| 1. |
- Amarenco, Pierre, et al.
(författare)
-
Ticagrelor Added to Aspirin in Acute Nonsevere Ischemic Stroke or Transient Ischemic Attack of Atherosclerotic Origin
- 2020
-
Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 51:12, s. 3504-3513
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose:Among patients with a transient ischemic attack or minor ischemic strokes, those with ipsilateral atherosclerotic stenosis of cervicocranial vasculature have the highest risk of recurrent vascular events.Methods:In the double-blind THALES (The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death) trial, we randomized patients with a noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2–30) or placebo added to aspirin (300–325 mg on day 1 followed by 75–100 mg daily for days 2–30) within 24 hours of symptom onset. The present paper reports a prespecified analysis in patients with and without ipsilateral, potentially causal atherosclerotic stenosis ≥30% of cervicocranial vasculature. The primary end point was time to the occurrence of stroke or death within 30 days.Results:Of 11 016 randomized patients, 2351 (21.3%) patients had an ipsilateral atherosclerotic stenosis. After 30 days, a primary end point occurred in 92/1136 (8.1%) patients with ipsilateral stenosis randomized to ticagrelor and in 132/1215 (10.9%) randomized to placebo (hazard ratio 0.73 [95% CI, 0.56–0.96], P=0.023) resulting in a number needed to treat of 34 (95% CI, 19–171). In patients without ipsilateral stenosis, the corresponding event rate was 211/4387 (4.8%) and 230/4278 (5.4%), respectively (hazard ratio, 0.89 [95% CI, 0.74–1.08]; P=0.23, Pinteraction=0.245). Severe bleeding occurred in 4 (0.4%) and 3 (0.2%) patients with ipsilateral atherosclerotic stenosis on ticagrelor and on placebo, respectively (P=NS), and in 24 (0.5%) and 4 (0.1%), respectively, in 8665 patients without ipsilateral stenosis (hazard ratio=5.87 [95% CI, 2.04–16.9], P=0.001).Conclusions:In this exploratory analysis comparing ticagrelor added to aspirin to aspirin alone, we found no treatment by ipsilateral atherosclerosis stenosis subgroup interaction but did identify a higher absolute risk and a greater absolute risk reduction of stroke or death at 30 days in patients with ipsilateral atherosclerosis stenosis than in those without. In this easily identified population, ticagrelor added to aspirin provided a clinically meaningful benefit with a number needed to treat of 34 (95% CI, 19–171).
|
|
| 2. |
- Bosch, Jackie, et al.
(författare)
-
Antihypertensives and Statin Therapy for Primary Stroke Prevention : A Secondary Analysis of the HOPE-3 Trial
- 2021
-
Ingår i: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 52:8, s. 2494-2501
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: The HOPE-3 trial (Heart Outcomes Prevention Evaluation-3) found that antihypertensive therapy combined with a statin reduced first stroke among people at intermediate cardiovascular risk. We report secondary analyses of stroke outcomes by stroke subtype, predictors, treatment effects in key subgroups. METHODS: Using a 2-by-2 factorial design, 12705 participants from 21 countries with vascular risk factors but without overt cardiovascular disease were randomized to candesartan 16 mg plus hydrochlorothiazide 12.5 mg daily or placebo and to rosuvastatin 10 mg daily or placebo. The effect of the interventions on stroke subtypes was assessed. RESULTS: Participants were 66 years old and 46% were women. Baseline blood pressure (138/82 mm Hg) was reduced by 6.0/3.0 mm Hg and LDL-C (low-density lipoprotein cholesterol; 3.3 mmol/L) was reduced by 0.90 mmol/L on active treatment. During 5.6 years of follow-up, 169 strokes occurred (117 ischemic, 29 hemorrhagic, 23 undetermined). Blood pressure lowering did not significantly reduce stroke (hazard ratio [H R], 0.80 [95% CI, 0.59-1.08]), ischemic stroke (H R, 0.80 [95% CI, 0.55-1.15]), hemorrhagic stroke (HR, 0.71 [95% CI, 0.34-1.48]), or strokes of undetermined origin (HR, 0.92 [95% CI, 0.41-2.08]). Rosuvastatin significantly reduced strokes (H R, 0.70 [95% CI, 0.52-0.95]), with reductions mainly in ischemic stroke (H R, 0.53 [95% CI, 0.37-0.78]) but did not significantly affect hemorrhagic (H R, 1.22 [95% CI, 0.59-2.54]) or strokes of undetermined origin (H R, 1.29 [95% CI, 0.57-2.95]). The combination of both interventions compared with double placebo substantially and significantly reduced strokes (HR, 0.56 [95% CI, 0.36-0.87]) and ischemic strokes (HR, 0.41 [95% CI, 0.23-0.72]). CONCLUSIONS: Among people at intermediate cardiovascular risk but without overt cardiovascular disease, rosuvastatin 10 mg daily significantly reduced first stroke. Blood pressure lowering combined with rosuvastatin reduced ischemic stroke by 59%. Both therapies are safe and generally well tolerated.
|
|
| 3. |
- Camen, Stephan, et al.
(författare)
-
Cardiac Troponin I and Incident Stroke in European Cohorts : Insights From the BiomarCaRE Project
- 2020
-
Ingår i: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 51:9, s. 2770-2777
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Stroke is a common cause of death and a leading cause of disability and morbidity. Stroke risk assessment remains a challenge, but circulating biomarkers may improve risk prediction. Controversial evidence is available on the predictive ability of troponin concentrations and the risk of stroke in the community. Furthermore, reports on the predictive value of troponin concentrations for different stroke subtypes are scarce.Methods: High-sensitivity cardiac troponin I (hsTnI) concentrations were assessed in 82 881 individuals (median age, 50.7 years; 49.7% men) free of stroke or myocardial infarction at baseline from 9 prospective European community cohorts. We used Cox proportional hazards regression to determine relative risks, followed by measures of discrimination and reclassification using 10-fold cross-validation to control for overoptimism. Follow-up was based upon linkage with national hospitalization registries and causes of death registries.Results: Over a median follow-up of 12.7 years, 3033 individuals were diagnosed with incident nonfatal or fatal stroke (n=1654 ischemic strokes, n=612 hemorrhagic strokes, and n=767 indeterminate strokes). In multivariable regression models, hsTnI concentrations were associated with overall stroke (hazard ratio per 1-SD increase, 1.15 [95% CI, 1.10-1.21]), ischemic stroke (hazard ratio, 1.14 [95% CI, 1.09-1.21]), and hemorrhagic stroke (hazard ratio, 1.10 [95% CI, 1.01-1.20]). Adding hsTnI concentrations to classical cardiovascular risk factors (C indices, 0.809, 0.840, and 0.736 for overall, ischemic, and hemorrhagic stroke, respectively) increased the C index significantly but modestly. In individuals with an intermediate 10-year risk (5%-20%), the net reclassification improvement for overall stroke was 0.038 (P=0.021).Conclusions: Elevated hsTnI concentrations are associated with an increased risk of incident stroke in the community, irrespective of stroke subtype. Adding hsTnI concentrations to classical risk factors only modestly improved estimation of 10-year risk of stroke in the overall cohort but might be of some value in individuals at an intermediate risk.
|
|
| 4. |
- Darehed, David, 1986-, et al.
(författare)
-
In-hospital delays in stroke thrombolysis : every minute counts
- 2020
-
Ingår i: Stroke. - : American Heart Association. - 0039-2499 .- 1524-4628. ; 51:8, s. 2536-2539
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Intravenous thrombolysis is a well-established treatment for acute ischemic stroke. Our aim was to quantify the effect of each minute delay in door-to-needle time (DNT) on 90-day survival, intracerebral hemorrhagic complication <36 hours, and functional outcomes at 3 months, in routine clinical practice.Methods: Our nationwide registry-based study included 14 132 adult patient admissions with ischemic stroke receiving intravenous thrombolysis from 2010 to 2017. Outcomes were analyzed using multivariable logistic regression, adjusting for potential confounders.Results: Median DNT was 47 minutes, with an improvement from 65 to 38 minutes during the study. Median age was 74 years, and median National Institutes of Health Stroke Scale 8 points. We found a significant impact of each minute delay in DNT with reduced odds of survival by 0.6%, increased odds of intracerebral hemorrhagic and worse activities of daily living by 0.3%, and worse living conditions and mobility by 0.4%.Conclusions: Improving DNT is a key factor in achieving good outcomes after stroke. We estimate that in Sweden alone in 2017, compared with 2010, the shorter DNT achieved have saved 38 lives, avoided 8 intracerebral hemorrhagic transformations, and spared, respectively, 36, 51, and 52 patients from a worsening in activities of daily living, living conditions, and mobility. DNT is sensitive for interventions and should be targeted in quality improvement efforts.
|
|
| 5. |
- Ding, Mozhu, et al.
(författare)
-
Cerebral Small Vessel Disease Associated With Atrial Fibrillation Among Older Adults : A Population-Based Study.
- 2021
-
Ingår i: Stroke. - : American Heart Association. - 0039-2499 .- 1524-4628. ; 52:8, s. 2685-2689
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Cerebral small vessel disease, as a potential mechanism underlying the association between atrial fibrillation (AF) and dementia, remains poorly investigated. In this cohort study, we sought to examine the association between AF and cerebral small vessel disease markers among older adults.METHODS: Data on 336 participants (age ≥60 years, mean 70.2 years; 60.2% women) free of dementia, disability, and cerebral infarcts were derived from the population-based Swedish National Study on Aging and Care in Kungsholmen. Structural brain magnetic resonance imaging examinations were performed at baseline (2001-2004) and follow-ups (2004-2007 and 2007-2010). Magnetic resonance imaging markers of cerebral small vessel disease included perivascular spaces, lacunes, and volumes of white matter hyperintensities, lateral ventricles, and total brain tissue. AF was assessed at baseline and follow-ups through clinical examinations, electrocardiogram, and medical records. Data were analyzed using linear mixed-effects models.RESULTS: At baseline, 18 persons (5.4%) were identified to have prevalent AF and 17 (5.6%) developed incident AF over the 6-year follow-up. After multivariable adjustment, AF was significantly associated with a faster annual increase in white matter hyperintensities volume (β coefficient=0.45 [95% CI, 0.04-0.86]) and lateral ventricular volume (0.58 [0.13-1.02]). There was no significant association of AF with annual changes in perivascular spaces number (β coefficient=0.53 [95% CI, -0.27 to 1.34]) or lacune number (-0.01 [-0.07 to 0.05]).CONCLUSIONS: Independent of cerebral infarcts, AF is associated with accelerated progression of white matter lesions and ventricular enlargement among older adults.
|
|
| 6. |
- Dorvall, Malin, 1991, et al.
(författare)
-
Mosaic Loss of Chromosome Y Is Associated With Functional Outcome After Ischemic Stroke.
- 2023
-
Ingår i: Stroke. - : Wolters Kluwer. - 1524-4628 .- 0039-2499. ; 54:9, s. 2434-2437
-
Tidskriftsartikel (refereegranskat)abstract
- Mosaic loss of chromosome Y (LOY) is associated with cardiovascular and neurodegenerative diseases in men, and genetic predisposition to LOY is associated with poor poststroke outcome. We, therefore, tested the hypothesis that LOY itself is associated with functional outcome after ischemic stroke.The study comprised male patients with ischemic stroke from the cohort studies SAHLSIS2 (Sahlgrenska Academy Study on Ischemic Stroke Phase 2; n=588) and LSR (Lund Stroke Register; n=735). We used binary logistic regression to analyze associations between LOY, determined by DNA microarray intensity data, and poor 3-month functional outcome (modified Rankin Scale score, >2) in each cohort separately and combined. Patients who received recanalization therapy were excluded from sensitivity analyses.LOY was associated with about 2.5-fold increased risk of poor outcome in univariable analyses (P<0.001). This association withstood separate adjustment for stroke severity and diabetes in both cohorts but not age. In sensitivity analyses restricted to the nonrecanalization group (n=987 in the combined cohort), the association was significant also after separate adjustment for age (odds ratio, 1.6 [95% CI, 1.1-2.4]) and when additionally adjusting for stroke severity and diabetes (odds ratio, 1.6 [95% CI, 1.1-2.5]).We observed an association between LOY and poor outcome after ischemic stroke in patients not receiving recanalization therapy. Future studies on LOY and other somatic genetic alterations in larger stroke cohorts are warranted.
|
|
| 7. |
- Eriksson, Marie, Professor, et al.
(författare)
-
Sex Differences in Stroke Care and Outcome 2005-2018 : Observations From the Swedish Stroke Register
- 2021
-
Ingår i: Stroke. - : AHA Journals. - 0039-2499 .- 1524-4628. ; 52:10, s. 3233-3242
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Previous studies of stroke management and outcome in Sweden have revealed differences between men and women. We aimed to analyze if differences in stroke incidence, care, and outcome have altered over time.METHODS: All stroke events registered in the Swedish Stroke Register 2005 to 2018 were included. Background variables and treatment were collected during the acute hospital stay. Survival data were obtained from the national cause of death register by individual linkage. We used unadjusted proportions and estimated age-adjusted marginal means, using a generalized linear model, to present outcome.RESULTS: We identified 335 183 stroke events and a decreasing incidence in men and women 2005 to 2018. Men were on average younger than women (73.3 versus 78.1 years) at stroke onset. The age-adjusted proportion of reperfusion therapy 2005 to 2018 increased more rapidly in women than in men (2.3%-15.1% in men versus 1.4%-16.9% in women), but in 2018, women still had a lower probability of receiving thrombolysis within 30 minutes. Among patients with atrial fibrillation, oral anticoagulants at discharge increased more rapidly in women (31.2%-78.6% in men versus 26.7%-81.9% in women). Statins remained higher in men (36.9%-83.7% in men versus 32.3%-81.2% in women). Men had better functional outcome and survival after stroke. After adjustment for women's higher age, more severe strokes, and background characteristics, the absolute difference in functional outcome was <1% and survival did not differ.CONCLUSIONS: Stroke incidence, care, and outcome show continuous improvements in Sweden, and previously reported differences between men and women become less evident. More severe strokes and older age in women at stroke onset are explanations to persisting differences.
|
|
| 8. |
- Gonçalves, Isabel, et al.
(författare)
-
Osteomodulin Gene Expression Is Associated with Plaque Calcification, Stability, and Fewer Cardiovascular Events in the CPIP Cohort
- 2022
-
Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 53:3, s. 79-84
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Stable atherosclerotic plaques are characterized by thick fibrous caps of smooth muscle cells, collagen, and macrocalcifications. Identifying factors of plaque stability is necessary to design drugs to prevent plaque rupture and symptoms. Osteomodulin, originally identified in bones, is expressed by bone synthesizing osteoblasts and involved in mineralization. In the present study, we analyzed osteomodulin expression in human carotid plaques, its link with plaque phenotype, calcification, and future cardiovascular events. Methods: Osteomodulin gene expression (OMD; n=82) was determined by RNA sequencing and osteomodulin protein levels by immunohistochemistry (n=45) in carotid plaques obtained by endarterectomy from patients with or without cerebrovascular symptoms from the CPIP (Carotid Plaque Imaging Project) cohort, Skåne University Hospital, Sweden. Plaque components were assessed by immunohistochemistry, RNA sequencing, and multiplex analysis. Patients were followed for cardiovascular events or cardiovascular death during a median of 57 or 70 months, respectively, using national registers. Results: OMD levels were increased in plaques from asymptomatic patients compared to symptomatics. High OMD levels were associated with fewer cardiovascular events during follow-up. OMD correlated positively with smooth muscle α-actin (ACTA2; r=0.73, P=10-13) and collagen (COL1A2; r=0.4, P=0.0002), but inversely with CD68 gene expression (r=-0.67, P=10-11), lipids (r=-0.37, P=0.001), intraplaque hemorrhage (r=-0.32, P=0.010), inflammatory cytokine, and matrix metalloproteinase plaque contents. OMD was positively associated with MSX2 (Msh Homeobox 2) (r=0.32, P=0.003), a marker of preosteoblast differentiation, BMP4 (bone morphogenetic protein) (r=0.50, P=0.000002) and BMP6 (r=0.47, P=0.000007), plaque calcification (r=0.35, P=0.016), and was strongly upregulated in osteogenically stimulated smooth muscle cells, which was further increased upon BMP stimulation. Osteomodulin protein was present in calcified regions. Osteomodulin protein levels were associated with plaque calcification (r=0.41, P=0.006) and increased in macrocalcified plaques. Conclusions: These data show that osteomodulin mRNA and protein levels are associated with plaque calcification in human atherosclerosis. Furthermore, osteomodulin mRNA, but not protein levels, is associated with plaque stability.
|
|
| 9. |
|
|
| 10. |
- Hankey, G. J., et al.
(författare)
-
Twelve-Month Outcomes of the AFFINITY Trial of Fluoxetine for Functional Recovery After Acute Stroke AFFINITY Trial Steering Committee on Behalf of the AFFINITY Trial Collaboration
- 2021
-
Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 52:8, s. 2502-2509
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. METHODS: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. RESULTS: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76-1.14]; P=0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; P=0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; P=0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; P=0.05), or seizures (11 [1.71%] versus 8 [1.25%]; P=0.64) at 12 months. CONCLUSIONS: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding.
|
|
