| 1. |
- Bakker, M. K., et al.
(författare)
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Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors
- 2020
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:12
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Tidskriftsartikel (refereegranskat)abstract
- Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits. Cross-ancestry genome-wide association analyses in individuals of European and East Asian ancestry identify 11 new risk loci for intracranial aneurysms and highlight a polygenic architecture explaining a substantial fraction of disease heritability.
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| 4. |
- Tolvanen, A. D., et al.
(författare)
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TIA model is attainable in Wistar rats by intraluminal occlusion of the MCA for 10 min or shorter
- 2017
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 1663, s. 166-173
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Tidskriftsartikel (refereegranskat)abstract
- Transient ischemic attack (TIA) has received only little attention in the experimental research field. Recently, we introduced a TIA model for mice, and here we set similar principles for simulating this human condition in Wistar rats. In the model: 1) transient nature of the event is ensured, and 2) 24 h after the event animals are free from any sensorimotor deficit and from any detectable lesion by magnetic resonance imaging (MRI). Animals experienced varying durations of ischemia (5, 10, 12.5, 15, 25, and 30 min, n = 6-8 per group) by intraluminal middle cerebral artery occlusion (MCAO). Ischemia severity and reperfusion rates were controlled by cerebral blood flow measurements. Sensorimotor neurological evaluations and MRI at 24 h differentiated between TIA and ischemic stroke. Hematoxylin and eosin staining and apoptotic cell counts revealed pathological correlates of the event. We found that already 12.5 min of ischemia was long enough to induce ischemic stroke in Wistar rats. Ten min or shorter durations induced neither gross neurological deficits nor infarcts visible on MRI, but histologically caused selective neuronal necrosis. A separate group of animals with 10 min of ischemia followed up to 1 week after reperfusion remained free of infarction and any MRI signal change. Thus, 10 min or shorter focal cerebral ischemia induced by intraluminal MCAO in Wistar rats provides a clinically relevant TIA the rat. This model is useful for studying molecular correlates of TIA. (C) 2017 Elsevier B.V. All rights reserved.
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| 5. |
- Aarnio, K., et al.
(författare)
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Cancer in Young Adults With Ischemic Stroke
- 2015
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 46:6, s. 1601-
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-Cancer is a risk factor for ischemic stroke. Little is known about cancer among young adults with ischemic stroke. We studied the frequency of cancer and its association with long-term risk of death among young patients with first-ever ischemic stroke. Methods-1002 patients aged 15 to 49 years, registered in the Helsinki Young Stroke Registry, and with a median follow-up of 10.0 years (interquartile range 6.5-13.8) after stroke were included. Historical and follow-up data were derived from the Finnish Care Register and Statistics Finland. Survival between groups was compared with the Kaplan-Meier life-table method, and Cox proportional hazard models were used to identify factors associated with mortality. Results-One or more cancer diagnosis was made in 77 (7.7%) patients, of whom 39 (3.9%) had cancer diagnosed prestroke. During the poststroke follow-up, 41 (53.2%) of the cancer patients died. Median time from prestroke cancer to stroke was 4.9 (1.0-9.5) years and from stroke to poststroke cancer was 6.7 (2.7-10.9) years. Poststroke cancer was associated with age >40 years, heavy drinking, and cigarette smoking. The cumulative mortality was significantly higher among the cancer patients (68.6%, 95% confidence interval 52.0%-85.3%) compared with patients without cancer (19.7%, 95% confidence interval 16.3%-23.2%). Active cancer at index stroke, melanoma, and lung/respiratory tract cancer had the strongest independent association with death during the follow-up when adjusted for known poststroke mortality prognosticators. Conclusions-Cancer, and especially active cancer and no other apparent cause for stroke, is associated with unfavorable survival among young stroke patients.
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| 6. |
- Aarnio, K., et al.
(författare)
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Cardiovascular events after ischemic stroke in young adults: A prospective follow-up study
- 2016
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 86:20, s. 1872-1879
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Tidskriftsartikel (refereegranskat)abstract
- Objectives:To study the long-term risk of recurrent cardiac, arterial, and venous events in young stroke patients, and whether these risks differed between etiologic subgroups.Methods:The study population comprised 970 patients aged 15-49 years from the Helsinki Young Stroke Registry (HYSR) who had an ischemic stroke in 1994-2007. We obtained follow-up data until 2012 from the Finnish Care Register and Statistics Finland. Cumulative 15-year risks were analyzed with life tables, whereas relative risks and corresponding confidence intervals (CI) were based on hazard ratios (HR) from Cox regression analyses.Results:There were 283 (29.2%) patients with a cardiovascular event during the median follow-up of 10.1 years (range 0.1-18.0). Cumulative 15-year risk for venous events was 3.9%. Cumulative 15-year incidence rate for composite vascular events was 34.0 (95% CI 30.1-38.2) per 1,000 person-years. When adjusted for age and sex, patients with an index stroke caused by high-risk sources of cardioembolism had the highest HR for any subsequent cardiovascular events (3.7; 95% CI 2.6-5.4), whereas the large-artery atherosclerosis group had the highest HR (2.7; 95% CI 1.6-4.6) for recurrent stroke compared with patients with stroke of undetermined etiology.Conclusions:The risk for future cardiovascular events after ischemic stroke in young adults remains high for years after the index stroke, in particular when the index stroke is caused by high-risk sources of cardioembolism or large-artery atherosclerosis.
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| 7. |
- Aarnio, Karoliina, et al.
(författare)
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Etiologic subtypes of first and recurrent ischemic stroke in young patients using A-S-C-O and TOAST classification criteria: A retrospective follow-up study
- 2024
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Ingår i: EUROPEAN STROKE JOURNAL. - 2396-9873 .- 2396-9881.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Scarce data exist on the etiology of recurrent ischemic strokes (ISs) among young adults. We analyzed the etiology of first-ever and recurrent events and the differences between them.Patients and methods: Patients aged 15-49 years with a first-ever IS in 1994-2007 were included in the Helsinki Young Stroke Registry. In this retrospective cohort study, data on recurrent ISs were identified from Care Register for Health Care until the end of 2017 and Causes of Death Register and from patient records until the end of 2020. All first-ever and recurrent ISs were classified using Atherosclerosis-Small vessel disease-Cardioembolism-Other Cause (A-S-C-O) and Trial of Org 10172 in Acute Stroke Treatment (TOAST) classifications.Results: A total of 970 patients were included (median age at index IS 46 years, interquartile range 43-48, 33% women), of which 155 (16.0%) patients had recurrent IS, with 8 (5.2%) fatal cases and 5 (3.2%) unverifiable cases. The median follow-up was 17.4 (IQR 13.9-21.7) years. Median time from the index event to the first recurrent event was 4.5 (interquartile range [IQR] 1.6-10.2) years. Recurrence was more often due to definite cardioembolism (10.7% vs 18.0%, p = 0.013), while the proportion of other definite A-S-C-O subgroups remained the same. With TOAST classification, the proportion of true cryptogenic ISs decreased (16.7% vs 6.7%, p = 0.003), while those with incomplete evaluation increased (9.3% vs 19.3%, p = 0.015). Other TOAST phenotypes remained the same.Conclusion: The proportion of definite cardioembolism increased at recurrence using the A-S-C-O classification and the number of cryptogenic ISs decreased using the TOAST classification, while cases with incomplete evaluation increased. Most etiologies remained the same.
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| 8. |
- Aarnio, Karoliina, et al.
(författare)
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Outcome of pregnancies and deliveries before and after ischaemic stroke
- 2017
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Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 2:4
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Limited data exist on the outcome of pregnancies and deliveries in women with ischaemic stroke. We investigated the incidence of pregnancy- and delivery-related complications in women with ischaemic stroke before and after pregnancy compared with stroke-free matched controls. Patients and methods: Of our 1008 consecutive patients aged 15–49 years with first-ever ischaemic stroke, 1994– 2007, we included women with pregnancy data before or after stroke recorded in the Medical Birth Register (MBR) (n¼152), and for them searched stroke-free controls matched by age, parity, year of birth, residential area and multiplicity (n¼608). Data on hospital admissions and deaths (1987–2014) came from national health registries. Poisson regression mixed models allowed comparison of the incidence of complications. Results: A total of 124 stroke mothers had 207 singleton pregnancies before and 45 mothers 68 pregnancies after stroke. The incidence rate ratio (IRR) for the composite outcome of pregnancy and delivery complications adjusted for socioeconomic status and maternal smoking was 1.43 (95% confidence interval [CI] 1.00–2.03, p¼0.05) for pre-stroke mothers, and 1.09 (95% CI 0.66–1.78) for post-stroke mothers, compared with matched controls. Similarly, the adjusted IRR for post-stroke hospital admission during pregnancy was 1.85 (95% CI 1.03–3.31). The IRR for perinatal death of the child was 3.43 (95% CI 0.57–20.53) before and 8.88 (95% CI 0.81–97.95) after stroke. Discussion and conclusions: Compared with stroke-free mothers, we found a higher incidence of pregnancy- and delivery-related complications in mothers with ischaemic stroke. Larger studies are needed to verify our results.
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| 9. |
- Aarnio, K., et al.
(författare)
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Return to work after ischemic stroke in young adults: A registry-based follow-up study
- 2018
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Ingår i: Neurology. - 1526-632X. ; 91:20, s. e1909-e1917
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We aimed to investigate the proportion of young patients not returning to work (NRTW) at 1 year after ischemic stroke (IS) and during follow-up, and clinical factors associated with NRTW. METHODS: Patients from the Helsinki Young Stroke Registry with an IS occurring in the years 1994-2007, who were at paid employment within 1 year before IS, and with NIH Stroke Scale score ≤15 points at hospital discharge, were included. Data on periods of payment came from the Finnish Centre for Pensions, and death data from Statistics Finland. Multivariate logistic regression analyses assessed factors associated with NRTW 1 year after IS, and lasagna plots visualized the proportion of patients returning to work over time. RESULTS: We included a total of 769 patients, of whom 289 (37.6%) were not working at 1 year, 323 (42.0%) at 2 years, and 361 (46.9%) at 5 years from IS. When adjusted for age, sex, socioeconomic status, and NIH Stroke Scale score at admission, factors associated with NRTW at 1 year after IS were large anterior strokes, strokes caused by large artery atherosclerosis, high-risk sources of cardioembolism, and rare causes other than dissection compared with undetermined cause, moderate to severe aphasia vs no aphasia, mild and moderate to severe limb paresis vs no paresis, and moderate to severe visual field deficit vs no deficit. CONCLUSIONS: NRTW is a frequent adverse outcome after IS in young adults with mild to moderate IS. Clinical variables available during acute hospitalization may allow prediction of NRTW. Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
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| 10. |
- Acciarresi, M., et al.
(författare)
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Prestroke CHA(2)DS(2)-VASc Score and Severity of Acute Stroke in Patients with Atrial Fibrillation: Findings from RAF Study
- 2017
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Ingår i: Journal of Stroke & Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057. ; 26:6, s. 1363-1368
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: The aim of this study was to investigate for a possible association between both prestroke CHA(2)DS(2)-VASc score and the severity of stroke at presentation, as well as disability and mortality at 90 days, in patients with acute stroke and atrial fibrillation (AF). Methods: This prospective study enrolled consecutive patients with acute ischemic stroke, AF, and assessment of prestroke CHA2DS2-VASc score. Severity of stroke was assessed on admission using the National Institutes of Health Stroke Scale (NIHSS) score (severe stroke: NIHSS >= 10). Disability and mortality at 90 days were assessed by the modified Rankin Scale (mRS < 3 or >= 3). Multiple logistic regression was used to correlate prestroke CHA(2)DS(2)-VASc and severity of stroke, as well as disability and mortality at 90 days. Results: Of the 1020 patients included in the analysis, 606 patients had an admission NIHSS score lower and 414 patients higher than 10. At 90 days, 510 patients had mRS >= 3. A linear correlation was found between the prestroke CHA(2)DS(2)-VASc score and severity of stroke (P = .001). On multivariate analysis, CHA(2)DS(2)-VASc score correlated with severity of stroke (P = .041) and adverse functional outcome (mRS = 3) (P = .001). A logistic regression with the receiver operating characteristic graph procedure (C-statistics) evidenced an area under the curve of .60 (P = .0001) for severe stroke. Furthermore, a correlation was found between prestroke CHA(2)DS(2)-VASc score and lesion size. Conclusions: In patients with AF, in addition to the risk of stroke, a high CHA(2)DS(2)-VASc score was independently associated with both stroke severity at onset and disability and mortality at 90 days.
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