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

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

Estimated glomerular filtration rate and risk of poor outcomes after stroke

We thank the data team of the Norfolk and Norwich University Hospital Stroke Services.Peer reviewedPostprin

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 (NNUHSR). The sample population consisted of 3,572 participants (mean age 74.96 ± 12.67) with ischemic stroke, who were consecutively admitted between 2003-2015. Patients were placed on one of three antiplatelet regimens at hospital discharge; aspirin monotherapy, aspirin plus dipyridamole and clopidogrel. Clopidogrel and aspirin plus dipyridamole was compared to aspirin. A direct comparison between clopidogrel and aspirin plus dipyridamole was also performed. Outcomes included all-cause mortality and a combined endpoint 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; 0-90 days, 91-365 days and 1-3 years. Aspirin plus dipyridamole was associated with a lower risk of mortality at 0-90 days; HR 0.62 (0.43-0.91). Clopidogrel was associated with a lower risk of mortality at 1-3 years; HR of 0.39 (0.26-0.60). Similar HRs were observed for the the corresponding time points in the composite outcome. In conclusion Patients with non-cardioembolic stroke may gain maximum benefit from aspirin plus dipyridamole initially (≤1 year) with a subsequent switch to clopidogrel, with regard to mortality and MACE outcomes

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

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 analysed data from a cohort of 8,013 stroke patients (mean (sd) 77.81±11.83 years) consecutively admitted over 11 years (January 2003–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-day, 14-day, 1-month, 3-month, 6-month, 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 males with hemorrhagic stroke. Elevated haemoglobin 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, this gave a pooled population of 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); OR 1.97(1.56– 2.47) and hemorrhagic stroke (4 studies); OR 1.46(1.23–1.74). Conclusions: There is strong evidence that patients with anemia have increased mortality in stroke. Targeted interventions in this patient population may improve outcomes and therefore require further evaluation

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

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

The authors would like to thank the patients of the NNUH Stroke Register cohort and the data team of the Norfolk and Norwich University Stroke Services. NNUH Stroke Register is maintained by the NNUH Stroke Services.Peer reviewedPostprin

Prevalence of orthostatic hypertension and its association with cerebrovascular diagnoses in patients with suspected TIA and minor stroke

Purpose: We aimed to compare the rate of stroke, transient ischemic attack, and cerebrovascular disease diagnoses across groups of patients based on their orthostatic blood pressure response in a transients ischemic attack clinic setting. Materials and Methods: We retrospectively analysed prospectively collected data from 3201 patients referred to a transient ischemic attack (TIA)/minor stroke outpatients clinic. Trained nurses measured supine and standing blood pressure using an automated blood pressure device and the patients were categorized based on their orthostatic blood pressure change into four groups: no orthostatic blood pressure rise, systolic orthostatic hypertension, diastolic orthostatic hypertension, and combined orthostatic hypertension. Then, four stroke physicians, who were unaware of patients' orthostatic BP response, assessed the patients and made diagnoses based on clinical and imaging data. We compared the rate of stroke, TIA, and cerebrovascular disease (either stroke or TIA) diagnoses across the study groups using Pearson's χ2 test. The effect of confounders was adjusted using a multivariate logistic regression analysis. Results: Cerebrovascular disease was significantly less common in patients with combined systolic and diastolic orthostatic hypertension compared to the "no rise" group [OR = 0.56 (95% CI 0.35–0.89]. The odds were even lower among the subgroups of patients with obesity [OR = 0.31 (0.12–0.80)], without history of smoking [OR 0.34 (0.15–0.80)], and without hypertension [OR = 0.42 (95% CI 0.19–0.92)]. We found no significant relationship between orthostatic blood pressure rise with the diagnosis of stroke. However, the odds of TIA were significantly lower in patients with diastolic [OR 0.82 (0.68–0.98)] and combined types of orthostatic hypertension [OR = 0.54 (0.32–0.93)]; especially in patients younger than 65 years [OR = 0.17 (0.04–0.73)] without a history of hypertension [OR = 0.34 (0.13–0.91)], and patients who did not take antihypertensive therapy [OR = 0.35 (0.14–0.86)]. Conclusion: Our data suggest that orthostatic hypertension may be a protective factor for TIA among younger and normotensive patients

Anaemia and incidence of post stroke dementia

Objectives: To assess the impact of anaemia on incidence of post-stroke dementia. Patients and Methods: We used data from a UK regional stroke register. To be eligible, patient must have survived to discharge and had anaemia by WHO criteria. Dementia status and other prevalent co-morbidities were assessed using ICD-10 codes. Patients were followed till May 2015 (mean follow-up 3.7 years, total person years = 27,769). Hazard Ratio for incident dementia was calculated using Cox-proportional hazards model controlling for potential confounders. Fine and Gray model was additionally constructed using mortality as the competing risk. Results: A total of 7,454 stroke patients were included with mean age (SD) of 75.9(12.3) years (50.2% men). Those with anaemia were older, has higher disability and co-morbidity burden prior to stroke. We observed a large amount of variation in the dementia incidence rates over time and that the hazard ratio increased every year. The significant association between anaemia and dementia incidence was lost after controlling for pre-stroke Modified Rankin score (HR1.17(0.97,1.40)). With every 20g/dL increase in Hb was associated with a significant reduction in the risk of dementia after adjustment for age, sex, stroke factors and disability but lost significance after adjustment for vascular risk factors. Competing risk analyses showed similar results. Conclusion: Whilst we found no evidence of anaemia as a risk factor for post-stroke dementia, the findings may be limited by potential under recognition of post stroke dementia