK, Kamel H. Congenital heart Disease, Atrial Fibrillation, and ischemic stroke risk. J Am Heart Assoc. 2024;13(17).
41.
go back to reference Kalezi ZE, Simbila AN, Nkya DA, Kubhoja SD, Majani NG, Furia FF. Infective endocarditis in children with heart diseases at Jakaya Kikwete Cardiac Institute, Tanzania: a cross-sectional study. BMC Pediatr. 2024;24(1):612.CrossRefPubMedPubMedCentral Kalezi ZE, Simbila AN, Nkya DA, Kubhoja SD, Majani NG, Furia FF. Infective endocarditis in children with heart diseases at Jakaya Kikwete Cardiac Institute, Tanzania: a cross-sectional study. BMC Pediatr. 2024;24(1):612.CrossRefPubMedPubMedCentral
42.
go back to reference Odat M, Marsool Marsool R, Nguyen MD, Idrees D, Hussein M, Ghabally AM. M, Pre- and post-surgery: advancements in artificial intelligence and machine learning models for enhancing patient management in infective endocarditis. Int J Surg (London, England). 2024;110(11):7202–14. https://doi.org/10.1097/JS9.0000000000002003. Odat M, Marsool Marsool R, Nguyen MD, Idrees D, Hussein M, Ghabally AM. M, Pre- and post-surgery: advancements in artificial intelligence and machine learning models for enhancing patient management in infective endocarditis. Int J Surg (London, England). 2024;110(11):7202–14. https://​doi.​org/​10.​1097/​JS9.​0000000000002003​.
44.
go back to reference Lanz J, Brophy JM, Therrien J, Kaouache M, Guo L, Marelli AJ. Stroke in adults with congenital heart disease incidence, cumulative risk, and predictors. Circulation. 2015;132:25.CrossRef Lanz J, Brophy JM, Therrien J, Kaouache M, Guo L, Marelli AJ. Stroke in adults with congenital heart disease incidence, cumulative risk, and predictors. Circulation. 2015;132:25.CrossRef
45.
go back to reference Attar H, Sachdeva A, Sundararajan S. Cardioembolic stroke in adults with a history of congenital heart disease. Stroke. 2016;47(5). Attar H, Sachdeva A, Sundararajan S. Cardioembolic stroke in adults with a history of congenital heart disease. Stroke. 2016;47(5).
46.
go back to reference Bonthrone AF, Stegeman R, Feldmann M, Claessens NHP, Nijman M, Jansen NJG et al. Risk factors for Perioperative Brain lesions in infants with congenital heart disease: a European collaboration. Stroke. 2022;53(12). Bonthrone AF, Stegeman R, Feldmann M, Claessens NHP, Nijman M, Jansen NJG et al. Risk factors for Perioperative Brain lesions in infants with congenital heart disease: a European collaboration. Stroke. 2022;53(12).
47.
go back to reference Ottaviani G, Buja LM. Congenital heart disease: Pathology, natural history, and interventions. In: Cardiovascular Pathology. 2022. Ottaviani G, Buja LM. Congenital heart disease: Pathology, natural history, and interventions. In: Cardiovascular Pathology. 2022.
48.
go back to reference Giannakoulas G, Ntiloudi D. Acquired cardiovascular disease in adult patients with congenital heart disease. Vol. 104, Heart. 2018. Giannakoulas G, Ntiloudi D. Acquired cardiovascular disease in adult patients with congenital heart disease. Vol. 104, Heart. 2018.
49.
go back to reference Prokšelj K. Stroke and systemic embolism in adult congenital heart disease. Int J Cardiol Congenital Heart Disease. 2023;12. Prokšelj K. Stroke and systemic embolism in adult congenital heart disease. Int J Cardiol Congenital Heart Disease. 2023;12.
50.
go back to reference Udine ML, Evans F, Burns KM, Pearson GD, Kaltman JR. Geographical variation in infant mortality due to congenital heart disease in the USA: a population-based cohort study. Lancet Child Adolesc Health. 2021;5(7). Udine ML, Evans F, Burns KM, Pearson GD, Kaltman JR. Geographical variation in infant mortality due to congenital heart disease in the USA: a population-based cohort study. Lancet Child Adolesc Health. 2021;5(7).
Metadata
Title
Risk of stroke in patients with congenital heart disease: a systematic review and meta-analysis
Authors
Ramez M. Odat
Muhammad Idrees
Hritvik Jain
Sakhr Alshwayyat
Husam Aldean H. Hussain
Basma Badrawy Khalefa
Ali O. Aldamen
Abdel Rahman K. Bani Yaseen
Bassel Alrabadi
Mohammad-Amer A. Tamimi
Ayham Mohammad Hussein
Hamdah Hanifa
Osama Aloudat
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2024
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-024-03967-8