Ulrike Waje-Andreassen

IL‐6: an early marker for outcome in acute ischemic stroke

Objectives –  Inflammation plays an important role in the pathophysiology of stroke. We correlated interleukin (IL)‐6, IL‐10, C‐reactive protein (CRP) and T‐lymphocyte subtype levels in acute ischemic stroke patients with stroke volume and clinical outcome.

Health-Related Quality of Life Among Young Adults With Ischemic Stroke on Long-Term Follow-Up

Background and Purpose— We sought to compare health-related quality of life (HRQoL) in young adults with ischemic stroke on long-term follow-up with controls and to evaluate HRQoL in clinically relevant patient subgroups. Methods— HRQoL was determined with the use of the 8 subscales of the Short-Form General Health Survey (SF-36). Subgroups of patients were defined by sex, age, functional status (modified Rankin Scale), marital status, education, depression (Montgomery-Åsberg Depression Rating Scale), and fatigue (Fatigue Severity Scale). SF-36 scores among patients were compared with SF-36 scores among age- and sex-matched controls and SF-36 scores available from the general Norwegian population. Results— SF-36 scores were obtained after a mean follow-up of 6.0 years among 190 young adults with ischemic stroke during 1988–1997 and among 215 responding controls (55%). The difference in HRQoL between patients, controls, and the general Norwegian population was restricted mainly to the 3 subscales physical functioning, general health, and social functioning (P<0.001). Subgroup analysis showed significantly reduced scores for all SF-36 items among patients who were depressed, suffered from fatigue, or unemployed. Linear regression analysis showed that fatigue and depression were major independent variables correlated with low HRQoL. Conclusions— Compared with controls and the general Norwegian population, low level of HRQoL among young adults with ischemic stroke was most pronounced in regard to physical functioning. Early identification and treatment of depression, fatigue, and physical disability may potentially improve HRQoL among stroke patients.

Systemic complement activation following human acute ischaemic stroke

The brain tissue damage after stroke is mediated partly by inflammation induced by ischaemia–reperfusion injury where the complement system plays a pivotal role. In the present study we investigated systemic complement activation and its relation to C‐reactive protein (CRP), a known complement activator, and other inflammatory mediators after acute ischaemic stroke. Sequential plasma samples from 11 acute stroke patients were obtained from the time of admittance to hospital and for a follow‐up period of 12 months. Nine healthy gender‐ and age‐matched subjects served as controls. The terminal SC5b‐9 complement complex (TCC), CRP, soluble adhesion molecules (L‐, E‐ and P‐ selectin, ICAM, VCAM) and cytokines [tumour necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐8] were analysed. All parameters were within normal values and similar to the controls the first hours after stroke. Terminal complement complex (TCC) increased significantly from 0·54 to 0·74 AU/ml at 72 h (P = 0·032), reached maximum at 7 days (0·90 AU/ml, P < 0·001), was still significantly increased at 12 days (0·70 AU/ml, P = 0·009) and thereafter normalized. CRP increased significantly from 1·02 to 2·11 mg/l at 24 h (P = 0·023), remained significantly increased for 1 week (2·53–2·94 mg/l, P = 0·012–0·017) and thereafter normalized. TCC and C‐reactive protein (CRP) correlated significantly (r = 0·36, P < 0·001). The increase in TCC and CRP correlated to the size of infarction (r = 0·80 and P = 0·017 for TCC; r = 0·72 and P = 0·043 for CRP). No significant changes were seen for adhesion molecules and cytokines. In conclusion, transitory systemic complement activation takes place after stroke. The early rise in CRP and the following TCC increase suggest a possible role for CRP in complement activation, which may contribute to inflammation after stroke.

Admission C – reactive protein after acute ischemic stroke is associated with stroke severity and mortality: The 'Bergen stroke study'

BackgroundThere is growing evidence that inflammation plays an important role in atherogenesis. Previous studies show that C-reactive protein (CRP), an inflammatory marker, is associated with stroke outcomes and future vascular events. It is not clear whether this is due a direct dose-response effect or rather an epiphenomenon. We studied the effect of CRP measured within 24 hours after stroke onset on functional outcome, mortality and future vascular events.MethodsWe prospectively studied 498 patients with ischemic stroke who were admitted within 24 hours after the onset of symptoms. CRP and NIH stroke scale (NIHSS) were measured at the time of admission. Short-term functional outcome was measured by modified Rankin scale (mRS) and Barthel ADL index (BI) 7 days after admission. Patients were followed for up to 2.5 years for long-term mortality and future vascular events data.ResultsThe median CRP at admission was 3 mg/L. High CRP was associated with high NIHSS (p = 0.01) and high long-term mortality (p < 0.0001). After adjusting for confounding variables, high CRP remained to be associated with high NIHSS (p = 0.02) and high long-term mortality (p = 0.002). High CRP was associated with poor short-term functional outcomes (mRS > 3; BI < 95) (p = 0.01; p = 0.03). However, the association was not significant after adjusting for confounding variables including stroke severity (p = 0.98; p = 0.88). High CRP was not associated with future vascular events (p = 0.98).ConclusionAdmission CRP is associated with stroke severity and long-term mortality when measured at least 24 hours after onset. There is a crude association between high CRP and short-term functional outcome which is likely secondary to stroke severity. CRP is an independent predictor of long-term mortality after ischemic stroke.

Etiology of first‐ever ischaemic stroke in European young adults: the 15 cities young stroke study

Risk factors for IS in young adults differ between genders and evolve with age, but data on the age‐ and gender‐specific differences by stroke etiology are scare. These features were compared based on individual patient data from 15 European stroke centers.

Demographic and geographic vascular risk factor differences in european young adults with ischemic stroke: The 15 cities young stroke study

Background and Purpose— We compared among young patients with ischemic stroke the distribution of vascular risk factors among sex, age groups, and 3 distinct geographic regions in Europe. Methods— We included patients with first-ever ischemic stroke aged 15 to 49 years from existing hospital- or population-based prospective or consecutive young stroke registries involving 15 cities in 12 countries. Geographic regions were defined as northern (Finland, Norway), central (Austria, Belgium, France, Germany, Hungary, The Netherlands, Switzerland), and southern (Greece, Italy, Turkey) Europe. Hierarchical regression models were used for comparisons. Results— In the study cohort (n=3944), the 3 most frequent risk factors were current smoking (48.7%), dyslipidemia (45.8%), and hypertension (35.9%). Compared with central (n=1868; median age, 43 years) and northern (n=1330; median age, 44 years) European patients, southern Europeans (n=746; median age, 41 years) were younger. No sex difference emerged between the regions, male:female ratio being 0.7 in those aged <34 years and reaching 1.7 in those aged 45 to 49 years. After accounting for confounders, no risk-factor differences emerged at the region level. Compared with females, males were older and they more frequently had dyslipidemia or coronary heart disease, or were smokers, irrespective of region. In both sexes, prevalence of family history of stroke, dyslipidemia, smoking, hypertension, diabetes mellitus, coronary heart disease, peripheral arterial disease, and atrial fibrillation positively correlated with age across all regions. Conclusions— Primary preventive strategies for ischemic stroke in young adults—having high rate of modifiable risk factors—should be targeted according to sex and age at continental level.

Fatigue among stroke patients on long-term follow-up. The Bergen Stroke Study

BACKGROUND To evaluate characteristics and mortality related to post-stroke fatigue (PSF). METHODS All surviving stroke patients admitted to the Stroke Unit, Haukeland University Hospital, between February 2006 and November 2008 were sent a postal questionnaire including the Fatigue Severity Scale (FSS), the hospital anxiety and depression scale (HADSD), and the Barthel Index (BI) at least 6 months after stroke onset. Survival among patients returning the questionnaire was determined by November 2009. PSF was defined as FSS score ≥5. RESULTS Among 377 patients returning the questionnaire, 42.3% had PSF. Logistic regression showed that PSF was independently associated with pre-stroke depression, leucoaraiosis, myocardial infarction, diabetes mellitus, pain, and sleeping disturbances. Mean FSS score was lower among TIA patients than among patients with minor cerebral infarction (patients with BI=100) (P=.002). Cox regression analysis showed mortality to be associated with PSF. CONCLUSION There is a multifactorial basis for PSF suggesting different therapy options. Cerebral lesions may cause PSF in some patients. Post-stroke fatigue is associated with higher mortality.

Prognostic value of blood interleukin-6 in the prediction of functional outcome after stroke: A systematic review and meta-analysis

We aimed to quantify the association of blood interleukin-6 (IL-6) concentrations with poor outcome after stroke and its added predictive value over clinical information. Meta-analysis of 24 studies confirmed this association with a weighted mean difference of 3.443 (1.592-5.294) pg/mL, despite high heterogeneity and publication bias. Individual participant data including 4112 stroke patients showed standardized IL-6 levels in the 4th quartile were independently associated with poor outcome (OR=2.346 (1.814-3.033), p<0.0001). However, the additional predictive value of IL-6 was moderate (IDI=1.5%, NRI=5.35%). Overall these results indicate an unlikely translation of IL-6 into clinical practice for this purpose.

Long-term mortality among young ischemic stroke patients in western Norway

Objectives –  To obtain data on long‐term mortality among young ischemic stroke patients compared with controls in this population‐based study.

Ischaemic stroke at a young age is a serious event – final results of a population-based long-term follow-up in Western Norway

Our population‐based long‐term follow‐up of young ischaemic stroke patients and controls showed 10‐fold increased mortality and fivefold increased arterial event rate nearly 12 years after study inclusion. We now assess memory, anxiety, depression and sleep in relation to employment and functional outcome, treatment goals and results from a last alive–dead survey.