Factors associated with progression of arterial stiffness in ischemic stroke survivors: the Norwegian Stroke in the Young Study.

BACKGROUND: Progressive arterial stiffening may increase the risk of recurrent cardiovascular events in ischemic stroke survivors. Information about factors associated with progressive arterial stiffening during the follow-up of young patients with ischemic stroke is lacking. METHODS: Arterial stiffness by carotid-femoral pulse wave velocity (cf-PWV) and ambulatory 24-hour blood pressure (24hBP) were assessed in 81 women and 190 men ≤60 years of age included in the Norwegian Stroke in the Young (NOR-SYS) study 3 months and 5.5 years after the incident ischemic stroke, representing baseline and follow-up. Covariables of change in cf-PWV were identified using linear regression analysis. RESULTS: At baseline, women had less prevalent hypertension (53% vs. 69%, p < 0.05), and lower clinic and 24hBP than men, whereas age, obesity, and prevalence of smoking and antihypertensive drug treatment did not differ. During follow-up, systolic 24hBP remained unchanged, while diastolic 24hBP fell significantly (p < 0.01). Cf-PWV was lower in women both at baseline (7.3 m/s vs. 8.1 m/s) and at follow-up (7.3 m/s vs. 8.0 m/s, both p < 0.001), but the average change during follow-up did not differ between genders. In linear regression analysis, an increase in cf-PWV at the 5-year follow-up was associated with the presence of hypertension and lower cf-PWV at baseline, and higher systolic 24hBP and lack of use of antihypertensive treatment at follow-up (all p < 0.05). CONCLUSION: In ischemic stroke survivors participating in the NOR-SYS study, the 5-year increase in cf-PWV did not differ between genders and was associated with higher systolic 24hBP and lack of antihypertensive treatment.

Progressive arterial stiffening increases the risk of recurrent stroke. More information about factors associated with progression of arterial stiffness in young ischemic stroke survivors is needed. This study followed 81 women and 190 men for 5 years and examined changes in arterial stiffness in relation to blood pressure levels and other factors.Arterial stiffness was measured using the carotid-femoral pulse wave velocity. We also measured blood pressure at study visits and over a 24-hour period while the study participants led their daily life. Measurements were performed 3 months after the index ischemic stroke (baseline) and repeated after an average of 5.5 years of follow-up.Our main finding was that hypertension is very common and is important for arterial health in young ischemic stroke survivors. An increase in arterial stiffness during follow-up was associated with hypertension, higher 24-hour blood pressure, and lack of use of blood pressure-lowering drugs in participants with hypertension. There were no differences between women and men.This study shows the importance of proper blood pressure management in young ischemic stroke survivors to avoid progressive stiffening of the arteries. The results also demonstrated the value of using 24-hour measurements rather than office measurements in the evaluation of blood pressure control during treatment.

Comparison of diffusion weighted imaging b0 with T2*-weighted gradient echo or susceptibility weighted imaging for intracranial hemorrhage detection after reperfusion therapy for ischemic stroke.

PURPOSE: Diffusion-weighted imaging (DWI) b0 may be able to substitute T2*-weighted gradient echo (GRE) or susceptibility-weighted imaging (SWI) in case of comparable detection of intracranial hemorrhage (ICH), thereby reducing MRI examination time. We evaluated the diagnostic accuracy of DWI b0 compared to T2*GRE or SWI for detection of ICH after reperfusion therapy for ischemic stroke. METHODS: We pooled 300 follow-up MRI scans acquired within 1 week after reperfusion therapy. Six neuroradiologists each rated DWI images (b0 and b1000; b0 as index test) of 100 patients and, after a minimum of 4 weeks, T2*GRE or SWI images (reference standard) paired with DWI images of the same patients. Readers assessed the presence of ICH (yes/no) and type of ICH according to the Heidelberg Bleeding Classification. We determined the sensitivity and specificity of DWI b0 for detection of any ICH, and the sensitivity for detection of hemorrhagic infarction (HI1 & HI2) and parenchymal hematoma (PH1 & PH2). RESULTS: We analyzed 277 scans of ischemic stroke patients with complete image series and sufficient image quality (median age 65 years [interquartile range, 54-75], 158 [57%] men). For detection of any ICH on DWI b0, the sensitivity was 62% (95% CI: 50-76) and specificity 96% (95% CI: 93-99). The sensitivity of DWI b0 was 52% (95% CI: 28-68) for detection of hemorrhagic infarction and 84% (95% CI: 70-92) for parenchymal hematoma. CONCLUSION: DWI b0 is inferior for detection of ICH compared to T2*GRE/SWI, especially for smaller and more subtle hemorrhages. Follow-up MRI protocols should include T2*GRE/SWI for detection of ICH after reperfusion therapy.

Interobserver Agreement on Intracranial Hemorrhage on Magnetic Resonance Imaging in Patients With Ischemic Stroke.

BACKGROUND: The Heidelberg Bleeding Classification, developed for computed tomography, is also frequently used to classify intracranial hemorrhage (ICH) on magnetic resonance imaging. Additionally, the presence of any ICH is frequently used as (safety) outcome measure in clinical stroke trials that evaluate acute interventions. We assessed the interobserver agreement on the presence of any ICH and the type of ICH according to the Heidelberg Bleeding Classification on magnetic resonance imaging in patients treated with reperfusion therapy. METHODS: We used 300 magnetic resonance imaging scans including susceptibility-weighted imaging or T2*-weighted gradient echo imaging of ischemic stroke patients within 1 week after reperfusion therapy. Six observers, blinded to clinical characteristics except for suspected location of the infarction, independently rated ICH according to the Heidelberg Bleeding Classification in random pairs. Percent agreement and Cohen's kappa (κ) were estimated for the presence of any ICH (yes/no), and for agreement on the Heidelberg Bleeding Classification class 1 and 2. For the Heidelberg Bleeding Classification class 1 and 2, weighted κ was estimated to take the degree of disagreement into account. RESULTS: In 297 of 300 scans, the quality of scans was sufficient to score ICH. Observers agreed on the presence or absence of any ICH in 264 of 297 scans (88.9%; κ 0.78 [95% CI, 0.71-0.85]). There was agreement on the Heidelberg Bleeding Classification class 1 and 2 and no ICH in class 1 and 2 in 226 of 297 scans (76.1%; κ 0.63 [95% CI, 0.56-0.69]; weighted κ 0.90 [95% CI, 0.87-0.93]). CONCLUSIONS: The presence of any ICH can be reliably scored on magnetic resonance imaging and can, therefore, be used as (safety) outcome measure in clinical stroke trials that evaluate acute interventions. Agreement of ICH types according to the Heidelberg Bleeding Classification is substantial and disagreements are small.

Comparison Between First-Ever Ischemic Stroke in Young Adults in 1988-1997 and 2008-2017.

Aim: To compare incidence of first-ever acute cerebral infarction, etiology and traditional risk factors in young adults 15-49 years in 1988-1997 and 2008-2017 in Hordaland County, Norway. Methods: Case-finding of young adults with acute cerebral infarction in 1988-1997 was done retrospectively by computer research from hospital registries in Hordaland County. Young adults with acute cerebral infarction living in the Bergen region in 2008-2017 were prospectively included in a database at Haukeland University Hospital. Traditional risk factors, etiology and modified Rankin scale score on discharge were registered. Results: Crude average incidence of acute cerebral infarction was 11.4 per 100.000 per year in 1988-1997 and 13.2 per 100.000 per year in 2008-2017 (P=0.04). The prevalence of prior myocardial infarction, angina pectoris, and dyslipidemia were lower in the 2008-2017 cohort (all P<0.05). Atherosclerosis was less common in the 2008-2017 cohort (P<0.001). Conclusion: The observed incidence of acute cerebral infarction in young adults increased from 1988-1997 to 2008-2017 in Hordaland County. Atherosclerosis was less common in the 2008-2017 cohort.

Vascular risk factors and staging of atherosclerosis in patients and controls: The Norwegian Stroke in the Young Study.

Objectives: We studied the prevalence of vascular risk factors (RFs) among 385 ischaemic stroke patients ⩽60 years and 260 controls, and their association with atherosclerosis in seven vascular areas. Methods: History of cardiovascular events (CVE), hypertension, diabetes mellitus (DM), dyslipidaemia, pack-years of smoking (PYS), alcohol, and physical inactivity were noted. Blood pressure, body mass index (BMI), waist-hip ratio (WHR), lipid profile, epicardial adipose tissue (EAT), visceral abdominal adipose tissue (VAT), and subcutaneous abdominal adipose tissue were measured. Numeric staging of atherosclerosis was done by standardized examination of seven vascular areas by right and left carotid and femoral intima-media thickness, electrocardiogram, abdominal aorta plaques, and the ankle-arm index. All results were age and sex-adjusted. Poisson regression analysis was applied. Results: At age ⩽49 years at least one RF was present in 95.6% patients versus 90.0% controls. Compared to controls, male patients and middle-aged female patients showed no significant differences. Young female patients compared to young female controls had a higher burden of RFs (94.3% vs 88.6%, p = 0.049). Poisson regression analysis combined for patients and controls, adjusted for age and sex, showed numeric staging of atherosclerosis associated with age, prior CVE, hypertension, DM, dyslipidaemia, PYS, alcohol, BMI, WHR, EAT, VAT, and an increased number of risk factors. Adjusted for all risk factors, numeric staging of atherosclerosis was associated with increasing age, hypertension, DM, PYS, and BMI. Conclusion: Vascular risk factors are highly prevalent in young- and middle-aged patients and controls, and are predictors of established atherosclerosis at study inclusion. Focus on main modifiable vascular RFs in primary prevention, and early and aggressive secondary treatment of patients are necessary to reduce further progression of atherosclerosis.

Obesity and the Risk of Cryptogenic Ischemic Stroke in Young Adults.

OBJECTIVES: We examined the association between obesity and early-onset cryptogenic ischemic stroke (CIS) and whether fat distribution or sex altered this association. MATERIALS AND METHODS: This prospective, multi-center, case-control study included 345 patients, aged 18-49 years, with first-ever, acute CIS. The control group included 345 age- and sex-matched stroke-free individuals. We measured height, weight, waist circumference, and hip circumference. Obesity metrics analyzed included body mass index (BMI), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), and a body shape index (ABSI). Models were adjusted for age, level of education, vascular risk factors, and migraine with aura. RESULTS: After adjusting for demographics, vascular risk factors, and migraine with aura, the highest tertile of WHR was associated with CIS (OR for highest versus lowest WHR tertile 2.81, 95%CI 1.43-5.51; P=0.003). In sex-specific analyses, WHR tertiles were not associated with CIS. However, using WHO WHR cutoff values (>0.85 for women, >0.90 for men), abdominally obese women were at increased risk of CIS (OR 2.09, 95%CI 1.02-4.27; P=0.045). After adjusting for confounders, WC, BMI, WSR, or ABSI were not associated with CIS. CONCLUSIONS: Abdominal obesity measured with WHR was an independent risk factor for CIS in young adults after rigorous adjustment for concomitant risk factors.

Sex differences in the Norwegian Tenecteplase Trial (NOR-TEST).

BACKGROUND AND PURPOSE: Sex differences in acute ischemic stroke is of increasing interest in the era of precision medicine. We aimed to explore sex disparities in baseline characteristics, management and outcomes in patients treated with intravenous thrombolysis included in the Norwegian Tenecteplase trial (NOR-TEST). METHODS: NOR-TEST was an open-label, randomized, blinded endpoint trial, performed from 2012 to 2016, comparing treatment with tenecteplase to treatment with alteplase within 4.5 h after acute ischemic stroke symptom onset. Sex differences at baseline, treatment and outcomes were compared using multivariable logistic regression models. Heterogeneity in treatment was evaluated by including an interaction term in the model. RESULTS: Of 1100 patients enrolled, 40% were women, and in patients aged >80 years, the proportion of women was greater than men (19% vs. 14%; p = 0.02). Women had a lower burden of cardiovascular risk factors, such as diabetes mellitus (11% vs. 15%; p = 0.05) and a higher mean high-density lipoprotein cholesterol level (1.7 ± 0.6 mmol/L vs. 1.3 ± 0.4 mmol/L; p < 0.001), and a higher proportion of women had never smoked (45% vs. 33%; p < 0.001) compared with men. While there was no sex difference in time from onset of symptoms to admission, door to needle time or in-hospital workup, women were admitted with more severe stroke (National Institutes of Health Stroke Scale [NIHSS] score 6.2 ± 5.6 vs. 5.3 ± 5.1; p = 0.01). Stroke mimic diagnosis was more common in women (21% vs. 15%; p = 0.01). There were no significant sex differences in clinical outcome, measured by the NIHSS, the modified Rankin Scale, intracranial hemorrhage and mortality. CONCLUSION: Women were underrepresented in number in NOR-TEST. The included women had a lower cardiovascular risk factor burden and more severe strokes.

The Course of Carotid Plaque Vulnerability Assessed by Advanced Neurosonology.

Background: Carotid artery atherosclerosis is a major risk factor for ischemic stroke. This risk is related to plaque vulnerability and is characterized by plaque morphology, intraplaque neovascularization, and cerebral microembolization. Advanced neurosonology can identify vulnerable plaques and aid in preventing subsequent stroke. We aimed to assess the time course of cerebral microembolization and intraplaque neovascularization during 6 months of follow-up and to explore the utility of advanced neurosonology in patients with acute cerebral ischemia. Methods: Fifteen patients with acute cerebral ischemia and carotid artery plaques underwent comprehensive extra- and intracranial ultrasound examinations, including microemboli detection and contrast-enhanced ultrasound. The examinations were repeated after 3 and 6 months. Results: We examined 28 plaques in 15 patients. The ultrasonographic features of plaque vulnerability were frequent in symptomatic and asymptomatic plaques. There were no significant differences in stenosis degree, plaque composition, plaque surface, neovascularization, or cerebral microembolization between symptomatic and asymptomatic plaques, but symptomatic plaques had a higher number of vulnerable features. None of the patients had recurrent clinical stroke or transient ischemic attack during the follow-up period. We observed a decrease in cerebral microembolization at 6 months, but no significant change in intraplaque neovascularization. Conclusions: In patients with acute cerebral ischemia and carotid artery plaques, cerebral microembolization decreased during 6 months of follow-up, indicating plaque stabilization. Clinical Trial Registration:ClinicalTrial.gov, identifier NCT02759653.

The impact of age and 24-h blood pressure on arterial health in acute ischemic stroke patients: The Norwegian stroke in the young study.

The impact of age and 24-h ambulatory blood pressure (ABPM) on arterial stiffness and carotid intima-media thickness (cIMT) in ischemic stroke patients younger than 60 years of age is poorly explored. A total of 385 acute ischemic stroke patients (aged 49.6±9.7 years, 68% men) were prospectively included and grouped in younger (15-44 years, n = 93) and middle-aged (45-60 years, n = 292). Arterial stiffness was measured by carotid-femoral pulse wave velocity (PWV), and cIMT by carotid ultrasound. 24-h ABPM was recorded. The middle-aged stroke patients had higher prevalence of smoking, hypertension, diabetes mellitus, metabolic syndrome and hypercholesterolemia, and had higher PWV and cIMT (all p < .05). In multivariable linear regression analyses adjusted for sex, BMI, smoking, diabetes mellitus, total cholesterol, high-density lipoprotein cholesterol, triglycerides, eGFR, systolic BP and concomitant antihypertensive treatment, 1SD (4.4 years) higher age was associated with higher PWV (ß = 0.44,R2  = 0.46, p < .001) in the younger group, and with higher mean cIMT (ß = 0.16, R2  = 0.21, p = .01) in the middle-aged group. In the middle-aged group, 24-h pulse pressure had a significant association with PWV (ß = 0.18, R2  = 0.19, p = .009), while the association with cIMT was attenuated (ß = 0.13, R2  = 0.16, p = .065). 24-h diastolic BP was associated with higher cIMT in the middle-aged group (ß = 0.24, p < .001, R2  = 0.23), but not with PWV in either age groups. Among ischemic stroke patients < 60 years, higher age was associated with increased arterial stiffness for patients up to age 44 years, and with cIMT in middle-aged patients. 24-h pulse pressure was associated with arterial stiffness, and 24-h diastolic BP was associated with cIMT only in middle-aged patients.

Clinical manifestation of acute cerebral infarcts in multiple arterial territories.

OBJECTIVES: We aimed to assess frequencies and radiological aspects of single- and multiterritory clinical manifestation among patients with acute cerebral infarcts in multiple arterial territories (MACI). MATERIALS & METHODS: We retrospectively reviewed admission records and diffusion-weighted magnetic resonance imaging of patients with MACI admitted to our stroke unit between 2006 and 2017. MACI was defined as acute cerebral ischemic lesions in at least two out of three arterial cerebral territories, that is, the left anterior, right anterior and the bilateral posterior territory. Patients with single- and multiterritory clinical manifestation were then compared for topographical distribution of the ischemic lesions, the number of ischemic lesions, and The Oxfordshire Community Stroke Project classification. RESULTS: Out of 311 patients with MACI, 222 (71.4%) presented with single-territory clinical manifestation. Involvement of the left hemisphere (OR = 0.37, 95% CI 0.16-0.82), less than five ischemic lesions (OR = 0.58, 95% CI 0.35-0.97), and partial anterior circulation infarct clinical stroke syndrome (OR = 0.57, 95% CI 0.34-0.97) were associated with single-territory clinical manifestation. Involvement of all three territories (OR = 2.58, 95% = 1.48-4.50), more than 10 ischemic lesions (OR = 2.30, 95% CI 1.32-4.01) and total anterior circulation infarct clinical stroke syndrome (OR = 3.31, 95% CI 1.39-7.86) were associated with multiterritory clinical manifestation. CONCLUSION: Most patients with MACI present with single-territory clinical manifestation on admission. Diffusion-weighted magnetic resonance imaging is therefore necessary for a definite diagnosis.

Prevalence of atherosclerosis and association with 5-year outcome: The Norwegian Stroke in the Young Study.

Objectives: We studied the prevalence of atherosclerosis among ischaemic stroke patients ≤60 years and controls at the time of the index stroke, and its association with occurrence of new cardiovascular events (CVEs) and mortality at a 5-year follow-up. Methods: Prevalent atherosclerosis was assessed for 385 patients and 260 controls in seven vascular areas by electrocardiogram (ECG), ankle-arm index (AAI) and measurement of right and left carotid and femoral intima-media thickness (cIMT and fIMT) and abdominal aorta plaques (AAP). Clinical end-points were any new CVE (stroke, angina, myocardial infarction or peripheral arterial disease) or death from any cause at 5-year follow-up. All results were sex- and age-adjusted; logistic regression and Cox proportional hazards models were applied. Results: Young patients ≤49 years had prevalent atherosclerosis in 1/2 of males and 1/3 of females. Compared with controls, young female patients showed significantly higher prevalent atherosclerosis, p = 0.024. Ischaemic ECG and mean cIMT were higher in young and middle-aged female patients (p = 0.044, p = 0.020, p = 0.023 and p <0.001, respectively). Mean fIMT was higher in middle-aged female patients (p <0.001). Cardiovascular events were associated with ischaemic ECG; AAI ≤0.9, fIMT ≥0.9 mm and increased number of areas with atherosclerosis (NAA) among patients, and with AAP, cIMT ≥0.9 mm, fIMT ≥0.9 mm and NAA among controls. Mortality was associated with higher age, ischaemic ECG and NAA among patients, and cIMT ≥0.9 mm among controls. Conclusion: Atherosclerosis is highly prevalent even in young stroke patients. Some areas and increasing NAA are associated with CVEs and death.

Association between Migraine and Cryptogenic Ischemic Stroke in Young Adults.

OBJECTIVE: To assess the association between migraine and cryptogenic ischemic stroke (CIS) in young adults, with subgroup analyses stratified by sex and presence of patent foramen ovale (PFO). METHODS: We prospectively enrolled 347 consecutive patients aged 18 to 49 years with a recent CIS and 347 age- and sex-matched (±5 years) stroke-free controls. Any migraine and migraine with (MA) and migraine without aura (MO) were identified by a screener, which we validated against a headache neurologist. We used conditional logistic regression adjusting for age, education, hypertension, diabetes, waist-to-hip ratio, physical inactivity, current smoking, heavy drinking, and oral estrogen use to assess independent association between migraine and CIS. The effect of PFO on the association between migraine and CIS was analyzed with logistic regression in a subgroup investigated with transcranial Doppler bubble screen. RESULTS: The screener performance was excellent (Cohen kappa > 0.75) in patients and controls. Compared with nonmigraineurs, any migraine (odds ratio [OR] = 2.48, 95% confidence interval [CI] = 1.63-3.76) and MA (OR = 3.50, 95% CI = 2.19-5.61) were associated with CIS, whereas MO was not. The association emerged in both women (OR = 2.97 for any migraine, 95% CI = 1.61-5.47; OR = 4.32 for MA, 95% CI = 2.16-8.65) and men (OR = 2.47 for any migraine, 95% CI = 1.32-4.61; OR = 3.61 for MA, 95% CI = 1.75-7.45). Specifically for MA, the association with CIS remained significant irrespective of PFO. MA prevalence increased with increasing magnitude of the right-to-left shunt in patients with PFO. INTERPRETATION: MA has a strong association with CIS in young patients, independent of vascular risk factors and presence of PFO. ANN NEUROL 2021;89:242-253.

Tenecteplase versus alteplase after acute ischemic stroke at high age.

BACKGROUND: Stroke prevalence is increasing with age. Alteplase is the only agent approved for thrombolytic treatment for patients with ischemic stroke, including patients ≥80 years. In the present study, the aim was to compare efficacy and safety of tenecteplase and alteplase in patients ≥80 years. METHODS: Data from the Norwegian Tenecteplase Stroke Trial, a randomized controlled trial comparing alteplase and tenecteplase, were assessed. RESULTS: Of the 273 patients ≥80 years included, mean age was 85.5 years.In the intention-to-treat analyses, 43.1% receiving tenecteplase and 39.9% receiving alteplase reached excellent functional outcome (modified Rankin Scale score 0-1) after 3 months (odds ratio (OR) 1.14, 95% confidence interval (CI) 0.70-1.85, p=0.59). No significant differences among patients in the two treatment groups regarding frequency of symptomatic intracranial hemorrhage during the first 48 h were identified (11 (8.5%) in the tenecteplase group, 10 (7.0%) in the alteplase group, OR 1.23, 95% CI 0.50-3.00, p 0.65). Death within 3 months occurred in 18 patients (14.3%) in the tenecteplase group and in 21 (15.3%) in the alteplase group (p 0.84). After excluding stroke mimics, the proportion of patients with excellent functional outcome was 44.1% in the tenecteplase group and 34.4% in the alteplase group (OR 1.50 CI 0.90-2.52, p 0.12). CONCLUSION: No differences in the efficacy and safety of tenecteplase versus alteplase in patients ≥80 years were identified. TRIAL REGISTRATION: Clinicaltrials.gov (NCT01949948).

The association of the metabolic syndrome with target organ damage: focus on the heart, brain, and central arteries.

INTRODUCTION: The metabolic syndrome (MetS) is an adverse metabolic state composed of obesity, hyperglycemia/pre-diabetes, hypertension, and dyslipidemia. It substantially increases the risk of type 2 diabetes, cardiovascular disease (CVD) and mortality, and has a huge impact on public health. AREA COVERED: The present review gives an update on the definition and prevalence of MetS, and its impact on cardiac structure and function as well as on the brain and central arteries. The association with CVD and mortality risk is discussed. Focus is mainly directed toward the subclinical target organ damage related to MetS. Data is also critically reviewed to provide evidence on the incremental prognostic value of overall MetS over its individual components. EXPERT COMMENTARY: MetS is a clinical risk condition associated with subclinical and clinical CVD and mortality. Roughly, 30% of the world population suffer from MetS. As all components of the MetS are modifiable, optimal preventive and therapeutic measures should be initiated to improve CV risk control, particularly aggressively treating hypertension and hyperglycemia, and encouraging people to adopt healthy lifestyle as early as possible is of great importance.

Association of increased arterial stiffness with diastolic dysfunction in ischemic stroke patients: the Norwegian Stroke in the Young Study.

BACKGROUND: Young and middle-aged ischemic stroke survivors have a high prevalence of hypertension, increased arterial stiffness and abnormal left ventricular (LV) geometry, which all are associated with the presence of LV diastolic dysfunction. However, the prevalence and covariates of diastolic dysfunction in these patients have not been reported. OBJECTIVES: To explore diastolic dysfunction in ischemic stroke patients aged 15-60 years included in the Norwegian Stroke in the Young Study. METHODS: Data from 260 patients with acute ischemic stroke was analyzed. Diastolic dysfunction was assessed by combining transmitral peak early flow (E), early diastolic mitral annular velocity (e'), E/e' ratio, left atrial volume index and peak tricuspid regurgitant jet velocity, following current European guidelines. Carotid-femoral pulse wave velocity at least 10 m/s by aplanation tonometry was defined as increased arterial stiffness. RESULTS: Prevalent diastolic dysfunction was found in 20% of patients (13% with diastolic dysfunction grade 1 and 7% with diastolic dysfunction grades 2-3). Patients with diastolic dysfunction were older and more likely to have hypertension, overweight, increased arterial stiffness, higher LV mass and less percentage nightly reduction in mean blood pressure (BP) (all P < 0.001). In a multivariable logistic regression analysis, diastolic dysfunction was associated with increased arterial stiffness [odds ratio 2.86 (95% confidence interval 1.05-7.79), P < 0.05] independent of age more than 45 years, overweight, hypertension, night-time BP reduction and LV mass. CONCLUSION: Among young and middle-aged ischemic stroke survivors, diastolic dysfunction was found in 20%. The presence of diastolic dysfunction was associated with increased arterial stiffness independent of higher age, overweight, hypertension, night-time BP reduction and LV mass.

Short-Term Outcome and In-Hospital Complications After Acute Cerebral Infarcts in Multiple Arterial Territories.

Background and Purpose- Patients with acute cerebral infarcts in multiple arterial territories (MACI) represent a substantial portion of the stroke population. There are no data on short-term outcome and in-hospital complications in patients with MACI. We compared patients with MACI with patients having acute cerebral infarct(s) in a single arterial territory. Methods- We analyzed 3343 patients with diffusion-weighted imaging-confirmed acute cerebral infarcts. MACI was defined as at least 2 acute cerebral ischemic lesions in at least 2 arterial cerebral territories. Patients with MACI were compared with patients with acute cerebral infarct(s) in a single arterial territory for relevant in-hospital complications and short-term outcome, namely National Institutes of Health Stroke Scale and modified Rankin Scale at day 7 after admission or at discharge when earlier. Results- A total of 311 patients (9.3%) met the definition of MACI. Both median National Institutes of Health Stroke Scale (2 [1-7] versus 1 [0-4]) and modified Rankin Scale (3 [1-4] versus 2 [1-3]) were higher in patients with MACI. MACI was independently associated with higher National Institutes of Health Stroke Scale and modified Rankin Scale. Deep venous thrombosis, myocardial infarction, and any complications were more frequent in patients with MACI. Conclusions- In-hospital complications were more frequent in patients with MACI, which may adversely affect short-term clinical and functional outcome. Closer follow-up of patients with MACI during hospitalization may prevent such events and negative progression.

Is atopic sensitization associated with indicators of early vascular ageing in adolescents?

BACKGROUND: Chronic systemic inflammation accelerates early vascular ageing. Atopic sensitization and allergic diseases may involve increased inflammatory activity. This study aimed to assess whether atopic sensitization and allergic diseases were associated with altered vascular biomarkers in Norwegian adolescents. METHODS: Distensibility coefficient of the common carotid arteries, carotid intima-media thickness and atopic sensitization (serum total and specific IgEs) were assessed in 95 Norwegian adolescents, who participated in the RHINESSA generation study. Symptoms of allergic disease were assessed by an interviewer-led questionnaire. RESULTS: Atopic sensitization was found in 33 (34.7%) of the adolescents. Symptomatic allergic disease was found in 11 (33.3%) of those with atopic sensitization. Distensibility coefficient of the common carotid arteries appeared to be lower in participants with atopic sensitization than in those without (46.99±8.07*10-3/kPa versus 51.50±11.46*10-3/kPa; p>0.05), while carotid intima-media thickness did not differ between these groups (0.50±0.04mm versus 0.50±0.04mm; p>0.05). Crude, as well as age- and sex-adjusted multiple regression, revealed no significant association, neither of atopic sensitization nor of allergic disease, with distensibility coefficient of the common carotid arteries and carotid intima-media thickness. CONCLUSIONS: Our results do not support the assumption of an adverse impact of atopic sensitization and/or allergic disease on distensibility coefficient of the common carotid arteries and carotid intima-media thickness in Norwegian adolescents. Further research is necessary to study whether the clinical severity of allergic diseases might be more important than the status of allergic disease or atopic sensitization.

Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO): echocardiography performance protocol.

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.

Five-year readmission and mortality differ by ischemic stroke subtype.

BACKGROUND: Ischemic stroke subtype may influence the risk of readmission and mortality after ischemic stroke (IS) and transient ischemic attack (TIA) due to differences in comorbidity, risk factors, and stroke severity. We aimed to study the five-year incidence and risk of all-cause readmission, cause-specific readmission and mortality after IS or TIA by stroke subtype. METHODS: The medical records of 1453 patients admitted with IS or TIA to the stroke unit at Haukeland University Hospital, Norway, between 2007 and 2012 were reviewed for identification of unplanned readmissions within five years after discharge. Stroke etiology was classified as large-artery atherosclerosis (LAA), cardioembolism (CE), small vessel occlusion (SVO), stroke of other determined etiology (SOE), multiple etiologies (ME), or cryptogenic stroke (CS). Kaplan-Meier estimates and Cox regression analyses were used to determine incidences and risk of readmission and death. RESULTS: The five-year incidence of all-cause readmission was 72.6% (74% LAA, 81% CE, 65% SVO, 55% SOE, 71% ME, and 67% CS), with infections, cardiac disease, stroke-related events and fractures as the most frequent causes. Compared to patients with other subtypes, SVO subtype had a 21% lower risk of all-cause readmission and a 48% lower risk of death, whereas CE had a 25% higher risk of all cause readmission and a 34% higher risk of death. CE subtype also had a 75% higher risk of readmission due to cardiac disease, whereas CS subtype had a 44% lower risk of readmission with cardiac disease. CONCLUSION: The five-year incidence of readmission and mortality varied among the stroke subtypes. The risk of readmission and death are especially high in patients with CE subtype, and lowest for patients with SVO subtype.

U-shaped relationship between hemoglobin level and severity of ischemic stroke.

BACKGROUND AND AIM: We aimed to explore the relation between hemoglobin level and ischemic stroke severity and short-term improvement in patients admitted to hospital within 3 hours of stroke onset. METHODS: The relation between stroke severity and hemoglobin was explored by locally weighted scatterplot smoothing (lowess smoother) curves. The effect of hemoglobin on short-term outcome was determined by means of linear regression analyses with NIHSS score day 7 as dependent variable after adjusting for confounders including NIHSS score on admission. Analyses were performed to disclose clinical factor associated with hemoglobin level. RESULTS: This study includes 905 ischemic stroke patients admitted within 3 hours of stroke onset. Lowess smoother curves showed a U-shaped relation between NIHSS score on admission and mRS score day 7 and hemoglobin level. Regression analysis showed low hemoglobin to be independently associated with females, high age, severe stroke, low systolic blood pressure, prior cerebral infarction, not smoking, not atrial fibrillation, and unknown etiology (all P < 0.05). Another regression analysis showed that high NIHSS score day 7 was independently associated with low hemoglobin after adjusting for confounders including NIHSS score on admission. CONCLUSIONS: We found a U-shaped relationship between hemoglobin level on admission and stroke severity. There was no U-shaped relationship between improvement and hemoglobin level. Poor short-term improvement was associated with low hemoglobin levels.