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.

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.

Calcium intake, calcium supplementation and cardiovascular disease and mortality in the British population: EPIC-norfolk prospective cohort study and meta-analysis.

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 (< 770 mg/day), intakes between 771 and 926 mg/day (second quintile) and 1074-1254 mg/day (fourth quintile) were associated with reduced all-cause mortality (HR 0.91 (0.83-0.99) and 0.85 (0.77-0.93), respectively) and cardiovascular mortality [HR 0.95 (0.87-1.04) and 0.93 (0.83-1.04)]. Compared to the first quintile of calcium intake, second, third, fourth, but not fifth quintiles were associated with fewer incident strokes: respective HR 0.84 (0.72-0.97), 0.83 (0.71-0.97), 0.78 (0.66-0.92) and 0.95 (0.78-1.15). The meta-analysis results suggest that high levels of calcium intake were associated with decreased all-cause mortality, but not cardiovascular mortality, regardless of average calcium intake. Calcium supplementation was associated with cardiovascular and all-cause mortality amongst women, but not men. Moderate dietary calcium intake may protect against cardiovascular and all-cause mortality and incident stroke. Calcium supplementation may reduce mortality in women.

Distribution, management and outcomes of AMI according to principal diagnosis priority during inpatient admission.

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.

Parkinson's disease and patient related outcomes in stroke: A matched cohort study.

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.

Individual and Combined Impact of Heart Failure and Atrial Fibrillation on Ischemic Stroke Outcomes.

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.

Myocardial infarction after acute ischaemic stroke: Incidence, mortality and risk factors.

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 and 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 10 mmol/L), total leucocyte count (1.25 [1.01-1.54] per 10 × 109 /L) and CRP (1.05 [1.02-1.08] per 10 mg/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 and 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 and 10 years after discharge. Cumulative MI incidence over 10 years was 5.4%. MI during all follow-up periods (discharge-1, 1-5, 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.