bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic value of myocardial redox signalling: a machine learning multi-omics approach
Authors: Kotanidis C P , Akawi N , Chauhan J , Polkinghorne M , Akoumianakis I , Antonopoulos A S , Foran D , Badi I , Farid S , Srivastava V , Krasopoulos G , Sayeed R , Channon K M , Antoniades C
Published: October 2024

Background

Oxidative stress has been proposed to be implicated in cardiovascular pathology. Studies have linked myocardial oxidative stress with the development of atrial fibrillation, but its role in the prediction of long-term outcomes and mortality is yet to be elucidated.

Purpose

To apply discovery network transcriptomics and genomics to atrial tissue (AT) obtained from patients undergoing cardiac surgery, to phenotype myocardial redox-state and identify potential therapeutic targets.

Methods

We included 1,032 patients undergoing cardiac surgery. Arm 1 included 258 patients in whom atrial tissue (right atrial appendage) was used for ex-vivo quantification of NOX-derived superoxide by lucigenin-enhanced chemiluminescence. Arm 2 included 414 patients in whom exploratory, unsupervised gene network analysis in human atrial tissue RNA sequencing data was performed to identify atrial tissue redox-sensitive signatures (blue signature). Arm 3 included 881 patients genotyped with the genome-wide SNP array UK Biobank Axiom Array and used for machine learning construction of GenRedOx, a SNP model built to predict the blue transcriptomic signature. Associations with future incidence of major adverse myocardial events (MAME: cardiovascular death and/or heart failure) was assessed across all arms using cox regression models (adjusted for age, sex, hypertension, dyslipidaemia, diabetes mellitus, body mass index, and plasma TNFa).

Results

Over a median follow-up of 5.27 years [IQR: 4.29-6.83] high atrial tissue (AT) NOX-derived superoxide was independently associated with MAME risk (Adj. HR[95%CI]: 11.7 [2.18 , 62.82], p=0.004, a). Unsupervised transcriptomic analysis in Arm 2 revealed 15 coexpressed gene ‘modules’ or 'signatures' (b). The blue signature was significantly associated with AT superoxide production with "immune response-regulating and activating signalling" being amongst the top enriched pathways. Patients with high eigengene values for the blue signature showed a 5.5-fold higher adjusted risk of MAME (c). In Arm 3, extreme gradient boosting of SNP data, trained using the blue transcriptomic signature as ground truth, revealed GenRedOx (d), a genomic artificial intelligence score, which was found to be prognostic of MAME in the validation stage (e). Homozygosity for the minor allele of SNP rs723897 in the Chemokine-Like Factor Super Family 7 (CMTM7) gene had the highest gain in the model.

Conclusion

We present for the first time two novel human myocardial transcriptomic and genomic signatures that reflect changes in redox state and identify long-term cardiovascular risk. Targeting pathways in the myocardium related with immune response signalling may lead to the development of novel therapeutics in cardiovascular disease.
In-hospital economic impact and mortality of bariatric surgery on congestive heart failure in the USA: a nationwide analysis
Authors: Perry J , Sinclair S , Akinti O A , Allen Mcnamara A M , Adarsh Balaji A B , Khan A
Published: October 2024

Background

Congestive Heart Failure (CHF) remains a significant economic burden in the inpatient setting. There is a complex correlation between obesity and Congestive Heart Failure (CHF). Bariatric surgery has emerged as a critical intervention for patients with morbid obesity. However, there is limited data on how this intervention impacts hospital economic metrics and patient outcomes in the context of CHF post-bariatric surgery.

Purpose

The purpose of this study is to assess the in-hospital economic impact and mortality among patients with congestive heart failure who have undergone bariatric surgery.

Methods

We queried the National Inpatient Sample from 2016 to 2020; this retrospective observational cohort study identified CHF patients who had undergone bariatric surgery through ICD-10 codes. Univariate and multivariate logistic regression analyses were performed to determine Total Charges (TOTCH) and Length of Stay (LOS), adjusting for confounders including the Elixhauser comorbidity index, hospital region, quarterly income, and hospital location to identify the economic impact on CHF (Table 1).

Results

Out of 25,900,000 patients with congestive heart failure, 5,983,684 (23%) were obese, and 208,220 (0.8%) had undergone bariatric surgery. The demographic profile showed a mean age of 63 predominance of females (65%) and the White population (69.5%) (Table 1). The mean TOTCH for patients undergoing bariatric surgery was $66,235, compared to $76,046 for those who did not undergo the surgery, with a significant mean decrease in TOTCH of -$11,454 (p<0.001, 95% CI: -$12,472 to -$10,435). The mean LOS was 5 days for patients with bariatric surgery versus 6 days for those without, showing a mean decrease in LOS of 0.93 days (95% CI: -0.99 to -0.87). Additionally, there was a significant decrease in overall mortality risk among patients who had bariatric surgery (2.1%) compared to those who did not (5%), with an (OR 0.4 p<0.001, 95% CI: 0.38 to 0.43).

Conclusion

Our research demonstrates that bariatric surgery in obese individuals with congestive heart failure (CHF) markedly decreases in-hospital mortality, reduces hospital charges, and shortens the length of hospital stays. These findings underscore the potential of bariatric surgery as a cost-effective intervention for improving outcomes in patients with CHF and obesity, highlighting the importance of considering surgical weight loss options in the management of CHF.Table 1
Association between echocardiographic parameters and abnormal spirometry among chronic heart failure patients
Authors: Phoksiri A , Srisuwan T , Tajarernmuang P , Osataphan N , Kanjanavanit R , Wongcharoen W , Phrommintikul A
Published: October 2024

Background

A significant proportion (10-40%) of heart failure (HF) patients have concomitant pulmonary disease which have negative effects on cardiovascular outcome of patients. Because of the similarities in symptoms between HF and pulmonary disease, the prevalence of concomitant pulmonary disease may be underestimated. Early detection manage accordingly may improve outcomes of HF patients. We aimed to study clinical and echocardiographic parameters identifying HF patients with concomitant pulmonary disease.

Methods

This cross-sectional study included adults (age≥18 years) who were diagnosed with HF. The echocardiogram, arterial blood gas and pulmonary function test (PFT) were performed. The patients were classified into normal and abnormal (obstructive and restrictive) PFT patterns. The primary outcome was the association between echocardiographic parameters and abnormal PFT. The receiver operating characteristic (ROC) curve was performed to evaluate diagnostic performance of echocardiographic parameter in detecting abnormal PFT.

Results

A total of 57 patients was enrolled, of which 32 patients (56.14%) had normal PFT, 14 patients (24.56%) had obstructive PFT, and 11 patients (19.30%) had restrictive PFT. The clinical characteristics were not different between groups. ROC curve demonstrated that only left atrial volume index (LAVI) and main pulmonary artery (MPA) diameter had significant diagnostic accuracy to predict abnormal PFT with AUC of 0.72 (95%CI 0.57-0.87) and 0.66 (95%CI 0.51-0.80) respectively. Using combination of LAVI (cutoff 40mm2/m2) and MPA diameter (cutoff 22.0 mm) had a sensitivity of 95.7% (95%CI 78.05-99.89%) and specificity of 41.94% (95%CI 24.55-60.92%) in detection patients with abnormal PFT.

Conclusion

Almost half of HF had concomitant abnormal PFT. The combination of LAVI and MPA diameter can identify patients with abnormal PFT with high negative predictive value and should be considered as screening parameters in HF patients.
Left atrial reservoir strain differentiates cardiac amyloidosis and hypertrophic cardiomyopathy
Authors: Winkelbauer L , Santner V , Schwegel N , Hoeller V , Gollmer J , Kolesnik E , Wallner M , Von Lewinski D , Zirlik A , Ablasser K , Verheyen N , Zach D
Published: October 2024

Aims

Availability of mortality-reducing therapies for cardiac amyloidosis (CA) has led to an increase in referral rates to tertiary care centers. Investigations to improve diagnosis rates are urgently needed, as diagnosis of CA requires a multimodal approach and its early diagnosis is crucial due to high mortality in untreated patients. The aim of this study is to evaluate the accuracy of the left atrial reservoir strain (LASr) in differentiating CA patients from patients with hypertrophic cardiomyopathy (HCM).

Methods

This is a cross-sectional analysis from the Graz HCM Registry, a prospective single-center cohort study enrolling consecutive patients with a HCM phenotype. This analysis included HCM and CA patients with valid standardized transthoracic echocardiographic examinations. Blinded investigators performed post-processing echocardiographic analyses in 100 HCM and 95 CA patients.

Results

Compared to HCM patients, CA patients were more frequently male [79 (83%) vs. 54 (54%); p<0.001] and older [78 (73-81) vs. 58 (47-70) years; p<0.001]. Moreover, CA patients had a lower BMI [25.0 (22.8-26.9) vs. 26.5 (24.3-29.7) kg/m²; p=0.002] as well as lower systolic [134±20 vs. 142±25 mmHg; p=0.018] and diastolic blood pressure [78±12 vs. 84±12 mmHg; p<0.001]. Additionally, CA patients had higher NT-proBNP [2533.0 (1146.0-5016.0) vs. 543.0 (195.0-1381.0) pg/ml; p<0.001] and lower eGFR [58.4±19.1 vs. 80.1±22.2 ml/min/1.73m²; p<0.001]. LASr was significantly worse in CA patients compared to HCM patients [9.2 (5.6-13.0) vs. 21.7 (14.8-27.6) %; p<0.001]. Multivariable logistic regression analysis revealed LASr as an independent predictor of CA [OR=0.936 (95% CI 0.877-0.998)], adjusting for covariates. ROC analysis showed an AUC of 0.80 (95% CI 0.73-0.86) for LASr to discriminate CA from HCM. LASr ≤14.3% demonstrated a 80% sensitivity and 79% specificity for the identification of CA patients. Sensitivity analyses involving 74 sex- and age-matched patients yielded materially unchanged results.

Conclusion

Compared to HCM patients, LASr was diminished in CA patients and an independent predictor of CA. Moreover, LASr showed high diagnostic accuracy in differentiating CA and HCM patients. Prospective studies are needed to evaluate the added value of left atrial strain in the diagnostic work-up of CA patients.ROC curve of LASr
Interleukin-6 and suPAR are associated with diastolic function in type 1 diabetes: The Thousand & 1 Study
Authors: Bahrami H , Jorgensen P G , Hove J D , Dixen U , Rasmussen L J H , Eugen-Olsen J , Rossing P , Jensen M T
Published: October 2024

Background

Heart failure (HF) is a common complication in individuals with type 1 diabetes (T1D). Inflammation is an important contributor to the pathogenesis and progression of both T1D and HF – especially HF with preserved ejection fraction (HFpEF). Diastolic dysfunction is a hallmark of HFpEF. Despite this, the association between diastolic function and inflammatory biomarkers is not well-known in individuals with T1D.

Methods

The Thousand & 1 study of individuals with T1D without known heart disease was studied. Diastolic parameters, including E/e’, was obtained by echocardiography and associated with Interleukin-6 (IL-6), soluble urokinase-type plasminogen activator receptor (suPAR) and high-sensitivity C-reactive protein (hsCRP). These inflammatory biomarkers were analysed as continuous variables and dichotomized in above/below 3 pg/mL (IL-6), 4 ng/mL (suPAR), and 4 mg/L (hsCRP). In multivariable regression analysis, adjustments were made for age, gender, body mass index, duration of diabetes, HbA1c, systolic blood pressure, left ventricular ejection fraction, glomerular filtration rate, albuminuria status, use of statins, tobacco use and physical activity levels. In an additional analyse, we also adjusted for N-terminal pro–B-type natriuretic peptide (NT-proBNP).

Results

We included 1,014 individuals (52% male, mean age 50±15). IL-6 was elevated in 207 individuals, suPAR in 182 individuals, and hsCRP in 863 individuals. Mean E/e’ was 7.6 and mean left ventricular ejection fraction was 58±5%. In fully adjusted models, inflammatory biomarkers were significantly associated with diastolic function. Thus, individuals with IL-6 > 3 pg/mL had 0.6 (95% confidence intervals: 0.2 to 1.0), P=0.001) higher E/e’ compared to individuals with IL-6 < 3 pg/mL. For every doubling of suPAR levels, E/e’ increased by 0.5 (0.2 to 0.9, P=0.003). For every doubling of hsCRP levels, E/e’ increased by 0.1 (0.02 to 0.2, P=0.022). Individuals with elevated levels of all three biomarkers had 1.9 (0.5 to 3.2, P=0.006) higher E/e’ compared to low levels of all three biomarkers. Including NTproBNP to the model did essentially not change the estimates.

Conclusions

Firstly, in T1D, elevated levels of IL-6, suPAR and hsCRP are associated with diastolic function assessed by E/e’, independent of traditional risk factors including NT-proBNP. Secondly, IL-6, suPAR and hsCRP may contain information about diastolic function in T1D which is not detected by NT-proBNP.Figure 1Figure 2
Point-of-care screening for heart failure with reduced ejection fraction using simple pulse oximetry
Authors: Bohm A , Jajcay N , Segev A , Lucka J , Kollarova M , Jankova J , Holly O , Schwarz S , Sebenova Jerigova V , Toth S , Johanesova L , Bezak B
Published: October 2024

Background

More than 64 million patients with heart failure (HF) are burdened with poor quality of life, frequent hospitalizations, and high readmission rates. While HF with reduced ejection fraction (HFrEF) accounts for approximately half of these patients, there is currently no effective tool for performing cost-effective and reliable early-stage screening. For this purpose, we derived and cross-validated a machine learning (ML) based system capable of identifying HFrEF based on analysis of the photoplethysmographic (PPG) signal recorded by a simple pulse-oximeter.

Methods

Patients attending a routine ambulatory check-up at an outpatient clinic were included in the study. Left ventricular ejection fraction was determined by standard transthoracic echocardiography. Diagnosis of HF was based on the latest ESC recommendations for HF. PPG was measured using a standard oximeter modified to record raw PPG signal. Before processing, the quality of the measured PPG signal was assessed by signal quality indices to determine whether the quality of signal was sufficient for further analysis. In brief, the signal processing involved noise removal, filtering for specific frequencies, automatic artifact detection and identification of individual heartbeats, on which specific parts of the signal and signal characteristics, necessary for further analysis, were identified. Four different ML processing pipelines with different approaches to feature selection and class balancing were deployed, validated using the K-fold cross-validation and compared.

Results

A total of 371 patients were included in the study: 54 patients with HFrEF (mean age 66.87 ± 14.35, 74.07% male) and 317 patients with HFmrEF (4), HFpEF (42) or no history of HF (271) (mean age 54.12 ± 17.79, 51.73% male). From the 4 ML pipelines, LightGBM with SMOTE + Edited Nearest Neighbors balancing had the highest cross-validated predictive performance for detection of HFrEF (c-statistics 0.8, CI 0.69 – 0.89).

Conclusions

Our results suggest that HFrEF can be effectively screened using a simple pulse oximeter, thanks to ML signal analysis. This solution could be adapted to a simple, non-invasive, readily available, time-saving, and inexpensive point-of-care diagnostic tool for primary care. Early disease detection and referral to a cardiologist (or HF specialist) would have a positive impact on patient morbidity and mortality.Receiver Operating Characteristics CurveModel Performance Metrics
High-Sensitivity Troponin-T and heart failure risk in individuals with suspected acute coronary syndrome
Authors: Byrne C , Kragholm K H , Torp-Pedersen C , Pareek M
Published: October 2024

Background

In individuals with suspected acute coronary syndrome (ACS), serial assessments of high-sensitivity cardiac troponin-T (hsTnT) levels demonstrate associations with both short- and long-term mortality and recurrent ischemic events. Nonetheless, the relationship with subsequent heart failure remains inadequately characterized.

Purpose

We investigated the association between single and serial hsTnT levels and subsequent hospitalization or outpatient medical encounters related to heart failure in individuals presenting with suspected ACS.

Methods

Utilizing Danish national registries from 2012 to 2019, we identified individuals without known heart failure who underwent dual hsTnT assessments ( 99th percentile upper reference limit: 13.5 ng/l), spaced 1-7 hours apart during hospitalization for myocardial infarction (MI), unstable angina, observation for suspected MI, or chest pain. Participants were categorized based on their hsTnT concentration patterns from the first to the second measurement (primary groups: normal, rising, persistently elevated, or falling) and the extent of hsTnT concentration alterations (secondary groups: <20%, >20 to 50%, or >50% in either direction). Additionally, they were grouped into quartiles based on the initial hsTnT measurement (<=9 ng/l, 10-15 ng/l, 16-66 ng/l, >=67 ng/l) to assess whether heightened hsTnT concentrations correlated with an increased risk of heart failure. Standardized risks of hospitalization or outpatient contacts for heart failure were computed using multivariable logistic regression with average treatment effect modeling.

Results

The study encompassed 26,835 individuals, of whom 38.9% received discharge diagnoses of MI, 5.1% were diagnosed with unstable angina, and 56.1% with observation for suspected MI or chest pain. Median age was 64.2 years, with 59.5% males. Prevalence of known cardiovascular disease included coronary disease in 18.1% of cases, prior revascularization in 7.2%, atrial fibrillation or flutter in 7.9%, and a history of stroke in 6.3%. Within the initial 30 days, 628 persons received a heart failure diagnosis, with an additional 960 diagnosed between days 31-365. Subjects displaying two normal hsTnT values exhibited the lowest standardized absolute risk (0.39% in days 0-30; 0.58% in days 31-365), while those with persistently elevated concentrations demonstrated the highest risk (6.45% in days 0-30; 7.05% in days 31-365) (Figure). Notably, the magnitude of hsTnT within each primary group did not affect heart failure risk. Conversely, heart failure risk exhibited a positive association with hsTnT concentrations measured in the initial sample.

Conclusions

In individuals presenting with suspected ACS, subjects with a sustained elevation in hsTnT levels showed the highest risk of subsequent heart failure events. Moreover, a dose-response association was observed between hsTnT concentrations and heart failure risk.Figure
Association of preoperative NT-proBNP with 30-day and five-year mortality after cardiac surgery
Authors: Poelzl L , Lohmann R , Theurl F , Puelacher C , Sterzinger P , Eder J , Oegren E , Gudbjartsson T , Jeppsson A , Grimm M , Bauer A , Poelzl G , Bonaros N , Holfeld J , Gollmann-Tepekoylu C
Published: October 2024

Background

Elevated levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) reflect cardiac status in heart failure patients and are independently associated with mortality and adverse cardiovascular outcomes in elective patients undergoing non-cardiac surgery. However, there is scarce evidence about the association between NT-proBNP and outcome after cardiac surgery in large patient populations.

Purpose

The aim of this study was to analyze the association of preoperative NT-pro-BNP levels with 30-day and five-year mortality after cardiac surgery.

Methods

A consecutive cohort of 6938 patients undergoing cardiac surgery was analyzed retrospectively. The relationship between preoperative NT-proBNP and 30-day and five-year mortality adjusted for EuroSCORE II was explored using a Cox proportional hazards model. The dynamics of preoperative NT-proBNP were analyzed by comparing the values at the time of diagnosis or assignment to surgery with the values on the day before surgery (n= 4739). Results were validated in an external cohort from the SWEDEHEART registry (n=3415).

Results

Median preoperative NT-proBNP was 552 ng/l. Death within 30 days occurred in 2.1% of the patients.

High preoperative NT-proBNP levels were associated with a higher 30-dayand 5-yearmortality. Preoperative NT-proBNP thresholds to identify patients at high-risk (>4000 ng/l), intermediate-risk (2000-4000 ng/l) and low-risk (<2000 ng/l) for 30-day mortality were determined. Patients in the intermediate or high-risk category had a higher risk for prolonged ICU stay (OR 2.52), ultrafiltration (OR 3.68), ECMO (OR 3.63), 30-day mortality (HR 2.79), and 5-year mortality (HR 2.41) (p-value all <0.001). Patients who improved in the preoperative NT-proBNP risk had a significant 30-day and five-year survival benefit.

Conclusions

Preoperative NT-proBNP levels are independently associated with 30-day and five-year mortality after cardiac surgery. NT-proBNP reduction prior to surgery might decrease 30-day and five-year mortality after cardiac surgery.NTproBNP is associated with outcome
PIRCHE-II: a new tool to predict rejection in cardiac transplantation?
Authors: Fischetti G , Giovannico L , Parigino D , Ramirez A D , Santeramo V , Savino L , Mazzone F , Silva A M , Di Bari N , Bottio T
Published: October 2024

Aim

This retrospective observational study aims to compare patients diagnosed with antibody-mediated or cell-mediated rejection with patients without episodes of rejection and study any predictors of rejection at follow-up with particular attention to PIRCHE-II scores.

Materials and Methods

We performed a retrospective evaluation of prospectively collected data of heart transplant patients from January 2022 to August 2023, at a single hospital. Preoperative, intraoperative and postoperative parameters are collected anonymously in our institutional database used for internal quality control. The primary endpoint was the incidence of rejection in one of three control endomyocardial biopsies. As pre-operative data, age, sex, BSA, blood group mismatch, risk such as dyslipidemia, hypertension, diabetes, peripheral vascular disease, COPD, previous cardiac surgery, PRA, ischemia time and post-operative infections. We evaluated patients at a mean follow-up of 106 (78 – 180) days. In patients who tested positive for cell-mediated or antibody-mediated rejection, the PIRCHE-II score was calculated.

Results

There were 45 patients with no diagnosis of rejection and they were aged 61 [50-65]; 22.2% were women, with a mean BSA of 1.87 ± 0.19. 22.2% had a blood type mismatch. They had a mean PIRCHE-II of 111.88 ± 43.6. There were 15 patients diagnosed with rejection and they were 63 years old [52 – 66]; 20.0% were women, with a mean BSA of 1.84 ± 0.23. 13.3% had a blood type mismatch. They had a mean PIRCHE-II of 113.70 ± 33.90. In multivariable analysis, the main predictors of rejection were plasma transfusions [OR 0.053, 95% CI, p=0.02], post-operative infections [OR 0.076, 95% CI, p=<0, 02] and the PIRCHE – II [OR 3.284, 95% CI, p=0.04].

The mean PIRCHE-II of patients who presented antibody-mediated or cell-mediated rejection was 113.70 ± 33.90 and that of patients who did not present any rejection was 111.88 ± 33.90;

Conclusion

According to the results obtained, the PIRCHE-II algorithm could be a tool in immunological risk stratification in patients undergoing cardiac transplantation. It is necessary, however, to apply PIRCHE-II to a larger number of patients and should also be considered in light of other factors such as the immunological status of the recipients, the immediate post-operative course (infections, CMV reactivation, blood component transfusions), which could constitute an immunological trigger and patient compliance in immunosuppressive therapy.Patients' featuresResuts
Associations of Cardiac myosin binding protein C to Troponin I in patients with chronic heart failure during exercise. A substudy of the SMARTEX-HF trial
Authors: Riveland E , Ushakova A , Valborgland T , Karlsen T , Dalen H , Prescott E , Omland T , Marber M , Ellingsen Ø , Larsen A I
Published: October 2024

Aim

Cardiac myosin binding protein C (cMyC) has shown promise being more sensitive than cardiac troponins, rising faster after myocardial infarction[i]. Its association to hs-cTnI in heart failure patients during physical activity is not known. The aim of this study was to assess the association between a novel biomarker: cMyC and the clinically used high sensitivity cardiac Troponin I (hs-cTnI) during a 12-week exercise training program in patients with chronic symptomatic heart failure with reduced ejection fraction (HFrEF). The changes of biomarkers in plasma levels in an intervention group, performing structured exercise programs, were compared to those in a control group, instructed to perform regular recommended exercise (RRE) according to current guidelines.

Methods and results

This was a post hoc analysis of the SMARTEX-HF trial in 215 patients with symptomatic heart failure (HF) with Left Ventricular Ejection Fraction (LVEF) <35% and NYHA II-III. The patients were randomly assigned to High Intensity Interval Training (HIIT, n=77), Moderate Continuous Training (MCT, n=65) or RRE, (n=73) for 12 weeks. Measurements and clinical data were acquired before and after the 12-week intervention. In 191 patients, plasma was available for hs-cTnI testing and in 189 patients plasma was available for cMyC testing.

Due to the lack of a normal distribution, the values were log transformed. There was a significant association of change in log hs-cTnI and change in log cMyC (Pearson correlation R=0.52 (95% CI 0.37- 0.66) p<0.001) (Figure 1).

For any 10% increase in cMyC level, the ratio of the hs-cTnI level increased with approximately 5% (Figure 2).

There was no association between the levels of cMyC at baseline and change in hs-cTnI at 12 weeks.

Conclusion

Changes in levels of the novel biomarker cMyC was significantly associated with hs-cTnI plasma levels in patients with symptomatic chronic HFrEF during a structured 12 week exercise training program. Being more sensitive, it may indicate a role as a future marker of subclinical myocardial damage.Models with adjustmentsMarginal effect at the mean
Association of genetically predicted human metabolomic gene expression with incident heart failure
Authors: Ahn H , Oexner R , Boas L , Zoccarato A , Shah A
Published: October 2024

Background

Heart failure (HF) represents a significant challenge both for patients and healthcare systems worldwide. Despite ongoing efforts, therapeutic options are limited. The underlying pathophysiology involves intricate changes in cardiac metabolism that strongly influence the clinical phenotype, thus potentially offering novel options for therapeutic targeting. Systematic prioritisation of metabolic genes regarding their phenotypic impact on HF is outstanding.

Purpose

We investigate the association of genetically predicted metabolic gene expression with the onset of HF within UK Biobank (UKB). We followed up on identified candidate genes using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) models of cardiomyocyte hypertrophy.

Methods

Utilising genomic data of 484,372 UKB participants and left ventricle-specific expression quantitative trait loci (eQTL) information from Genotype-Tissue Expression (GTEx) project, we predicted genetically regulated gene expression using established methods (PrediXcan) for all metabolic genes. Subsequently, we employed per-gene Cox proportional hazards (COX-PH) models to assess the association of genetically predicted metabolic gene expression with incident HF. We adjusted models for clinical risk using established risk models (Pooled Cohort Equations to Prevent HF (PCP-HF)).

To validate our findings in vitro, we subjected hiPSC-CMs to a sympathomimetic stimulus via treatment with endothelin-1 (ET-1; 10 nM). We evaluate alterations in expression via real-time quantitative polymerase chain reaction (RT-qPCR) and establish methods for assessing hypertrophic remodelling.

Results

COX-PH models revealed the predicted expression of 104/1515 metabolic genes to be independently associated with the onset of HF. Subsequent refinement with a meta-analysis of commonly dysregulated genes in end-stage HF narrowed our findings to 46 candidate genes, of which several were known for their role in HF pathophysiology. We further traced nine genes for validation in hiPSC-CM models and showed significant dysregulation of several genes following the treatment with ET-1.

Flow cytometry measured hiPSC-CM hypertrophy following sympathomimetic stimulation (p=0.036). Extracellular flux analysis revealed canonical changes following treatment with ET-1.

Conclusions

The study revealed several metabolic genes associated with incident HF, thus confirming previous findings and highlighting novel, putative therapeutic target genes. We confirmed transcriptional changes in an in vitro model. Ongoing work includes further validation via silencing candidate genes in hiPSC-CMs and subjection to the established phenotypic in vitro models.
Global health
Authors:   Organised by: EUPHA, ASPHER,   Moderators: Henrique Barros (ASPHER), Iveta Nagyova (EUPHA)
Published: October 2024

Global health emphasizes the importance of addressing health challenges that transcend national borders and require strong international collaboration and governance. This concept is grounded in collaborative transnational actions aimed at promoting health for all, reducing disparities, and protecting against threats. Strengthening health systems, public health infrastructure, improving health service delivery, and ensuring equal access to healthcare for all are key focus areas in global health.

This plenary will address several major health challenges and critical issues, such as the rising burden of non-communicable diseases, re-emerging pandemics, environmental threats, and the suboptimal responses of national healthcare systems to manage these challenges. The need to focus on vulnerable and marginalized populations, particularly those affected by migration and ethnicity, will be highlighted. The discussion will also showcase the importance of including ethnic minority and Indigenous people’s perspectives in health policy and decision-making processes, as well as addressing the social determinants of health that disproportionately affect these communities.

Central to the discussion on global health is the role of global health policy and diplomacy, focusing on how countries can collaborate to address health threats and challenges, shaping international strategies and frameworks. Innovation, including reverse innovation and the development of evidence-informed policies and effective public health strategies that can be implemented globally and is relevant also in resource-constrained contexts, is another critical aspect in addressing the intersection of health and development. Finally, strong public health leadership is needed to shape practices and policies, as well as fostering the next generation of global health leaders.

The multifaceted nature of global health calls for a comprehensive approach to health—one that integrates policy, leadership, and equity into the core of public health strategies. The integration of health into all policies at the global level is vital for creating supportive environments, policies, services, and communications that promote better health for all.

Moderators

Iveta Nagyova

President EUPHA

Henrique Barros

President ASPHER

Speakers/Panellists

Emma Rawson Te Patu

President World Federation of Public Health Associations

Charles Agyemang

Professor of Global Migration, Ethnicity & Health, University of Amsterdam, Netherlands

Agnès Buzyn

Former Minister of Health and Social Affairs, France

Moredreck Chibi

Public Health Innovation Lead, WHO Regional Office for Europe
Inequalities in healthy life expectancy and risk factors for poor health in small geographic areas
Authors: Steel N , Saunders M , Bachmann M , Shabuz Z , Dalton A , Enwo O , Brainard J , Jones C , Burke A
Published: October 2024

Background

Reducing inequality in healthy life expectancy (HLE) is a UK government ambition and requires more detailed knowledge of interrelated morbidity and mortality risks at smaller areas than is routinely available. We assessed HLE and risk factors in small areas.

Methods

We used publicly available data to estimate HLE in 2011 and 2021 at birth and age 65 for males and females for 128 Middle layer Super Output Areas (MSOA) in Norfolk and Waveney, described the distribution using geospatial mapping, and analysed associations with risk factors using linear regression.

Results

Mean HLE at birth was 66.5 years (standard deviation 4.3; range 52.0 to 73.0) for men and 67.5 (3.9; 56.0 to 74.0) for women, and at age 65 was 10.9 years (1.8; 6.0 to 16.0) and 12.2 (1.9; 5.0 to 15.0) respectively in 2021. The range in HLE increased between 2011 and 2021 by 2.8 years for men and 1.6 years for women. HLE was usually lower and risks higher in urban and coastal areas. Lower HLE at area level was associated with lower weekly income, physical inactivity, air pollution, alcohol admissions, living alone as an older person and diet not meeting ‘5 a Day’. HLE at age 65 in 2021 increased by: 0.2 (95% CI 0.1,0.2) years for men and 0.2 (0.2,0.3) for women for each £10 rise in weekly net income after housing expenditure; 0.1 (0.1,0.2) years for men for each 10 fewer alcohol attributable hospital admissions per 100,000 admissions; 0.66 (0.31,1.00) years for men and 0.53 (0.15,0.91) years for women per 1 μg/m3 less 2.5 mm particulate matter concentration in air pollution; 0.6 (0.2,1.0) years for men and 0.6 (0.1,1.0) years for women for each 10% fewer people being physically inactive (multiple regression).

Conclusions

This innovative approach can be used to monitor risks and inform targeted public health interventions at a local level more relevant to local policy makers. Stronger public health surveillance systems are needed to accurately monitor a wider variety of local data on risks.

Key messages

• Healthy life expectancy at age 65 varies by over 10 years for men and women between different small geographic areas in an English county, alongside local variation in risk factors for poor health.

• Lower HLE at area level was associated with lower weekly income, physical inactivity, air pollution, alcohol admissions, living alone as an older person and diet not meeting ‘5 a Day’.
NCD prevention and control in Kenya: feasibility study of health kiosks in markets “HEKIMA Study”
Authors: Harding S , Kaduka l , Olale J , Mutai J , Mbuka S , Bosire M , Obuya M , Mitaru D , Ochieng R
Published: October 2024

Introduction

Non-communicable diseases (NCDs) account for 50% of hospital admissions and 55% of hospital mortality in Kenya. Cardiovascular diseases (CVDs) lead NCD mortality at 14% due to high prevalence of multiple risk factors. Community markets are social institutions with untapped potential for public health. HEKIMA is a multi-phased theoretically driven intervention exploring whether health kiosks in community markets, manned by community health workers (CHWs) and supervised by health centre (HC) nurses, can improve the reach of preventive care to vulnerable communities.

Methods

A mixed methods study in Vihiga County targeting 320 participants aged 15 years and above. Nurses and CHWs were trained to deliver evidence-based CVD health promotion, risk screening, and early intervention. Multi-sector stakeholder consultations, readiness assessments of markets and HCs, and semi-structured interviews informed intervention development. Evaluation use the Re-AIM framework.

Results

At 6 months of intervention there 2224 kiosk users which exceeded target of 300; 61% primary school education; 77% females; median age - males 48y, females 52y. Proportion with high blood pressure, overweight, obesity, and diabetes 48%, 32%, 25% and 12% respectively. 30% were referred to HC, and 34% followed up at least once at the kiosk. High acceptability of HEKIMA among CHWs, nurses and market users led to HEKIMA kiosks being integrated in the primary healthcare pathway. Key enablers were multi-sectoral alliance of government, civic organisations, community market champions, local businesses and health sector; culture centred coproduction and capacity building Challenges included understaffing, commodity supplies and seasonality.

Conclusions

HEKIMA successfully promoted NCD prevention and control, particularly among vulnerable populations. Scaling up across Kenya is planned to explore translational impacts in different contexts.

Key messages

• Multisectoral alliance critical for prevention of NCDs.

• Theoretically underpinned complex systems interventions addresse inequities.
1.C. Round table: Navigating the 17th European Public Health Conference: A Guide for First-Time Attendees
Authors:   Organised by: EUPHAnxt, EUPHA,   Chair persons: Monica Brînzac (EUPHAnxt)
Published: October 2024

Are you attending the European Public Health Conference for the first time? If yes, this session is for you. Join us for an engaging session tailored specifically for first-time attendees of the 17th European Public Health Conference in Lisbon, Portugal. This session aims to provide newcomers with valuable insights and strategies to maximize their experience and effectively navigate the conference.

Our seasoned conference veterans will share practical tips on a range of topics, including, but not being limited to:

1. Conference Navigation: Learn how to navigate the conference programme, the venue efficiently, locate sessions of interest, and make the most of your time between sessions.

2. Networking: Discover the importance of networking in the field of public health and gain strategies for initiating meaningful conversations, building professional relationships, and expanding your professional network.

3. Session Selection: Gain insights into selecting sessions and workshops that align with your interests, career goals, and areas of expertise. Learn how to prioritize your schedule and make the most of concurrent sessions.

4. Poster Presentations: Understand the significance of poster presentations and how to effectively engage with presenters. Discover techniques for synthesizing information and asking insightful questions.

5. Self-Care: Explore strategies for maintaining physical and mental well-being throughout the conference, including tips for managing fatigue, staying hydrated, and finding moments of relaxation amidst the hustle and bustle.

Whether you’re a student, researcher, practitioner, or policymaker, this session will equip you with the tools and knowledge needed to navigate the 17th European Public Health Conference with confidence and make the most of this invaluable opportunity for professional development and networking.

Key messages

• First-time attendee at the European Public Health Conference? Don’t miss this tailored session for essential insights and strategies to maximize your experience in Lisbon.

• Join seasoned veterans for practical tips on navigating the conference, networking effectively, selecting sessions, engaging with poster presentations, and prioritizing self-care.

Speakers/Panelists

Robert Klarecki

EPH Conference Office

Jinane Ghattas

Sciensano, Brussels, Belgium
Mapping geographic health disparities in 11 high-income nations
Authors: MacKinnon N , Emery V , Waller J , Ange B , Ambade P , Gunja M , Watson E
Published: October 2024

Health care delivery faces a myriad of challenges globally with well-documented health inequities based on geographic location. Yet, researchers and policy makers have a limited understanding of the frequency of geographic health disparities. In this survey study, we analyzed results from the 2020 Commonwealth Fund International Health Policy (IHP) Survey-a nationally representative, self-reported, and cross-sectional survey of adults from Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, the UK, and the US. Eligible adults older than age 18 years were included by random sampling. Survey data were compared for the association of area type (rural or urban) with 10 health indicators across 3 domains: health status and socioeconomic risk factors, affordability of care, and access to care. Across the 11 countries and 10 health indicators and 3 domains (health status and socioeconomic risk factors, affordability of care, access to care), there were 21 occurrences of geographic health disparities. The indicators with the most occurrences of geographic health disparities were in the access to care domain. Differences in number of disparities reported by country suggest that health policy and decision makers in the US should look to Canada, Norway, and the Netherlands to improve geographic-based health equity.
Burden of disease due to ambient particulate matter pollution in Germany from 2010 to 2021
Authors: Plass D , Kienzler S , Wintermeyer D
Published: October 2024

Background

Worldwide, according to the global burden of disease (GBD) study, around 118 million disability-adjusted life years (DALYs) were attributable to ambient particulate matter (PM2.5) in 2019. Further, 97% of Europe’s urban population are exposed to annual average levels of PM2.5 above the World Health Organization’s guideline value of 5 µg/m³. In Germany, considerable efforts have been made to reduce PM2.5-emissions, which resulted in a continuous decrease of exposure. We estimated the burden of disease attributable to PM2.5-exposure in Germany for a time series from 2010 to 2021.

Methods

We used the environmental burden of disease (EBD) methodology developed by the WHO. For the exposure assessment we combined annual average measured and modelled PM2.5-concentrations with information on population density at a 2-by-2 km² grid. Using the exposure-response functions from GBD 2019, we estimated the EBD for chronic obstructive pulmonary diseases, type 2 diabetes mellitus, lung cancer, stroke and ischemic heart diseases (IHD). National surveys and register data were used to estimate the baseline burden of disease.

Results

In total, we estimated 232,863 (95%-CI: 153,716-314,882) DALYs attributable to PM2.5 in 2021. We observed a reduction of about 50% compared to 2010. The highest attributable burden was estimated for IHD with 70,197 (95%-CI: 42,609-101,785) DALYs, which is about 8% of the overall IHD-burden. The mortality-to-morbidity ratio revealed that years lost due to death (YLLs) had a higher share (69.9%) of overall DALYs with 162,561 (95%-CI: 106,918-222,567) YLLs.

Discussion

Despite a decreasing trend of the EBD for PM2.5 in Germany since 2010, our results show that there is still a long way to a pollutant free environment as envisaged by the EU’s zero pollution ambition. Using EBD as a standardized methodology and the DALYs as the core measure allows to have a comprehensive and comparable overview of the impact of PM2.5 on population health.

Key messages

• Ambient particulate matter pollution is an important environmental risk factor in Germany.

• The decreasing trends is encouraging but there is still a long way to go to meet the objectives of the EU’s zero pollution ambition.
How was the impact of heatwaves on daily hospital admissions in Portugal (2000-2018)?
Authors: Alho A , Oliveira A P , Viegas S , Nogueira P
Published: October 2024

Background

Climate change has increased the frequency, intensity, and duration of heatwaves, posing a serious threat to public health. While the link between high temperatures and premature mortality has been extensively studied, the comprehensive quantification of heatwave impacts on morbidity remains understudied.

Methods

We assessed the relationship between heatwaves and daily hospital admissions at a county level in Portugal, considering all major diagnostic categories and age groups, over a 19-year period from 2000 to 2018. Our nationwide study included a comprehensive geospatial analysis, integrating over 12 million hospital admission records with heatwave events indexed by the Excess Heat Factor (EHF), covering all 278 mainland counties. To estimate the impact of heatwaves on hospital admissions, we applied negative binomial regression models at both national and county levels.

Results

A statistically significant overall 18·9% increase in daily hospital admissions was found during heatwave days (IRR=1·189, 95% CI: 1·179-1·198). This impact affected all age groups, with pediatric ages being the most affected (21·7%), followed by the working-age (19·7%) and elderly individuals (17·2%). All 25 Major Disease Diagnostic Categories experienced significant increases, particularly Burns (34·3%), Multiple Significant Trauma (26·8%), and Infectious and Parasitic Diseases (25·4%). Notable rises were also observed in Endocrine, Nutritional, and Metabolic (25·1%), Mental (23%), Respiratory (22·4%), and Circulatory (15·8%) diseases.

Conclusions

Our results provide statistically significant evidence of the association between heatwaves and increased hospitalizations across all age groups and for all major causes of disease. This is the first study to estimate the full extent of heatwaves’ impact on hospitalizations using the EHF index over a comprehensive 19-year period, encompassing an entire country, and spanning 25 disease categories during multiple heatwave events.

Key messages

• There is a clear association between heatwaves and increased hospital admissions across all age groups and Major Diagnostic Categories.

• Our data offer crucial information to guide policymakers in effectively and efficiently allocating resources to address the profound healthcare consequences resulting from climate change.
High-resolution modeling and projection of heat-related mortality in Germany under climate change
Authors: Wang J Y , Nikolaou N , an der Heiden M , Irrgang C
Published: October 2024

Heat is a leading cause of premature deaths during summer months. Understanding the relationship between high temperatures and excess mortality is crucial for designing effective prevention and adaptation plans. Traditional statistical methods have been repeatedly applied to analyze heat-related mortality. However, spatially and temporally high-resolution analyses are challenging due to fragmented data archives across different agglomeration levels, especially for mortality data. We propose a neural network-based model to estimate heat-related mortality. This approach allows for high temporal and spatial resolution estimations, such as regional heat risk during specific heatwaves. Using Germany as a case study, we calculated heat-related excess mortality rates at the district level and visualized the dynamics of local health risks within a heatwave. Overall, we estimated a total of 48,000 heat-related deaths in Germany over the last decade (2014-2023), with most occurring during specific heatwave events. For example, in 2023, the heatwave from July 7-14 contributed approximately 28% (1100 deaths) to the total of about 3,900 heat-related deaths for the entire year. This estimation is consistent with previously published reports from the Robert Koch Institute (RKI), considering the resolution differences in the input data. In addition, we combined our model with shared socio-economic pathways (SSPs) of future climate change, assuming a static population and baseline mortality rate. The results suggest that heat-related risk in Germany could further increase by a factor of 2.5 (SSP245) to 9 (SSP370) without adaptation to extreme heat. Our approach is a valuable tool for the monitoring of regional heat-related risks as well as scenario-based risks projections for the future. The results of the model can help develop climate-driven public health strategies, aiding in the identification of local risks during heatwaves and in long-term resilience planning.

Key messages

• High-resolution modeling of heat-related mortality helps us to develop targeted adaptation and prevention plans.

• The majority of heat-related mortality occurs during heatwaves in summer.