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Background Gingivitis, i.e. inflammation of the gums, is often induced by dental plaque. However, its exact link to the oral microbiota remains unclear.Methods In a case-control study involving 120 participants, comprising 60 cases and 60 controls (mean age (SD) 36.6 (7.6) years; 50% males), nested within a prospective multicentre cohort study, we examined the oral microbiome composition of gingivitis patients and their controls using shotgun metagenomic sequencing of saliva samples. Participants underwent clinical and radiographic oral health examinations, including bleeding on probing (BOP), at six tooth sites. BOP ≥33% was considered ‘generalized gingivitis/initial periodontitis’(GG/IP), and BOP

Background Little is known how individual time-in-therapeutic-range (TTR) impacts the effectiveness and safety of warfarin therapy compared to direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF).Objective To compare the effectiveness and safety of standard dose DOACs to warfarin in patients with AF, while categorizing warfarin treated patients into quartiles based on their individual TTR.Materials and methods We conducted a nationwide study including all patients with new-onset AF between 2011 and 2018 in Finland. Hazard ratios (HR) were calculated using Cox regression analysis with the inverse probability of treatment weighted method to assess the risks of ischaemic stroke (IS), intracranial haemorrhage (ICH) and mortality for users of apixaban (n = 12,426), dabigatran (n = 4545), rivaroxaban (n = 12,950) and warfarin (n = 43,548).Results The median TTR for warfarin users was 72%. Compared to the second best TTR quartile (reference), the risk of IS was higher in the two poorest TTR quartiles, and lower in the best TTR quartile and on rivaroxaban [2.35 (95% confidence interval, 1.85–2.85), 1.44 (1.18–1.75), 0.60 (0.47–0.77) and 0.72 (0.56–0.92)]. These differences were non-significant for apixaban and dabigatran. HR of ICH was 6.38 (4.88–8.35) and 1.87 (1.41–2.49) in the two poorest TTR groups, 1.44 (1.02–1.93) on rivaroxaban, and 0.58 (0.40–0.85) in the best TTR group compared to the reference group. Mortality was higher in the two poorest TTR groups and lowest in the best TTR group.Conclusions The outcome was unsatisfactory in the two lowest TTR quartiles – in half of the patients treated with warfarin. The differences between the high TTR groups and standard dose DOACs were absent or modest.

Background: Catheter ablation is a well-established treatment to prevent atrial fibrillation (AF) and atrial flutter (AFL) recurrences and to relieve symptoms, whereas pacemaker implantation and atrioventricular node (AVN) ablation is used for rate control when medical therapy fails. Aims: We investigated temporal trends and patient characteristics in catheter ablation procedures for AF, AFL and AVN in Finland between 2012–2018. Methods: Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a registry-based study including all patients with AF or AFL in Finland between 2012–2018. Results: The number of patients with AF or AFL diagnosis in Finland increased from 185 057 to 243 802 between 2012–2018 and a total of 8954 first-time catheter ablation procedures were performed. Of them, 4909 (54.8 %) were AF ablations, 2731 (30.5 %) AFL ablations and 1314 (14.7 %) AVN ablations. The procedural numbers increased from 457/year to 934/year for AF, from 223/year to 553/year for AFL and from 114/year to 238/year for AVN. Altogether, 0.65% of all patients with diagnosed AF or AFL underwent AF, AFL or AVN ablation in 2018. The mean age of the patients increased in all ablation groups. Patients undergoing AF and AFL ablations were predominantly men (69.7 % and 74.6 % respectively) whereas patients undergoing AVN ablation were more often women (56.9%). Conclusions: The use of catheter ablation more than doubled during 2012–2018 and the increase was particularly seen in the elderly patients. Nevertheless, only a minority of AF and AFL patients were treated with catheter ablations.

Abstract Individuals with type 1 diabetes (T1D) carry a markedly increased risk of stroke, with distinct clinical and neuroimaging characteristics as compared to those without diabetes. Using whole-exome or whole-genome sequencing of 1,051 individuals with T1D, we aimed to find rare and low-frequency genomic variants associated with stroke in T1D. We analysed the genome comprehensively with single-variant analyses, gene aggregate analyses, and aggregate analyses on genomic windows, enhancers and promoters. In addition, we attempted replication in T1D using a genome-wide association study (N = 3,945) and direct genotyping (N = 3,263), and in the general population from the large-scale population-wide FinnGen project and UK Biobank summary statistics. We identified a rare missense variant on SREBF1 exome-wide significantly associated with stroke (rs114001633, p.Pro227Leu, p-value = 7.30 × 10–8), which replicated for hemorrhagic stroke in T1D. Using gene aggregate analysis, we identified exome-wide significant genes: ANK1 and LRRN1 displayed replication evidence in T1D, and LRRN1, HAS1 and UACA in the general population (UK Biobank). Furthermore, we performed sliding-window analyses and identified 14 genome-wide significant windows for stroke on 4q33-34.1, of which two replicated in T1D, and a suggestive genomic window on LINC01500, which replicated in T1D. Finally, we identified a suggestively stroke-associated TRPM2-AS promoter (p-value = 5.78 × 10–6) with borderline significant replication in T1D, which we validated with an in vitro cell-based assay. Due to the rarity of the identified genetic variants, future replication of the genomic regions represented here is required with sequencing of individuals with T1D. Nevertheless, we here report the first genome-wide analysis on stroke in individuals with diabetes.

Objectives Atrial fibrillation (AF) is associated with increased mortality. Previous studies have reported conflicting results in temporal trends of mortality after AF diagnosis. We aim to address this disparity by investigating the 1-year mortality and causes of death in Finnish patients diagnosed with AF between 2010 and 2017.Design The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) study is a nationwide retrospective register-based cohort study.Setting The FinACAF study has gathered information on all Finnish AF patients between 2004 and 2018, with information from all national healthcare registers and data from all levels of care (primary, secondary and tertiary care).Participants We included patients with an incident AF diagnosis (International Classification of Diseases, 10th Revision code I48) between 2010 and 2017. To ensure a cohort of only incident AF, we excluded patients who used any oral anticoagulant during the year before cohort entry as well as patients with a recorded use of warfarin between 2004 and 2006. Patients under 20 years of age were excluded, and patients with permanent migration abroad before 1 January 2019 were excluded, N=157 658.Primary outcome measures 1-year all-cause, cardiovascular (CV) and cause-specific mortality following AF diagnosis.Results The study cohort consisted of 157 658 incident AF cases (50.1% male, mean age 72.9 years). Both all-cause and CV mortality declined from cohort entry years 2010–2017 (from 12.9% to 10.6%, mortality rate ratio (MRR) 0.77; 95% CI 0.73 to 0.82 in cohort entry year 2017 with 2010 as reference; and from 7.4% to 5.2%, MRR 0.68; 95% CI 0.63 to 0.74, respectively). Overall mortality and CV mortality were lower in women than in men throughout the study period (MRR 0.66; 95% CI 0.63 to 0.69 and MRR 0.53; 95% CI 0.50 to 0.56, respectively). Deaths attributable to ischaemic heart disease decreased during the study period (from 30.7% to 21.6%, MRR 0.51; 95% CI 0.49 to 0.62 in 2017 vs 2010), whereas dementia and Alzheimer’s disease increased as a cause of death over time (6.2% to 9.9%, MRR 1.19; 95% CI 0.96 to 1.48 in 2017 vs 2010). The CHA2DS2-VASc score associated strongly with 1-year survival (p

Abstract Background As the retina is suggested to mirror the brain, we hypothesized that diabetic retinopathy and macular edema are indicative of stroke risk in type 1 diabetes and sought to assess this association in individuals with type 1 diabetes. Methods We included 1,268 adult FinnDiane Study participants with type 1 diabetes (age 38.7 ± 11.8 years, 51.7% men vs. 48.3% women, and 31.5% had diabetic kidney disease), data on baseline diabetic retinopathy severity, and first stroke during our observational follow-up. Retinopathy was graded by the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, and macular edema as clinically significant (CSME) or not. Strokes identified from registries were confirmed from medical files. Adjusted hazard ratios (HR) for stroke by retinopathy severity and CSME were calculated by Cox models adjusted for clinical confounders, including diabetic kidney disease. Results During median 18.0 (14.1–19.3) follow-up years, 130 strokes (96 ischemic, 34 hemorrhagic) occurred. With no–very mild (ETDRS 10–20) retinopathy as reference, the adjusted HR for stroke was 1.79 (95%CI 1.02–3.15) in non-proliferative (ETDRS 35–53), and 1.69 (1.02–2.82) in proliferative (ETDRS 61–85) retinopathy. Corresponding adjusted HR for ischemic stroke was 1.68 (0.91–3.10) in non-proliferative and 1.35 (0.77–2.36) in proliferative retinopathy. The adjusted HR for hemorrhagic stroke was 2.84 (0.66–12.28) in non-proliferative and 4.31 (1.16–16.10) in proliferative retinopathy. CSME did not increase HR for any stroke type after adjustment for clinical confounders (data not shown). Conclusions Stroke incidence increases with the severity of diabetic retinopathy independently of comorbid conditions, including diabetic kidney disease.

Background The influence of burden of atherosclerosis in the brain supplying arteries on mortality in patients with acute ischemic stroke or transient ischemic attack is poorly known. We assessed whether total burden of atherosclerosis within cervicocerebral arteries is associated with long‐term mortality. Methods and Results A total of 406 patients (median age, 71.8 years; 57.9% male) with acute ischemic stroke or transient ischemic attack were included and their cervicocerebral arteries imaged with computed tomography angiography. The presence of atherosclerotic findings was scored for 25 artery segments and points were summed as a Cervicocerebral Atherosclerosis Burden (CAB) score, analyzed as quartiles. Data on all‐cause mortality came from Statistics Finland. After a median follow‐up of 7.3 years, 147 (33.5%) patients had died. Compared with surviving patients, those who died had a higher median CAB score (5, interquartile range 2–10 versus 11, 7–16; P

BackgroundThe relationship between baseline perihematomal edema (PHE) and inflammation, and their impact on survival after intracerebral hemorrhage (ICH) are not well understood.ObjectiveAssess the association between baseline PHE, baseline C-reactive protein (CRP), and early death after ICH.MethodsAnalysis of pooled data from multicenter ICH registries. We included patients presenting within 24 h of symptom onset, using multifactorial linear regression model to assess the association between CRP and edema extension distance (EED), and a multifactorial Cox regression model to assess the association between CRP, PHE volume and 30-day mortality.ResultsWe included 1,034 patients. Median age was 69 (interquartile range [IQR] 59–79), median baseline ICH volume 11.5 (IQR 4.3–28.9) mL, and median baseline CRP 2.5 (IQR 1.5–7.0) mg/L. In the multifactorial analysis [adjusting for cohort, age, sex, log-ICH volume, ICH location, intraventricular hemorrhage (IVH), statin use, glucose, and systolic blood pressure], baseline log-CRP was not associated with baseline EED: for a 50% increase in CRP the difference in expected mean EED was 0.004 cm (95%CI 0.000–0.008, p = 0.055). In a further multifactorial analysis, after adjusting for key predictors of mortality, neither a 50% increase in PHE volume nor CRP were associated with higher 30-day mortality (HR 0.97; 95%CI 0.90–1.05, p = 0.51 and HR 0.98; 95%CI 0.93–1.03, p = 0.41, respectively).ConclusionHigher baseline CRP is not associated with higher baseline edema, which is also not associated with mortality. Edema at baseline might be driven by different pathophysiological processes with different effects on outcome.

Introduction: Type 1 diabetes (T1D) is an important risk factor for cerebral small vessel disease (SVD). Cerebral microbleeds (CMB) and white matter hyperintensities (WMH) can already be observed in early midlife in individuals with T1D, even though generally, this pathology is seen decades later in those without diabetes. Whether these changes affect cognitive functions, remains unclear. We investigated the associations of CMB and WMH with processing speed and attention in adults with T1D without major neurological symptoms. Methods: As part of an ongoing FinnDiane sub-study, brain magnetic resonance imaging, and extensive clinical and neuropsychological examinations were done for 142 participants with T1D (age 47.2±7.6 years, diabetes duration 31.6±11.0 years). CMB and WMH were evaluated visually by an experienced neuroradiologist and categorized according to number and severity (CMB: 0 vs 1-2 vs ≥3; WMH: Fazekas score 0 vs ≥1). The assessment of processing speed and attention included the Wechsler Adult Intelligence Scale-IV (WAIS-IV) Coding and Symbol search subtests, the Stroop test, and the computerized Flexible Attention Test (FAT) Simple Visuomotor Speed, Numbers and Number-Letter subtasks. Results: CMB (≥3) and mild WMH were associated with poorer performance in WAIS-IV Coding and Symbol Search, and Stroop and FAT subtasks (p

Conclusions: We found smaller thalamus volume fractions in individuals with Type 1 diabetes as compared to those without diabetes, as well as reductions in brain volume fractions related to signs of cSVD in individuals with Type 1 diabetes.

AbstractBackground In young patients, up to 40% of ischemic strokes remain cryptogenic despite modern-day diagnostic work-up. There are limited data on blood pressure (BP) behavior in these patients. Thus, we aimed to compare ambulatory blood pressure (ABP) profiles between young patients with a recent cryptogenic ischemic stroke (CIS) and stroke-free controls.Patients and Methods In this substudy of the international multicenter case–control study SECRETO (NCT01934725), 24-hour ambulatory blood pressure monitoring (ABPM) was performed in consecutive 18–49-year-old CIS patients and stroke-free controls. The inclusion criteria were met by 132 patients (median age, 41.9 years; 56.1% males) and 106 controls (41.9 years; 56.6% males). We assessed not only 24-hour, daytime, and nighttime ABP but also hypertension phenotypes and nocturnal dipping status.Results 24-hour and daytime ABP were higher among controls. After adjusting for relevant confounders, a non-dipping pattern of diastolic blood pressure (DBP) was associated with CIS in the entire sample (odds ratio, 3.85; 95% confidence interval, 1.20–12.42), in participants without antihypertensives (4.86; 1.07–22.02), and in participants without a patent foramen ovale (PFO) (7.37; 1.47–36.81). After excluding patients in the first tertile of the delay between the stroke and ABPM, a non-dipping pattern of DBP was not associated with CIS, but a non-dipping pattern of both systolic BP and DBP was (4.85; 1.37–17.10). In participants with a PFO and in those without hypertension by any definition, no associations between non-dipping patterns of BP and CIS emerged.Conclusions Non-dipping patterns of BP were associated with CIS in the absence of a PFO but not in the absence of hypertension. This may reflect differing pathophysiology underlying CIS in patients with versus without a PFO. Due to limitations of the study, results regarding absolute ABP levels should be interpreted with caution.Key MessagesNocturnal non-dipping patterns of blood pressure were associated with cryptogenic ischemic stroke except in participants with a patent foramen ovale and in those without hypertension by any definition, which may indicate differing pathophysiology underlying cryptogenic ischemic stroke in patients with and without a patent foramen ovale.It might be reasonable to include ambulatory blood pressure monitoring in the diagnostic work-up for young patients with ischemic stroke to detect not only the absolute ambulatory blood pressure levels but also their blood pressure behavior.

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.

BackgroundOral contraceptives (OCs) are generally safe but vascular risk factors increase OC-associated ischemic stroke risk. We performed a case-control study to evaluate whether a genomic risk score for ischemic stroke modifies OC-associated ischemic stroke risk.MethodsThe Genetics of Early-Onset Stroke study includes 332 premenopausal women (136 arterial ischemic stroke cases and 196 controls) with data on estrogen-containing OC use within 30 days before the index event (for cases) or interview (for controls). Using a previously validated genetic risk score (metaGRS) for ischemic stroke based on 19 polygenic risk scores for stroke and stroke-associated risk factors, we stratified our combined case-control sample into tertiles of genomic risk. We evaluated the association between OC use and ischemic stroke within each tertile. We tested if the association between OC use and ischemic stroke depended on the genomic risk of stroke using logistic regression with an OC use × metaGRS interaction term. These analyses were performed with and without adjustment for smoking, hypertension, diabetes, coronary heart disease, and body mass index.ResultsAfter adjustment for vascular risk factors, the odds ratio of OC use was 3.2 (1.7–6.3) overall and increased from the lower, middle, and upper tertile of genomic risk from 1.6 (0.5–5.4) to 2.5 (0.08–8.2) to 13.7 (3.8–67.3) respectively, and a p-value for interaction of 0.001.ConclusionsOur results suggest that genomic profile may modify the OC-associated ischemic stroke risk. Larger studies are warranted to determine whether a genomic risk score could be clinically useful in reducing OC-associated ischemic stroke.

IntroductionCurrent guidelines recommend that patients with cerebral venous thrombosis (CVT) should be treated with vitamin K antagonists (VKAs) for 3–12 months. Direct oral anticoagulants (DOACs), however, are increasingly used in clinical practice. An exploratory randomized controlled trial including 120 patients with CVT suggested that the efficacy and safety profile of dabigatran (a DOAC) is similar to VKAs for the treatment of CVT, but large-scale prospective studies from a real-world setting are lacking.MethodsDOAC-CVT is an international, prospective, observational cohort study comparing DOACs to VKAs for the prevention of recurrent venous thrombotic events after acute CVT. Patients are eligible if they are 18 years or older, have a radiologically confirmed CVT, and have started oral anticoagulant treatment (DOAC or VKA) within 30 days of CVT diagnosis. Patients with an absolute contra-indication for DOACs, such as pregnancy or severe renal insufficiency, are excluded from the study. We aim to recruit at least 500 patients within a three-year recruitment period. The primary endpoint is a composite of recurrent venous thrombosis and major bleeding at 6 months of follow-up. We will calculate an adjusted odds ratio for the primary endpoint using propensity score inverse probability treatment weighting.DiscussionDOAC-CVT will provide real-world data on the comparative efficacy and safety of DOACs versus VKAs for the treatment of CVT.Clinical trial registrationClinicalTrials.gov, NCT04660747.

Abstract Background Patients with wake-up ischemic stroke are frequently excluded from thrombolytic treatment due to unknown symptom onset time and limited availability of advanced imaging modalities. The Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST) is a randomized controlled trial of intravenous tenecteplase 0.25 mg/kg and standard care versus standard care alone (no thrombolysis) in patients who wake up with acute ischemic stroke and can be treated within 4.5 h of wakening based on non-contrast CT findings. Objective To publish the detailed statistical analysis plan for TWIST prior to unblinding. Methods The TWIST statistical analysis plan is consistent with the Consolidating Standard of Reporting Trials (CONSORT) statement and provides clear and open reporting. Discussion Publication of the statistical analysis plan serves to reduce potential trial reporting bias and clearly outlines the pre-specified analyses. Trial registration ClinicalTrials.gov NCT03181360 . EudraCT Number 2014-000096-80 . WHO ICRTP registry number ISRCTN10601890 .

Background Patients with aortic stenosis (AS) have been underrepresented in the trials evaluating direct oral anticoagulants (DOACs) in atrial fibrillation (AF). We aimed to assess whether AS impacts outcomes in patients with AF and estimate the effects of DOACs versus warfarin in patients with AF and AS. Methods and Results The registry‐based FinACAF (Finnish Anticoagulation in Atrial Fibrillation) study covered all patients with AF diagnosed during 2007 to 2018 in Finland. Hazard ratios (HRs) of first‐ever gastrointestinal bleeding, intracranial bleeding, any bleeding, ischemic stroke, and death were estimated with cause‐specific hazards regression adjusted for anticoagulant exposure variables. We identified 183 946 patients (50.5% women; mean age, 71.7 [SD, 13.5] years) with incident AF without prior bleeding or ischemic stroke, of whom 5231 (2.8%) had AS. The crude incidence rate of all outcomes was higher in patients with AS than in patients without AS. After propensity score matching, AS was associated with the hazard of any bleeding, gastrointestinal bleeding, and death but not with intracranial bleeding or ischemic stroke (adjusted HRs, 1.36 [95% CI, 1.25–1.48], 1.63 [95% CI, 1.43–1.86], 1.32 [95% CI, 1.26–1.38], 0.96 [95% CI, 0.78–1.17], and 1.11 [95% CI, 0.99–1.25], respectively). Among patients with AS, DOACs were associated with a lower risk of ischemic stroke when compared with warfarin, while bleeding and mortality did not differ between DOACs and warfarin. Conclusions AS is associated with substantially higher risk of gastrointestinal bleeding in patients with AF. DOACs may be more effective in preventing ischemic stroke than warfarin in patients with AF and AS. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04645537.

IntroductionDiabetic neuropathy and diabetic eye disease are well known complications of type 1 diabetes. We hypothesized that chronic hyperglycemia also damages the optic tract, which can be measured using routine magnetic resonance imaging. Our aim was to compare morphological differences in the optic tract between individuals with type 1 diabetes and healthy control subjects. Associations between optic tract atrophy and metabolic measures, cerebrovascular and microvascular diabetic complications were further studied among individuals with type 1 diabetes.MethodsWe included 188 subjects with type 1 diabetes and 30 healthy controls, all recruited as part of the Finnish Diabetic Nephropathy Study. All participants underwent a clinical examination, biochemical work-up, and brain magnetic resonance imaging (MRI). Two different raters manually measured the optic tract.ResultsThe coronal area of the optic chiasm was smaller among those with type 1 diabetes compared to non-diabetic controls (median area 24.7 [21.0-28.5] vs 30.0 [26.7-33.3] mm2, p

Background: Low socioeconomic status has been associated with higher risk of ischemic stroke and death in patients with atrial fibrillation (AF). However, whether socioeconomic status affects risk of bleeding events is unknown. We assessed the hypothesis that low income and educational attainment are associated with higher risk of bleeding in patients with AF. Methods: The registry-based FinACAF study covers all patients with AF in Finland during 2007–2018. Patients were divided into income quartiles and three categories based on their educational attainment. Outcomes of interest were the first-ever gastrointestinal (GI), intracranial (IC) and any bleeding. Results: We identified 205 019 patients (50.9 % female; mean age 72.3 (SD 13.4) years) with incident AF without prior bleeding. Mean follow-up time was 4.0 (SD 3.2) years, during which 25 013 (12.2 %) patients experienced first-ever any bleeding (incidence rate 3.07 (95 % CI 3.03–3.10) /100 patient-years). Low income was independently associated with hazard of any bleeding as well as GI and IC bleeding (adjusted hazard ratios (HRs) comparing lowest vs highest income quartile: 1.13 (1.08–1.17), 1.32 (1.23–1.41) and 1.15 (1.06–1.24), respectively). Income-related bleeding disparities were larger among younger patients under 65 years and among men. Education-related bleeding disparities were smaller than income related-disparities (adjusted HRs comparing lowest vs highest educational category: any bleeding 1.06 (1.02–1.11), GI bleeding 1.16 (1.08–1.24), IC bleeding 1.10 (0.93–1.09)) Conclusions: Patients with AF and low income are at higher risk of bleeding, especially GI bleeding.

Abstract Background Accurate measurement of left atrial (LA) volumes is needed in cardiac diagnostics and the follow up of heart and valvular diseases. Geometrical assumptions with 2D methods for LA volume estimation contribute to volume misestimation. In this study, we test agreement of 3D and 2D methods of LA volume detection and explore contribution of 3D LA axis orientation and LA shape in introducing error in 2D methods by cardiovascular magnetic resonance imaging. Methods 30 patients with prior first-ever ischemic stroke and no known heart disease, and 30 healthy controls were enrolled (age 18–49) in a substudy of a prospective case–control study. All study subjects underwent cardiac magnetic resonance imaging and were pooled for this methodological study. LA volumes were calculated by biplane area-length method from both conventional long axis (LAVAL-LV) and LA long axis-oriented images (LAVAL-LA) and were compared to 3D segmented LA volume (LAVSAX) to assess accuracy of volume detection. 3D orientation of LA long axis to left ventricular (LV) long axis and to four-chamber plane were determined, and LA 3D sphericity indices were calculated to assess sources of error in LA volume calculation. Shapiro–Wilk test, Bland–Altman analysis, intraclass and Pearson correlation, and Spearman’s rho were used for statistical analysis. Results Biases were − 9.9 mL (− 12.5 to − 7.2) for LAVAL-LV and 13.4 (10.0–16.9) for LAVAL-LA [mean difference to LAVSAX (95% confidence interval)]. End-diastolic LA long axis 3D deviation angle to LV long axis was 28.3 ± 6.2° [mean ± SD] and LA long axis 3D rotation angle to four-chamber plane 20.5 ± 18.0°. 3D orientation of LA axis or 3D sphericity were not correlated to error in LA volume calculation. Conclusions Calculated LA volume accuracy did not improve by using LA long axis-oriented images for volume calculation in comparison to conventional method. We present novel data on LA axis orientation and a novel metric of LA sphericity and conclude that these measures cannot be utilized to assess error in LA volume calculation. Trial registration Main study Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) has been registered previously.

Background: In patients with atrial fibrillation (AF), socioeconomic disparities have been reported in the use of oral anticoagulant therapy and outcomes, but whether income also affects the utilization of antiarrhythmic therapies (AATs) for rhythm control is unknown. We assessed the hypothesis that AF patients with higher income are more likely to receive AATs. Methods: The nationwide retrospective registry based FinACAF cohort study covers all patients with AF from all levels of care in Finland. Patients were divided in AF diagnosis year and age-group specific income quintiles according to their highest annual income during 2004–2018. The primary outcome was the use of any AAT, including cardioversion, catheter ablation, and fulfilled antiarrhythmic drug (AAD) prescription. Results: We identified 188 175 patients (mean age 72.6 ± 13.0 years; 49.6% female) with incident AF during 2010–2018. Patients in higher income quintiles had consistently higher use of all AAT modalities. When compared to patients in the lowest income quintile, the adjusted incidence rate ratios (95% CI) in the highest quintile were 1.53 (1.48–1.59) for any AAT, 1.71 (1.61–1.81) for AADs, 1.43 (1.37–1.49) for cardioversion, and 2.00 (1.76–2.27) for catheter ablation. No temporal change during study period was observed in the magnitude of income disparities in AAT use, except for a decrease in income-related differences in the use of AADs. Conclusion: Profound income-related disparities exist in AAT use among patients with AF in Finland, especially in the use catheter ablation.

Objectives Mental health conditions (MHCs) have been associated with undertreatment of unrelated medical conditions, but whether patients with MHCs face disparities in receiving rhythm control therapies for atrial fibrillation (AF) is currently unknown. We assessed the hypothesis that MHCs are associated with a lower use of antiarrhythmic therapies (AATs).Design A nationwide retrospective registry-based cohort study.Setting The Finnish AntiCoagulation in Atrial Fibrillation cohort included records on all patients with AF in Finland during 2007–2018 identified from nationwide registries covering all levels of care as well as drug purchases. MHCs of interest were diagnosed depression, bipolar disorder, anxiety disorder, schizophrenia and any MHC.Participants We identified 239 222 patients (mean age 72.6±13.2 years; 49.8% women) with incident AF, in whom the prevalence of any MHC was 19.9%.Outcomes Primary outcome was use of any AAT, including cardioversion, catheter ablation, and fulfilled antiarrhythmic drug (AAD) prescription.Results Lower overall use of any AAT emerged in patients with any MHC than in those without MHC (16.9% vs 22.9%, p

Objective Atrial fibrillation (AF) is a worldwide healthcare challenge owing to population ageing. In this study, we assessed the current trends in the incidence and prevalence of AF for the first time in an unselected, nationwide population.Methods In the Finnish Anticoagulation in Atrial Fibrillation study, we gathered comprehensive data including all primary, secondary and tertiary healthcare visits and drug reimbursement from national healthcare registers to identify all patients with incident AF between 2004 and 2018 in Finland. Incident AF was defined as new-onset AF occurring after 2007. Time trends for the incidence and prevalence of AF were calculated and stratified by sex and age.Results A total of 411 387 patients with AF diagnosis were documented in Finland during 2004–2018. In 2018, the incidence and prevalence of AF in the total Finnish population were 469/100 000 and 4.1%, respectively. The incidence of new-onset AF in the adult population (≥20 years) increased from 471/100 000 in 2007 to 604/100 000 in 2018, but the age-adjusted incidence remained stable. The prevalence of AF increased in the adult population from 2.5% to 5.2%, and was higher in men than in women (5.9% vs 4.6%, p

Abstract Low socioeconomic status has been associated with poor outcomes in patients with atrial fibrillation (AF). However, little is known about socioeconomic disparities in adherence to stroke prevention with direct oral anticoagulants (DOACs). We assessed the hypothesis that AF patients with higher income or educational levels have better adherence to DOACs in terms of treatment implementation and persistence. The used nationwide registry‐based FinACAF cohort covers all patients with incident AF starting DOACs in Finland during 2011–2018. The implementation analyses included 74 222 (mean age 72.7 ± 10.5 years, 50.8% female) patients, and persistence analyses included 67 503 (mean age 75.3 ± 8.9 years, 53.6% female) patients with indication for permanent anticoagulation (CHA2DS2‐VASc score >1 in men and >2 in women). Patients were divided into income quartiles and into three categories based on their educational attainment. Therapy implementation was measured using the medication possession ratio (MPR), and patients with MPR ≥0.90 were defined adherent. Persistence was measured as the incidence of therapy discontinuation, defined as the first 135‐day period without DOAC purchases after drug initiation. Patients with higher income or education were consistently more likely adherent to DOACs in the implementation phase (comparing the highest income or educational category to the lowest: adjusted odds ratios 1.18 (1.12–1.25) and 1.21 (1.15–1.27), respectively). No association with income or educational levels was observed on the incidence of therapy discontinuation. In conclusion, we observed that income and educational levels both have independent positive association on the implementation of DOAC therapy but no association on therapy persistence in patients with AF.

The association between stroke and cancer is well-established. Because of an aging population and longer survival rates, the frequency of synchronous stroke and cancer will become even more common. Different pathophysiologic mechanisms have been proposed how cancer or cancer treatment directly or via coagulation disturbances can mediate stroke. Increased serum levels of D-dimer, fibrin degradation products, and CRP are more often seen in stroke with concomitant cancer, and the clot retrieved during thrombectomy has a more fibrin- and platelet-rich constitution compared with that of atherosclerotic etiology. Multiple infarctions are more common in patients with active cancer compared with those without a cancer diagnosis. New MRI techniques may help in detecting typical patterns seen in the presence of a concomitant cancer. In ischemic stroke patients, a newly published cancer probability score can help clinicians in their decision-making when to suspect an underlying malignancy in a stroke patient and to start cancer-screening studies. Treating stroke patients with synchronous cancer can be a delicate matter. Limited evidence suggests that administration of intravenous thrombolysis appears safe in non-axial intracranial and non-metastatic cancer patients. Endovascular thrombectomy is probably rather safe in these patients, but probably futile in most patients placed on palliative care due to their advanced disease. In this topical review, we discuss the epidemiology, pathophysiology, and prognosis of ischemic and hemorrhagic strokes as well as cerebral venous thrombosis and concomitant cancer. We further summarize the current evidence on acute management and secondary preventive therapy.

AbstractBackground Non-vitamin K antagonist oral anticoagulants (NOAC) have superior safety and comparable efficacy profile compared to vitamin-K antagonists (VKAs), with more convenient dosing schemes. However, issues with adherence to the NOACs remain unsolved.Aims We sought to investigate the adherence to oral anticoagulation (OAC) and baseline factors associated with poor adherence after ischaemic stroke in patients with atrial fibrillation (AF).Methods We recruited hospitalised patients (2013–2019) from two prospective stroke registries in Larissa and Helsinki University Hospitals and invited survived patients to participate in a telephone interview. We assessed adherence with the Adherence to Refills and Medications Scale (ARMS) and defined poor adherence as a score of over 17. In addition to demographics, individual comorbidities, and stroke features, we assessed the association of CHA2DS2-VASc and SAMe-TT2R2 scores with poor adherence.Results Among 396 patients (median age 75.0 years, interquartile range [IQR] 70–80; 57% men; median time from ischaemic stroke to interview 21 months [IQR 12–33]; median ARMS score 17 [IQR 17–19]), 56% of warfarin users and 44% of NOAC users reported poor adherence. In the multivariable regression model adjusted for site, sex, and age, poor adherence was independently associated with tertiary education, absence of heart failure, smoking history, use of VKA prior to index stroke, and prior ischaemic stroke. CHA2DS2-VASc and SAMe-TT2R2 scores were not associated with poor adherence.Conclusions Adherence was poor in half of AF patients who survived an ischaemic stroke. Independent patient-related factors, rather than composite scores, were associated with poor adherence in these patients.KEY MESSAGESAdherence was poor in half of the atrial fibrillation patients who survived an ischaemic stroke.Independent patient-related factors rather than composite scores were associated with poor adherence.The findings support the importance of recognising adherence support as a crucial part of holistic patient care recommended by recent AF guideline.

Background Mental health conditions (MHCs) are associated with poor outcomes in patients with atrial fibrillation. However, persistence of oral anticoagulation therapy in patients with atrial fibrillation and MHCs is unknown. We aimed to evaluate the effect of MHCs on the persistence of direct oral anticoagulant (DOAC) use in patients with atrial fibrillation based on a nationwide cohort. Methods and Results The nationwide registry‐based FinACAF (Finnish Anticoagulation in Atrial Fibrillation) cohort included 67 503 patients with incident atrial fibrillation and indication for permanent oral anticoagulation (CHA2DS2‐VASc score >1 in men and >2 in women) starting DOAC therapy between 2011 and 2018. MHCs of interest were depression, bipolar disorder, anxiety disorder, schizophrenia, and composite of any MHC. The main outcome was nonpersistence of DOAC use, defined as the first 120‐day period without DOAC purchases after drug initiation. The mean age of the patients was 75.3±8.9 years, 53.6% were women, and the prevalence of any MHC was 17.8%. Persistence after 1 year from DOAC initiation was 79.3% in patients without MHCs and 77.2% in patients with any MHC, and after 2 years were 64.4% and 60.6%, respectively (P

Aims Little is known about rural-urban differences in the treatment and outcomes in patients with atrial fibrillation (AF). We aimed to assess whether the initiation of oral anticoagulant (OAC) therapy in patients with AF differs between those with rural and urban residence. Methods The registry-based FinACAF cohort covers all patients with AF from all levels of care in Finland. Patients were divided into rural and urban categories and into urbanization degree tertiles based on their municipality of residence at the time of AF diagnosis. The outcome was the first redeemed OAC prescription. Results We identified 222 419 patients (50.1% female; mean age 72.8 (SD 13.2) years) with incident AF during 2007–2018. Urban residence was associated with a lower rate of OAC therapy initiation (adjusted subdistribution hazard ratio (SHR) (95% CI) 0.96 (0.95–0.97)). Correspondingly, an inverse graded dose-response relationship was observed between higher urbanization degree tertile and OAC initiation rate (highest tertile compared to lowest: adjusted SHR (95% CI) 0.94 (0.93–0.95)). The adoption of direct oral anticoagulants for stroke prevention was faster among patients with urban residence. Conclusion This nationwide cohort study documented that urban residence is associated with a slightly lower rate of OAC therapy initiation in patients with incident AF, but faster adoption of direct oral anticoagulant use.

Background: The incidence of ischemic stroke in young patients is increasing and associated with unfavorable prognosis due to high risk of recurrent cardiovascular events. In many young patients the cause of stroke remains unknown, referred to as cryptogenic stroke. Neuroimaging frequently suggests a proximal source of embolism in these strokes. We developed a comprehensive step-by-step echocardiography protocol for a prospective study with centralized reading to characterize preclinical cardiac changes associated with cryptogenic stroke. Methods and study design: SECRETO (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome; NCT01934725) is an ongoing multicenter case–control study enrolling patients (target n = 600) aged 18–49 years hospitalized due to first-ever ischemic stroke of undetermined etiology and age- and sex-matched controls (target n = 600). A comprehensive assessment of cardiovascular risk factors and extensive cardiac imaging with transthoracic and transesophageal echocardiography, electrocardiography and neurovascular imaging is performed. Transthoracic and transesophageal echocardiograms will be centrally read, following an extensive protocol particularly emphasizing the characteristics of left atrium, left atrial appendage and interatrial septum. Conclusions: A detailed assessment of both conventional and unconventional vascular risk factors and cardiac imaging with transthoracic and transesophageal echocardiography are implemented in SECRETO, aiming to establish indirect and direct risk factors and causes for cryptogenic stroke and novel pathophysiological brain–heart pathways. This may ultimately enable more personalized therapeutic options for these patients.

Abstract Background Hypertension is one of the strongest risk factors for stroke in the general population, while systolic blood pressure has been shown to independently increase the risk of stroke in type 1 diabetes. The aim of this study was to elucidate the association between different blood pressure variables and risk of stroke in type 1 diabetes, and to explore potential nonlinearity of this relationship. Methods We included 4105 individuals with type 1 diabetes without stroke at baseline, participating in the nationwide Finnish Diabetic Nephropathy Study. Mean age at baseline was 37.4 ± 11.9 years, median duration of diabetes 20.9 (interquartile range 11.5–30.4) years, and 52% were men. Office systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. Based on these pulse pressure (PP) and mean arterial pressure (MAP) were calculated. Strokes were classified based on medical and autopsy records, as well as neuroimaging. Cox proportional hazard models were performed to study how the different blood pressure variables affected the risk of stroke and its subtypes. Results During median follow-up time of 11.9 (9.21–13.9) years, 202 (5%) individuals suffered an incident stroke; 145 (72%) were ischemic and 57 (28%) hemorrhagic. SBP, DBP, PP, and MAP all independently increased the risk of any stroke. SBP, PP, and MAP increased the risk of ischemic stroke, while SBP, DBP, and MAP increased the risk of hemorrhagic stroke. SBP was strongly associated with stroke with a hazard ratio of 1.20 (1.11–1.29)/10 mmHg. When variables were modeled using restricted cubic splines, the risk of stroke increased linearly for SBP, MAP, and PP, and non-linearly for DBP. Conclusions The different blood pressure variables are all independently associated with increased risk of stroke in individuals with type 1 diabetes. The risk of stroke, ischemic stroke, and hemorrhagic stroke increases linearly at blood pressure levels less than the current recommended treatment guidelines.

Introduction Cerebral small-vessel disease is common in neurologically asymptomatic individuals with type 1 diabetes. The retinal vasculature is thought to mirror the brain’s vasculature, but data on this association are limited in type 1 diabetes. Our aim was to study associations between diabetic retinopathy severity and cerebral small-vessel disease in type 1 diabetes.Research design and methods For this cross-sectional study, we enrolled 189 participants with type 1 diabetes (median age 40 (33–45) years; 53% female; diabetes duration 21.6 (18.2–30.7) years) and 29 healthy age-matched and sex-matched controls as part of the Finnish Diabetic Nephropathy Study. Participants underwent a clinical investigation, brain MRI, and fundus imaging. Signs of cerebral small-vessel disease in brain MRIs were analyzed in relation to diabetic retinopathy severity (Early Treatment Diabetic Retinopathy Study (ETDRS) score).Results In type 1 diabetes, participants with cerebral small-vessel disease had higher ETDRS scores (35 (20–61) vs 20 (20–35), p=0.022) and a higher prevalence of proliferative diabetic retinopathy than those without cerebral small-vessel disease (25% vs 9%, p=0.002). In adjusted analysis, proliferative diabetic retinopathy was associated with cerebral small-vessel disease (OR 2.57 (95% CI 1.04 to 6.35)). Median ETDRS score (35 (20–65) vs 20 (20–35), p=0.024) and proliferative diabetic retinopathy prevalence were higher (29% vs 13%, p=0.002) in participants with versus without cerebral microbleeds. ETDRS scores increased by number of cerebral microbleeds (p=0.001), both ETDRS score (OR 1.05 (95% CI 1.02 to 1.09)) and proliferative diabetic retinopathy (8.52 (95% CI 1.91 to 37.94)) were associated with >2 cerebral microbleeds in separate multivariable analysis. We observed no association with white matter hyperintensities or lacunar infarcts.Conclusions Presence of cerebral small-vessel disease on brain MRI, particularly cerebral microbleeds, is associated with the severity of diabetic retinopathy.

Background Recent studies suggest left atrial (LA) dysfunction in cryptogenic stroke. We studied the dynamics of right atrium (RA) and right atrial appendage (RAA) in young adults with cryptogenic stroke. We hypothesised that bi-atrial dysfunction and blood stagnation might contribute to thrombosis formation in patients with patent foramen ovale (PFO), as deep venous thrombosis is detected only in the minority of patients.Methods Thirty patients (aged 18–49) with a first-ever cryptogenic stroke and 30 age-matched and sex-matched stroke-free controls underwent cardiac magnetic resonance (CMR) imaging. An approach to estimate the RAA volume was developed, using crista terminalis and pectinate muscles as anatomical landmarks. Atrial expansion indices were calculated as (maximal volume – minimal volume) ×100%/minimal volume. Total pulmonary to systemic blood flow ratio (Qp/Qs) was based on phase contrast CMR. Right-to-left shunt (RLS) was evaluated with transoesophageal echocardiography in 29 patients and transcranial Doppler in 30 controls, moderate-to-severe RLS considered as clinically significant.Results We found that RA and RAA volumes were similar between patients and controls. Also, RA expansion index was similar, but RAA (95.6%±21.6% vs 108.7%±25.8%, p=0.026) and LA (126.2%±28% vs 144.9%±36.3%, p=0.023) expansion indices were lower in patients compared with controls. Seven (24%) of 29 patients had an RLS compared with 1 (3%) of 30 controls (p=0.012). Among 59 study subjects, RLS was associated with lower RA (81.9%±15.9% vs 98.5%±29.5%, p=0.030), RAA (84.7%±18% vs 105.6%±24.1%, p=0.022), LA (109.8%±18.6% vs 140.1%±33.7%, p=0.017) and LAA (median 102.9% (IQR 65.6%–121.7%) vs 229.1% (151.8%–337.5%], p=0.002) expansion indices and lower Qp/Qs ratio (0.91±0.06 vs 0.98±0.07, p=0.027).Conclusions This study suggests bi-atrial dysfunction in young adults with cryptogenic stroke, associated with moderate-to-severe RLS. Dysfunction of the atria and atrial appendages may be an additional mechanism for PFO-related stroke.Trial registration number NCT01934725.

Background and Purpose: Non-traumatic intracerebral hemorrhage (ICH) in younger population is a relatively rare event but is associated with considerable mortality and poor functional outcome. Imaging plays a crucial role in determining the underlying cause and guide treatment of ICH. In up to 41% of patients in prior studies, the underlying cause remained elusive. However, the usage of MRI as part of diagnostic work-up was scanty. We aimed to analyze MRI findings of ICH in younger patients and assess specificity and sensitivity of MRI in detecting structural or local underlying causes of ICH.Methods: We included patients aged 15–49 years with first-ever ICH identified from a prospective hospital discharge registry, 2000–2010. All study patients underwent MRI within 3 months of ICH. Imaging data was analyzed by a senior neuroradiologist blinded to final clinical diagnosis. We calculated the diagnostic accuracy of MRI in detecting structural/local underlying causes.Results: Of our 116 patients (median age, 39; 67% males), structural/local causes were the leading causes of ICH (50.0%), and of these, bleeding cavernomas (23.3%) were the most frequent followed by arteriovenous malformations (12.9%), cerebral venous thrombosis (CVT) (7.8%), brain tumors (5.2%), and moyamoya disease (0.9%). Lobar location of ICH was more prevalent in younger patients. MRI was highly sensitive (90.0%; 95% confidence interval, 79.5–96.2%) for detection of structural/local causes compared with angiographic imaging (55.6%; 95% CI, 40.0–70.4%), while MRI was less specific (87.3%; 95% CI, 75.5–94.7%) for structural/local causes, compared with angiographic imaging (97.4%; 95% CI, 86.5–99.9%).Conclusion: MRI was highly sensitive for the detection of structural and local causes underlying ICH in young adults. Thus, MRI should be considered in the diagnostic work-up of all young ICH patients to enable targeted secondary prevention.

Background Ischemic stroke in young individuals often remains cryptogenic. Some of these strokes likely originate from the heart, and atrial fibrosis might be one of the etiological mechanisms. In this pilot study, we investigated whether advanced echocardiography findings of the left atrium (LA) of young cryptogenic stroke patients differ from those of stroke‐free controls. Methods and Results We recruited 30 cryptogenic ischemic stroke patients aged 18 to 49 years and 30 age‐ and sex‐matched stroke‐free controls among participants of the SECRETO (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome) study (NCT01934725). We measured basic left ventricular parameters and detailed measures of the LA, including 4‐dimensional volumetry, speckle tracking epsilon, strain rate, and LA appendix orifice variation. Data were compared as continuous parameters and by tertiles. Compared with controls, stroke patients had smaller LA reservoir volumes (10.2 [interquartile range, 5.4] versus 13.2 [5.4] mL; P=0.030) and smaller positive epsilon values (17.8 [8.5] versus 20.8 [10.1]; P=0.023). In the tertile analysis, stroke patients had significantly lower left atrial appendage orifice variation (3.88 [0.75] versus 4.35 [0.90] mm; P=0.043), lower LA cyclic volume change (9.2 [2.8] versus 12.8 [3.5] mL; P=0.023), and lower LA contraction peak strain rate (−1.8 [0.6] versus −2.3 [0.6]; P=0.021). We found no statistically significant differences in left ventricular measures. Conclusions This preliminary comparison suggests altered LA dynamics in young patients with cryptogenic ischemic stroke, and thus that LA wall pathology might contribute to these strokes. Our results await confirmation in a larger sample.

BACKGROUND:Up to 50% of ischemic strokes in the young after thorough diagnostic work-up remain cryptogenic or associated with low-risk sources of cardioembolism such as patent foramen ovale (PFO). We studied with cardiac magnetic resonance (CMR) imaging, whether left ventricular (LV) non-compaction-a possible source for embolic stroke due to sluggish blood flow in deep intertrabecular recesses-is associated with cryptogenic strokes in the young. METHODS:Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is an international prospective multicenter case-control study of young adults (aged 18-49 years) presenting with an imaging-positive first-ever ischemic stroke of undetermined etiology. In this pilot substudy, 30 cases and 30 age- and sex-matched stroke-free controls were examined with CMR. Transcranial Doppler (TCD) bubble test was performed to evaluate the presence and magnitude of right-to-left shunt (RLS). RESULTS:There were no significant differences in LV volumes, masses or systolic function between cases and controls; none of the participants had non-compaction cardiomyopathy. Semi-automated assessment of LV non-compaction was highly reproducible. Non-compacted LV mass (median 14.0 [interquartile range 12.6-16.0] g/m2 vs. 12.7 [10.4-16.6] g/m2, p = 0.045), the ratio of non-compacted to compacted LV mass (mean 25.6 ± 4.2% vs. 22.8 ± 6.0%, p = 0.015) and the percentage of non-compacted LV volume (mean 17.6 ± 2.9% vs. 15.7 ± 3.8%, p = 0.004) were higher in cases compared to controls. In a multivariate conditional logistic regression model including non-compacted LV volume, RLS and body mass index, the percentage of non-compacted LV volume (odds ratio [OR] 1.55, 95% confidence interval [CI] 1.10-2.18, p = 0.011) and the presence of RLS (OR 11.94, 95% CI 1.14-124.94, p = 0.038) were independently associated with cryptogenic ischemic stroke. CONCLUSIONS:LV non-compaction is associated with a heightened risk of cryptogenic ischemic stroke in young adults, independent of concomitant RLS and in the absence of cardiomyopathy. CLINICAL TRIAL REGISTRATION:SECRETO; NCT01934725. Registered 4th September 2013. https://clinicaltrials.gov/ct2/show/NCT01934725.

Background and purpose: Degenerative change of the corpus callosum might serve as a clinically useful surrogate marker for net pathological cerebral impact of diabetes type 1. We compared manual and automatic measurements of the corpus callosum, as well as differences in callosal cross-sectional area between subjects with type 1 diabetes and healthy controls.Materials and methods: This is a cross-sectional study on 188 neurologically asymptomatic participants with type 1 diabetes and 30 healthy age- and sex-matched control subjects, recruited as part of the Finnish Diabetic Nephropathy Study. All participants underwent clinical work-up and brain MRI. Callosal area was manually measured and callosal volume quantified with FreeSurfer. The measures were normalized using manually measured mid-sagittal intracranial area and volumetric intracranial volume, respectively.Results: Manual and automatic measurements correlated well (callosal area vs. volume: ρ = 0.83, p < 0.001 and mid-sagittal area vs. intracranial volume: ρ = 0.82, p < 0.001). We found no significant differences in the callosal measures between cases and controls. In type 1 diabetes, the lowest quartile of normalized callosal area was associated with higher insulin doses (p = 0.029) and reduced insulin sensitivity (p = 0.033). In addition, participants with more than two cerebral microbleeds had smaller callosal area (p = 0.002).Conclusion: Manually measured callosal area and automatically segmented are interchangeable. The association seen between callosal size with cerebral microbleeds and insulin resistance is indicative of small vessel disease pathology in diabetes type 1.

Introduction Worldwide, 2 million patients aged 18–50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients.Methods and analysis The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18–50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence.Ethics and dissemination Ethical approval for the GOAL study has already been obtained from the Medical Review Ethics Committee region Arnhem-Nijmegen. Additionally and when necessary, approval will also be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of worldwide differences in risk factors, causes and outcome of young stroke patients.

Background Recent studies have shown an increasing prevalence of vascular risk factors in young adults with ischemic stroke (IS). However, the strength of the association between all vascular risk factors and early‐onset IS has not been fully established. Methods and Results We compared 961 patients with a first‐ever IS at 25 to 49 years to 1403 frequency‐matched stroke‐free controls from a population‐based cohort study (FINRISK). Assessed risk factors included an active malignancy, atrial fibrillation, cardiovascular disease, current smoking status, a family history of stroke, high low‐density lipoprotein cholesterol, high triglycerides, low high‐density lipoprotein cholesterol, hypertension, and type 1 and type 2 diabetes mellitus. We performed subgroup analyses based on age, sex, and IS etiology. In a fully adjusted multivariable logistic regression analysis, significant risk factors for IS consisted of atrial fibrillation (odds ratio [OR], 10.43; 95% confidence interval [CI], 2.33–46.77], cardiovascular disease (OR, 8.01; 95% CI, 3.09–20.78), type 1 diabetes mellitus (OR, 6.72; 95% CI, 3.15–14.33), type 2 diabetes mellitus (OR, 2.31; 95% CI, 1.35–3.95), low high‐density lipoprotein cholesterol (OR, 1.81; 95% CI, 1.37–2.40), current smoking status (OR, 1.81; 95% CI, 1.50–2.17), hypertension (OR, 1.43; 95% CI, 1.17–1.75), and a family history of stroke (OR, 1.37; 95% CI, 1.04–1.82). High low‐density lipoprotein cholesterol exhibited an inverse association with IS. In the subgroup analyses, the most consistent associations appeared for current smoking status and type 1 diabetes mellitus. Conclusions Our study establishes the associations between 11 vascular risk factors and early‐onset IS, among which atrial fibrillation, cardiovascular disease, and both type 1 and 2 diabetes mellitus in particular showed strong associations.

Background In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation (HT). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT, (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT. Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3–8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0–6.0) of those without HT; 53.1% of patients with HT were deceased or disabled compared with 35.8% of those without HT. On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24–2.35). Conclusions In patients with HT, anticoagulation was initiated about 12 days later than patients without HT. This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability.