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We examined the relative associations of aortic and carotid artery stiffness with cerebrovascular disease (CeVD), cognition, and dementia subtypes in a memory clinic cohort of 272 participants (mean age = 75.4, SD = 6.8). We hypothesized that carotid artery stiffness would have greater effects on outcomes, given its proximate relationship to the brain. Aortic and carotid artery stiffness were assessed with applanation tonometry and carotid ultrasonography, respectively. CeVD markers included white matter hyperintensities (WMH), lacunes, cerebral microbleeds, cortical infarcts, and intracranial stenosis. Cognition was assessed by the Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and a neuropsychological battery. Multivariable linear regression was conducted to determine associations of arterial stiffness with WMH and cognition, while logistic regression analysed associations with CeVD markers and dementia subtypes. Carotid artery stiffness z-score was associated with WMH, cortical infarcts, vascular cognitive impairment, and MMSE, independent of age, sex, education, vascular risk factors, and aortic stiffness z-score. Although aortic stiffness z-score was independently associated with cortical infarcts, this became non-significant after further adjusting for carotid artery stiffness z-score. We found that carotid artery stiffness had greater effects on CeVD, cognitive function and impairment in memory clinic patients compared to aortic stiffness. [ABSTRACT FROM AUTHOR]

Background: Carotid artery stiffness is associated with cognitive impairment and dementia, however, the underlying mechanism remains unknown. We examined the association of carotid artery stiffness with cerebral small vessel disease (CSVD) markers, cognitive impairment, dementia with its subtypes, as well as cognitive performance. Method: In this case‐control study, 272 subjects from a memory clinic underwent physical and medical evaluation along with carotid ultrasonography, 3T brain magnetic resonance imaging and detailed neuropsychological assessment. Carotid ultrasonography was conducted to assess arterial compliance (AC), pressure‐strain elastic modulus (Ep), β‐index, augmentation index (AI), and pulse wave velocity‐β (PWV‐β). Brain MRIs were graded for white matter hyperintensities (WMH), lacunes, and cerebral microbleeds (CMBs). Participants were classified as no cognitive impairment, cognitive impairment no dementia, as well as dementia and its subtypes; Alzheimer's disease (AD) and vascular dementia (VaD). Cognition was assessed using NINDS–Canadian Stroke Network harmonization neuropsychological battery. Result: Increased carotid β‐index (β = 0.73, P<0.001), Ep (β = 0.86, P<0.001), and PWV‐β (β = 0.83, P<0.001) were independently associated with WMH. Ep (OR = 1.42, 95%CI = 1.05–1.93), and PWV‐β (OR = 1.43, 95%CI = 1.05–1.94) were associated with presence of lacunes. Ep was associated with AD (OR = 1.59, 95%CI = 1.01‐2.73) and VaD (OR = 2.23, 95%CI = 1.04‐5.94). Additionally, PWV‐β was associated with VaD (OR = 2.24, 95%CI = 1.07–5.62). All carotid artery stiffness measurements, except AI, were associated with worse performance in global cognition, visuomotor speed and memory after adjusting for age, sex, education, hypertension, diabetes, hyperlipidaemia, cardiovascular disease, and smoking. These associations became attenuated but remained significant with global cognition after adjusting for CSVD markers (β‐index; β = ‐0.27, P = 0.04), Ep; β = ‐0.30, P = 0.03), and PWV‐β; β = ‐0.32, P = 0.02). Conclusion: Carotid artery stiffening is associated with WMH, lacunes, and etiologic subtypes of dementia. Carotid artery stiffening is also associated with global cognition independent of CSVD. Elevated carotid artery stiffness may help identify patients at risk for developing CSVD and dementia. [ABSTRACT FROM AUTHOR]

Introduction: The prognostic utility of plasma proteomics for cognitive decline and dementia in a Southeast Asian population characterized by high cerebrovascular disease (CeVD) burden is underexplored., Methods: We examined this in a Singaporean memory clinic cohort of 528 subjects (n = 300, CeVD; n = 167, incident cognitive decline) followed-up for 4 years., Results: Of 1441 plasma proteins surveyed, a 12-protein signature significantly predicted cognitive decline (q-value < .05). Sixteen diverse biological processes were implicated in cognitive decline. Ten proteins independently predicted incident dementia (q-value < .05). A unified prediction model combining plasma proteins with clinical risk factors increased the area under the curve for outcome prediction from 0.62 to 0.85. External validation in the cerebrospinal fluid proteome of an independent Caucasian cohort replicated four of the significantly predictive plasma markers for cognitive decline namely: GFAP, NEFL, AREG, and PPY., Discussion: The prognostic proteins prioritized in our study provide robust signals in two different biological matrices, representing potential mechanistic targets for dementia and cognitive decline., Highlights: A total of 1441 plasma proteins were profiled in a Singaporean memory clinic cohort. We report prognostic plasma protein signatures for cognitive decline and dementia. External validation was performed in the cerebrospinal fluid proteome of a Caucasian cohort. A concordant proteomic signature was identified across both biofluids and cohorts. Further studies are needed to explore the therapeutic implications of these proteins for dementia., (© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: Clinical assessment in emergency departments (EDs) for possible acute myocardial infarction (AMI) requires at least one cardiac troponin (cTn) blood test. The turn-around time from blood draw to posting results in the clinical portal for central laboratory analysers is ~1-2 hours. New generation, high-sensitivity, point-of-care cardiac troponin I (POC-cTnI) assays use whole blood on a bedside (or near bedside) analyser that provides a rapid (8 min) result. This may expedite clinical decision-making and reduce length of stay. Our purpose is to determine if utilisation of a POC-cTnI testing reduces ED length of stay. We also aim to establish an optimised implementation process for the amended clinical pathway., Methods and Analysis: This quality improvement initiative has a pragmatic multihospital stepped-wedge cross-sectional cluster randomised design. Consecutive patients presenting to the ED with symptoms suggestive of possible AMI and having a cTn test will be included. Clusters (comprising one or two hospitals each) will change from their usual-care pathway to an amended pathway using POC-cTnI-the 'intervention'. The dates of change will be randomised. Changes occur at 1 month intervals, with a minimum 2 month 'run-in' period. The intervention pathway will use a POC-cTnI measurement as an alternate to the laboratory-based cTn measurement. Clinical decision-making steps and logic will otherwise remain unchanged. The POC-cTnI is the Siemens (Erlangen Germany) Atellica VTLi high-sensitivity cTnI assay. The primary outcome is ED length of stay. The safety outcome is cardiac death or AMI within 30 days for patients discharged directly from the ED., Ethics and Dissemination: Ethics approval has been granted by the New Zealand Southern Health and Disability Ethics Committee, reference 21/STH/9. Results will be published in a peer-reviewed journal. Lay and academic presentations will be made. Māori-specific results will be disseminated to Māori stakeholders., Trial Registration Number: ACTRN12619001189112., Competing Interests: Competing interests: Siemens Healthcare had no part in the writing of the protocol, and will play no part in the data analysis, interpretation or writing of manuscripts. JWP reports consultancy with Upstream, Luminoma, Siemens Healthineers, Quidel Corporation and Radiometer Health. NM has received honoraria from Abbott Diagnostics, Roche Diagnostics, Siemens Healthineers and LumiraDx and the University of Edinburgh have received research grants from Siemens Healthineers and Abbott Diagnostics unrelated to this work. LC has received honoraria/speakers’ fees from Abbott Diagnostics, Beckman Coulter and Siemens Healthineers, and institutional research grants from Siemens Healthineers, Beckman Coulter and Abbott Diagnostics unrelated to this work. ASJ reports work with all major diagnostic companies. FP reports research grants with Brainbox, Quidel; Consultancies with Abbott, Brainbox, Instrument Labs, Janssen, Osler, Roche, Siemens, Spinchip, Vifor; Stock/Ownership Interests with AseptiScope, Brainbox, Braincheck, Coagulo, Comprehensive Research Associates LLC, Comprehensive Research Management, Emergencies in Medicine LLC, Fast, Forrest Devices, Ischemia DX LLC, Lucia, Prevencio, RCE Technologies, ROMTech, ScPharma, Trivirum, Upstream. MT has received honoraria and research funding from Abbott, Alere, Beckman, QuidelOrtho, Radiometer, Roche and Siemens., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The relationship of serial NT-proBNP (N-terminal pro-B-type natriuretic peptide) measurements with changes in cardiac features and outcomes in heart failure (HF) remains incompletely understood. We determined whether common clinical covariates impact these relationships., Methods and Results: In 2 nationwide observational populations with HF, the relationship of serial NT-proBNP measurements with serial echocardiographic parameters and outcomes was analyzed, further stratified by HF with reduced versus preserved left ventricular ejection fraction, inpatient versus outpatient enrollment, age, obesity, chronic kidney disease, atrial fibrillation, and attainment of ≥50% guideline-recommended doses of renin-angiotensin system inhibitors and β-blockers. Among 1911 patients (mean±SD age, 65.1±13.4 years; 26.6% women; 62% inpatient and 38% outpatient), NT-proBNP declined overall, with more rapid declines among inpatients, those with obesity, those with atrial fibrillation, and those attaining ≥50% guideline-recommended doses. Each doubling of NT-proBNP was associated with increases in left ventricular volume (by 6.1 mL), E/e' (transmitral to mitral annular early diastolic velocity ratio) (by 1.4 points), left atrial volume (by 3.6 mL), and reduced left ventricular ejection fraction (by -2.1%). The effect sizes of these associations were lower among patients with HF with preserved ejection fraction, atrial fibrillation, or advanced age ( P interaction <0.001). A landmark analysis identified that an SD increase in NT-proBNP over 6 months was associated with a 27% increase in the risk of the composite event of HF hospitalization or all-cause death between 6 months and 2 years (adjusted hazard ratio, 1.27 [95% CI, 1.15-1.40]; P <0.001)., Conclusions: The relationships between NT-proBNP and structural/functional remodeling differed by age, presence of atrial fibrillation, and HF phenotypes. The association of increased NT-proBNP with increased risk of adverse outcomes was consistent in all subgroups.

Aims: In acute coronary syndrome (ACS) patients without advanced renal dysfunction [estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2], early (within 24 h of admission) angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) is the guideline-directed medical therapy. The clinical efficacy of early ACEI/ARB therapy among ACS patients with advanced renal dysfunction remains unclear., Methods and Results: Among 184 850 ACS patients hospitalized from July 2014 to December 2018 in the Chinese National Electronic Disease Surveillance System Platform (CNEDSSP) cohort and 113 650 ACS patients enrolled from November 2014 to December 2019 in the Improving Care for Cardiovascular Disease in China-ACS Project (CCC-ACS) cohort, we identified 3288 and 3916 ACS patients with admission eGFR < 30 mL/min/1.73 m2 [2647 patients treated with ACEI/ARB (36.7%)], respectively. After 1:1 propensity score matching (PSM) in each cohort, Kaplan-Meier analysis showed that early ACEI/ARB use was associated with a 39% [hazard ratio (HR): 0.61, 95% confidence interval (95% CI): 0.45-0.82] and a 34% (HR: 0.66, 95% CI: 0.46-0.95) reduction in in-hospital mortality in CNEDSSP and CCC-ACS cohorts, respectively, which was consistent in multiple sensitivity analyses. A random effect meta-analysis of the two cohorts after PSM revealed a 32% reduction (risk ratio: 0.68, 95% CI: 0.55-0.84) in in-hospital mortality among ACEI/ARB users., Conclusions: Based on two nationwide cohorts in China in contemporary practice, we demonstrated that ACEI/ARB therapy initiated within 24 h of admission is associated with a reduction in in-hospital mortality in ACS patients with advanced renal dysfunction., Clinical Trial Registration: CCC-ACS project was registered at URL: https://www.clinicaltrials.gov. (Unique identifier: NCT02306616)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

This chapter describes an epitope-directed approach to generate antipeptide monoclonal antibodies to multiple nonoverlapping protein sites using a cocktail of fusion peptides as immunogen. It provides a step-by-step protocol on how antigenic peptides on a target protein can be identified by in silico prediction and discusses considerations for final peptide selection. Each antigenic peptide (10-20 amino acids long) is displayed as three-copy inserts on the surface exposed loop of a thioredoxin scaffold protein. The corresponding DNA coding sequence specifying the tripeptide insert flanked by Gly-Ser-Gly-Ser-Gly linkers is cloned in-frame into the Rsr II site of the thioredoxin gene in the pET-32a vector. The presence of a C-terminal polyhistidine tag (His 6 -tag) allows the soluble fusion proteins to be purified by one-step native immobilized metal affinity chromatography (IMAC) to greater than 95% purity. Multiple thioredoxin fusion proteins are mixed in equimolar concentrations and used as an immunogen cocktail for animal immunization. The use of short antigenic peptides of known sequence facilitates direct epitope mapping requiring only small mutagenesis scan peptide libraries in the multipin peptide format., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)