Search

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.

Introduction 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 Study inclusion criteria included: (i) any observational/interventional studies of participants aged ≥18 years (ii) which 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-19th 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 (HR/OR), with 95% confidence interval. Results Twenty studies (n = 61669; 47.3% women) were eligible, of which thirteen were included in the meta-analysis (n = 55456; 47.3% women). Median (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 2 studies (HR:1.39, 1.05-1.84) and near doubled odds of stroke/cerebrovascular disease (OR:1.94, 1.52-2.48). Lack of association with other outcomes may be due to weak evidence or low statistical power. Conclusions 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.

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.

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.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.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).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.

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.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 hospitalisation4 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.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.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.

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

Background: Higher anticholinergic burden from medications is associated with increased risk of cardiovascular disease and cognitive function decline. A mechanistic pathway has never been established. We aimed to determine whether chronic inflammation may mediate these associations. Methods: Participants were drawn from the European Prospective Investigation into Cancer, Norfolk cohort (40-79 years at baseline). The anticholinergic cognitive burden score (ACB) was calculated at baseline/first (1HC) (1993/97) and second (2HC) (1998/2000) health checks. Plasma 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 1HC and 2HC, respectively. The prospective association was also examined between 1HC ACB and 2HC inflammatory markers. All models adjusted for age, sex, lifestyle factors, co-morbidities and medications. Results: 17,678 and 22,051 participants were included in cross-sectional analyses for CRP, and fibrinogen, respectively. A total of 5,101 participants with available data for TNF-α and IL-6 were included in the longitudinal analyses. Cross-sectionally, a point increase in the ACB was associated with a significant increase in all inflammatory markers (beta (standard error): fibrinogen – 0.035g/l (0.006), pConclusion: Higher anticholinergic burden was significantly associated with higher inflammatory markers. Inflammation may mediate the relationship between exposure to anticholinergic medications and adverse outcomes

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.

Background/Aims Systemic Lupus Erythematosus (SLE) is a multisystem autoimmune disease with variable presentation and clinical manifestations. Previous research has established the higher risk of incident cardiovascular disease and stroke in SLE patients. However, the evidence on how stroke outcomes differ between SLE and non-SLE patient groups in contemporary practice is limited. Furthermore, given that SLE tends to affect predominantly females, with a female-to-male ratio of 9:1, the question remains if and to what extent stroke outcomes might differ between males and females with SLE. Thus, we aimed to explore sex-specific acute stroke outcomes amongst patients with comorbid SLE. Methods A total of 316,531 records representing 1,581,430 acute stroke hospitalisations between 2015 and 2018 from the United States National Inpatient Sample (NIS) were analysed. The primary exposure of interest was comorbid SLE. Patients were grouped according to SLE status and sex (no SLE-reference, male with SLE, female with SLE). Outcome measures of interest (in-patient mortality, length-of-stay in hospital [LoS] and routine home discharge) were examined utilising multivariable logistic regressions, adjusting for age, ethnicity, stroke type, receipt of revascularisation therapies, region, hospital status and 49 comorbidities including major cardiovascular disease. Results The median (interquartile range) age was 71 (60-82) years. There were 940 (0.06%) males and 6110 (0.39%) females with SLE. After adjustments, female patients with SLE had 21% increased odds of dying in hospital, adjusted odds ratios (aOR) = 1.21, 95% CI (0.92 - 1.61), whereas the risk of in-patient mortality for male patients with SLE was 24% lower compared to the reference group, aOR = 0.76 (0.32 - 1.81). However, none of the differences in the in-patient mortality were of statistical significance. Secondly, compared to patients without SLE, females with SLE had significantly longer hospitalisation, aOR=1.20 (1.06 - 1.36), while there was no significant difference for males with SLE, aOR=1.06 (0.75 - 1.49). The odds of being routinely discharged were 28% lower for females with SLE, aOR=0.72, (0.63 - 0.82), in comparison to a non-significant increase in the odds of 18% for males with SLE, aOR=1.18, (0.84 - 1.65). Conclusion Our results highlight the sex differences in acute stroke outcomes in patients with SLE. Due to a small sample size of males with SLE, our findings need to be cautiously interpreted. Further understanding of the influence of SLE amongst male patients with acute stroke is needed. Disclosure S. Jesenakova: None. T.A. Pana: None. B. Carter: None. M.O. Mohamed: None. M.A. Mamas: None. P.K. Myint: None.

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 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

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

Rationale: Proinflammatory cytokines have been identified as potential targets for lowering vascular risk. Experimental evidence and Mendelian randomization suggest a role of MCP-1 (monocyte chemoattractant protein-1) in atherosclerosis and stroke. However, data from large-scale observational studies are lacking. Objective: To determine whether circulating levels of MCP-1 are associated with risk of incident stroke in the general population. Methods and Results: We used previously unpublished data on 17 180 stroke-free individuals (mean age, 56.7±8.1 years; 48.8% men) from 6 population-based prospective cohort studies and explored associations between baseline circulating MCP-1 levels and risk of any stroke, ischemic stroke, and hemorrhagic stroke during a mean follow-up interval of 16.3 years (280 522 person-years at risk; 1435 incident stroke events). We applied Cox proportional-hazards models and pooled hazard ratios (HRs) using random-effects meta-analyses. After adjustments for age, sex, race, and vascular risk factors, higher MCP-1 levels were associated with increased risk of any stroke (HR per 1-SD increment in ln-transformed MCP-1, 1.07; 95% CI, 1.01–1.14). Focusing on stroke subtypes, we found a significant association between baseline MCP-1 levels and higher risk of ischemic stroke (HR, 1.11 [1.02–1.21]) but not hemorrhagic stroke (HR, 1.02 [0.82–1.29]). The results followed a dose-response pattern with a higher risk of ischemic stroke among individuals in the upper quartiles of MCP-1 levels as compared with the first quartile (HRs, second quartile: 1.19 [1.00–1.42]; third quartile: 1.35 [1.14–1.59]; fourth quartile: 1.38 [1.07–1.77]). There was no indication for heterogeneity across studies, and in a subsample of 4 studies (12 516 individuals), the risk estimates were stable after additional adjustments for circulating levels of IL (interleukin)-6 and high-sensitivity CRP (C-reactive protein). Conclusions: Higher circulating levels of MCP-1 are associated with increased long-term risk of stroke. Our findings along with genetic and experimental evidence suggest that MCP-1 signaling might represent a therapeutic target to lower stroke risk.Visual Overview: An online visual overview is available for this article.

Whilst cancer is a risk factor for acute ischaemic stroke (AIS), its impact on AIS prognosis between metastatic and non-metastatic (MC and NMC) disease is poorly understood. Furthermore, the receipt of intravenous thrombolysis (IVT) and endovascular thrombectomy (ET) and their outcomes is poorly researched. AIS admissions from the National Inpatient Sample (NIS) were included (October 2015–December 2017). Multivariable logistic regressions adjusting for a wide range of confounders analysed the relationship between NMC and MC and AIS in-hospital outcomes (mortality, prolonged hospitalisation &gt, 4 days and routine home discharge). Interaction terms with IVT and ET were also computed to explore their impact amongst cancer patients. A total of 221,249 records representative of 1,106,045 admissions were included. There were 38,855 (3.51%) AIS admissions with co-morbid cancer: NMC = 53.78% and MC = 46.22%. NMC was associated with 23% increased odds of in-hospital mortality (odds ratio (95% confidence interval) = 1.23 (1.07–1.42)), which was mainly driven by pancreatic and respiratory cancers. This association was entirely offset by both IVT and ET. MC was associated with two-fold increased odds of in-hospital mortality (2.16 (1.90–2.45)), which was mainly driven by respiratory, pancreatic and colorectal cancers. This association was only offset by ET. Both NMC and MC were significantly associated with prolonged hospitalisation and decreased odds of routine discharge. Cancer patients are at higher odds of acute adverse outcomes after AIS and warrant robust primary prevention. IVT and ET improve these outcomes and should thus be offered routinely unless otherwise contraindicated in this group of stroke patients.

Background: In recent years, there has been a growing interest in outcomes of patients with acute myocardial infarction (AMI) using large administrative datasets. The present study was designed to compare the characteristics, management strategies and acute outcomes between patients with primary and secondary AMI diagnoses in a national cohort of patients. Methods: All hospitalisations of adults (>= 18 years) with a discharge diagnosis of AMI in the US National Inpatient Sample from January 2004 to September 2015 were included, stratified by primary or secondary AMI. The International Classification of Diseases, ninth revision and Clinical Classification Software codes were used to identify patient comorbidities, procedures and clinical outcomes. Results: A total of 10 864 598 weighted AMI hospitalisations were analysed, of which 7 186 261 (66.1%) were primary AMIs and 3 678 337 (33.9%) were secondary AMI. Patients with primary AMI diagnoses were younger (median 68 vs 74 years, P < .001) and less likely to be female (39.6% vs 48.5%, P < .001). Secondary AMI was associated with lower odds of receipt of coronary angiography (aOR 0.19 ; 95%CI 0.18-0.19) and percutaneous coronary intervention (0.24 ; 0.23-0.24). Secondary AMI was associated with increased odds of MACCE (1.73 ; 1.73-1.74), mortality (1.71 ; 1.70-1.72), major bleeding (1.64 ; 1.62- 1.65), cardiac complications (1.69 ; 1.65-1.73) and stroke (1.68 ; 1.67-1.70) (P < .001 for all). Conclusions: Secondary AMI diagnoses account for one-third of AMI admissions. Patients with secondary AMI are older, less likely to receive invasive care and have worse outcomes than patients with a primary diagnosis code of AMI. Future studies should consider both primary and secondary AMI diagnoses codes in order to accurately inform clinical decision-making and health planning.

Background and PurposeWhilst cancer is a risk factor for acute ischaemic stroke (AIS), its impact on AIS prognosis between metastatic and non-metastatic (MC and NMC) disease is poorly understood. Furthermore, the receipt of intravenous thrombolysis (IVT) and endovascular thrombectomy (ET) and their outcomes is poorly researched.MethodsAIS admissions from the National Inpatient Sample (NIS) were included (October 2015-December 2017). Multivariable logistic regressions adjusting for a wide range of confounders analysed the relationship between NMC and MC and AIS in-hospital outcomes (mortality, prolonged hospitalisation >4 days and routine home discharge). Interaction terms with IVT and ET were also computed to explore their impact amongst cancer patients.Results221,249 records representative of 1,106,045 admissions were included. There were 38,855 (3.51%) patients with co-morbid cancers: NMC=53.78% and MC=46.22%. NMC was associated with 23% increased odds of in-hospital mortality (odds ratio (95% confidence interval) = 1.23 (1.07-1.42)), which was mainly driven by pancreatic and respiratory cancers. This association was entirely offset by both IVT and ET. MC was associated with 2-fold increased odds of in-hospital mortality (2.16 (1.90-2.45)), which was mainly driven by respiratory, pancreatic and colorectal cancers. This association was only offset by ET. Both NMC and MC were significantly associated with prolonged hospitalisation and decreased odds of routine discharge.ConclusionsCancer patients are at higher odds of acute adverse outcomes after AIS and warrant robust primary prevention. IVT and ET improve these outcomes and should thus be offered routinely unless otherwise contraindicated in this group of stroke patients.

Background Atrial fibrillation (AF) and heart failure (HF) carry a poor prognosis in acute ischaemic stroke (AIS). The impact of revascularisation therapies on outcomes in these patients is not fully understood. Method National Inpatient Sample (NIS) AIS admissions (January 2004–September 2015) were included (n = 4,597,428). Logistic regressions analysed the relationship between exposures (neither AF nor HF-reference, AF-only, HF-only, AF + HF) and outcomes (in-hospital mortality, length-of-stay >median and moderate-to-severe disability on discharge), stratifying by receipt of intravenous thrombolysis (IVT) or endovascular thrombectomy (ET). Results 69.2% patients had neither AF nor HF, 16.5% had AF-only, 7.5% had HF-only and 6.7% had AF + HF. 5.04% and 0.72% patients underwent IVT and/or ET, respectively. AF-only and HF-only were each associated with 75–85% increase in the odds of in-hospital mortality. AF + HF was associated with greater than two-fold increase in mortality. Patients with AF-only, HF-only or AF + HF undergoing IVT had better or at least similar in-hospital outcomes compared to their counterparts not undergoing IVT, except for prolonged hospitalisation. Patients undergoing ET with AF-only, HF-only or AF + HF had better (in-hospital mortality, discharge disability, all-cause bleeding) or at least similar (length-of-stay) outcomes to their counterparts not undergoing ET. Compared to AIS patients without AF, AF patients had approximately 50% and more than two-fold increases in the likelihood of receiving IVT or ET, respectively. Conclusions We confirmed the combined and individual impact of co-existing AF or HF on important patient-related outcomes. Revascularisation therapies improve these outcomes significantly in patients with these comorbidities.

Importance: Human genetics and studies in experimental models support a key role of monocyte-chemoattractant protein-1 (MCP-1) in atherosclerosis. Yet, the associations of circulating MCP-1 levels with risk of coronary heart disease and cardiovascular death in the general population remain largely unexplored. Objective: To explore whether circulating levels of MCP-1 are associated with risk of incident coronary heart disease, myocardial infarction, and cardiovascular mortality in the general population. Data Sources and Selection: Population-based cohort studies, identified through a systematic review, that have examined associations of circulating MCP-1 levels with cardiovascular end points. Data Extraction and Synthesis: Using a prespecified harmonized analysis plan, study-specific summary data were obtained from Cox regression models after excluding individuals with overt cardiovascular disease at baseline. Derived hazard ratios (HRs) were synthesized using random-effects meta-analyses. Main Outcomes and Measures: Incident coronary heart disease (myocardial infarction, coronary revascularization, and unstable angina), nonfatal myocardial infarction, and cardiovascular death (from cardiac or cerebrovascular causes). Results: The meta-analysis included 7 cohort studies involving 21401 individuals (mean [SD] age, 53.7 [10.2] years; 10012 men [46.8%]). Mean (SD) follow-up was 15.3 (4.5) years (326392 person-years at risk). In models adjusting for age, sex, and race/ethnicity, higher MCP-1 levels at baseline were associated with increased risk of coronary heart disease (HR per 1-SD increment in MCP-1 levels: 1.06 [95% CI, 1.01-1.11]; P =.01), nonfatal myocardial infarction (HR, 1.07 [95% CI, 1.01-1.13]; P =.02), and cardiovascular death (HR, 1.12 [95% CI, 1.05-1.20]; P

The role of dietary calcium in cardiovascular disease prevention is unclear. We aimed to determine the association between calcium intake and incident cardiovascular disease and mortality. Data were extracted from the European Prospective Investigation of Cancer, Norfolk (EPIC-Norfolk). Multivariable Cox regressions analysed associations between calcium intake (dietary and supplemental) and cardiovascular disease (myocardial infarction, stroke, heart failure, aortic stenosis, peripheral vascular disease) and mortality (cardiovascular and all-cause). The results of this study were pooled with those from published prospective cohort studies in a meta-analsyis, stratifying by average calcium intake using a 700 mg/day threshold. A total of 17,968 participants aged 40–79 years were followed up for a median of 20.36 years (20.32–20.38). Compared to the first quintile of calcium intake (

Introduction: Left Ventricular Assist Devices (LVAD) decrease cardiac mechanical work and metabolic demand and may decrease cardiomyocyte oxidative stress, followed by cell cycle re-entry and cell regeneration. We tested whether LVAD long-term support is associated with myocardial regeneration. Methods: Viability fluorodeoxyglucose (18FDG) - positron-emission tomography scans were performed >3 months after LVAD implantation and every 6 months thereafter. 4 patients aged 18-70 with end-stage non-ischemic (NICM, n=3) or ischemic cardiomyopathy (ICM, n=1) were included. Low metabolic activity myocardial regions of interest (ROI) at Results: LV ejection fraction ranged 0-35% at baseline. Two patients (LVAD speed 2660 rotations per minute - RPM, output 3.4-4.1 and 5.6-5.9 liters per minute (LPM), respectively) underwent 2 scans before cardiac transplantation, exhibiting borderline increased global signal (1-4%) and significantly increased 18FDG signal in the baseline low-intensity ROI on the follow-up scan (67.7, 75.7%). The other 2 patients (LVAD parameters: 5600 RPM/ 4.6-5.8 LPM; 9200 RPM/ 4.3-4.8 LPM) exhibited decreased global 18FDG signal (10-16%) and increased signal in the co-registered baseline low-intensity ROIs (1.7-21.5%) (Figure). Conclusions: LVAD long-term support is associated with a global decrease in myocardial 18FDG uptake signal over time, and with increased viability signal in baseline low-intensity ROIs, suggestive of myocardial regeneration in metabolically inactive regions. Future research is required to identify patient subgroups that are most likely to exhibit high regeneration potential upon long-term LVAD support.

Objective To evaluate post-stroke outcomes in patients with Parkinson's disease (PD). Methods A matched cohort study was performed. Stroke patients with PD and non-PD controls were extracted from the Thailand Universal Insurance Database. Logistic regressions were used to evaluate the association between PD and in-hospital outcomes (mortality and complications). The PD-associated long-term mortality was evaluated using Royston-Parmar models. Results A total of 1967 patients with PD were identified between 2003 and 2015 and matched to controls (1:4) by age, sex, admission year, and stroke type. PD patients had decreased odds of in-hospital death: OR (95% CI) 0.66 (0.52 – 0.84) and 0.61 (0.43 – 0.85) after ischaemic and haemorrhagic strokes, respectively. PD was associated with a length-of-stay greater than median (4 days) after both stroke types: 1.37 (1.21 – 1.56) and 1.45 (1.05 – 2.00), respectively. Ischaemic stroke patients with PD also had increased odds of developing pneumonia, sepsis and AKI: 1.52 (1.2 – 1.83), 1.54 (1.16 – 2.05), and 1.33 (1.02 – 1.73). In haemorrhagic stroke patients, PD was associated with pneumonia: 1.89 (1.31 – 2.72). Survival analyses showed that PD was protective against death in the short term (HR=0.66; 95% CI 0.53–0.83 ischaemic, and HR=0.50; 95% CI 0.37 – 0.68 haemorrhagic stroke), but leads to an increased mortality risk approximately 1 and 3 months after ischaemic and haemorrhagic stroke, respectively. Conclusion PD is associated with a reduced mortality risk during the first 2–4 weeks post-admission but an increased risk thereafter, in addition to increased odds of in-hospital complications and prolonged hospitalisation.

Background: Patients with diabetes mellitus (DM) have been found to be at an increased risk of suffering a stroke. However, research on the impact of DM on stroke outcomes is limited. Objectives: We aimed to examine the influence of DM on outcomes in ischaemic (IS) and haemorrhagic stroke (HS) patients. Methods: We included 608,890 consecutive stroke patients from the Thailand national insurance registry. In-hospital mortality, sepsis, pneumonia, acute kidney injury (AKI), urinary tract infection (UTI) and cardiovascular events were evaluated using logistic regressions. Long-term analysis was performed on first-stroke patients with a determined pathology (n = 398,663) using Royston-Parmar models. Median follow-ups were 4.21 and 4.78 years for IS and HS, respectively. All analyses were stratified by stroke sub-type. Results: Mean age (SD) was 64.3 (13.7) years, 44.9% were female with 61% IS, 28% HS and 11% undetermined strokes. DM was associated with in-hospital death, pneumonia, sepsis, AKI and cardiovascular events (odds ratios ranging from 1.13-1.78, p < 0.01) in both stroke types. In IS, DM was associated with long-term mortality and recurrence throughout the follow-up: HRmax (99% CI) at t = 4108 days: 1.54 (1.27, 1.86) and HR (99% CI) = 1.27(1.23,1.32), respectively. In HS, HRmax (t = 4108 days) for long-term mortality was 2.10 (1.87, 2.37), significant after day 14 post-discharge. HRmax (t = 455) for long-term recurrence of HS was 1.29 (1.09, 1.53), significant after day 116 post-discharge. Conclusions: Regardless of stroke type, DM was associated with in-hospital death and complications, long-term mortality and stroke recurrence.

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).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).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.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.

Background: The COVID-19 pandemic has claimed almost half a million deaths worldwide. Reliance on government-led policies have been heightened during the pandemic to mitigate the spread of disease. Which of these policies are associated with important outcomes other than mortality rates remains unknown. Hence, we aimed to determine the associations between government public health policies on the severity of the COVID-19 pandemic. Methods: This ecological study utilised publicly accessible data on seventeen policy indicators of Containment, Economic and Health systems and their respective Stringency Index described by the Blavatnik school of Government. Countries reporting >25 daily COVID-related deaths until end May 2020 were included. We assessed the association of individual SI with the profile of severity of COVID-19 by using several outcomes; mean mortality rate, time to peak, peak deaths per 100,000 population, cumulative deaths after peak per 100,000 population and ratio of the mean slope of the descending curve to the mean slope of the ascending curve. Analyses were stratified according to age, income and region. Spearman rank-order tests were employed to measure associations. Results were presented descriptively and direct comparisons were made. Findings: Twenty-two countries were included. Containment policies appeared more effective in younger populations and debt/contract relief in older populations. In European countries, containment policies were generally associated with good outcomes. In non-European countries, school closures alone had the strongest association with most of the outcomes examined. In high-income countries, health system policies such as public information campaigns and testing were generally effective, in contrast to low-income countries. Interpretation: Containment policies may be effective when targeted towards younger populations and occur in high-income or European countries. Health system policies have not been as effective in low-income and non-European countries. Funding Statement: None. Declaration of Interests: None. Ethics Approval Statement: Due to the ecological study design and the use of publicly accessible data, ethical approval was not required.

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

As one of the fastest growing portions of the population, nonagenarians will constitute a significant percentage of the stroke patient population in the near future. Nonagenarians are nevertheless not specifically targeted by most clinical guidelines. In this review, we aimed to summarise the available evidence guiding stroke prevention and treatment in this age group. Several recent observational studies have shown that the benefits of anticoagulation for the oldest old patients with atrial fibrillation may outweigh the bleeding risk. A sub-analysis of the IST-3 trial has shown for the first time that thrombolysis treatment in acute ischaemic stroke may be beneficial and safe even in octogenarian patients and older. Several recent observational studies have assessed thrombolysis in nonagenarians. The latest of these has shown better disability outcomes without increased rates of symptomatic intracerebral haemorrhage with thrombolysis. Nonagenarian stroke patients may benefit from similar preventative and therapeutic strategies as their younger counterparts. A few important exceptions include primary prevention using aspirin or statins. Patient selection is nevertheless essential given the increased adverse event rates. Patient preference should play a key role in the decision-making process. Clinical trials including more nonagenarian patients are required to yield more robust evidence.

Objectives: To determine the risk factor profiles associated with post-acute ischaemic stroke (AIS) myocardial infarction (MI) over long-term follow-up. Methods: This observational study includes prospectively identified AIS patients (n=9840) admitted to a UK regional centre between January 2003-December 2016 (median follow-up: 4.72 years). Predictors of post-stroke MI during follow up were examined using logistic and Cox regression models for in-hospital and post-discharge events, respectively. MI incidence was determined using a competing risk non-parametric estimator. The influence of post-stroke MI on mortality was examined using Cox regressions. Results: Mean age (SD) of study participants was 77.3(12.2) years (48% males). Factors associated with in-hospital MI (OR(95%CI)) were increasing blood glucose (1.80(1.17-2.77) per 10mmol/L), total leukocyte count (1.25(1.01-1.54) per 10x109/L), and CRP (1.05(1.02-1.08) per 10mg/L increase). Age (HR(95%CI) =1.03(1.01-1.06)), coronary heart disease (1.59(1.01-2.50)), chronic kidney disease (2.58(1.44-4.63)), and cancers (1.76(1.08-2.89)) were associated with incident MI between discharge and one year follow-up. Age ((1.02(1.00-1.03)), diabetes (1.96(1.38-2.65)), congestive heart failure (2.07(1.44-2.99), coronary heart disease (1.81(1.31-2.50)), hypertension (1.86(1.24-2.79)), and peripheral vascular disease (2.25(1.40-3.63)) were associated with incident MI between 1-5 years after discharge. Diabetes (2.01(1.09-3.72)), hypertension (3.69(1.44-9.45)), and peripheral vascular disease (2.46(1.02-5.98)) were associated with incident MI between 5-10 years after discharge. Cumulative MI incidence over 10 years was 5.4%. MI during all follow-up periods (discharge-1 year, 1-5 years, 5-10 years) was associated with increased risk of death (respective HR(95%CI)=3.26(2.51-4.15), 1.96(1.58-2.42) and 1.92(1.26-2.93)). Conclusions: In conclusion, prognosis is poor in post-stroke MI. We highlight a range of potential areas to focus preventative efforts.

ObjectiveWe aimed to examine the impact of heart failure (HF) on stroke mortality (in-hospital and postdischarge) and recurrence in a national stroke cohort from Thailand.MethodsWe used a large, insurance-based database including all stroke admissions in the public health sector in Thailand between 2004 and 2015. Logistic and Royston-Parmar regressions were used to quantify the effect of HF on in-hospital and long-term outcomes, respectively. All models were adjusted for age, sex and comorbidities and stratified by stroke type: acute ischaemic stroke (AIS) or intracerebral haemorrhage (ICH). Multistate models were constructed using flexible survival techniques to predict the impact of HF on the disease course of a patient with stroke (baseline-[recurrence]-death). Only first-ever cases of AIS or ICH were included in the multistate analysis.Results608 890 patients (mean age 64.29±13.72 years, 55.07% men) were hospitalised (370 527 AIS, 173 236 ICH and 65 127 undetermined pathology). There were 398 663 patients with first-ever AIS and ICH. Patients were followed up for a median (95% CI) of 4.47 years (4.45 to 4.49). HF was associated with an increase in postdischarge mortality in AIS (HR [99% CI] 1.69 [1.64 to 1.74]) and ICH (2.59 [2.07 to 3.26]). HF was not associated with AIS recurrence, while ICH recurrence was only significantly increased within the first 3 years after discharge (1.79 [1.18 to 2.73]).ConclusionsHF increases the risk of mortality in both AIS and ICH. We are the first to report on high-risk periods of stroke recurrence in patients with HF with ICH. Specific targeted risk reduction strategies may have significant clinical impact for mortality and recurrence in stroke.