Publications by authors named "Cc Lang"

Background: Prior studies have demonstrated an association between retinal vascular features and cardiovascular disease (CVD), however most studies have only evaluated a few simple parameters at a time. Our aim was to determine whether a deep-learning artificial intelligence (AI) model could be used to predict CVD outcomes from routinely obtained diabetic retinal screening photographs and to compare its performance to a traditional clinical CVD risk score.

Methods: We included 6127 individuals with type 2 diabetes without myocardial infarction or stroke prior to study entry.

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Aims: Iron deficiency (ID) is highly prevalent in patients with heart failure (HF) and associated with morbidity and poor prognosis, but pathophysiological mechanisms are unknown. We aimed to identify novel biological pathways affected by ID.

Methods And Results: We studied 881 patients with HF from the BIOSTAT-CHF cohort.

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Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a public health threat as it affects approximately 38% of the adult population worldwide, with its prevalence rising in step with that of obesity and type 2 diabetes. Beyond the implications of MASLD for liver health, it is also associated with cardiovascular and vascular dysfunction. Although the many shared risk factors and common metabolic milieu might indicate that cardiovascular disease and MASLD are discrete outcomes from common systemic pathogeneses, a growing body of evidence has identified a potential causal relationship between MASLD and coronary artery disease, which is the leading cause of morbidity and mortality in people with MASLD and all-cause mortality worldwide.

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Background: We evaluated the potential of circulating bone morphogenetic protein 10 (BMP10) as a biomarker for atrial stress and remodelling in patients with heart failure (HF), in comparison to N-terminal pro-B-type natriuretic peptide (NT-proBNP). We also assessed the predictive value of BMP10 for adverse clinical outcomes.

Methods: BMP10 levels were quantified in 2085 chronic HF patients from the European BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) cohort and in 1487 patients from the Scottish validation cohort.

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  • Dilated cardiomyopathy (DCM) is a major cause of heart failure, and this study analyzes genetic factors by examining 14,256 DCM cases and 36,203 participants from the UK Biobank for related traits.
  • Researchers discovered 80 genomic risk loci and pinpointed 62 potential effector genes tied to DCM, including some linked to rare variants.
  • The study uses advanced transcriptomics to explore how cellular functions contribute to DCM, showing that polygenic scores can help predict the disease in the general population and emphasize the importance of genetic testing and development of precise treatments.
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Importance: Aortic stenosis (AS) and coronary artery disease (CAD) frequently coexist. However, it is unknown which genetic and cardiovascular risk factors might be AS-specific and which could be shared between AS and CAD.

Objective: To identify genetic risk loci and cardiovascular risk factors with AS-specific associations.

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Importance: Development of myocardial fibrosis in patients with aortic stenosis precedes left ventricular decompensation and is associated with an adverse long-term prognosis.

Objective: To investigate whether early valve intervention reduced the incidence of all-cause death or unplanned aortic stenosis-related hospitalization in asymptomatic patients with severe aortic stenosis and myocardial fibrosis.

Design, Setting, And Participants: This prospective, randomized, open-label, masked end point trial was conducted between August 2017 and October 2022 at 24 cardiac centers across the UK and Australia.

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  • Atopic dermatitis (AD) causes significant skin issues and itching, greatly affecting people's quality of life, yet many treatment needs remain unmet.
  • A study involving 98 patients from Austria and Switzerland highlighted that most had moderate to severe AD and experienced issues like pruritus and multiple flares, with many reporting negative effects on sleep and mental health.
  • The findings emphasize the ongoing challenges in AD management, including delays in diagnosis and the need for more effective therapies to enhance patient well-being.*
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  • A study aimed to improve the identification of patients with type 2 diabetes (T2D) who are at risk for major cardiovascular events by combining clinical risk scores with a genetic coronary heart disease (CHD) polygenic risk score (PRS).
  • The research involved analyzing data from 10,556 T2D individuals aged 40-79, finding that the CHD PRS could significantly enhance risk prediction for major adverse cardiovascular events (MACE), especially among those initially classified at low risk.
  • The results indicated that using the CHD PRS alongside traditional clinical risk assessments provided better forecasting of cardiovascular risks, potentially allowing for more tailored treatment strategies.
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  • Chronic kidney disease (CKD) is common in heart failure patients and affects their health outcomes.
  • The study looked at 478 heart failure patients to see how CKD impacts them differently based on two types of heart failure: HFrEF and HFpEF.
  • Both types of heart failure had similar risks of death or hospital visits due to heart issues, and CKD affected them in ways that weren't too different, even though their overall health profiles varied.
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  • Semaglutide, a GLP-1 receptor agonist used for weight loss, may lower the risk of serious cardiovascular issues in individuals with obesity, but its specific effects on those with pre-existing heart conditions, like atherosclerotic cardiovascular disease and heart failure, were unclear.
  • The SELECT trial, a comprehensive study involving adult participants with cardiovascular disease and high BMI, examined the impact of weekly injections of semaglutide versus placebo on heart-related outcomes, particularly focusing on those with varying types of heart failure.
  • Researchers looked for differences in cardiovascular events, analyzing data to see if treatment efficacy and safety were affected by heart failure type and participants’ initial health characteristics.
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  • The study examined heart failure patients with initially low ejection fractions who later showed improvement, identifying about 20% of these individuals achieving a significant increase in heart function after 9 months.* -
  • Patients with improved ejection fraction experienced lower rates of rehospitalization and mortality compared to those with persistently low function, with consistent results found in two separate patient registries.* -
  • Five key predictors for improvement were identified: female sex, absence of ischemic heart disease, higher initial ejection fraction, and smaller heart sizes, allowing the development of a predictive model to better assess who may improve.*
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  • * Key discussions included the prevalence of AD, advancements in treatment and management, and the importance of considering environmental and lifestyle factors affecting patients.
  • * The forum emphasizes the need for increased awareness and collaboration among stakeholders to close the gap between research advancements and practical applications in patient care.
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  • The study investigates the role of interleukin-17 (IL-17) in heart failure (HF), noting that high IL-17 levels correlate with more severe HF in patients.
  • Elevated IL-17 concentrations are associated with increased hospitalizations and higher mortality rates, along with changes in several inflammatory proteins and pathways.
  • The findings suggest that IL-17 could be a potential target for addressing inflammation in heart failure patients.
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Background And Aims: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have beneficial effects in heart failure (HF), including reverse remodelling, but the mechanisms by which these benefits are conferred are unclear. Inflammation is implicated in the pathophysiology of heart failure (HF) and there are some pre-clinical data suggesting that SGLT2 inhibitors may reduce inflammation. There is however a lack of clinical data.

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Objective: Obesity increases deposition of extracellular matrix (ECM) components of cardiac tissue. Since obesity aggregates with insulin resistance and heart disease, it is imperative to determine whether the increased ECM deposition contributes to this disease cluster. The hypotheses tested in this study were that in cardiac tissue of obese mice i) increased deposition of ECM components (collagens and hyaluronan) contributes to cardiac insulin resistance and that a reduction in these components improves cardiac insulin action and ii) reducing excess collagens and hyaluronan mitigates obesity-associated cardiac dysfunction.

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Aims: Transthoracic echocardiography is recommended in all patients with acute coronary syndrome but is time-consuming and lacks an evidence base. We aimed to assess the feasibility, diagnostic accuracy, and time efficiency of hand-held echocardiography in patients with acute coronary syndrome and describe the impact of echocardiography on clinical management in this setting.

Methods And Results: Patients with acute coronary syndrome underwent both hand-held and transthoracic echocardiographies with agreement between key imaging parameters assessed using kappa statistics.

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Background: Intralymphatic immunotherapy (ILIT) represents a promising novel approach treating allergic diseases. However, no standardized procedures or recommendations have been established or reported, despite the recognized fact that treatment efficacy relies on the ability to inject the allergen intranodally.

Objective: We aim to provide a critical appraisal of ILIT as a method of allergen immunotherapy and to deliver practical recommendations for accurate ILIT.

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Aims: Electronic health records (EHR) linked to Digital Imaging and Communications in Medicine (DICOM), biological specimens, and deep learning (DL) algorithms could potentially improve patient care through automated case detection and surveillance. We hypothesized that by applying keyword searches to routinely stored EHR, in conjunction with AI-powered automated reading of DICOM echocardiography images and analysing biomarkers from routinely stored plasma samples, we were able to identify heart failure (HF) patients.

Methods And Results: We used EHR data between 1993 and 2021 from Tayside and Fife (~20% of the Scottish population).

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Aging is a major driving force for many diseases but the relationship between chronological age, the aging process and age-related diseases is not fully understood. Fragmentation and loss of ultra-long-lived elastin are key features in aging and several age-related diseases leading to increased mortality. By comparing the relationship between age and elastin turnover with healthy volunteers, we show that accelerated elastin turnover by age-disease interaction is a common feature of age-related diseases.

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Background: Mitral regurgitation (MR) frequently coexists with heart failure (HF).

Objectives: To better understand potential pathophysiological differences between patients with HF with or without moderate-severe MR, we compared differentially expressed circulating biomarkers between these two groups.

Methods: The Olink Proteomics® Multiplex Cardiovascular (CVD) -II, CVD-III, Immune Response and Oncology-II panels of 363 unique proteins from different pathophysiological domains were used to investigate the biomarker profiles of HF patients from index and validation cohorts of the BIOSTAT-CHF study stratified according to the presence of moderate-to-severe MR or no-mild MR.

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  • Concerns about allergic reactions to dental materials are increasing among patients, prompting a need to analyze current sensitization patterns.
  • A study of 2730 patients revealed that women, particularly those over 40, showed the highest sensitization rates to metals like nickel and palladium, as well as to (meth)acrylates.
  • The findings suggest that patch testing for contact allergies should also include (meth)acrylates and natural substances like propolis, rather than focusing solely on metals.
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Increased deposition of extracellular matrix (ECM) components such as collagens and hyaluronan contributes to the pathogenesis of obesity-associated insulin resistance in muscle, liver, and adipose tissue. Despite the significance of the heart in cardiovascular and metabolic diseases, maladaptive ECM remodelling in obesity-associated cardiac insulin resistance and cardiac dysfunction has not been studied. Using genetic and pharmacological approaches in mice fed a high fat (HF) diet, we demonstrated a tight association between increased ECM deposition with cardiac insulin resistance.

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  • Major advances in heart failure treatment haven't significantly reduced mortality, indicating that current therapies might be missing key biological pathways.
  • A study integrated genetic and molecular data from over 2,500 heart failure patients to identify critical pathways linked to mortality, validating the results with a separate group of nearly 1,800 patients.
  • Four major pathways associated with higher death rates were found: PI3K/Akt, MAPK, Ras signaling, and resistance to epidermal growth factor inhibitor, which are linked to reduced activation of the protective ERBB2 receptor influenced by neuregulin.
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