Long-term risk of recurrent vascular events and mortality in young stroke patients: Insights from a multicenter study.

BACKGROUND: Although the incidence of stroke in the young is rising, data on long-term outcomes in these patients are scarce. We thus aimed to investigate the long-term risk of recurrent vascular events and mortality in a multicenter study. METHODS: We followed 396 consecutive patients aged 18-55 years with ischemic stroke (IS) or transient ischemic attack (TIA) enrolled in three European centers during the period 2007-2010. A detailed outpatient clinical follow-up assessment was performed between 2018 and 2020. When an in-person follow-up visit was not possible, outcome events were assessed using electronic records and registry data. RESULTS: During a median follow-up of 11.8 (IQR 10.4-12.7) years, 89 (22.5%) patients experienced any recurrent vascular event, 62 (15.7%) had any cerebrovascular event, 34 (8.6%) had other vascular events, and 27 (6.8%) patients died. Cumulative 10-year incidence rate per 1000 person-years was 21.6 (95% CI 17.1-26.9) for any recurrent vascular event and 14.9 (95% CI 11.3-19.3) for any cerebrovascular event. The prevalence of cardiovascular risk factors increased over time, and 22 (13.5%) patients lacked any secondary preventive medication at the in-person follow-up. After adjustment for demographics and comorbidities, atrial fibrillation at baseline was found to be significantly associated with recurrent vascular events. CONCLUSIONS: This multicenter study shows a considerable risk of recurrent vascular events in young IS and TIA patients. Further studies should investigate whether detailed individual risk assessment, modern secondary preventive strategies, and better patient adherence may reduce recurrence risk.

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.

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.

Preceding and poststroke infections in young adults with first-ever ischemic stroke: effect on short-term and long-term outcomes.

BACKGROUND AND PURPOSE: Poststroke infections (PSIs) worsen the outcome in acute ischemic stroke, but the effect of preceding infection (PI) is controversial. Data on young patients are scarce. We characterized PI and PSI in young adults with first-ever stroke and studied whether they are associated with 3-month and long-term outcomes, recurrent vascular events, and death. METHODS: From our database of 1008 consecutive patients aged 15 to 49 years, we included in the present study those who had brain imaging done within the first 2 days from stroke onset. Outcomes were unfavorable at 3 months and during long-term follow-up, vascular events, and all-cause death. Logistic regression and Cox proportional models were used to determine associations between infections and clinical outcomes. RESULTS: A total of 681 patients (62.3% men) fulfilled the inclusion criteria. Of these, 70 (10.3%) had PI, most commonly upper respiratory tract infection, and 103 (15.1%) had PSI, most commonly pneumonia. After adjusting for sex, age, and risk factors, both PI (odds ratio, 2.86; 95% confidence interval, 1.48-5.54) and PSI (odds ratio, 2.26; 95% confidence interval, 1.08-4.76) were independently associated with unfavorable 3-month outcome. PSI was also associated with long-term (follow-up, 7.8±4.0 years) higher risk of all-cause death. CONCLUSIONS: In young patients with ischemic stroke, both PI and PSIs are associated with unfavorable short-term outcome. PSIs are also associated with higher long-term mortality.

Stroke in Patients with Atrial Fibrillation: Epidemiology, Screening, and Prognosis.

Atrial fibrillation (AF) is the most common sustained arrythmia and one of the strongest risk factors and causal mechanisms of ischemic stroke (IS). Acute IS due to AF tends to be more severe than with other etiology of IS and patients with treated AF have reported to experience worse outcomes after endovascular treatment compared with patients without AF. As cardioembolism accounts for more than a fifth of ISs and the risk of future stroke can be mitigated with effective anticoagulation, which has been shown to be effective and safe in patients with paroxysmal or sustained AF, the screening of patients with cryptogenic IS (CIS) for AF is paramount. Embolic stroke of undetermined source (ESUS) is a subtype of CIS with a high likelihood of cardioembolism. The European Stroke Organization and European Society of Cardiology guidelines recommend at least 72 h of screening when AF is suspected. The longer the screening and the earlier the time point after acute IS, the more likely the AF paroxysm is found. Several methods are available for short-term screening of AF, including in-hospital monitoring and wearable electrocardiogram recorders for home monitoring. Implantable loop monitors provide an effective long-term method to screen patients with high risk of AF after IS and artificial intelligence and convolutional neural networks may enhance the efficacy of AF screening in the future. Direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists in both primary and secondary prevention of IS in AF patients. Recent data from the randomized controlled trials (RCT) also suggest that early initiation of DOAC treatment after acute IS is safe compared to later initiation. Anticoagulation treatment may still predispose for intracranial bleeding, particularly among patients with prior cerebrovascular events. Left atrial appendix closure offers an optional treatment choice for patients with prior intracranial hemorrhage and may offer an alternative to oral anticoagulation even for patients with IS, but these indications await validation in ongoing RCTs. There are still controversies related to the association of found AF paroxysms in CIS patients with prolonged screening, pertaining to the optimal duration of screening and screening strategies with prolonged monitoring techniques in patients with ESUS. In this review, we summarize the current knowledge of epidemiology, screening, and prognosis in AF patients with stroke.

Association of post-stroke-initiated antidepressants with long-term outcomes in young adults with ischaemic stroke.

OBJECTIVE: We examined the association between initiation of antidepressants within the first year after ischaemic stroke (IS) in young adults and long-term fatal and non-fatal cardiovascular events, as well as all-cause mortality. PATIENTS AND METHODS: The Helsinki Young Stroke Registry (HYSR) includes patients aged 15-49 years with their first-ever IS occurring 1994-2007. From nationwide registers, we obtained data on prescriptions (1993-2011) and outcomes of interest (1994-2011). Time of initiating post-stroke antidepressants (PSADs) was defined as time of the first filled prescription for antidepressants within the first year from IS. To account for non-random assignment of PSADs, we performed propensity score matching and studied the relationship between PSAD initiation and outcomes using Cox regression models with time-varying coefficients. RESULTS: Of all patients (n = 888), 206 (23.2%) initiated PSADs within the first year, of which 203 (98.5%) could be matched to 406 non-initiators. In this matched sample of 609 patients, the median follow-up time was 8.1 (interquartile range [IQR] 5.0-12.6) years and 169 (28.9%) patients had any cardiovascular events, 95 (15.8%) had recurrent ischaemic or haemorrhagic strokes and 106 (17.4%) died. Adjusted for sociodemographics and cardiovascular comorbidities, PSAD initiation was associated with recurrent ischaemic or haemorrhagic stroke 5-10 years after IS (hazard ratio [HR] 3.07, 95% confidence interval [CI] 1.32-7.12). No association emerged between PSAD initiation and other outcomes. CONCLUSIONS: In young adults, PSAD initiation within the first year after IS was associated with a heightened hazard of recurrent ischaemic or haemorrhagic stroke in the long term. Future studies are needed to verify the results and to further study the nature of this finding.KEY MESSAGESInitiation of post-stroke antidepressants (PSADs) within the first year after ischaemic stroke (IS) was associated with a heightened hazard of recurrent ischaemic or haemorrhagic stroke in the long term.Patients starting antidepressants after IS should be followed up more closely in case of recurrent events.Future studies are needed to verify the results and to further study the nature of this finding.

Initiation of antidepressants in young adults after ischemic stroke: a registry-based follow-up study.

OBJECTIVE: Data on post-stroke use of antidepressants in young individuals are scarce. We examined pattern and factors associated with initiating post-stroke antidepressants (PSAD) after ischemic stroke (IS) in young adults. METHODS: Helsinki Young Stroke Registry includes patients aged 15-49 years with first-ever IS, 1994-2007. Data on prescriptions, hospitalizations and death came from nationwide registers. We defined time of initiating PSAD as time of the first filled prescription for antidepressants within 1 year from IS. We assessed factors associated with initiating PSAD with multivariable Cox regression models, allowing for time-varying effects when appropriate. RESULTS: We followed 888 patients, of which 206 (23.2%) initiated PSAD. Higher hazard of starting PSAD within the first 100 days appeared among patients with mild versus no limb paresis 2.53 (95% confidence interval 1.48-4.31) and during later follow-up among those with silent infarcts (2.04; 1.27-3.28), prior use of antidepressants (2.09; 1.26-3.46) and moderate versus mild stroke (2.06; 1.18-3.58). The relative difference in the hazard rate for moderate-severe limb paresis persisted both within the first 100 days (3.84, 2.12-6.97) and during later follow-up (4.54; 2.51-8.23). The hazard rate was higher throughout the follow-up among smokers (1.48; 1.11-1.97) as well as lower (1.78; 1.25-2.54) and upper white-collar workers (2.00; 1.24-3.23) compared to blue-collar workers. CONCLUSION: One-fourth of young adults started PSADs within 1 year from IS. We identified several specific clinical characteristics associated with PSAD initiation, highlighting their utility in assessing the risk of post-stroke depression during follow-up.

Return to work after ischemic stroke in young adults: A registry-based follow-up study.

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.