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Recurrent stroke: risk factors, predictors and prognosis
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.ORCID iD: 0000-0003-1598-4690
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background Many risk factors for stroke are well characterized and might, at least to some extent, be similar for first-ever stroke and for recurrent stroke events. However, previous studies have shown heterogeneous results on predictors and rates of stroke recurrence. Patients who survive spontaneous intracerebral hemorrhage (ICH) often have compelling indications for antithrombotic (AT) treatment (antiplatelet (AP) and/or anticoagulant (AC) treatment), but due to controversy of the decision to treat, a large proportion of these patients are untreated. In the absence of evidence from randomized controlled trials (RCTs), there is need for more high- quality observational data on the clinical impact of, and optimal timing of AT in ICH survivors. The aims of this thesis were to assess time trends in stroke recurrence, to determine the factors associated with an increased risk of stroke recurrence – including socioeconomic factors – and to determine to what extent ICH survivors with and without atrial fibrillation (AF) receive AT treatment and to determine the optimal timing (if any) of such treatment. 

Methods The population-based Monitoring Trends and Determinants of Cardiovascular Disease (MONICA) stroke incidence register was used to assess the epidemiology and predictors of stroke recurrence after ischemic stroke (IS) and ICH from 1995 to 2008 in northern Sweden. Riksstroke, the Swedish stroke register, linked with the National Patient Register and the Swedish Dispensed Drug Register, made it possible to identify survivors of first-ever ICH from 2005 to 2012 with and without concomitant AF to investigate to what extent these patients were prescribed AP and AC therapy. The optimal timing of initiating treatment following ICH in patients with AF 2005–2012 was described through separate cumulative incidence functions for severe thrombotic and hemorrhagic events and for the combined endpoint “vascular death or non-fatal stroke”. Riksstroke data on first-ever stroke patients from 2001 to 2012 was linked to the Longitudinal Integration Database for Health Insurance and Labour market studies to add information on education and income to investigate the relationship between socioeconomic status and risk of recurrence.

Results Comparison between the cohorts of 1995–1998 and 2004–2008 showed declining risk of stroke recurrence (hazard ratio: 0.64, 95% confidence interval (CI): 0.52-0.78) in northern Sweden. Significant factors associated with an increased risk of stroke recurrence were age and diabetes. Following ICH, a majority (62%) of recurrent stroke events were ischemic.  The nationwide Riksstroke study confirmed the declining incidence, and it further concluded that low income, primary school as highest attained level of education, and living alone were associated with a higher risk of recurrence beyond the acute phase. The inverse effects of socioeconomic status on risk of recurrence did not differ between men and women and persisted over the study period.

Of Swedish ICH-survivors with AF, 8.5% were prescribed AC and 36.6% AP treatment, within 6 months of ICH. In patients with AF, predictors of AC treatment were less severe ICH, younger age, previous anticoagulation, valvular disease and previous IS. High CHA2DS2-VASc scores did not seem to correlate with AC treatment. We observed both an increasing proportion of AC treatment at time of the initial ICH (8.1% in 2006 compared with 14.6% in 2012) and a secular trend of increasing AC use one year after discharge (8.3% in 2006 versus 17.2% in 2011) (p<0.001 assuming linear trends). In patients with high cardiovascular event risk, AC treatment was associated with a reduced risk of vascular death and non-fatal stroke with no significantly increased risk of severe hemorrhage. The benefit appeared to be greatest when treatment was started 7–8 weeks after ICH. For high-risk women, the total risk of vascular death or stroke recurrence within three years was 17.0% when AC treatment was initiated eight weeks after ICH and 28.6% without any antithrombotic treatment (95% CI for difference: 1.4% to 21.8%). For high-risk men, the corresponding risks were 14.3% vs. 23.6% (95% CI for difference: 0.4% to 18.2%).

Conclusion Stroke recurrence is declining in Sweden, but it is still common among stroke survivors and has a severe impact on patient morbidity and mortality. Age, diabetes and low socioeconomic status are predictors of stroke recurrence. Regarding ICH survivors with concomitant AF, physicians face the clinical dilemma of balancing the risks of thrombosis and bleeding. In awaiting evidence from RCTs, our results show that AC treatment in ICH survivors with AF was initiated more frequently over the study period, which seems beneficial, particularly in high-risk patients. The optimal timing of anticoagulation following ICH in AF patients seems to be around 7–8 weeks following the hemorrhage.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet , 2016. , 66 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1847
Keyword [en]
stroke, risk factors, atrial fibrillation, anticoagulant, antiplatelet, intracerebral hemorrhage, stroke recurrence, socioeconomic status
National Category
Other Clinical Medicine
Research subject
Medicine
Identifiers
URN: urn:nbn:se:umu:diva-127304ISBN: 978-91-7601-579-7OAI: oai:DiVA.org:umu-127304DiVA: diva2:1045473
Public defence
2016-12-02, Hörsal Betula, Norrlands Universitetssjukhus, Umeå, 13:00 (Swedish)
Opponent
Supervisors
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2011-0657Swedish Research Council, 2011-2395
Available from: 2016-11-11 Created: 2016-11-07 Last updated: 2016-11-21Bibliographically approved
List of papers
1. Long-Term Risk and Predictors of Recurrent Stroke Beyond the Acute Phase
Open this publication in new window or tab >>Long-Term Risk and Predictors of Recurrent Stroke Beyond the Acute Phase
2014 (English)In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 45, no 6, 1839-1841 p.Article in journal (Refereed) Published
Abstract [en]

Background and Purpose-Previous studies have shown heterogeneous results on predictors and rates of stroke recurrence. This study set out to investigate the long-term risk and predictors of recurrent stroke in Northern Sweden 1995 to 2008.

Methods-In the population-based Monitoring Trends and Determinants of Cardiovascular Disease (MONICA) stroke incidence registry, stroke survivors of either ischemic stroke or intracerebral hemorrhage were followed for recurrent stroke or death. Cox regression was used to identify predictors of stroke recurrence.

Results-The study comprised 6700 patients and 26 597 person-years. During follow-up, 928 (13.9%) patients had a recurrent stroke. Comparison between the first time period (1995-1998) and the last (2004-2008) showed declined risk of stroke recurrence (hazard ratio, 0.64 [95% confidence interval, 0.52-0.78]). Previous myocardial infarction was less prevalent in the most recent cohort (P<0.001). Predictors of stroke recurrence were age (hazard ratio, 1.03 [95% confidence interval, 1.02-1.04]) and diabetes mellitus (hazard ratio, 1.34 [95% confidence interval, 1.15-1.57]). After an index intracerebral hemorrhage (n=815), a major part of recurrent events were ischemic (63%), and compared with the ischemic stroke group (n=5885), a tendency toward lower risk of recurrence was observed.

Conclusions-Despite declining recurrence rates in this relatively young stroke population, almost one third are either dead or have experienced a second stroke in 5 years.

Keyword
epidemiology, stroke
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-91150 (URN)10.1161/STROKEAHA.114.005060 (DOI)000337090700049 ()
Available from: 2014-07-16 Created: 2014-07-15 Last updated: 2016-11-09Bibliographically approved
2. Antithrombotic treatment following intracerebral hemorrhage in patients with and without atrial fibrillation. A nationwide study based on Riksstroke
Open this publication in new window or tab >>Antithrombotic treatment following intracerebral hemorrhage in patients with and without atrial fibrillation. A nationwide study based on Riksstroke
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2015 (English)In: International Journal of Stroke, ISSN 1747-4930, E-ISSN 1747-4949, Vol. 10, 294-295 p.Article in journal, Meeting abstract (Other academic) Published
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-108168 (URN)000359304002050 ()
Note

Supplement: 2 Special Issue: SI Meeting Abstract: ESOC-1343

Available from: 2015-09-09 Created: 2015-09-04 Last updated: 2016-11-09Bibliographically approved
3. Optimal timing of anticoagulant treatment following intracerebral hemorrhage in patients with atrial fibrillation
Open this publication in new window or tab >>Optimal timing of anticoagulant treatment following intracerebral hemorrhage in patients with atrial fibrillation
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(English)Manuscript (preprint) (Other academic)
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-127404 (URN)
Available from: 2016-11-10 Created: 2016-11-10 Last updated: 2016-11-10
4. Socioeconomic status and the risk of stroke recurrence. Persisting gaps observed in a nationwide Swedish study 2001-2012
Open this publication in new window or tab >>Socioeconomic status and the risk of stroke recurrence. Persisting gaps observed in a nationwide Swedish study 2001-2012
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(English)Manuscript (preprint) (Other academic)
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-127405 (URN)
Available from: 2016-11-10 Created: 2016-11-10 Last updated: 2016-11-10

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