Download PDF
Thromb Haemost 2022; 122(11): 1921-1931
DOI: 10.1055/a-1873-9092
Atherosclerosis and Ischaemic Disease

Comparison of Risk of Serious Cardiovascular Events after Hemorrhagic versus Ischemic Stroke: A Population-Based Study

Ralph K. Akyea 
1   Primary Care Stratified Medicine, School of Medicine, University of Nottingham, Nottingham, United Kingdom
,
Georgios Georgiopoulos 
2   Cardiovascular Imaging, School of Biomedical Engineering and Imaging Sciences, St. Thomas Hospital, King's College London, London, United Kingdom
,
Barbara Iyen
1   Primary Care Stratified Medicine, School of Medicine, University of Nottingham, Nottingham, United Kingdom
,
Joe Kai
1   Primary Care Stratified Medicine, School of Medicine, University of Nottingham, Nottingham, United Kingdom
,
Nadeem Qureshi
1   Primary Care Stratified Medicine, School of Medicine, University of Nottingham, Nottingham, United Kingdom
,
George Ntaios
3   Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
› Author Affiliations Funding R.K.A. is funded by a National Institute for Health Research School for Primary Care Research (NIHR SPCR) PhD Studentship award. The views expressed are those of the authors and not necessarily those of the NIHR, the NHS, or the Department of Health and Social Care.
› Further Information
Also available at
    Permissions and Reprints

Abstract

Background Patients with ischemic stroke are considered a very high risk population for subsequent cardiovascular events and guidelines recommend intensive preventive strategies. However, there is no clear recommendation that patients with hemorrhagic stroke should also be regarded as a very high cardiovascular risk population.

Objective To compare the risk of subsequent cardiovascular morbidity/mortality between patients with incident hemorrhagic and ischemic stroke.

Methods Patients aged ≥18 years with incident hemorrhagic or ischemic stroke between 1998 and 2017 and no prior history of serious vascular event were identified from UK Clinical Practice Research Datalink (CPRD GOLD) linked to Hospital Episode Statistics data.

Results The cohort included 32,091 patients with an overall follow-up of 381,237 person-years (median: 11.8 years). After adjusting for potential confounders, patients with incident hemorrhagic stroke had no significantly different risk of subsequent cardiovascular morbidity compared with patients with incident ischemic stroke—coronary heart disease (CHD; hazard ratio [HR]: 0.86, 95% confidence interval [CI]: 0.56–1.32), recurrent stroke (HR: 0.92, 95% CI: 0.83–1.02), peripheral vascular disease (PVD; HR: 1.15, 95% CI:0.56–2.38), or heart failure (HR: 1.03, 95% CI: 0.61–1.74). Patients with incident hemorrhagic stroke had significantly higher risk of subsequent cardiovascular disease (CVD)-related mortality (HR: 2.35, 95% CI: 2.04–2.72) and all-cause mortality (HR: 2.16, 95% CI: 1.94–2.41). Propensity-score matched analysis of 1,039 patients with hemorrhagic stroke and 1,039 with ischemic stroke showed similar risk in subsequent cardiovascular morbidity—CHD (stratified HR [sHR]: 0.92, 95% CI: 0.55–1.54), recurrent stroke (sHR: 0.93, 95% CI: 0.82–1.02), PVD (sHR: 1.04 95% CI: 0.45–2.41), or heart failure (sHR: 0.71, 95% CI: 0.39–1.27).

Conclusion The risk of subsequent cardiovascular events is similar between patients with incident hemorrhagic and ischemic stroke. Patients with previous hemorrhagic stroke should be regarded as a population at very high risk for subsequent CVD.

Keywords

hemorrhagic stroke - ischemic stroke - propensity-score matching - electronic health records - cardiovascular outcomes

Author Contributions

R.K.A. and G.N. were involved in the study conception. Analysis was done by R.K.A. and G.G. The manuscript was drafted by R.K.A. All authors reviewed and approved the final version of the manuscript. R.K.A. is the guarantor.


Supplementary Material



Publication History

Received: 16 January 2022

Accepted: 10 June 2022

Accepted Manuscript online:
10 June 2022

Article published online:
08 September 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Mach F, Baigent C, Catapano AL. et al; ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020; 41 (01) 111-188
    CrossrefPubMedGoogle Scholar
  • 2 Herrett E, Gallagher AM, Bhaskaran K. et al. Data resource profile: Clinical Practice Research Datalink (CPRD). Int J Epidemiol 2015; 44 (03) 827-836
    CrossrefPubMedGoogle Scholar
  • 3 NHS Digital. Hospital Episode Statistics (HES) [Internet]. NHS Digit. 2019 . Accessed June 21, 2019 at: https://digital.nhs.uk/data-and-information/data-tools-and-services/data-services/hospital-episode-statistics
    PubMedGoogle Scholar
  • 4 Office for National Statistics. Deaths registration data [Internet]. ONS. 2018 . Accessed June 21, 2019 at: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths
    PubMedGoogle Scholar
  • 5 Department of Communities and Local Government. English indices of deprivation 2015 [Internet]. 2015 . Accessed July 10, 2016 at: https://www.gov.uk/government/statistics/english-indices-of-deprivation-2015
    PubMedGoogle Scholar
  • 6 Akyea RK, Vinogradova Y, Qureshi N. et al. Sex, age, and socioeconomic differences in nonfatal stroke incidence and subsequent major adverse outcomes. Stroke 2021; 52: 396-405
    CrossrefPubMedGoogle Scholar
  • 7 Mathur R, Bhaskaran K, Chaturvedi N. et al. Completeness and usability of ethnicity data in UK-based primary care and hospital databases. J Public Health (Oxf) 2014; 36 (04) 684-692
    CrossrefPubMedGoogle Scholar
  • 8 Shinozaki T, Mansournia MA, Matsuyama Y. On hazard ratio estimators by proportional hazards models in matched-pair cohort studies. Emerg Themes Epidemiol 2017; 14: 6
    CrossrefPubMedGoogle Scholar
  • 9 Klein JP, Moeschberger ML. Survival Analysis: Techniques for Censored and Truncated Data. 1st ed.. New York, NY: Springer; 1997
    CrossrefGoogle Scholar
  • 10 Royston P. Multiple imputation of missing values: update of ice. Stata J 2005; 5: 527-536
    CrossrefPubMedGoogle Scholar
  • 11 Rubin DB. Multiple Imputation for Nonresponse in Surveys. New York, NY: Wiley; 1987
    CrossrefGoogle Scholar
  • 12 Li L, Poon MTC, Samarasekera NE. et al. Risks of recurrent stroke and all serious vascular events after spontaneous intracerebral haemorrhage: pooled analyses of two population-based studies. Lancet Neurol 2021; 20 (06) 437-447
    CrossrefPubMedGoogle Scholar
  • 13 Murthy SB, Zhang C, Diaz I. et al. Association between intracerebral hemorrhage and subsequent arterial ischemic events in participants from 4 population-based cohort studies. JAMA Neurol 2021; 78 (07) 809-816
    CrossrefPubMedGoogle Scholar
  • 14 Jørgensen HS, Nakayama H, Raaschou HO, Olsen TS. Intracerebral hemorrhage versus infarction: stroke severity, risk factors, and prognosis. Ann Neurol 1995; 38 (01) 45-50
    CrossrefPubMedGoogle Scholar
  • 15 Barber M, Roditi G, Stott DJ, Langhorne P. Poor outcome in primary intracerebral haemorrhage: results of a matched comparison. Postgrad Med J 2004; 80 (940) 89-92
    CrossrefPubMedGoogle Scholar
  • 16 Ntaios G, Papavasileiou V, Michel P, Tatlisumak T, Strbian D. Predicting functional outcome and symptomatic intracranial hemorrhage in patients with acute ischemic stroke: a glimpse into the crystal ball?. Stroke 2015; 46 (03) 899-908
    CrossrefPubMedGoogle Scholar
  • 17 Ntaios G, Lip GYH. Difficult situations in anticoagulation after stroke: between Scylla and Charybdis. Curr Opin Neurol 2016; 29 (01) 42-48
    CrossrefPubMedGoogle Scholar
  • 18 RESTART Collaboration. Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial. Lancet Lancet 2019; 393: 2613-2623
    CrossrefPubMedGoogle Scholar
  • 19 Sembill JA, Kuramatsu JB, Schwab S, Huttner HB. Resumption of oral anticoagulation after spontaneous intracerebral hemorrhage. Neurol Res Pract 2019; 1: 12
    CrossrefPubMedGoogle Scholar
  • 20 Weitz JI, Chan NC. Advances in antithrombotic therapy. Arterioscler Thromb Vasc Biol 2019; 39 (01) 7-12
    CrossrefPubMedGoogle Scholar
  • 21 Sagris D, Ntaios G, Georgiopoulos G. et al. Recommendations for lipid modification in patients with ischemic stroke or transient ischemic attack: a clinical guide by the Hellenic Stroke Organization and the Hellenic Atherosclerosis Society. Int J Stroke 2021; 16 (06) 738-750
    CrossrefPubMedGoogle Scholar
  • 22 Sagris D, Ntaios G, Georgiopoulos G, Pateras K, Milionis H. Proprotein Convertase Subtilisin-Kexin Type 9 inhibitors and stroke prevention: a meta-analysis. Eur J Intern Med 2021; 85: 130-132
    CrossrefPubMedGoogle Scholar
  • 23 Ntaios G, Milionis H. Low-density lipoprotein cholesterol lowering for the prevention of cardiovascular outcomes in patients with ischemic stroke. Int J Stroke 2019; 14 (05) 476-482
    CrossrefPubMedGoogle Scholar
  • 24 Milionis H, Ntaios G, Korompoki E, Vemmos K, Michel P. Statin-based therapy for primary and secondary prevention of ischemic stroke: a meta-analysis and critical overview. Int J Stroke 2020; 15 (04) 377-384
    CrossrefPubMedGoogle Scholar
  • 25 Sanz-Cuesta BE, Saver JL. Lipid-lowering therapy and hemorrhagic stroke risk: comparative meta-analysis of statins and PCSK9 inhibitors. Stroke 2021; 52 (10) 3142-3150
    CrossrefPubMedGoogle Scholar
  • 26 Krishnamurthi RV, Feigin VL, Forouzanfar MH. et al; Global Burden of Diseases, Injuries, Risk Factors Study 2010 (GBD 2010), GBD Stroke Experts Group. Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990-2010: findings from the Global Burden of Disease Study 2010. Lancet Glob Health 2013; 1 (05) e259-e281
    CrossrefPubMedGoogle Scholar