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- Franceschini, N., et al.
(författare)
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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans. © 2018, The Author(s).
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| 4. |
- Marini, S., et al.
(författare)
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Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/Ethnicity A Meta-analysis
- 2019
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Ingår i: Jama Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:4, s. 480-491
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Genetic studies of intracerebral hemorrhage (ICH) have focused mainly on white participants, but genetic risk may vary or could be concealed by differing nongenetic coexposures in nonwhite populations. Transethnic analysis of risk may clarify the role of genetics in ICH risk across populations. OBJECTIVE To evaluate associations between established differences in ICH risk by race/ethnicity and the variability in the risks of apolipoprotein E (APOE) epsilon 4 alleles, the most potent genetic risk factor for ICH. DESIGN, SETTING, AND PARTICIPANTS This case-control study of primary ICH meta-analyzed the association of APOE allele status on ICH risk, applying a 2-stage clustering approach based on race/ethnicity and stratified by a contributing study. A propensity score analysis was used to model the association of APOE with the burden of hypertension across race/ethnic groups. Primary ICH cases and controls were collected from 3 hospital- and population-based studies in the United States and 8 in European sites in the International Stroke Genetic Consortium. Participants were enrolled from January 1, 1999, to December 31, 2017. Participants with secondary causes of ICH were excluded from enrollment. Controls were regionally matched within each participating study. MAIN OUTCOMES AND MEASURES Clinical variables were systematically obtained from structured interviews within each site. APOE genotype was centrally determined for all studies. RESULTS In total, 13 124 participants (7153 [54.5%] male with a median [interquartile range] age of 66 [56-76] years) were included. In white participants, APOE epsilon 2 (odds ratio [OR], 1.49; 95% CI, 1.24-1.80; P < .001) and APOE epsilon 4 (OR, 1.51; 95% CI, 1.23-1.85; P < .001) were associated with lobar ICH risk; however, within self-identified Hispanic and black participants, no associations were found. After propensity score matching for hypertension burden, APOE epsilon 4 was associated with lobar ICH risk among Hispanic (OR, 1.14; 95% CI, 1.03-1.28; P = .01) but not in black (OR, 1.02; 95% CI, 0.98-1.07; P = .25) participants. APOE epsilon 2 and epsilon 4 did not show an association with nonlobar ICH risk in any race/ethnicity. CONCLUSIONS AND RELEVANCE APOE epsilon 4 and epsilon 2 alleles appear to affect lobar ICH risk variably by race/ethnicity, associations that are confirmed in white individuals but can be shown in Hispanic individuals only when the excess burden of hypertension is propensity score-matched; further studies are needed to explore the interactions between APOE alleles and environmental exposures that vary by race/ethnicity in representative populations at risk for ICH.
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| 5. |
- Veltkamp, R., et al.
(författare)
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Characteristics of Recurrent Ischemic Stroke after Embolic Stroke of Undetermined Source: Secondary Analysis of a Randomized Clinical Trial
- 2020
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149. ; 77:10, s. 1233-1240
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Tidskriftsartikel (refereegranskat)abstract
- Importance: The concept of embolic stroke of undetermined source (ESUS) unifies a subgroup of cryptogenic strokes based on neuroimaging, a defined minimum set of diagnostic tests, and exclusion of certain causes. Despite an annual stroke recurrence rate of 5%, little is known about the etiology underlying recurrent stroke after ESUS. Objective: To identify the stroke subtype of recurrent ischemic strokes after ESUS, to explore the interaction with treatment assignment in each category, and to examine the consistency of cerebral location of qualifying ESUS and recurrent ischemic stroke. Design, Setting, and Participants: The NAVIGATE-ESUS trial was a randomized clinical trial conducted from December 23, 2014, to October 5, 2017. The trial compared the efficacy and safety of rivaroxaban and aspirin in patients with recent ESUS (n = 7213). Ischemic stroke was validated in 309 of the 7213 patients by adjudicators blinded to treatment assignment and classified by local investigators into the categories ESUS or non-ESUS (ie, cardioembolic, atherosclerotic, lacunar, other determined cause, or insufficient testing). Five patients with recurrent strokes that could not be defined as ischemic or hemorrhagic in absence of neuroimaging or autopsy were excluded. Data for this secondary post hoc analysis were analyzed from March to June 2019. Interventions: Patients were randomly assigned to receive rivaroxaban, 15 mg/d, or aspirin, 100 mg/d. Main Outcomes and Measures: Association of recurrent ESUS with stroke characteristics. Results: A total of 309 patients (205 men [66%]; mean [SD] age, 68 [10] years) had ischemic stroke identified during the median follow-up of 11 (interquartile range [IQR], 12) months (annualized rate, 4.6%). Diagnostic testing was insufficient for etiological classification in 39 patients (13%). Of 270 classifiable ischemic strokes, 156 (58%) were ESUS and 114 (42%) were non-ESUS (37 [32%] cardioembolic, 26 [23%] atherosclerotic, 35 [31%] lacunar, and 16 [14%] other determined cause). Atrial fibrillation was found in 27 patients (9%) with recurrent ischemic stroke and was associated with higher morbidity (median change in modified Rankin scale score 2 [IQR, 3] vs 0 (IQR, 1]) and mortality (15% vs 1%) than other causes. Risk of recurrence did not differ significantly by subtype between treatment groups. For both the qualifying and recurrent strokes, location of infarct was more often in the left (46% and 54%, respectively) than right hemisphere (40% and 37%, respectively) or brainstem or cerebellum (14% and 9%, respectively). Conclusions and Relevance: In this secondary analysis of randomized clinical trial data, most recurrent strokes after ESUS were embolic and of undetermined source. Recurrences associated with atrial fibrillation were a minority but were more often disabling and fatal. More extensive investigation to identify the embolic source is important toward an effective antithrombotic strategy. Trial Registration: ClinicalTrials.gov Identifier: NCT02313909.. © 2020 American Medical Association. All rights reserved.
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| 6. |
- Andsberg, Gunnar, et al.
(författare)
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PreHospital Ambulance Stroke Test : pilot study of a novel stroke test
- 2017
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Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - London, UK : BioMed Central. - 1757-7241. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is a need for a prehospital stroke test that in addition to high sensitivity for stroke, also is able to communicate stroke severity similar to the National Institute of Health Stroke Scale (NIHSS).METHODS: The PreHospital Ambulance Stroke Test (PreHAST), an eight item test based on NIHSS, which scores stroke severity from 0-19 points, was designed and adapted for the ambulance services. In the pilot study the ambulance nurses used PreHAST to assess patients with suspected stroke in the prehospital setting. Regardless of the results after PreHAST testing the patients were triaged with a provisional stroke diagnosis. The PreHAST scores were compared with the final diagnosis and the ability to differentiate stroke and transient ischemic attacks (TIA) with ongoing symptoms at evaluation from non-stroke patients was analysed.RESULTS: 69 patients were included in the study, 26 had stroke/TIA and 43 other diagnoses. All stroke/TIA patients were identified by PreHAST (sensitivity 100% (95% CI; 87-100%)). The specificity increased with higher PreHAST scores and the discriminative capacity for PreHAST for different cut off values showed an area under the curve of 0.77 (95%CI; 0.66-0.88) in the receiver operating characteristic (ROC) analysis.DISCUSSION: PreHAST is designed for high sensitivity, screening for a broad range of stroke symptoms including most key components of NIHSS. The promising sensitivity between 87 and 100% in our study has to be confirmed in a larger study also including multiple centres. Higher PreHAST scores implied more typical patterns of stroke and accordingly the proportion of stroke mimics decrease with higher scores. However, also stroke mimics with epilepsy/seizure and patients with deficit after prior stroke could show higher PreHAST scores. Other prehospital stroke tests that evaluate stroke severity have been designed with the main purpose to screen for large vessel occlusion. The advantage of PreHAST is the dual purpose not only to evaluate stroke severity but also to screen for stroke in general.CONCLUSIONS: PreHAST is a new screening test of stroke adapted for ambulance services that in addition to high sensitivity for stroke, provides a grading system with increasing specificity with higher scores.
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| 8. |
- Jönsson, Ann-Cathrin, et al.
(författare)
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Falls After Stroke : A Follow-up after Ten Years in Lund Stroke Register
- 2021
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Ingår i: Journal of Stroke & Cerebrovascular Diseases. - : Elsevier BV. - 1532-8511 .- 1052-3057. ; 30:6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate incidence of self-reported falls and associated factors in a ten-year perspective after stroke.METHODS: From a population-based cohort of first-ever stroke patients (n = 416) included in the Lund Stroke Register between March 1, 2001, and February 28, 2002, we performed a follow up of all 145 survivors ten years after stroke. We collected data on age, gender, main stroke type, living and housing situation, general health status (question 1 in the Short Form Health Survey (SF-36), dizziness, physical activity, Barthel Index, mobility aids, moving ability inside/outside, and health-related quality of life as defined by the EuroQol 3 dimension scale (EQ-5D-3L). Factors that may relate to falls were compared between those who had experienced falls after stroke or not.RESULTS: Ten years after stroke, 49 patients (34 %) reported falls and 96 patients (66 %) reported no falls. Compared to patients with no falls, those who reported falls were older (median age 83.3 years vs 75.6 years; p < 0.001), more often lived alone, were more dependent in daily living, had less physical activity, poorer general health status, more often needed mobility aids, were more often unable to move alone outside, and had poorer health-related quality of life in all items in EQ-5D-3L except pain/discomfort.CONCLUSIONS: Falls had occurred in approximately one third of the participants ten years after the stroke, and were strongly associated with several measures of frailty. Our results indicate that fall prevention should in particular focus on those at high risk of falls.
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| 10. |
- Jönsson, Ann-Cathrin, et al.
(författare)
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Prevalence and intensity of pain after stroke: a population based study focusing on patients' perspectives.
- 2005
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - 1468-330X. ; , s. 590-595
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine prevalence and intensity of pain after stroke, focusing on patients' perspectives. METHODS: During a one year period, 416 first-ever stroke patients were included in the population based Lund Stroke Register. After 4 and 16 months (median), 297 patients (98% of survivors) were followed up. Worst pain intensity during the previous 48 hours was assessed on a visual analogue scale (VAS), range 0 to 100: a score of 0 to 30 was defined as no or mild pain; 40 to 100 as moderate to severe pain. NIH stroke scale (NIHSS) score and HbA1c were assessed at baseline. At 16 months, screening for depression was done using the geriatric depression scale (GDS-20), and cognition with the mini-mental state examination (MMSE). Predictors of pain were determined by multivariate analyses. RESULTS: Moderate to severe pain was reported by 96 patients (32%) after four months (VAS median=60). Predictors of pain were younger age (p=0.01), female sex (p=0.006), higher NIHSS score (p<0.001), and raised HbA1c (p=0.001) at stroke onset. At 16 months, only 62 patients (21%) had moderate to severe pain, but pain intensity was more severe (median VAS score=70; p<0.016). Higher pain intensity correlated with female sex, worse GDS-20 score, better MMSE score, and raised HbA1c. Pain was persistent in 47%, disturbed sleep in 58%, and required rest for relief in 40% of patients. CONCLUSIONS: Although prevalence of pain after stroke decreased with time, after 16 months 21% had moderate to severe pain. Late pain after stroke was on average more severe, and profoundly affected the patients' wellbeing.
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