Serum Albumin and Post-Stroke Outcomes: Analysis of UK Regional Registry Data, Systematic Review, and Meta-Analysis.

Hypoalbuminemia associates with poor acute ischemic stroke (AIS) outcomes. We hypothesised a non-linear relationship and aimed to systematically assess this association using prospective stroke data from the Norfolk and Norwich Stroke and TIA Register. Consecutive AIS patients aged ≥40 years admitted December 2003-December 2016 were included. Outcomes: In-hospital mortality, poor discharge, functional outcome (modified Rankin score 3-6), prolonged length of stay (PLoS) > 4 days, and long-term mortality. Restricted cubic spline regressions investigated the albumin-outcome relationship. We updated a systematic review (PubMed, Scopus, and Embase databases, January 2020-June 2023) and undertook a meta-analysis. A total of 9979 patients were included; mean age (standard deviation) = 78.3 (11.2) years; mean serum albumin 36.69 g/L (5.38). Compared to the cohort median, albumin < 37 g/L associated with up to two-fold higher long-term mortality (HRmax; 95% CI = 2.01; 1.61-2.49) and in-hospital mortality (RRmax; 95% CI = 1.48; 1.21-1.80). Albumin > 44 g/L associated with up to 12% higher long-term mortality (HRmax1.12; 1.06-1.19). Nine studies met our inclusion criteria totalling 23,597 patients. Low albumin associated with increased risk of long-term mortality (two studies; relative risk 1.57 (95% CI 1.11-2.22; I2 = 81.28)), as did low-normal albumin (RR 1.10 (95% CI 1.01-1.20; I2 = 0.00)). Strong evidence indicates increased long-term mortality in AIS patients with low or low-normal albumin on admission.

Elevated inflammatory biomarkers and poor outcomes in intracerebral hemorrhage.

BACKGROUND: Accumulating evidence suggests that spontaneous intracerebral hemorrhage (ICH) is associated with a reactive neuroinflammatory response. However, it remains unclear if circulating inflammatory biomarkers are associated with adverse outcomes in ICH. To address this knowledge gap, we conducted a cohort study using a prospectively maintained stroke register in the United Kingdom to assess the prognostic value of admission inflammatory biomarkers in ICH. METHODS: The Norfolk and Norwich Stroke and TIA Register recorded consecutive ICH cases. The primary exposures of interest were elevation of white cell count (WCC; > 10 × 109/L), elevation of c-reactive protein (CRP; > 10 mg/L), and co-elevation of both biomarkers, at the time of admission. Modified Poisson and Cox regressions were conducted to investigate the relationship between co-elevation of WCC and CRP at admission and outcomes following ICH. Functional outcome, multiple mortality timepoints, and length of stay were assessed. RESULTS: In total, 1714 ICH cases were identified from the register. After adjusting for covariates, including stroke-associated pneumonia, co-elevation of WCC and CRP at admission was independently associated with significantly increased risk of poor functional outcome (RR 1.08 [95% CI 1.01-1.15]) and inpatient mortality (RR 1.21 [95% CI 1.06-1.39]); and increased 90-day (HR 1.22 [95% CI 1.03-1.45]), and 1-year mortality (HR 1.20 [95% CI 1.02-1.41]). Individual elevation of WCC or CRP was also associated with poor outcomes. CONCLUSIONS: Elevated inflammatory biomarkers were associated with poor outcomes in ICH. This study indicates that these readily available biomarkers may be valuable for prognostication and underscore the importance of inflammation in ICH.

Predicting 10-year stroke mortality: development and validation of a nomogram.

Predicting long-term stroke mortality is a clinically important and unmet need. We aimed to develop and internally validate a 10-year ischaemic stroke mortality prediction score. In this UK cohort study, 10,366 patients with first-ever ischaemic stroke between January 2003 and December 2016 were followed up for a median (interquartile range) of 5.47 (2.96-9.15) years. A Cox proportional-hazards model was used to predict 10-year post-admission mortality. The predictors associated with 10-year mortality included age, sex, Oxfordshire Community Stroke Project classification, estimated glomerular filtration rate (eGFR), pre-stroke modified Rankin Score, admission haemoglobin, sodium, white blood cell count and comorbidities (atrial fibrillation, coronary heart disease, heart failure, cancer, hypertension, chronic obstructive pulmonary disease, liver disease and peripheral vascular disease). The model was internally validated using bootstrap resampling to assess optimism in discrimination and calibration. A nomogram was created to facilitate application of the score at the point of care. Mean age (SD) was 78.5 ± 10.9 years, 52% female. Most strokes were partial anterior circulation syndromes (38%). 10-year mortality predictors were: total anterior circulation stroke (hazard ratio, 95% confidence intervals) (2.87, 2.62-3.14), eGFR < 15 (1.97, 1.55-2.52), 1-year increment in age (1.04, 1.04-1.05), liver disease (1.50, 1.20-1.87), peripheral vascular disease (1.39, 1.23-1.57), cancers (1.37, 1.27-1.47), heart failure (1.24, 1.15-1.34), 1-point increment in pre-stroke mRS (1.20, 1.17-1.22), atrial fibrillation (1.17, 1.10-1.24), coronary heart disease (1.09, 1.02-1.16), chronic obstructive pulmonary disease (1.13, 1.03-1.25) and hypertension (0.77, 0.72-0.82). Upon internal validation, the optimism-adjusted c-statistic was 0.76 and calibration slope was 0.98. Our 10-year mortality model uses routinely collected point-of-care information. It is the first 10-year mortality score in stroke. While the model was internally validated, further external validation is also warranted.

Modified early warning score and risk of mortality after acute stroke.

OBJECTIVE: An accurate prediction tool may facilitate optimal management of patients with acute stroke from an early stage. We evaluated the association between admission modified early warning score (MEWS) and mortality in patients with acute stroke. METHOD: Data from the Anglia Stroke Clinical Network Evaluation Study (ASCNES) were analysed. We evaluated the association between admission MEWS and four outcomes; in-patient, 7-day, 30-day and 1-year mortality. Logistic regression models were used to calculate the odds of all mortality timeframes, whereas Cox proportional hazards models were used to calculate mortality at 1 year. Five univariate and multivariate models were constructed, adjusting for confounders. Patients with a moderate (2-3) or high (≥4) scores were compared to patients with a low score (0-1). RESULTS: The study population consisted of 2006 patients. A total of 1196 patients had low MEWS, 666 had moderate MEWS and 144 had a high MEWS. A high MEWS was associated with increased mortality as an in-patient (OR 4.93, 95 % CI: 2.88-8.42), at 7 days (OR 7.53, 95 % CI: 4.24-13.38), at 30 days (OR 5.74, 95 % CI: 3.38-9.76) and 1-year (HR 2.52, 95 % CI 1.88-3.39). At 1 year, model 5 had a 1.02 OR (95 % CI 0.83-1.24) with moderate MEWS and 2.52 (95 % CI 1.88-3.39) with high MEWS. CONCLUSION: Elevated MEWS on admission is a potential marker for acute-stroke mortality and may therefore be a useful risk prediction tool, able to guide clinicians attempting to prognosticate outcomes for patients with acute-stroke.

Predictors of mortality and disability in stroke-associated pneumonia.

Whilst stroke-associated pneumonia (SAP) is common and associated with poor outcomes, less is known about the determinants of these adverse clinical outcomes in SAP. To identify the factors that influence mortality and morbidity in SAP. Data for patients with SAP (n = 854) were extracted from a regional Hospital Stroke Register in Norfolk, UK (2003-2015). SAP was defined as pneumonia occurring within 7 days of admission by the treating clinicians. Mutlivariable regression models were constructed to assess factors influencing survival and the level of disability at discharge using modified Rankin Scale [mRS]. Mean (SD) age was 83.0 (8.7) years and ischaemic stroke occurred in 727 (85.0%). Mortality was 19.0% at 30 days and 44.0% at 6 months. Stroke severity assessment using National Institutes of Health Stroke Scale was not recorded in the data set although Oxfordshire Community Stroke Project was Classification. In the multivariable analyses, 30-day mortality was independently associated with age (OR 1.04, 95% CI 1.01-1.07, p = 0.01), haemorrhagic stroke (2.27, 1.07-4.78, p = 0.03) and pre-stroke disability (mRS 4-5 v 0-1: 6.45, 3.12-13.35, p < 0.001). 6-month mortality was independently associated with age (< 0.001), pre-stroke disability (p < 0.001) and certain comorbidities, including the following: dementia (6.53, 4.73-9.03, p < 0.001), lung cancer (2.07, 1.14-3.77, p = 0.017) and previous transient ischemic attack (1.94, 1.12-3.36, p = 0.019). Disability defined by mRS at discharge was independently associated with age (1.10, 1.05-1.16, p < 0.001) and plasma C-reactive protein (1.02, 1.01-1.03, p = 0.012). We have identified non-modifiable determinants of poor prognosis in patients with SAP. Further studies are required to identify modifiable factors which may guide areas for intervention to improve the prognosis in SAP in these patients.

Does prior antithrombotic therapy influence recurrence and bleeding risk in stroke patients with atrial fibrillation or atrial flutter?

BACKGROUND: Whilst antithrombotic therapy is recommended in people with atrial fibrillation, little is known about the survival benefits of antithrombotic treatment in those with both high ischaemic and bleeding risk scores. We aim to describe the distribution of these risk scores in those with a prior diagnosis of atrial fibrillation who have suffered stroke and to determine the net clinical benefit of antithrombotic treatment. METHODS: We used regional stroke register data in the UK. Patients with a prior diagnosis of atrial fibrillation and ischaemic or haemorrhagic stroke patients were selected and their ischaemic stroke risk score (CHA2DS2-VASc) and bleeding risk score (HEMORR2HAGES) scores retrospectively calculated. Logistic regression and Cox proportional hazards models were constructed to determine the association between antithrombotic therapy prior to stroke and in-hospital and long-term mortality. RESULTS: A total of 1928 stroke patients (mean age 81.3 years (standard deviation 8.5), 56.8% women) with prior atrial fibrillation were included. Of these, 1761 (91.3%) suffered ischaemic stroke. The most common phenotype (64%) was of those with both high CHA2DS2-VASc (≥2) and high HEMORR2HAGES score (≥4). In our fully adjusted model, patients on antithrombotic treatment with both high ischaemic and bleeding risk had a significant reduction in odds of 31% for in-hospital mortality (odds ratio 0.69 (95% confidence interval 0.48-1.00: p = 0.049)) and 17% relative risk reduction for long-term mortality (hazard ratio 0.83 (95% confidence interval 0.71-0.97: p = 0.02)). CONCLUSIONS: Our study suggests that antithrombotic treatment has a prognostic benefit following incident stroke in those with both high ischaemic risk and high bleeding risk. This should be considered when choosing treatment options in this group of patients.

Individual and Combined Impact of Heart Failure and Atrial Fibrillation on Ischemic Stroke Outcomes.

Background and Purpose- We aimed to determine individual and combined effects of atrial fibrillation (AF) and heart failure (HF) on acute ischemic stroke outcomes: in-hospital mortality, length-of-stay, and poststroke disability; long-term mortality and stroke recurrence. Methods- Prospective cohort study of patients with acute ischemic stroke admitted to a UK center with a catchment population of ≈900 000 between 2004 and 2016. Exposure groups were patients with neither AF nor HF (reference group), those with AF but without HF, those with HF but without AF, and those with AF+HF. Logistic and Cox regressions were used to model in-hospital and long-term outcomes, respectively. Results- A total of 10 816 patients with a mean age±SD =77.9±12.1 years, 48% male were included. Only 30 (4.9%) of the patients with HF but not AF were anticoagulated at discharge. Both AF (odds ratio, 1.24 [95% CI, 1.07-1.43]), HF (odds ratio, 1.40 [1.10-1.79]), and their combination (odds ratio, 2.23 [1.83-2.72]) were associated with increased odds of in-hospital mortality. All 3 exposure groups were associated with increased length-of-stay, while only AF predicted increased disability (1.36 [1.12-1.64]). Patients were followed for a median of 5.5 and 3.7 years for mortality and recurrence, respectively. Long-term mortality was associated with AF (hazard ratio, 1.45 [95% CI, 1.33-1.59]), HF (2.07 [1.83-2.36]), and their combination (2.20 [1.96-2.46]). Recurrent stroke was associated with AF 1.50 (1.26-1.78), HF (1.33 [1.01-1.75]), and AF with HF (1.62 [1.28-2.07]). Conclusions- The AF-associated excess risk of stroke recurrence was independent of comorbid HF. HF without AF was also associated with a significant risk of recurrence. Anticoagulation for secondary stroke prevention in patients with HF without AF may require further evaluation in a clinical trial setting.

Low estimated glomerular filtration rate and pneumonia in stroke patients: findings from a prospective stroke registry in the East of England.

PURPOSE: Low estimated glomerular filtration rate (eGFR) (<60 mL/min/1.73 m2) is a recognized risk factor for pneumonia in general population. While pneumonia is common after stroke, the association between levels of eGFR and pneumonia in stroke patient population has not yet been examined thoroughly. PATIENTS AND METHODS: Using data of 10,329 patients from the Norfolk and Norwich Stroke Registry between January 2003 and April 2015, we examined the association of poststroke pneumonia (in-hospital and after discharge) with low eGFR and when eGFR is divided into the complete spectrum of clinically relevant categories; (≥90) (ref.), 60-89, 45-59, 30-44, 15-30, and <15 mL/min/1.73 m2). RESULTS: In all, 1,519 (14.7%) developed in-hospital pneumonia and 1,037 (12.9%) developed pneumonia after hospital discharge. In age- and sex-adjusted model, low eGFR was associated with in-hospital pneumonia (subdistribution hazard ratio (sHR): 1.13; 95% CI: 1.01-1.25) and pneumonia after discharge (sHR: 1.20; 95% CI: 1.07-1.38). In fully adjusted model, association remained significant for pneumonia after hospital discharge. When eGFR was categorized in all clinically relevant categories, association with in-hospital pneumonia tended to be "U" shaped (eg, compared to eGFR ≥90, sHR for 60-89 was 0.78; 95% CI: 0.62-0.99 and for <15 was 1.06; 95% CI: 0.71-1.60) and association with pneumonia after discharge tended to increase with decline in eGFR level such that risk was almost two fold higher at eGFR <15 (sHR: 1.85; 95% CI: 1.01-3.51). Association for in-hospital pneumonia was driven mainly by aspiration pneumonia, whereas association in stroke survivors was predominantly for nonaspiration pneumonia. CONCLUSION: In stroke patients, low eGFR at admission was associated with pneumonia, particularly severely reduced eGFR with nonaspiration pneumonia after hospital discharge. eGFR could form the basis for identifying patients at high risk of poststroke pneumonia.

Effect of Antiplatelet Therapy (Aspirin + Dipyridamole Versus Clopidogrel) on Mortality Outcome in Ischemic Stroke.

The optimal regimen of antiplatelet therapy for secondary prevention in noncardioembolic ischemic stroke remains controversial. We aimed to determine which regimen was associated with the greatest reduction in adverse outcomes. We analysed prospectively collected data from the Norfolk and Norwich University Hospital Stroke Register. The sample population consisted of 3,572 participants (mean age 74.96 ± 12.67) with ischemic stroke, who were consecutively admitted between 2003 and 2015. Patients were placed on one of three antiplatelet regimens at hospital discharge; aspirin monotherapy, aspirin plus dipyridamole and clopidogrel. Clopidogrel and aspirin plus dipyridamole were compared to aspirin. A direct comparison between clopidogrel and aspirin plus dipyridamole was also performed. Outcomes included all-cause mortality and a combined end point of all-cause mortality and incidence of major adverse cardiac events (stroke or myocardial infarction). Cox-regression models adjusted for potential confounders at the following time periods after discharge; 0 to 90 days, 91 to 365 days, and 1 to 3 years. Aspirin plus dipyridamole was associated with a lower risk of mortality at 0 to 90 days; hazard ratio (HR) 0.62 (0.43 to 0.91). Clopidogrel was associated with a lower risk of mortality at 1 to 3 years; HR of 0.39 (0.26 to 0.60). Similar HRs were observed for the corresponding time points in the composite outcome. In conclusion, patients with noncardioembolic stroke may gain maximum benefits from aspirin plus dipyridamole initially (≤1 year) with a subsequent switch to clopidogrel, with regard to mortality and major adverse cardiac eventsoutcomes.

Long-Term Factors Associated With Falls and Fractures Poststroke.

BACKGROUND: Risk factors for poststroke falls and fractures remain poorly understood. This study aimed to evaluate which factors increased risk of these events after stroke. METHODS: Data from 7,267 hospitalized stroke patients were acquired from the Norfolk and Norwich University Hospital Stroke Register from 2003-2015. The impacts of multiple patient level and stroke characteristics and comorbidities on post-discharge falls and fractures were assessed. Univariate and multivariable models were constructed, adjusting for multiple confounders, using binary logistic regression for short-term analysis (up to 1-year post-discharge) and Cox-proportional hazard models for longer term analysis (1-3, 3-5, and 0-10 years follow-up). RESULTS: The mean age (SD) was 76.3 ± 12.1 years at baseline. 1,138 (15.7%) participants had an incident fall; and 666 (9.2%) an incident fracture during the 10-year follow-up (total person years = 64,447.99 for falls and 67,726.70 for fractures). Half of the sample population were females (50.6%) and the majority had an ischemic stroke (89.8%). After adjusting for confounders: age, sex, previous history of falls, and atrial fibrillation were associated with an increased risk of both falls and fractures during follow-up. Furthermore, chronic kidney disease and hyperlipidemia were associated with an increased risk of falls, while previous stroke/transient ischemic attack increased fracture risk. Total anterior circulation stroke and a prestroke modified Rankin Scale score of 3-5 were associated with decreased risk of both events, with hypertension and cancer decreasing risk of falls only. CONCLUSION: We identified demographic, stroke-related, and comorbid factors associated with poststroke falls and fracture incidence. Further studies are required to examine and establish the relationship between reversible factors and further explore the role of preventative measures to prevent poststroke falls and fractures.

Hyperglycaemia and the SOAR stroke score in predicting mortality.

BACKGROUND: We assessed the association between admission blood glucose levels and acute stroke mortality and examined whether there was any incremental value of adding glucose status to the validated acute stroke mortality predictor - the SOAR (stroke subtype, Oxford Community Stroke Project classification, age, and pre-stroke modified Rankin) score. METHODS: Data from Norfolk and Norwich University Hospital stroke and Transient Ischaemic Attack register (2003-2013) and Anglia Stroke Clinical Network Evaluation Study (2009-2012) were analysed. Multivariable logistic regression analysis assessed the association between admission blood glucose levels with inpatient and 7-day mortality. The prognostic ability of the SOAR score was then compared with the SOAR with glucose score. RESULTS: A total of 5575 acute stroke patients (ischaemic stroke: 89.2%) with mean age (standard deviation) of 76.97 ( ± 11.88 ) years were included. Both borderline hyperglycaemia (7.9-11.0 mmol/L) and hyperglycaemia (>11.0 mmol/L) when compared to normoglycaemia (4.0-7.8 mmol/L) were associated with both 7-day and inpatient mortality after controlling for sex, age, Oxford Community Stroke Project classification and pre-stroke modified Rankin score. Both the SOAR stroke score and SOAR-G score were good predictors of inpatient stroke mortality [area under the curve: 0.82 (95% confidence interval: 0.81-0.84) and 0.83 (95% confidence interval: 0.81-0.84)], respectively. These scores were also good at predicting outcomes in both patients with and without diabetes. CONCLUSION: High blood glucose levels at admission were associated with worse acute stroke mortality outcomes. The constituents of the SOAR stroke score were good at predicting mortality after stroke.

Impact of anaemia on acute stroke outcomes depends on the type of anaemia: Evidence from a UK stroke register.

BACKGROUND: Previous research has demonstrated an association between anaemia and poor outcomes in acute stroke. This study aimed to assess the impact of anaemia on stroke by anaemia subtype. METHODS: Data from a prospective UK Regional Stroke Register were used to assess the association between hypochromic microcytic and normochromic normocytic anaemia on inpatient-mortality, length of stay (LOS) and discharge modified Rankin scale (mRS). Analysis was stratified by stroke subtypes and multivariable logistic regression, adjusting for potential confounders, was used to quantify this association. Patients who were not anaemic were the reference category. RESULTS: A total of 8167 stroke patients (admitted between 2003 and 2015) were included, mean age (SD) 77.39±11.90years. Of these, 3.4% (n=281) had hypochromic microcytic anaemia and 15.5% (n=1262) had normochromic normocytic anaemia on admission. Normochromic normocytic anaemia was associated with increased odds of in-patient mortality OR 1.48 (1.24-1.77), 90-day mortality OR 1.63 (1.38-1.92), longer LOS OR 1.21 (1.06-1.40), defined as >7days, and severe disability defined as discharge mRS≥3 OR 1.31 (1.06-1.63), in patients with ischaemic stroke. Hypochromic microcytic anaemia was associated with 90-day mortality OR 1.90 (1.40-2.58) and a longer LOS OR 1.57 (1.20-2.05) in patients with ischaemic stroke. CONCLUSIONS: Hypochromic microcytic and normochromic normocytic anaemia are associated with differing outcomes in terms of inpatient mortality and post stroke disability. While it is unclear if anaemia per se or another underlying cause is responsible for adverse outcomes, subtype of anaemia appears to be relevant in stroke prognosis.

A History of Falls is Associated with a Significant Increase in Acute Mortality in Women after Stroke.

BACKGROUND AND PURPOSE: The risks of falls and fractures increase after stroke. Little is known about the prognostic significance of previous falls and fractures after stroke. This study examined whether having a history of either event is associated with poststroke mortality. METHODS: We analyzed stroke register data collected prospectively between 2003 and 2015. Eight sex-specific models were analyzed, to which the following variables were incrementally added to examine their potential confounding effects: age, type of stroke, Oxfordshire Community Stroke Project classification, previous comorbidities, frailty as indicated by the prestroke modified Rankin Scale score, and acute illness parameters. Logistic regression was applied to investigate in-hospital and 30-day mortality, and Cox proportional-hazards models were applied to investigate longer-term outcomes of mortality. RESULTS: In total, 10,477 patients with stroke (86.1% ischemic) were included in the analysis. They were aged 77.7±11.9 years (mean±SD), and 52.2% were women. A history of falls was present in 8.6% of the men (n=430) and 20.2% of the women (n=1,105), while 3.8% (n=189) of the men and 12.9% of the women (n=706) had a history of both falls and fractures. Of the outcomes examined, a history of falls alone was associated with increased in-hospital mortality [odds ratio (OR)=1.33, 95% confidence interval (CI)=1.03-1.71] and 30-day mortality (OR=1.34, 95% CI=1.03-1.73) in women in the fully adjusted models. The Cox proportional-hazards models for longer-term outcomes and the history of falls and fractures combined showed no significant results. CONCLUSIONS: The history of falls is an important factor for acute stroke mortality in women. A previous history of falls may therefore be an important factor to consider in the short-term stroke prognosis, particularly in women.

Pre-Stroke Modified Rankin Scale: Evaluation of Validity, Prognostic Accuracy, and Association with Treatment.

BACKGROUND AND PURPOSE: The modified Rankin Scale (mRS) was designed to measure poststroke recovery but is often used to describe pre-stroke disability. We sought to evaluate three aspects of pre-stroke mRS: validity as a measure of pre-stroke disability; prognostic accuracy and association of pre-stroke mRS scores, and process of care. METHODS: We used data from a large, UK clinical registry. For analysis of validity, we compared pre-stroke mRS against other markers of pre-stroke function (age, comorbidity index, care needs). For analysis of prognostic accuracy, we described univariable and multivariable models comparing pre-stroke mRS and other prognostic variables against a variety of outcomes (early and late mortality, length of stay, institutionalization, incident complications). Finally, we described association of pre-stroke mRS and components of evidence-based stroke care (early neuroimaging, admission to stroke unit, assessment of swallow). RESULTS: We analyzed data of 2,491 stroke patients. Concurrent validity analyses suggested statistically significant, but modest correlations between pre-stroke mRS and chosen variables (rho >0.40; p < 0.0001 for all). Every point increase of pre-stroke mRS was associated with poorer outcomes for our prognostic variables (unadjusted p < 0.001). This association held when corrected for other covariates. For example, pre-stroke mRS 4-5 odds ratio (OR): 6.84 (95% CI: 4.24-11.03) for 1 year mortality compared to mRS 0 in adjusted model. There was a difference between pre-stroke mRS and treatment, with higher pre-stroke mRS more likely to receive evidence-based care. CONCLUSION: Results suggest that pre-stroke mRS has some concurrent validity and is a robust predictor of prognosis. This association is not explained by the influence of pre-stroke mRS on care pathways.

A 6-Point TACS Score Predicts In-Hospital Mortality Following Total Anterior Circulation Stroke.

BACKGROUND AND PURPOSE: Little is known about the factors associated with in-hospital mortality following total anterior circulation stroke (TACS). We examined the characteristics and comorbidity data for TACS patients in relation to in-hospital mortality with the aim of developing a simple clinical rule for predicting the acute mortality outcome in TACS. METHODS: A routine data registry of one regional hospital in the UK was analyzed. The subjects were 2,971 stroke patients with TACS (82% ischemic; median age=81 years, interquartile age range=74-86 years) admitted between 1996 and 2012. Uni- and multivariate regression models were used to estimate in-hospital mortality odds ratios for the study covariates. A 6-point TACS scoring system was developed from regression analyses to predict in-hospital mortality as the outcome. RESULTS: Factors associated with in-hospital mortality of TACS were male sex [adjusted odds ratio (AOR)=1.19], age (AOR=4.96 for ≥85 years vs. <65 years), hemorrhagic subtype (AOR=1.70), nonlateralization (AOR=1.75), prestroke disability (AOR=1.73 for moderate disability vs. no symptoms), and congestive heart failure (CHF) (AOR=1.61). Risk stratification using the 6-point TACS Score [T=type (hemorrhage=1 point) and territory (nonlateralization=1 point), A=age (65-84 years=1 point, ≥85 years=2 points), C=CHF (if present=1 point), S=status before stroke (prestroke modified Rankin Scale score of 4 or 5=1 point)] reliably predicted a mortality outcome: score=0, 29.4% mortality; score=1, 46.2% mortality [negative predictive value (NPV)=70.6%, positive predictive value (PPV)=46.2%]; score=2, 64.1% mortality (NPV=70.6, PPV=64.1%); score=3, 73.7% mortality (NPV=70.6%, PPV=73.7%); and score=4 or 5, 81.2% mortality (NPV=70.6%, PPV=81.2%). CONCLUSIONS: We have identified the key determinants of in-hospital mortality following TACS and derived a 6-point TACS Score that can be used to predict the prognosis of particular patients.

Time to Computerized Tomography Scan, Age, and Mortality in Acute Stroke.

BACKGROUND: Time to computerized tomography (CT) is important to institute appropriate and timely hyperacute management in stroke. We aimed to evaluate mortality outcomes in relation to age and time to CT scan. METHODS: We used routinely collected data in 8 National Health Service trusts in East of England between September 2008 and April 2011. Stroke cases were prospectively identified and confirmed. Odds ratios (ORs) for unadjusted and adjusted models for age categories (<65, 65-74, 75-84, and ≥85 years) as well as time to CT categories (<90 minutes, ≥90 to <180 minutes, ≥180 minutes to 24 hours, and >24 hours) and in-hospital and early (<7 days) mortality outcomes were calculated. RESULTS: Of the 7693 patients (mean age 76.1 years, 50% male) included, 1151 (16%) died as inpatients and 336 (4%) died within 7 days. Older patients and those admitted from care home had a significantly longer time from admission until CT (P < .001). Patients who had earlier CT scans were admitted to stroke units more frequently (P < .001) but had higher in-patient (P < .001) and 7-day mortality (P < .001). Whereas older age was associated with increased odds of mortality outcomes, longer time to CT was associated with significantly reduced mortality within 7 days (corresponding ORs for the above time periods were 1.00, .61 [95% confidence interval {CI}: .39-.95], .39 [.24-.64], and .16 [.08-.33]) and in-hospital mortality (ORs 1.00, .86 [.64-1.15], .57 [.42-.78] and .71 [.52-.98]). CONCLUSIONS: Older age was associated with a significantly longer time to CT. However, using CT scan time as a benchmarking tool in stroke may have inherent limitations and does not appear to be a suitable quality marker.

Impact of Hemoglobin Levels and Anemia on Mortality in Acute Stroke: Analysis of UK Regional Registry Data, Systematic Review, and Meta-Analysis.

BACKGROUND: The impact of hemoglobin levels and anemia on stroke mortality remains controversial. We aimed to systematically assess this association and quantify the evidence. METHODS AND RESULTS: We analyzed data from a cohort of 8013 stroke patients (mean±SD, 77.81±11.83 years) consecutively admitted over 11 years (January 2003 to May 2015) using a UK Regional Stroke Register. The impact of hemoglobin levels and anemia on mortality was assessed by sex-specific values at different time points (7 and 14 days; 1, 3, and 6 months; 1 year) using multiple regression models controlling for confounders. Anemia was present in 24.5% of the cohort on admission and was associated with increased odds of mortality at most of the time points examined up to 1 year following stroke. The association was less consistent for men with hemorrhagic stroke. Elevated hemoglobin was also associated with increased mortality, mainly within the first month. We then conducted a systematic review using the Embase and Medline databases. Twenty studies met the inclusion criteria. When combined with the cohort from the current study, the pooled population had 29 943 patients with stroke. The evidence base was quantified in a meta-analysis. Anemia on admission was found to be associated with an increased risk of mortality in both ischemic stroke (8 studies; odds ratio 1.97 [95% CI 1.57-2.47]) and hemorrhagic stroke (4 studies; odds ratio 1.46 [95% CI 1.23-1.74]). CONCLUSIONS: Strong evidence suggests that patients with anemia have increased mortality with stroke. Targeted interventions in this patient population may improve outcomes and require further evaluation.

Hyponatremia predicts mortality after stroke.

BACKGROUND: Hyponatremia, the commonest electrolyte imbalance encountered in clinical practice, is associated with adverse outcomes. Despite this, understanding of the association between hyponatremia and stroke mortality outcome is limited. AIMS: To investigate the association between admission serum sodium and mortality at various time-points after stroke. METHODS: Cases of acute stroke admitted to Norfolk and Norwich University Hospital consecutively from January 2003 until June 2013 were included, with mortality outcomes ascertained until the end of December 2013. Odds ratios or hazards ratios for death were constructed for various time-points (within seven-days, 8-30 days, within one-year, and over full follow-up). RESULTS: There were 8540 participants included (47·4% male, mean age 77·3 (±12·0) years). Point prevalence of hypernatremia and hyponatremia were 3·3% and 13·8%, respectively. In fully adjusted models controlling for age, gender, prestroke modified Rankin score, stroke type, Oxford community stroke project class, and laboratory biochemical and hematological results, the odds ratio (up to one-year)/hazards ratio (for full follow-up) for the above time-points were 1·00, 1·11, 1·03, 1·05 for mild hyponatremia; 1·97, 0·78, 1·11, 1·2 for moderate hyponatremia; 3·31, 1·57, 2·45, 1·67 for severe hyponatremia; and 0·47, 1·23, 1·30, 1·10 for hypernatremia. When stratified by age groups, outcomes were poorer in younger hyponatremic patients (aged <75 years). CONCLUSION: Hyponatremia is prevalent in acute stroke admissions and is independently associated with higher mortality in patients <75 years.

The shock index predicts acute mortality outcomes in stroke.

BACKGROUND: Shock index (SI) (ratio between heart rate and systolic blood pressure) has been shown to be associated with poor mortality outcomes in trauma and pneumonia; however it has yet to be examined in stroke. We aimed to examine the relationship between SI and acute outcomes of inpatient, 3-day and 7-day mortality in stroke. Secondly, we aimed to compare SI and systolic blood pressure (SBP) alone in predicting above outcomes. METHODS: Data from a multicentre prospective cohort study conducted between October 2009 and September 2012 in eight NHS trusts in East of England were analysed. The relationships between SI, SBP and study outcomes were assessed using multivariable logistic regression models using mid-quintile groups as the reference category. Receiver operating characteristic (ROC) curves assessed the discriminating ability between the SI and SBP models. RESULTS: A total of 2121 stroke patients were included (47.4% men; mean age 77.10 (sd) 12.40) years. The lowest quintile of the SI, had an increased odds of 3-day and 7-day mortality, adjusted odds ratio (AOR) 2.45 (95% CI:1.16-5.17) and 1.88 (1.01-3.49), respectively. Patients with the highest quintile of SI also had increased odds of in-patient, 3-day and 7-day mortality, AORs 1.85 (1.17-2.92), 2.18 (1.03-4.63) and 2.45 (1.34-4.49), respectively. Similarly, SBP had a U-shape relationship with mortality. All measures had an ROC area under the curve >0.8 but there was no difference in the discriminating ability between SI and SBP. CONCLUSIONS: SI at extremely high and low values appeared to predict stroke mortality and appears to be particularly useful in predicting very early (3-day) mortality.

The SOAR stroke score predicts inpatient and 7-day mortality in acute stroke.

BACKGROUND AND PURPOSE: An accurate prognosis is useful for patients, family, and service providers after acute stroke. METHODS: We validated the Stroke subtype, Oxfordshire Community Stroke Project Classification, Age, and prestroke Rankin stroke score in predicting inpatient and 7-day mortality using data from 8 National Health Service hospital trusts in the Anglia Stroke and Heart Clinical Network between September 2008 and April 2011. RESULTS: A total of 3547 stroke patients (ischemic, 92%) were included. An incremental increase of inpatient and 7-day mortality was observed with increase in Stroke subtype, Oxfordshire Community Stroke Project Classification, Age, and prestroke Rankin stroke score. Using a cut-off of ≥3, the area under the receiver operator curves values for inpatient and 7-day mortality were 0.80 and 0.82, respectively. CONCLUSIONS: A simple score based on 4 easily obtainable variables at the point of care may potentially help predict early stroke mortality.