The individual and combined impacts of pre-existing diabetes and dementia on ischemic stroke outcomes: a registry-based cohort study.

BACKGROUND: Individually, diabetes mellitus and dementia are associated with poorer outcomes after stroke. However, the combined impact of these pre-existing factors on acute ischemic stroke (AIS) outcomes has not been examined. METHODS: All consecutive patients with AIS admitted to Norfolk and Norwich University Hospitals between 2003 and 2016 (catchment population ~ 900,000) were divided into four groups: those with neither diabetes nor dementia (reference), with diabetes without dementia, with dementia without diabetes, and with both co-morbidities. In-hospital mortality, length of hospital stay (LoS), and disability outcomes were analysed using logistic regressions. Post-discharge mortality and recurrence were assessed using Cox regressions. Additionally, interaction terms were added to the models for the short-term outcomes and long-term mortality to test for synergistic effects of diabetes and dementia. Models were adjusted for age, sex, Oxfordshire Community Stroke Project classification, comorbidities, hematological and biochemical measures, and antithrombotic medications. RESULTS: The cohort was 10,812 patients with 52% females and a median age of 80. The median follow-up was 3.8 years for stroke recurrence and 5.5 years for mortality. No significant differences between the four groups existed for in-hospital mortality and post-stroke disability. Patients with dementia had significantly longer LoS (OR 2.25 [95% CI: 1.34-3.77] and 1.31 [1.02-1.68] with and without diabetes, respectively). Patients with both comorbidities had the highest risk of stroke recurrence (HR 2.06 [1.12-3.77]), followed by those with only dementia (1.59 [1.15-2.20]) and only diabetes (1.25 [1.06-1.49]). Similarly, the patient group with both diabetes and dementia had the highest long-term mortality risk (1.76 [1.33-2.37]). The hazard ratios for patients with only dementia and only diabetes were 1.71 [1.46-2.01] and 1.19 [1.08-1.32], respectively. No significant interactions were seen between diabetes and dementia with regards to their effects on the outcomes. CONCLUSION: Individual and cumulative impacts of the two conditions on long-term mortality and stroke recurrence were notable. However, no synergistic impact of the two comorbidities were seen on the stroke outcomes tested in our study. Therefore, tailoring the management of stroke patients based on additional requirements associated with each pre-existing condition will be more impactful towards improving outcomes.

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.

A combined DHA-rich fish oil and cocoa flavanols intervention does not improve cognition or brain structure in older adults with memory complaints: results from the CANN randomized, controlled parallel-design study.

BACKGROUND: There is evidence that both omega-3 long-chain polyunsaturated fatty acids (PUFAs) (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and cocoa flavanols can improve cognitive performance in both healthy individuals and in those with memory complaints. However, their combined effect is unknown. OBJECTIVES: To investigate the combined effect of EPA/DHA and cocoa flavanols (OM3FLAV) on cognitive performance and brain structures in older adults with memory complaints. METHODS: A randomized placebo-controlled trial of DHA-rich fish oil (providing 1.1 g/d DHA and 0.4 g/d EPA) and a flavanol-rich dark chocolate (providing 500 mg/d flavan-3-ols) was conducted in 259 older adults with either subjective cognitive impairment or mild cognitive impairment. Participants underwent assessment at baseline, 3 mo, and 12 mo. The primary outcome was the number of false-positives on a picture recognition task from the Cognitive Drug Research computerized assessment battery. Secondary outcomes included other cognition and mood outcomes, plasma lipids, brain-derived neurotrophic factor (BDNF), and glucose levels. A subset of 110 participants underwent structural neuroimaging at baseline and at 12 mo. RESULTS: 197 participants completed the study. The combined intervention had no significant effect on any cognitive outcomes, with the exception of reaction time variability (P = 0.007), alertness (P < 0.001), and executive function (P < 0.001), with a decline in function observed in the OM3FLAV group (118.6 [SD 25.3] at baseline versus 113.3 [SD 25.4] at 12 mo for executive function) relative to the control, and an associated decrease in cortical volume (P = 0.039). Compared with the control group, OM3FLAV increased plasma HDL, total cholesterol ratio (P < 0.001), and glucose (P = 0.008) and reduced TG concentrations (P < 0.001) by 3 mo, which were sustained to 12 mo, with no effect on BDNF. Changes in plasma EPA and DHA and urinary flavonoid metabolite concentrations confirmed compliance to the intervention. CONCLUSIONS: These results suggest that cosupplementation with ω-3 PUFAs and cocoa flavanols for 12 mo does not improve cognitive outcomes in those with cognitive impairment. This trial was registered at clinicaltrials.gov as NCT02525198.

Orthostatic hypertension and major adverse events: a systematic review and meta-analysis.

AIMS: The role of orthostatic hypertension (OHT) in cardiovascular disease (CVD) and mortality is unclear. We aimed to determine if this association exists through a systematic review and meta-analysis. METHODS AND RESULTS: Study inclusion criteria included: (i) any observational/interventional studies of participants aged ≥18 years (ii) that assessed the relationship between OHT and (iii) at least one outcome measure-all-cause mortality (primary outcome), coronary heart disease, heart failure, stroke/cerebrovascular disease, or neurocognitive decline. MEDLINE, EMBASE, Cochrane, clinicaltrials.gov, and PubMed were independently searched by two reviewers (inception-19 April 2022). Critical appraisals were conducted using the Newcastle-Ottawa Scale. Random-effects meta-analysis was performed using a generic inverse variance method, and narrative synthesis or pooled results were presented as an odds or hazards ratio (OR/HR), with 95% confidence interval. Twenty studies (n = 61 669; 47.3% women) were eligible, of which 13 were included in the meta-analysis (n = 55 456; 47.3% women). Median interquartile range (IQR) follow-up for prospective studies was 7.85 (4.12, 10.83) years. Eleven studies were of good quality, eight fair, and one poor. Relative to orthostatic normotension (ONT), systolic OHT (SOHT) was associated with a significant 21% greater risk of all-cause mortality (HR: 1.21, 1.05-1.40), 39% increased risk of CVD mortality based on two studies (HR: 1.39, 1.05-1.84), and near doubled odds of stroke/cerebrovascular disease (OR: 1.94, 1.52-2.48). The lack of association with other outcomes may be due to weak evidence or low statistical power. CONCLUSION: Patients with SOHT may have higher mortality risk relative to those with ONT and increased odds of stroke/cerebrovascular disease. Whether interventions can reduce OHT and improve outcomes should be explored.

Orthostatic hypertension (OHT) is defined as an arbitrary rise in upper (systolic) and/or lower (diastolic) blood pressure readings on standing. We performed a thorough literature search and combined the evidence of impact of OHT on future adverse events, including death, heart attack, heart failure, stroke, falls, and impaired cognition. We found the following:Twenty studies that investigated the association between OHT and future adverse events. Of these, 13 were eligible to be included in the combined evidence (meta-analysis). This formed a total sample of 61 669 participants (47.3% women), of which 55 456 (47.3% women) were included in the meta-analysis.Systolic OHT (SOHT) was associated with a significant 21% increased risk for death from any cause, a 39% greater risk of death due to heart and blood vessel disease and near doubled odds of stroke or brain vessel disease. Furthermore, three of four studies found a significant association between SOHT and impaired cognition. Diastolic OHT was not found to be associated with these outcomes. The lack of association with other outcomes investigated may be due to weak evidence.Eleven studies were of good quality, eight fair, and one poor. Differences in study design, study criteria, and study populations mean that the results need interpreting with caution. Future robust studies can build on this evidence to assess if treatment to reduce OHT would improve future outcomes.

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.

The relationship between nutritional status at the time of stroke on adverse outcomes: a systematic review and meta-analysis of prospective cohort studies.

CONTEXT AND OBJECTIVE: The impact of existing malnutrition on stroke outcomes is poorly recognised and treated. Evidence was systematically reviewed and quantified by meta-analysis. METHODS: MEDLINE, EMBASE and Web of Science were searched from inception to 11 January 2021 and updated in July. Prospective cohort studies, in English, evaluating anthropometric and biomarkers of nutrition on stroke outcomes were included. Risk of bias was assessed using the Scottish Intercollegiate Guidelines Network checklist. RESULTS: Twenty-six studies (n = 156 249) were eligible (follow-up: One month-14 years). Underweight patients had increased risk of long-term mortality (adjusted hazard ratio = 1.65,1.41-1.95), whilst overweight (0.80,0.74-0.86) and obese patients (0.80,0.75-0.85) had decreased risk compared to normal weight. Odds of mortality decreased in those with high serum albumin (odds ratio = 0.29,0.18-0.48) and increased with low serum albumin (odds ratio = 3.46,1.78-6.74) compared to normal serum albumin (30-35 g/L). Being malnourished compared to well-nourished, as assessed by the Subjective Global Assessment (SGA) or by a combination of anthropometric and biochemical markers increased all-cause mortality (odds ratio = 2.38,1.85-3.06) and poor functional status (adjusted odds ratio = 2.21,1.40-3.49). CONCLUSION: Nutritional status at the time of stroke predicts adverse stroke outcomes.

Body Mass Index and Mortality, Recurrence and Readmission after Myocardial Infarction: Systematic Review and Meta-Analysis.

The following study aimed to systematically review and meta-analyse the literature on the relations between markers of nutritional status and long-term mortality, recurrence and all-cause hospital readmission following myocardial infarction (MI). Medline, EMBASE and Web of Science were searched for prospective cohort studies reporting the relationship between anthropometric and biochemical markers of nutritional status and nutritional assessment tools on long-term mortality, recurrence and all-cause hospital readmission in adult patients with an MI. Two reviewers conducted screening, data extraction and critical appraisal independently. Random-effects meta-analysis was performed. Twenty-seven studies were included in the qualitative synthesis and twenty-four in the meta-analysis. All eligible studies analysed BMI as their exposure of interest. Relative to normal weight, mortality was highest in underweight patients (adjusted Hazard Ratio (95% confidence interval): 1.42 (1.24-1.62)) and lower in both overweight (0.85 (0.76-0.94)) and obese patients (0.86 (0.81-0.91)), over a mean follow-up ranging from 6 months to 17 years. No statistically significant associations were identified between different BMI categories for the outcomes of recurrence and hospital readmission. Patients with low BMI carried a significant mortality risk post-MI; however due to the known limitations associated with BMI measurement, further evidence regarding the prognostic utility of other nutritional markers is required.

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.

Long Term Prognostic Impact of Sex-specific Longitudinal Changes in Blood Pressure. The EPIC-Norfolk Prospective Population Cohort Study.

AIMS: We aimed to determine the sex differences in longitudinal systolic and diastolic blood pressure (SBP and DBP) trajectories in mid-life and delineate the associations between these and mortality (all-cause, cardiovascular, and non-cardiovascular) and incident cardiovascular disease (CVD) in old age. METHODS AND RESULTS: Participants were selected from the European Prospective Investigation into Cancer, Norfolk (EPIC-Norfolk) cohort study. Sex-specific trajectories were determined using group-based trajectory models using three clinic BP measurements acquired between 1993 and 2012 (mean exposure ∼12.9 years). Multivariable Cox regressions determined the associations between trajectories and incident outcomes over the follow-up (median follow-up 9.4 years). A total of 2897 men (M) and 3819 women (F) were included. At baseline, women were younger (F-55.5, M-57.1), had a worse cardiometabolic profile and were less likely to receive primary CVD prevention including antihypertensive treatment (F-36.0%, M-42.0%). Over the exposure period, women had lower SBP trajectories while men exhibited more pronounced SBP decreases over this period. Over the follow-up period, women had lower mortality (F-11.9%, M-20.5%) and CVD incidence (F-19.8%, M-29.6%). Compared to optimal SBP (≤120 mmHg) and DBP (≤70 mmHg) trajectories, hypertensive trajectories were associated with increased mortality and incident CVD in both men and women during follow-up at univariable level. These associations were nevertheless not maintained upon extensive confounder adjustment including antihypertensive therapies. CONCLUSION: We report sex disparities in CVD prevention which may relate to worse cardiometabolic profiles and less pronounced longitudinal SBP decreases in women. Effective anti-hypertensivetherapy may offset the adverse outcomes associated with prolonged exposure to high blood pressure.

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.

Bioelectrical Impedance Versus Biochemical Analysis of Hydration Status: Predictive Value for Prolonged Hospitalisation and Poor Discharge Destination for Older Patients.

Dehydration is prevalent in hospitalised patients and is associated with increased morbidity and mortality, particularly among the elderly (≥65 years). We aimed at comparing the performance of intracellular water to extracellular water ratio (ICW/ECW), calculated through a bioelectrical impedance analysis (BIA) of blood urea nitrogen, with the creatinine ratio (BUN/Cr) to predict poor outcomes in a cohort of prospectively identified patients. Data were combined from a cohort of elderly patients (≥65 years) admitted to hospital with fragility fracture (n = 125) and older adults aged ≥50 years admitted to hospital with stroke (n = 40). The association between hydration status and study outcomes (unfavourable discharge destination (rehabilitation, another ward, or death) and prolonged hospitalisation (>10 days)) was examined using logistic regression. The overall diagnostic accuracy of each hydration status measurement was assessed using the area under the receiver operating characteristic (ROC) curve. In 165 participants (mean age (SD) of 76.7 (9.2) years), an ICW/ECW ratio below the 25th percentile was associated with increased odds of poor discharge destination (OR (95% CI) = 4.25 (1.59-11.34)). Neither the relationship between the BUN/Cr ratio and prolonged stay nor discharge destination was significant. A BIA could be used utilised in conjunction with biochemical measurements to inform patient prognosis.

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.

Variations in Rates of Discharges to Nursing Homes after Acute Hospitalization for Stroke and the Influence of Service Heterogeneity: An Anglia Stroke Clinical Network Evaluation Study.

Nursing home placement after stroke indicates a poor outcome but numbers placed vary between hospitals. The aim of this study is to determine whether between-hospital variations in new nursing home placements post-stroke are reliant solely on case-mix differences or whether service heterogeneity plays a role. A prospective, multi-center cohort study of acute stroke patients admitted to eight National Health Service acute hospitals within the Anglia Stroke and Heart Clinical Network between 2009 and 2011 was conducted. We modeled the association between hospitals (as a fixed-effect) and rates of new discharges to nursing homes using multiple logistic regression, adjusting for important patient risk factors. Descriptive and graphical data analyses were undertaken to explore the role of hospital characteristics. Of 1335 stroke admissions, 135 (10%) were discharged to a nursing home but rates varied considerably from 6% to 19% between hospitals. The hospital with the highest adjusted odds ratio of nursing home discharges (OR 4.26; 95% CI 1.69 to 10.73), was the only hospital that did not provide rehabilitation beds in the stroke unit. Increasing hospital size appeared to be related to an increased odds of nursing home placement, although attenuated by the number of hospital stroke admissions. Our results highlight the potential influence of hospital characteristics on this important outcome, independently of patient-level factors.

Can cardiovascular risk management be improved by shared care with general practice to prevent cognitive decline following stroke/TIA? A feasibility randomised controlled trial (SERVED memory).

BACKGROUND: Cognitive impairment and dementia following cerebrovascular disease are increasingly common in the UK. One potential strategy to prevent post-stroke cognitive decline is multimodal vascular risk factor management. However, its efficacy remains uncertain and its application in vulnerable patients with incident cerebrovascular disease and early cognitive impairment has not been assessed. The primary aim of this study was to assess the feasibility of recruitment and retention of patients with early cognitive impairment post-stroke or transient ischaemic attack (TIA) to a trial of enhanced vascular risk factor management combining primary and secondary care. METHODS: In this single centre, open label trial adults with a recent stroke or TIA and mild cognitive impairment (MCI) were randomised 1:1 to a three-monthly multimodal vascular risk factor intervention jointly delivered by the trial team and General Practitioner (GP), or control (defined as usual care from the GP). Chosen risk factors were blood pressure (BP), total cholesterol, blood glucose (HbA1C) in those with diabetes, and heart rate and adequacy of anticoagulation in those with atrial fibrillation (AF). Similar patients with normal cognition were enrolled in an embedded observational cohort and also received usual care from the GP. Repeat cognitive screening was undertaken in all participants after 12 months. RESULTS: Seventy three participants were recruited to the randomised trial and 94 to the observational cohort (21.8% of those screened). From the randomised trial 35/73 (47.9%) dropped out before final follow-up. In all groups guideline based rates of risk factor control were mostly poor at baseline and did not significantly improve during follow-up. The observational cohort demonstrated greater decline in cognitive test scores at 12 months, with no difference between the randomised groups. CONCLUSIONS: Recruitment to such a study was feasible, but retention of participants was difficult and generally poor rates of risk factor control suggested insufficient application of the intervention. Consequently, successful scaling up of the trial would require protocol changes with less reliance on primary care services. Any future trial should include participants with normal cognition post-stroke as they may be at greatest risk of cognitive decline. TRIAL REGISTRATION: ISRCTN, ISRCTN42688361 . Registered 16 April 2015.

What is the optimal blood pressure level for patients with atrial fibrillation treated with direct oral anticoagulants?

OBJECTIVE: Limited data exist to inform blood pressure (BP) thresholds for patients with atrial fibrillation prescribed direct oral anticoagulants (DOAC) therapy in the real world setting. METHODS: SBP was measured in 9051 primary care patients in England on DOACs for atrial fibrillation with postinitiation BP levels available within the Clinical Practice Research Datalink. The incidence rate for the primary outcome of the first recorded event (defined as a diagnosis of first stroke, recurrent stroke, myocardial infarction, symptomatic intracranial bleed, or significant gastrointestinal bleed) and of secondary outcomes all-cause mortality and cardiovascular mortality were calculated by postinitiation BP groups. RESULTS: The Cox proportional hazard ratio of an event [crude and adjusted hazard ratio 1.04 (95% confidence interval (CI) 1.00-1.08), P = 0.077 and 0.071, respectively] did not differ significantly with a 10 mmHg increase in SBP. The hazard of all-cause mortality [crude hazard ratio 0.83 (95% CI 0.80-0.86), P = 0.000; adjusted hazard ratio 0.84 (95% CI 0.81-0.87), P = 0.000] and cardiovascular mortality [crude hazard ratio 0.92 (95% CI 0.85-0.99), P = 0.021; adjusted hazard ratio 0.93 (95% CI 0.86-1.00), P = 0.041] demonstrated a significant inverse relationship with a 10 mmHg increase in SBP. Patients with a SBP within 161-210 mmHg had the lowest all-cause death rate, while patients with SBP within 121-140 mmHg had the lowest cardiovascular death rate. CONCLUSION: SBP values below 161 mmHg are associated higher all-cause mortality, but lower event risk in patients with atrial fibrillation on DOAC therapy. The nadir SBP for lowest event rate was 120 mmHg, for lowest cardiovascular mortality was 130 mmHg and for lowest all-cause mortality was 160 mmHg. This demonstrates a need for a prospective interventional study of BP control after initiation of anticoagulation.

A calcium channel or angiotensin converting enzyme inhibitor/angiotensin receptor blocker regime to reduced blood pressure variability in acute ischaemic stroke (CAARBS): A feasibility trial.

BACKGROUND: Trials of lowering blood pressure in patients with acute ischaemic stroke not undergoing thrombolysis have not demonstrated improved outcomes with intervention. Rather than absolute levels, it may be that blood pressure variability is important. However, there are no prospective randomised trials investigating the benefit of reducing blood pressure variability in this patient group. AIMS: The primary aim of this trial was to determine the feasibility of recruitment to a randomised trial investigating the effect of different antihypertensive medications on blood pressure variability. METHODS: CAARBS was a multi-centre, open-label, randomised parallel group controlled feasibility trial. Adults with a first mild-moderate ischaemic stroke or transient ischaemic attack, requiring antihypertensive therapy for secondary prevention, were randomised to a calcium channel blocker or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. Blood pressure and variability were measured at baseline, three weeks, and three months. Compliance with measurements and treatment was monitored. RESULTS: Fourteen patients were recruited to the trial (0.6% of those screened), nine of whom completed follow-up. The majority of patients screened (98.1%) were ineligible. Compliance with the intervention was good, as were measurement completion rates (88.9% or higher in all cases except ambulatory measurements). No major adverse events were recorded. CONCLUSIONS: Recruitment to the trial was difficult due to patient ineligibility, suggesting that the current protocol is unlikely to be successful if scaled for a definitive trial. However, the intervention was safe, and compliance was good, suggesting a future trial with modified eligibility criteria could be successful. TRIAL REGISTRATION: ISRCTN10853487.

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 7454 stroke patients were included with mean age SD of 75.912.3 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 20 g/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.

Self-Monitoring and Management of Blood Pressure in Patients with Stroke or TIA: An Economic Evaluation of TEST-BP, A Randomised Controlled Trial.

BACKGROUND: Prevention of secondary stroke following initial ictus is an important focus of after-stroke care. Blood pressure (BP) is a key risk factor, so usual care following stroke or transient ischaemic attack includes regular BP checks and monitoring of anti-hypertensive medication. This is traditionally carried out in primary care, but the evidence supporting self-monitoring and self-guided management of BP in the general population with hypertension is growing. OBJECTIVE: Our objective was to estimate the cost effectiveness of treatment as usual (TAU) versus (1) self-monitoring of BP (S-MON) and (2) self-monitoring and guided self-management of anti-hypertensive medication (S-MAN). METHODS: This was a within-trial economic evaluation of a randomised controlled trial estimating the incremental cost per 1 mmHg BP reduction and per quality-adjusted life-year (QALY) gained over a 6-month time horizon from the perspective of the UK National Health Service (NHS). RESULTS: Data were evaluable for 140 participants. Costs per patient were £473, £853 and £1035; mean reduction in systolic BP (SBP) was 3.6, 6.7 and 6.1 mmHg, and QALYs accrued were 0.427, 0.422 and 0.423 for TAU, S-MON and S-MAN, respectively. No statistically significant differences in incremental costs or outcomes were detected. On average, S-MAN was dominated or extended dominated. The incremental cost per 1 mmHg BP reduction from S-MON versus TAU was £137. CONCLUSION: On average, S-MAN is an inefficient intervention. S-MON may be cost effective, depending on the willingness to pay for a 1 mmHg BP reduction, although it yielded fewer QALYs over the within-trial time horizon. Decision modelling is required to explore the longer-term costs and outcomes.

Association between different methods of assessing blood pressure variability and incident cardiovascular disease, cardiovascular mortality and all-cause mortality: a systematic review.

BACKGROUND: Blood pressure variability (BPV) is a possible risk factor for adverse cardiovascular outcomes and mortality. There is uncertainty as to whether BPV is related to differences in populations studied, measurement methods or both. We systematically reviewed the evidence for different methods to assess blood pressure variability (BPV) and their association with future cardiovascular events, cardiovascular mortality and all-cause mortality. METHODS: Literature databases were searched to June 2019. Observational studies were eligible if they measured short-term BPV, defined as variability in blood pressure measurements acquired either over a 24-hour period or several days. Data were extracted on method of BPV and reported association (or not) on future cardiovascular events, cardiovascular mortality and all-cause mortality. Methodological quality was assessed using the CASP observational study tool and data narratively synthesised. RESULTS: Sixty-one studies including 3,333,801 individuals were eligible. BPV has been assessed by various methods including ambulatory and home-based BP monitors assessing 24-hour, "day-by-day" and "week-to-week" variability. There was moderate quality evidence of an association between BPV and cardiovascular events (43 studies analysed) or all-cause mortality (26 studies analysed) irrespective of the measurement method in the short- to longer-term. There was moderate quality evidence reporting inconsistent findings on the potential association between cardiovascular mortality, irrespective of methods of BPV assessment (17 studies analysed). CONCLUSION: An association between BPV, cardiovascular mortality and cardiovascular events and/or all-cause mortality were reported by the majority of studies irrespective of method of measurement. Direct comparisons between studies and reporting of pooled effect sizes were not possible.