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.

Comparison of the prognostic performance of the CURB-65 and a modified version of the pneumonia severity index designed to identify high-risk patients using the International Community-Acquired Pneumonia Collaboration Cohort.

BACKGROUND: Although the PSI and CURB-65 represent well-validated prediction rules for pneumonia prognosis, PSI was designed to identify patients at low risk and CURB- 65 patients at high risk of mortality. We compared the prognostic performance of a modified version of the PSI designed to identify high-risk patients (i.e., PSI-HR) to CURB-65 in predicting short-term mortality. METHODS: Using data from 6 pneumonia cohorts, we designed PSI-HR as a 6-class prediction rule using the original prognostic weights of all PSI variables and modifying the risk score thresholds to define risk classes. We calculated the proportion of low-risk and high-risk patients using CURB-65 and PSI-HR and 30-day mortality in these subgroups. We compared the rules' sensitivity, specificity, positive and negative predictive values for mortality at all risk class thresholds and assessed discriminatory power using areas under their receiver operating characteristic curves (AUROCs). RESULTS: Among 13,874 patients with pneumonia, 1,036 (7.5%) died. For PSI-HR versus CURB-65, aggregate mortality was lower in low-risk patients (1.6% vs. 2.2%, p = 0.005) and higher in high-risk patients (36.5% vs. 32.2%, p = 0.27). PSI-HR had higher sensitivities than CURB-65 at all thresholds; PSI-HR also had higher specificities at the 3 lowest thresholds and specificities within 0.5% points of CURB-65 at the 2 highest thresholds. The AUROC was larger for PSI-HR than CURB- 65 (0.82 vs. 0.77, p < 0.0001). CONCLUSIONS: PSI-HR demonstrated superior prognostic accuracy to CURB-65 at the lower end of the severity spectrum and identified high-risk patients with nonsignificant higher short-term mortality at the higher end.

Association between serum secretory phospholipase A2 and risk of ischaemic stroke.

BACKGROUND AND PURPOSE: Previous literature has demonstrated an association between high serum levels of type II secretory phospholipase A2 (sPLA2) concentration and an increased risk of coronary artery disease. However, such association has not been established in terms of ischaemic stroke risk. The aim was to evaluate the association between both sPLA2 concentration and activity as continuous variables with risk of future ischaemic stroke. METHODS: A nested case-control study was conducted using data from the European Prospective Investigation into Cancer-Norfolk study. Cases (n = 145) in the current study were participants who developed ischaemic stroke during follow-up, with controls (n = 290) matched in a 2:1 ratio based on age and sex. Statistical analyses were performed using SPSS (version 25.0) software. Logistic regression was used to determine odds ratios (OR) and corresponding 95% confidence intervals (95% CIs) for ischaemic stroke. RESULTS: After adjusting for a wide array of cardiovascular confounders, sPLA2 activity was found to be associated with an increased risk of ischaemic stroke using both multiple imputations with chained equations and complete case analysis: OR 1.20 (95% CI 1.01-1.43) and OR 1.23 (95% CI 1.01-1.49), respectively. However, sPLA2 concentration was not found to be associated with increased risk of ischaemic stroke. CONCLUSIONS: The activity of sPLA2, but not sPLA2 concentration, is associated with an increased risk of future ischaemic stroke. This finding may be significant in risk group stratification, allowing targeted prophylactic treatment, or the development of novel therapeutic agents.

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.

Association of chronic kidney disease with outcomes in acute stroke.

Previous studies have found an association between chronic kidney disease and poor outcomes in stroke patients. However, there is a paucity of literature evaluating this association by stroke type. We therefore aimed to explore the association between CKD and stroke outcomes according to type of stroke. The data consisting of 594,681 stroke patients were acquired from Universal Coverage Health Security Insurance Scheme Database in Thailand. Binary logistic regression was used to assess the relationship of CKD and outcomes, which were as follows; in-hospital mortality, long length of stay (>3 days), pneumonia, sepsis, respiratory failure and myocardial infarction. Results: after fully adjusting for covariates, CKD was associated with increased odds of in-hospital mortality in patients with ischemic (OR 1.32; 95% CI = 1.27-1.38), haemorrhagic (OR 1.31; 95% CI = 1.24-1.39), and other undetermined stroke type (OR 1.44; 95% CI = 1.21-1.73). CKD was found to be associated with increased odds of pneumonia, sepsis, respiratory failure and myocardial infarction in ischaemic stroke. While CKD was found to be associated with increase odds of sepsis, respiratory failure, and myocardial infarction, decrease odds of pneumonia was observed in patients with haemorrhagic stroke. In other undetermined stroke type, CKD was found to only be associated with increase odds of sepsis and respiratory failure, while there is no significant association of CKD and increase or decrease odds with pneumonia and myocardial infarction. CKD was associated with poor outcomes in all stroke types. CKD should be considered as part of stroke prognosis as well as identifying at risk patient population for in-hospital complications.

Pneumonia and Risk of Serious Adverse Outcomes in Hospitalized Strokes in Thailand.

BACKGROUND: The impact of stroke associated pneumonia (SAP) on stroke complications is not well understood; we aimed to study the association between SAP and adverse outcomes including in-hospital mortality, prolonged length of stay and the risk of developing common serious complications (sepsis, respiratory failure, and convulsions). METHODS: We retrospectively analyzed data from a cohort of 610,668 stroke patients drawn from the Universal Coverage Health Security Scheme (a national insurance database) in Thailand which covers ∼80% of the Thai population. Patients were hospitalized between October 2004 and January 2013. RESULTS: Pneumonia was present in 9.6 % (n = 58,586) of patients. Aspiration pneumonia was present in 6.2% (n = 38,060) and nonaspiration pneumonia in 3.4% (n = 20,526). After adjusting for age, sex, stroke type, and comorbidities, patients with SAP had significantly higher odds of in-hospital mortality (odds ratio [OR] 2.90: 2.83-2.96), long length of stay (OR 13.11: 12.83-13.40), sepsis (OR 8.49: 8.22-8.76), respiratory failure (OR 4.37: 4.27-4.48), and convulsions (OR 2.09: 2.00-2.17). On subanalysis, patients with nonaspiration pneumonia were found to have higher odds of adverse outcomes compared to aspiration pneumonia; the corresponding ORs (95% confidence interval) for above outcomes were 1.25 (1.21-1.30), 2.40 (2.32-2.49), 1.34 (1.28-1.40), 1.80 (1.73-1.88), and 1.19 (1.11-1.28), respectively. CONCLUSIONS: SAP is associated with higher odds of inpatient mortality, long length of stay, and risk of developing serious stroke complications. Nonaspiration pneumonia is associated with significantly higher likelihood of adverse outcomes compared to aspiration pneumonia in this patient population. Early identification and treatment of SAP is vital in reducing adverse outcomes in acute stroke.

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.

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.

Rheumatic Mitral Valve Disease Is Associated With Worse Outcomes in Stroke: A Thailand National Database Study.

BACKGROUND AND PURPOSE: Rheumatic valvular heart disease is associated with the increased risk of cerebrovascular events, although there are limited data on the prognosis of patients with rheumatic mitral valve disease (RMVD) after stroke. METHODS: We examined the association between RMVD and both serious and common cardiovascular and noncardiovascular (respiratory and infective) complications in a cohort of hospitalized stroke patients based in Thailand. Factors associated with in-hospital mortality were also explored. Data were obtained from a National Insurance Database. All hospitalized strokes between October 1, 2004, and January 31, 2013, were included in the current study. Characteristics and outcomes were compared for RMVD and non-RMVD patients. Logistic regression, propensity score matching, and multivariate models were used to assess study outcomes. RESULTS: In total, 594 681 patients (mean [SD] age=64 [14.5] years) with a diagnosis of stroke (ischemic=306 154; hemorrhagic=195 392; undetermined=93 135) were included in this study, of whom 5461 had RMVD. Results from primary analyses showed that after ischemic stroke, and controlling for potential confounding covariates, RMVD was associated (P<0.001) with increased odds for cardiac arrest (odds ratio [95% confidence interval]=2.13 [1.68-2.70]), shock (2.13 [1.64-2.77]), arrhythmias (1.70 [1.21-2.39]), respiratory failure (2.09 [1.87-2.33]), pneumonia (2.00 [1.81-2.20]), and sepsis (1.39 [1.19-1.63]). In hemorrhagic stroke patients, RMVD was associated with increased odds (fully adjusted model) for respiratory failure (1.26 [1.01-1.57]), and in patients with undetermined stroke, RMVD was associated with increased odds (fully adjusted analyses) for shock (3.00 [1.46-6.14]), respiratory failure (2.70 [1.91-3.79]), and pneumonia (2.42 [1.88-3.11]). CONCLUSIONS: RMVD is associated with the development of cardiac arrest, shock, arrhythmias, respiratory failure, pneumonia, and sepsis after acute stroke.

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.