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.

Sex-specific lifetime risk of cardiovascular events: the European Prospective Investigation into Cancer-Norfolk prospective population cohort study.

AIMS: Better understanding of sex differences in cardiovascular disease (CVD) is essential in tailoring appropriate preventative strategies. Using a large population-based study with follow-up >25 years, we aimed to determine sex-specific lifetime risks of incident CVD and cardiovascular (CV) mortality amongst populations with and without prevalent CVD. METHODS AND RESULTS: Participants were drawn from the European Prospective Investigation into Cancer-Norfolk and followed up for a median of 26.2 years. Sex-specific lifetime risks were ascertained accounting for the competing risk of death. Models were adjusted for ethnicity and time-updated covariates: material deprivation, CV risk factors, lifestyle factors, comorbidities, and medication. A total of 23 859 participants [54.5% women; mean age (standard deviation) 59.2 (9.3) years at baseline] were included. Adjusted lifetime risks of incident CVD were higher in men than in women (69.1 vs. 57.7% at age 75): cause-specific hazard ratio (cHR) (99% confidence interval)-1.49 (1.41-1.57), while the risks of CV mortality at age 75 were 4.4% (men) and 3.1% (women): cHR-1.42 (1.31-1.54). Myocardial infarction was the predominant first presentation in men until the eighth decade. In women, the first CVD manifestations after their sixth decade were predominantly atrial fibrillation and stroke. The male-associated excess relative risks of incident CVD and CV mortality were halved in people with prevalent CVD. CONCLUSION: We characterized the sex-specific lifetime CV risks in a large cohort. Men had substantially higher risk of incident CVD and CV mortality than women, which was attenuated amongst people with prevalent CVD. Our findings provide an evidence base for sex-specific CV prevention.

In this population-based study, we aimed to understand the sex-specific lifetime trajectories of different heart and circulatory disorders and their relationship with death from heart disease. We included ∼24 000 participants in the analyses, who were followed up for >25 years. Men had a higher lifetime risk of heart and circulatory disorders compared with women. Heart attacks were the predominant first presentation in men until the eighth decade, while in women this was manifested as heart rhythm disorders and stroke after their sixth decade. The excess risk of death from heart disease observed in men with pre-existing heart disease was attenuated compared with those free of heart disease at baseline. In conclusion, men and women require tailored heart disease prevention efforts given the marked sex disparities in heart disease and death over the very long-term highlighted by our study.

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.

Race and sex disparities in acute outcomes of patients with acute ischemic stroke and diabetes mellitus. A national inpatient sample study.

BACKGROUND: Diabetes Mellitus (DM) disproportionately affects racial minority groups and is a well-established risk factor for ischemic stroke and worse stroke outcomes. Whether racial disparities exist in acute outcomes of patients presenting with Acute Ischemic Stroke (AIS) and comorbid DM, including potential differences in the administration of evidence-based reperfusion therapy, remains unclear. We aimed to assess whether racial and sex differences exist in the acute outcomes and treatment of patients with DM presenting with AIS. METHODS: January 2016-December 2018 AIS admissions with diabetes were extracted from the US National Inpatient Sample (NIS). Multivariable logistic regressions assessed the association between race, sex, and differences in in-hospital outcomes (mortality, hospitalisation >4 days, routine discharge, and stroke severity). Further models assessed the relationship between race, sex, and receipt of thrombolysis and thrombectomy. All models were adjusted for relevant confounders, including comorbidities and stroke severity. RESULTS: 92,404 records representative of 462,020 admissions were extracted. Median (IQR) age was 72 (61-79), with 49 % women, 64 % White, 23 % African American, and 10 % Hispanic patients. African Americans had lower odds of in-hospital mortality compared to Whites (adjusted odds ratio; 99 % confidence interval=0.72;0.61-0.86), but were more likely to have prolonged hospitalisation (1.46;1.39-1.54), be discharged to locations other than home (0.78;0.74-0.82) and have moderate/severe stroke (1.17;1.08-1.27). Additionally, African American (0.76;0.62-0.93) and Hispanic patients (0.66;0.50-0.89) had lower odds of receiving thrombectomy. Compared to men, women had increased odds of in-hospital mortality (1.15;1.01-1.32). CONCLUSIONS: Racial and sex disparities exist in both evidence-based reperfusion therapy and in-hospital outcomes amongst patients with AIS and diabetes. Further measures are needed to address these disparities and reduce the excess risk of adverse outcomes among women and African American patients.

Sex-Specific Outcomes of Acute Stroke in Patients with Systemic Lupus Erythematosus: A National Inpatient Sample Study.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder associated with increased stroke risk. Its association with stroke outcomes remains poorly understood. In this study, we aimed to compare the sex-specific SLE-associated acute stroke outcomes. Methods: Stroke hospitalisations between 2015 and 2018 from the National Inpatient Sample were analysed. The associations between SLE and outcomes (inpatient mortality, length-of-stay > 4 days and routine discharge) were examined using multivariable logistic regressions, stratifying by sex and adjusting for age, race, stroke type, revascularisation, hospital characteristics and comorbidities. Results: A total of 316,531 records representing 1,581,430 hospitalisations were included. Median (interquartile range) age was 71 (60−82) years. There were 940 (0.06%) males and 6110 (0.39%) females with SLE. There were no associations between SLE and mortality amongst either females (odds ratio (95% confidence interval) = 1.11 (0.84−1.48)) or males (0.81 (0.34−1.94)). Nevertheless, SLE was associated with prolonged hospitalisation (1.17 (1.03−1.32)) and lower odds of routine discharge (0.82 (0.72−0.94)) amongst females. There were no associations between SLE and other adverse outcomes amongst males. Conclusions: The association between SLE and acute stroke outcomes was influenced by sex. While SLE was not associated with mortality in either sex, females with SLE had higher odds of prolonged hospitalisation and lower odds of routine home discharge compared to patients without SLE, while males did not exhibit this increased risk.

[Sex differences in stroke mortality in Thailand : A National cohort study]. / Différences sexuelles dans la mortalité par accident vasculaire cérébral en Thaïlande : une étude de cohorte nationale.

BACKGROUND: Over half of the growing global stroke-mortality burden is accounted for by the East-Asian-subcontinent alone. Sex differences in stroke-mortality in the Asian population is yet to be assessed in the literature. We aimed to assess the sex-differences in mortality following stroke in a large cohort of Thai-patients. METHOD: All stroke admissions between 2004-2015 were included from the Thailand public-health-insurance-database. The association between sex and mortality was assessed in-hospital, at 1 month, 1 year and 5 years, using multivariable Cox-regressions, separately for ischaemic-stroke (IS), haemorrhagic-stroke (HS) and stroke-of-undetermined-type(SUT), adjusting for confounders. RESULTS: 608,890 patients were included: 370,527 patients with IS(60.9%), 173,236 with HS(28.5%) and 65,127 with SUT(10.6%). Women were older than men in all three groups and had higher prevalence of comorbidities. Adjusted hazard-ratios(HRs) of mortality showed women had higher mortality post-IS compared to men (in-hospital: HR: 1.20; 95% CI: 1.17-1.23; 1 month: HR: 1.17; 95% CI: 1.15-1.20; 1 year: HR: 1.10; 95% CI: 1.09-1.12 and 5 years: HR: 1.02; 95% CI: 1.01-1.03). Women also had higher mortality after HS (in-hospital: HR: 1.02; 95% CI: 1.00-1.04; 1 month: HR: 1.08; 95% CI: 1.06-1.10; 1 year: HR: 1.04; 95% CI: 1.03-1.06 and 5 years: HR: 1.09; 95% CI: 1.08-1.11), and SUT (in-hospital: HR: 1.04; 95% CI: 1.03-1.06; 1 month: HR: 1.20; 95% CI: 1.14-1.27; 1 year: HR: 1.14; 95% CI: 1.09-1.18 and 5 years: HR: 1.06; 95% CI: 1.03-1.10). CONCLUSIONS: Compared to men, women were older at time of stroke-diagnosis and had higher burden of stroke risk-factors. Women also had higher mortality after stroke regardless of stroke-type or duration since stroke-onset. Post-IS, excess stroke-mortality in women was greatest during the in-hospital period, whereas excess stroke-mortality increased with time in women who had HS. No clear relationship was found between duration since stroke-onset and mortality in patients who had SUT.

Body Fat Percentage and the Long-term Risk of Fractures. The EPIC-Norfolk Prospective Population Cohort Study.

BACKGROUND: This cohort study aimed to determine the association between body fat percentage (BF%), incident fractures and calcaneal broadband ultrasound attenuation (BUA). METHODS: Participants were drawn from the EPIC-Norfolk Prospective Population Cohort Study (median follow-up = 16.4 years). Cox models analysed the relationship between BF% and incident fractures (all and hip). Linear and restricted cubic spline (RCS) regressions modelled the relationship between BF% and BUA. RESULTS: 14,129 participants (56.2 % women) were included. There were 1283 and 537 incident all and hip fractures respectively. The participants had a mean (standard deviation) age of 61.5 (9.0) years for women and 62.9 (9.0) years for men. Amongst men, BF% was not associated with incident all fractures. While BF% < 23 % (median) was not associated with hip fractures, BF% > 23 % was associated with increased risk of hip fractures by up to 50 % (hazard ratio (95 % confidence interval) = 1.49 (1.06-2.12)). In women, BF% < 39 % (median) was associated with up to 32 % higher risk of all fractures (1.32 (1.13-1.44)), while BF% > 35 % was not associated with this outcome. Higher BF% was associated with lower risk of incident hip fractures in women. Higher BF% was associated with higher BUA amongst women. Higher BF% up to ~23 % was associated with higher BUA amongst men. CONCLUSIONS: Higher BF% is associated with lower risk of fractures in women. While there was no association between BF% and all fractures in men, increasing BF% >23 % was associated with higher risk of hip fractures in men. This appears to be independent of estimated bone mineral density. Fracture prevention efforts need to consider wider physical, clinical, and environmental factors.

Does Estimated Glomerular Filtration Rate Predict In-Hospital Mortality in Acutely Unwell Hospitalized Oldest Old?

Globally the population of older adults is the fastest growing age group. Estimated glomerular filtration rate (eGFR) is an estimation of true kidney function with lower eGFR associated with higher mortality. However, few studies explore eGFR's prognostic value in the nonagenarian. We investigated the association between eGFR on admission and mortality among the nonagenarians hospitalised with acute illness. A retrospective analysis of a prospective cohort study included patients aged ≥ 90 admitted into three acute medical assessment units or acute geriatric wards in England and Scotland between November 2008 and January 2009. Association between eGFR and all-cause mortality was evaluated using the Cox proportional hazard models controlling for potential confounders including frailty. 392 patients with mean (SD) 93.0 ± 2.6 years (68.45% women) were included. The median (IQR) eGFR was 26.61 (18.41-40.41) mL/min/1.732. 63 died in in hospital. Low eGFR was not associated with mortality (Hazard ratio (HR) 1.00 (95% CI 0.98-1.02) overall or in sub-group analysis by frailty (HR 0.96 (0.92-1.01)) or by eGFR of ≤30 (HR 1.01 (0.95-1.06). We found no evidence of prognostic value of eGFR in predicting in-hospital mortality in the acutely unwell hospitalised nonagenarians.

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.

Gender differences in mortality of hospitalised stroke patients. Systematic review and meta-analysis.

OBJECTIVE: Gender differences in mortality after stroke remains unclear in the current literature. We therefore aimed to systematically review the gender differences in mortality up to five years after ischaemic (IS) or haemorrhagic stroke (HS) to address this evidence gap. METHODS: The literature was systematically searched using Ovid EMBASE, Ovid Medline, and Web of Science databases, from inception-November 2021. The quality of evidence was appraised using the CASP Cohort-study checklist. Unadjusted and adjusted odds and hazard ratios were meta-analysed, separately for IS and HS and a subgroup analysis of age-stratified mortality data was conducted. RESULTS: Forty-one studies were included (n = 8,128,700; mean-age 68.5 yrs; 47.1% female). 37 studies were included in meta-analysis (n = 8, 8008, 110). Compared to men, women who had an IS had lower mortality risk in-hospital (0.94; 95%CI 0.91-0.97), at one-month (0.87; 95%CI 0.77-0.98), 12-months (0.94; 95%CI 0.91-0.98) and five-years (0.93 95%CI 0.90-0.96). The subgroup analysis showed that this gender difference in mortality was present in women ≥ 70 years up to one-month post-IS (in-hospital: 0.94; 95%CI 0.91-0.97; one-month: 0.87; 95% CI 0.77-0.98), however, in women < 70 years this difference was no longer present. Nevertheless, analysis of crude data showed women were at higher risk of mortality in-hospital, at 12-months and five-years (in-hospital: 1.05; 95%CI 1.03-1.07, 12-months: 1.10; 95%CI 1.06-1.14, five-years: 1.06; 95%CI 1.02-1.10). After HS, women had higher mortality risk in-hospital (1.03; 95%CI 1.01-1.04) however, no gender differences were found post-discharge. CONCLUSION: The gender differences in post-stroke mortality differ by stroke type, age group and follow-up. Crude stroke mortality in women is higher than in men and this appears to be driven by pre-existing comorbidities. In adjusted models, women have a lower mortality risk following IS, independent of duration of follow-up. After HS, women had higher mortality in hospital however, no gender differences after hospital discharge were found.

Biomarker Determinants of Early Anthracycline-Induced Left Ventricular Dysfunction in Breast Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE: Breast cancer is the leading cause of cancer-related mortality amongst women. One of the most common chemotherapeutic agents used to treat breast cancer, anthracyclines, are associated with anthracycline-induced cardiotoxicity (ACIC). The aim of this meta-analysis was to quantify the predictive performance of biomarkers for early ACIC presentation in the breast cancer population. METHODS: Five databases were searched from inception to 1 January, 2022. Studies reporting the association between worsening left ventricular ejection fraction and biomarker level change were included. Overall, study heterogeneity varied between I2 0 and 78%. The primary outcome was incident left ventricular dysfunction, defined as left ventricular ejection fraction < 50-55% or a 10%-point decrease, in patients with breast cancer with congruent ≥ doubling of biomarker serology levels (growth differentiation factor 15, Galectin-3, pro B-type natriuretic peptide, high-sensitivity cardiac troponin T, placental growth factor, myeloperoxidase, high-sensitivity C-reactive protein, Fms-Related Tyrosine Kinase 1), 3 months after anthracycline exposure, relative to pre-anthracycline exposure levels, expressed as random effects, hazard ratios. The STRING protein interaction database was explored for experimentally validated biomarker interactions. RESULTS: Of 1458 records screened, four observational studies involving 1167 patients, with a low risk of bias, were included in this systematic review and meta-analysis. Doubling of growth differentiation factor 15 and Galectin-3 levels was associated with an increased risk of early ACIC, hazard ratio 3.74 (95% confidence interval 2.68-5.24) and hazard ratio 4.25 (95% confidence interval 3.1-5.18), respectively. Biomarker interactome analysis identified two putative ACIC biomarkers, neuropilin-1 and complement factor H. CONCLUSIONS: This is the first meta-analysis quantifying the association of biomarkers and early ACIC presentation in the breast cancer population. This may be of clinical relevance in the timely identification of patients at high risk of ACIC, allowing for closer monitoring and chemotherapy adjustments.

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.

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.

Higher anticholinergic burden from medications is associated with significant increase in markers of inflammation in the EPIC-Norfolk prospective population-based cohort study.

BACKGROUND: Higher medication anticholinergic burden is associated with increased risk of cardiovascular disease and cognitive decline. A mechanistic pathway has not been established. We aimed to determine whether inflammation may mediate these associations. METHODS: Participants were drawn from the European Prospective Investigation into Cancer, Norfolk cohort (40-79 years at baseline). Anticholinergic burden score (ACB) was calculated at first (1HC) (1993/97) and second (2HC) (1998/2000) health checks. Fibrinogen and C-reactive protein (CRP) were measured during 1HC and tumour necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) during 2HC. Cross-sectional associations between ACB and inflammatory markers were examined for both health checks. Prospective associations were also examined between 1HC ACB and 2HC inflammatory markers. Models were adjusted for age, sex, lifestyle factors, comorbidities and medications. RESULTS: In total, 17 678 and 22 051 participants were included in cross-sectional analyses for CRP, and fibrinogen, respectively. Furthermore, 5101 participants with data on TNF-α and IL-6 were included in the prospective analyses. Cross-sectionally, compared to ACB = 0, ACB ≥ 4 was associated with higher fibrinogen, beta (95% confidence interval) = 0.134 g/L (0.070, 0.199), CRP 1.175 mg/L (0.715, 1.634), IL-6 0.593 pg/mL (0.254, 0.932) and TNF-α 0.137 pg/mL (0.033, 0.241). In addition, a point increase in ACB was associated with higher levels of all markers. Prospectively, compared to ACB = 0, ACB ≥ 4 was associated with higher IL-6(pg/mL) of 0.019 (-0.323, 0.361) and TNF-α (pg/mL) of 0.202% (0.81, 0.323). A unit increase in ACB was associated with a significantly higher TNF-α and IL-6. CONCLUSION: Higher ACB was associated with higher inflammatory markers. Inflammation may mediate the relationship between anticholinergic medications and adverse outcomes.

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.

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.

Shock index predicts up to 90-day mortality risk after intracerebral haemorrhage.

BACKGROUND: Shock index (SI - heart rate/systolic blood pressure) has been studied as a measure of haemodynamic status. We aimed to determine whether SI measures within 72 h of admission were associated with adverse outcomes in intracerebral haemorrhage (ICH). METHODS: Patients were drawn from the Virtual International Stroke Trials Archive-Intracerebral Haemorrhage (VISTA-ICH). Multivariable Cox regressions modelled the relationship between SI (on admission, 24, 48, 72 h) and mortality (at 3-, 7-, and 90-days), 90-day incident pneumonia and cardiovascular events (MACE). Ordinal logistic regressions modelled the relationship between SI and 90-day modified Rankin Scale (mRS). RESULTS: 979 patients were included. Baseline SI was not associated with mortality. 24 h SI > 0.7 was associated with 7-day mortality (hazard ratio (95% confidence interval) = 3.14 (1.37-7.19)). 48 h and 72 h SI > 0.7 were associated with 7-day (4.23 (2.07-8.66) and 3.24 (1.41-7.42) respectively) and 90-day mortality (2.97 (1.82-4.85) and 2.05 (1.26-3.61) respectively). SI < 0.5 at baseline, 48 h and 72 h was associated with decreased pneumonia risk. 24 h and 48 h SI > 0.7was associated with increased MACE risk. 48 h and 72 h SI > 0.7 was associated with increased odds of higher 90-day mRS. CONCLUSION: Higher-than-normal SI subsequent to initial encounter was associated with higher post-ICH mortality at 3, 7, and 90 days. Lower-than-normal SI was associated with a decreased risk of incident pneumonia.

An Ecological Study Assessing the Relationship between Public Health Policies and Severity of the COVID-19 Pandemic.

Reliance on government-led policies have heightened during the COVID-19 pandemic. Further research on the policies associated with outcomes other than mortality rates remains warranted. We aimed to determine associations between government public health policies on the severity of the COVID-19 pandemic. This ecological study including countries reporting ≥25 daily COVID-related deaths until end May 2020, utilised public data on policy indicators described by the Blavatnik school of Government. Associations between policy indicators and severity of the pandemic (mean mortality rate, time to peak, peak deaths per 100,000, cumulative deaths after peak per 100,000 and ratio of mean slope of the descending curve to mean slope of the ascending curve) were measured using Spearman rank-order tests. Analyses were stratified for age, income and region. Among 22 countries, containment policies such as school closures appeared effective in younger populations (rs = -0.620, p = 0.042) and debt/contract relief in older populations (rs = -0.743, p = 0.009) when assessing peak deaths per 100,000. In European countries, containment policies were generally associated with good outcomes. In non-European countries, school closures were associated with mostly good outcomes (rs = -0.757, p = 0.049 for mean mortality rate). In high-income countries, health system policies were generally effective, contrasting to low-income countries. Containment policies may be effective in younger populations or in high-income or European countries. Health system policies have been most effective in high-income countries.

Thrombolysis in acute ischaemic stroke patients with chronic kidney disease.

OBJECTIVE: We aimed to determine whether chronic kidney disease (CKD) is associated with adverse in-hospital outcomes after acute ischaemic stroke (AIS) and whether this association is dependent on thrombolysis administration. METHODS: 885,537 records representative of 4,283,086 AIS admissions were extracted from the US National Inpatient Sample (2005-2015) and categorized into 3 mutually exclusive groups: no CKD, CKD without end-stage renal disease (ESRD) and ESRD. Outcomes (mortality, prolonged hospitalisation >4 days and disability on discharge-derived using discharge destination as a proxy) were compared between groups using multivariable logistic regressions. Separate models containing interaction terms with thrombolysis were also computed. RESULTS: The median age (interquartile range) of the cohort was 73 (61-83) years and 47.32% were men. Compared with the no CKD group, both CKD/no ESRD group (odds ratio (99% confidence interval) = 1.04 (1.0003-1.09), p = 0.009) and the ESRD groups (2.06 (1.90-2.25), p < 0.001) had significantly increased odds of in-hospital mortality. Patients with CKD/No ESRD (1.03 (1.02-1.06), p < 0.001) and ESRD (1.44 (1.37-1.51), p < 0.001) were at higher odds of prolonged hospitalisation. Patients with CKD/No ESRD (1.13 (1.10-1.15), p < 0.001) and ESRD (1.34 (1.26-1.41), p < 0.001) were also at higher odds of moderate-to-severe disability on discharge. Interaction terms between thrombolysis and the CKD/ESRD groups were not statistically significant (p > 0.01) for any outcome. CONCLUSIONS: Renal dysfunction was independently associated with worse in-hospital outcomes in the acute phase of AIS. These associations were not influenced by the use of thrombolysis as an emergency treatment for AIS. CKD/ESRD should not represent sole contraindications to thrombolysis for AIS.