High Levels Research Articles

Epicardial carbohydrate antigen 125 (CA-125) levels, associated with neutrophils activity in heart failure: No differences regarding sex

Abstract Background Carbohydrate antigen 125 (CA125), is the name of the soluble part of mucin-16, after being cleaved, which is detected and increased into circulation in congestive heart failure (HF) patients. Purpose We aimed to study plasma and epicardial fat markers related to inflammation, fibrosis, adiposity, and its association with plasma and epicardial CA125 for understanding the underlying mechanisms of heart failure and the differences between men and women. Methods We have included women and men undergoing open heart surgery (n=134). Epicardial fat biopsy and blood were obtained before the procedure under signed consent. Immunohistochemistry, ELISA, multiplex-Luminex, and real-time PCR were used for analyzing protein or mRNA expression levels of CA125 and markers. Results Out of 135, 57 patients suffered heart failure (HF). CA125 was expressed on the epicardium. Their levels were positively related to neutrophils, monocytes, and fibroblasts-related markers and negatively to adiposity markers. Both, plasma and epicardial CA125 levels were increased in HF patients. In this group of patients, epicardial CA125 levels were positively associated with circulating and local neutrophil activity, measured by defensin 3 levels. After testing all markers between women and men in HF patients, we observed similar levels in plasma and epicardial CA125. However, higher plasma and epicardial adiposity markers and lower mesothelial marker ITLN-1 were detected in women than in men. Conclusion CA125 is expressed in epicardial cells and its higher levels in HF might explain the higher detected levels in plasma. Its association with local and peripheral neutrophils-related markers with CA125 suggests its common pathophysiological mechanism in women and men. However, high plasma and epicardial adiposity and low mesothelial marker ITNL-1 in epicardium in women might explain the differential mechanism in HF.

Association between lipoprotein particle concentration and size and progression of coronary plaque: the MACS Longitudinal Coronary CT angiography study

Abstract Background People living with HIV have greater risk of cardiovascular diseases (CVD) than people without HIV and tend to have different risk profiles, including higher serum triglycerides and lower LDL cholesterol levels. Nuclear magnetic resonance (NMR) provides a detailed phenotype of lipoproteins. Purpose To examine the associations between lipoprotein particle concentrations and size and progression of coronary artery plaque among people living with and without HIV, and whether these associations differ by HIV serostatus. Methods Men with no clinical CVD in the Multicenter AIDS Cohort Study (MACS) who underwent a coronary CT angiography at baseline (2010-13) and follow-up (2015-17) were included. NMR spectroscopy was completed on fasting serum samples at baseline. Logistic regression models for the change in total coronary plaque volume (in tertiles) were estimated with NMR-derived lipoproteins as predictors. Levels were log-transformed and standardized to make results comparable. Models were adjusted for demographics, statin use and HIV serostatus (model 1) with addition of CVD risk factors (model 2). Interactions by HIV serostatus were also tested. Results A total of 549 men (314 with HIV; 235 without HIV) were included. Mean age was 53 ±7 years; 58% were White, 30% Black, and 12% Hispanic. Coronary plaque was present in 70% and plaque volume progressed in 79% of the cohort. Among men with HIV, 81% had undetectable HIV RNA and 12% had a diagnosis of AIDS at baseline. Men with HIV had significantly higher levels of small LDL-P, and total, medium and large VLDL-P levels compared to men without HIV, and lower levels of total, small and large HDL-P (Table 1). Men with HIV had significantly greater progression of plaque volume (37 mm3) compared to men without HIV (31 mm3, p<0.05). Levels of total and small LDL-P concentrations were directly associated with plaque progression, whereas large HDL-P was inversely associated with plaque progression in the combined sample (Model 2). Associations between total and small LDL-P with plaque progression were stronger in men with HIV than in men without HIV in models 1 and 2 (interaction p<0.01). While associations in fully adjusted models for total VLDL-P and small VLDL-P were significant in men without HIV, there were no significant associations between these particle concentrations with coronary plaque progression among men without HIV (interaction p< 0.01) (Model 2, Table 2). Conclusion Associations between lipid particle concentrations and coronary plaque progression differed between men with and without HIV, with stronger associations seen in men without HIV for total and small LDL-P. Despite having higher VLDL and lower HDL particle concentrations at baseline, these particle concentrations were only associated with plaque progression in men without HIV. Further research is needed to elucidate HIV specific factors for plaque progression to tailor risk reduction strategies.

Assessing the impacts of climate change on the vulnerability of coastal aquifers to the seawater intrusion

In most coastal areas, groundwater is affected by saltwater intrusion. Climate change effects, such as the sea-level rise and rainfall change are the climatic factors affecting the saltwater intrusion into groundwater. This study examines the vulnerability of the Abdan-Lamidan coastal aquifer to the intrusion of Persian Gulf saline waters under different hydrological conditions. First, the SIMCLIM model was used to calculate the regional sea-level rise of the Gulf under 24 future AOGCMs projections. The results showed that the increase in water level under the ensemble of AOGCM models and two RCP2.6 and RCP8.5 scenarios is 6.7 and 7.8 cm in 2050 compared to 2013. Then, the GALDIT vulnerability index was used to assess the vulnerability of the aquifer under the current condition and future scenarios. The results showed that parts of the aquifer that are currently at lower levels would be more vulnerable to sea-level rise in the future periods.

RACK1 contributes to the upregulation of embryonic genes in a model of cardiac hypertrophy

Receptors for activated C kinases (RACKs) have been shown to coordinate PKC-mediated hypertrophic signalling in mice. However, little information is available on its participation in embryonic gene expression. This study investigated the involvement of RACK1 in the expression of embryonic genes in a zebrafish (ZF) ex vivo heart culture model by using phenylephrine (PE) or a growth factors cocktail (GFs) as a prohypertrophic/regeneration stimulus. Blebbistatin (BL) inhibition has also been studied for its ability to block the signal transduction actions of some PEs. qRT‒PCR and immunoblot analyses confirmed the upregulation of RACK1 in the PE- and GFs-treated groups. BL administration counteracted PE-induced hypertrophy and downregulated RACK1 expression. Immunohistochemical analyses of the heart revealed the colocalization of RACK1 and embryonic genes, namely, Gata4, Wt1, and Nfat2, under stimulation, whereas these genes were expressed at lower levels in the BL treatment group. Culturing ZF heart cells activated via GFs treatment increased the expression of RACK1. The overexpression of RACK1 induced by the transfection of recombinant RACK1 cDNA in ZF heart cells increased the expression of embryonic genes, especially after one week of GFs treatment. In summary, these results support the involvement of RACK1 in the induction of embryonic genes during cardiac hypertrophy/GFs stimulation in a fish heart model, which can be used as an alternative study model for mammals.

Secretoneurin plasma levels are decreased after catheter ablation for atrial fibrillation, patients with AF produce lower SN levels than healthy individuals

Abstract Background Secretoneurin (SN) is a novel biomarker with potential use in cardiovascular medicine. The main effect of SN is mediated through its inhibition of calmodulin-dependent kinase II (CaMKII), which influences calcium handling[1], plasma SN levels differ in ischemic vs. dilated cardiomyopathy [2]. We aim to associate the levels of SN pre- and postprocedurally and according to the type of atrial fibrillation (AF). Methods We prospectively enrolled patients indicated for catheter ablation (CA) for AF, sequentially sampled patients for SN before, during and after CA for AF. We also sampled healthy individuals as controls. SN was analysed from venous, left atrial and coronary sinus (CS) blood by the use of the ELISA method. Values are expressed as means±SD, variables are compared by standard statistical methods. Results A total of 104 patients (59.4% male) with AF aged 64±10.4, with BMI 30.1±5 and 34 healthy individuals (38% male) were included in the analysis. SN plasma levels were significantly lower 32.3±15.1 after the procedure (SN2) as compared to levels before (SN1) 38.4±17.5 pmol/L (P=0.02, Fig.1). SN was not associated with any marker of cardiac injury or overload, echocardiographic parameters, or ablation characteristics (P=NS), even though Troponin I was significantly increased after the procedure (P<0.0001, Fig.2). Left atrial SN was numerically higher 40.9±19.1 than SN sampled from CS 32.9±13 (P=NS).The SN levels in our patients with AF were generally lower than in healthy individuals (50.7±15.3 pmol/L) before (P=0.0004) as well as after the procedure (P=0.0001). Conclusion Catheter ablation of AF leads to a decrease in SN plasma levels even though markers of cardiac injury are increased. Patients with AF irrespective of actual rhythm produce lower levels of SN than healthy individuals.

What characterizes normotensive individuals with obesity and normal systolic heart function? A descriptive study from the SCAPIS cohort

Abstract Background Heart failure and cardiovascular disease are strongly related to obesity, and the incidence of these conditions shows a linear relationship with increasing body mass index (BMI). Despite these known facts, some individuals with obesity show no clinical signs of heart disease or arterial hypertension (AH). Purpose We aimed to investigate the characteristics of individuals with obesity without impaired left ventricular function and left ventricular hypertrophy (termed systolic heart function, SHF) and AH, compared to individuals with obesity with signs of impaired SHF or AH, and individuals without obesity with and without signs of impaired SHF or AH. Method A cross-sectional analysis was performed of the 4,692 individuals who had undergone a transthoracic echocardiography within the Swedish CArdioPulmonary bioImage Study (SCAPIS). Participants were divided into four groups: 1) individuals with obesity (BMI³30 kg/m2) without impaired SHF (normal left ventricular systolic function and left ventricular mass) and no AH (based upon the absence of antihypertensive treatment) (ObSHF/AH-, n=623; 13%), 2) individuals with obesity with impaired SHF or AH (ObSHF/AH+, n=252; 5%), 3) individuals without obesity and without impaired SHF and no AH (NObSHF/AH-, n=3179; 68%) and 4) individuals without obesity with impaired left ventricular systolic function, left ventricular hypertrophy or AH (NObSHF/AH+, n=638; 14%). Individuals in group 1 (ObSHF/AH-;) were compared to those in groups 2-4 through descriptive analyses. Results Compared to ObSHF/AH+ individuals, ObSHF/AH- subjects showed significantly lower HbA1c (p<0.001), fasting plasma glucose (p<0.001), triglyceride (p<0.001), NT-proBNP (p=0.035) and troponin I (p<0.001) levels. Furthermore, no significant differences between the two obese groups could be seen regarding BMI (p=0.074), whereas waist-to-hip ratio was lower in ObSHF/AH- subjects (p<0.001). ObSHF/AH- individuals had higher glucose and lipid levels as well as higher blood pressure than individuals without obesity. Interestingly, no differences were seen between ObSHF/AH- and NObSHF/AF- subjects regarding NT-proBNP (p=0.864) and troponin I levels (p=0.110). Furthermore, left ventricular mass index (LVMI) was significantly higher in ObSHF/AH- subjects compared to NObSHF/AH- individuals (73.8 vs. 72.1 g/m2, p=0.015) and the ejection fraction was significantly lower (57.4 vs. 59.6 %, p<0.001). Conclusion When ObSHF/AH- and NObSHF/AH- subjects were compared, markers of cardiac damage/remodeling did not differ significantly, indicating that heart function might be preserved despite a worsened metabolic profile and an obese phenotype, through putative protective mechanisms yet to be explored. However, parameters of SHF were unfavorable for ObSHF/AH- when compared to NObSHF/AH-, further implicating preclinical cardiac impairment in individuals with obesity.

An Elevated FIB-4 Score is associated with the severity of heart failure

Abstract Background Liver disease and heart failure (HF) are known to be closely associated. Non-invasive tests (NIT), such as the FIB-4 score, have been recommended by different guidelines to rule out advanced liver fibrosis and to stratify the risk of liver-related outcomes in patients with chronic liver diseases. Purpose Thus, our goal was to evaluate the connection between the FIB-4 index, heart failure, associated comorbidities, and cardiological biomarkers that predict the risk of liver fibrosis in patients with heart failure. Methods HF patients hospitalized in the cardiology department were divided into a group with an FIB-4 index <1.3 (indicating a low risk of liver fibrosis) (n=53) and a group with an FIB-4 index ≥1.3 (indicating intermediate and high risk of fibrosis) (n=59). Clinical examinations, laboratory results, echocardiography with Vivid E95-GE Healthcare, non-invasive body mass analysis with Body Composition Analyzer (Tanita Pro), and measurements of NT-proBNP, growth differentiation factor 15 (GDF-15), galectin-3, fatty acid-binding protein (FABP), copeptin, and vascular endothelial growth factor (VEGF) concentrations were performed. Results The patients with an FIB-4 index ≥1.3 had significantly higher: left ventricular volume index (LAVI) (p=0.004), E/E’ ratio (p=0.004) and lower left ventricular ejection fraction (p=0.003) compared to group with low risk of liver fibrosis. There were no differences in body mass compartments between groups except for ECW/TBW (%) - an index of body water distribution, which was lower in low-risk liver fibrosis group (p=0.0002). Patients with an FIB-4 index ≥1.3 had also lower: GFR MDRD (median 59.95 vs 85.1 mL/min/1.73 m²; p<0.001), total cholesterol (116.5 vs 15 mg/dL; p=0.002), LDL cholesterol (median 56 vs 93 mg/dL; p<0.0001) and HDL cholesterol (median 39 vs 47 mg/dL; p=0.03). Regarding heart failure biochemical biomarkers, patients with low risk of liver fibrosis had significantly lower level of NT-proBNP (median 37 vs 161 pg/ml; p<0.0001), GDF-15 (median 399.6 vs 898.9 pg/ml; p<0.0001) and FABP (median 101 vs 264,7 pg/ml; p=0.04). In a multiple logistic regression model the factors that were independently associated with the risk of liver fibrosis in HF patients based on an FIB-4 index were GDF-15 >724 pg/ml (OR 33.7, 95%CI: 6.5-174.2; p=0.0001), and NT-proBNP >129 pg/ml (OR 19.9, 95% CI: 3.8-103; p=0.0001) (Figure 1) Conclusion Our study suggests association between an elevated FIB-4 score and heart functions, and kidney impairment with fluid overload but not with higher total and low density cholesterols fractions or percentage of fat. Higher GDF-15 and NT-proBNP levels are independently associated with the risk of liver fibrosis based on an FIB-4 index. FIB-4 index in HF patients is an easy method to monitor the risk of liver fibrosis and might help to predict the HF progression and CVD complications.

Prognostic value of baseline and follow-up ECG in patients with biopsy-proven fulminant myocarditis

Abstract Background Fulminant myocarditis represents a life-threatening condition with poor outcomes characterized by increased short- and long-term mortality and need for heart transplant. Treatment largely relies on mechanical support and immunosuppressive therapy guided by histologic and virology findings but reliable short-term prognostic markers guiding therapy and management are still lacking. We hypothesised that baseline and short-term ECG evolution may provide relevant easily accessible prognostic information in these patients. Purpose We sought to assess the prognostic value of baseline and short-term follow-up ECG in patients affected by fulminant myocarditis. Methods We retrospectively enrolled patients with biopsy-proven fulminant myocarditis according to current diagnostic criteria. We evaluated baseline and follow-up ECG (performed 3 to 7 days after admission) together with clinical, laboratory and histologic data. The primary endpoint was a composite of in-hospital mortality or need for urgent heart transplantation. Results We enrolled 39 patients (22/39 M, 56.4%) and a mean age of 38 years. Histology demonstrated lymphocytic myocarditis in 35/39 cases, 2 eosinophilic and 1 giant cell myocarditis, 1 sarcoidosis. All patients received vasopressor and/or inotrope therapy with 19/39 requiring mechanical circulatory support. Follow-up ECGs were performed after 4.8±1.3 days from admission. The primary endpoint was reached in 7/39 patients (17.9%) with 5 deaths and 2 urgent cardiac transplants. These patients more commonly required mechanical (85.7% vs 40.6%, p=0.044) or extracorporeal membrane oxygenator (85.7% vs 12.5%, p<0.001) support and showed higher lactate levels on admission (11.0±7.3 vs 4.2±3.1 mmol/L, p=0.001). They also more frequently had cardiac arrest as first clinical presentation (50. 0% vs 9.7%, p=0.022) and sustained ventricular tachycardia (71.4% vs 15.6%, p=0.007) in the acute phase. Patients with a worse outcome showed persistence of low voltages (< 5 mm in all peripheral leads) at follow-up ECG (100.0% vs 37.5%, p=0.003) with lower R wave amplitude in lead II (1.1±0.9 vs 4.0±2.6 mm, p=0.004), III (0.7±0.5 vs 2.5±2.2 mm, p=0.043), aVF (0.9±0.7 vs 3.0±2.0 mm, p=0.01) and V6 (3.0±2.8 vs 7.5±4.2 mm, p=0.011) and reduced S wave amplitude in V1 (2.6±3.9 vs 6.4±4.4 mm, p=0.047), V2 (3.9±3.9 vs 10.2±6.7 mm, p=0.035), V3 (3.3±3.2 vs 10.7±6.7 mm, p=0.007) leads. Low QRS voltages at baseline ECG were not associated with worse prognosis (71.4% vs 46.9%, p=0.407). No significant difference in terms of steroid (85.7% vs 78.1%, p=0.929) or other immunosuppressive (14.3% vs 31.2%, p=0.366) therapy was observed between the groups. Conclusions In patients with fulminant myocarditis, persistence of low QRS voltages at 5-day follow-up ECG is associated with adverse in-hospital outcomes. Short-term ECG evolution can identify high-risk patients requiring earlier and more intensive mechanical and pharmacological treatment.

Red-cell omega-3 fatty acids associate with increased hippocampal volume and superior longitudinal cognition in atrial fibrillation

Abstract Background Atrial fibrillation (AF) is associated with cognitive impairment and dementia. Omega-3 Fatty Acids (n-3 FAs) have anti-thrombotic, anti-inflammatory and anti-oxidative properties; however, their neuroprotective effects remain controversial. Here, we report the association of n-3 FAs with both structural (hippocampal volume) and functional (cognition) readouts in a large cohort of AF pts. Purpose a) To determine the association of n-3 FAs and left and right hippocampal volume at baseline in AF pts. b) To assess the predictive value of HV and n-3 FAs for the risk of cognitive impairment after a 7-year follow-up period. Methods This prospective ongoing multicenter Swiss Atrial Fibrillation study (Swiss-AF) included 2,359 pts with documented AF and baseline red-cell n-3 FAs levels, measured by gas chromatography and mass spectrometry. Hippocampal volume (HV) and segmentation based intracranial volume (ICV) were analyzed by FreeSurfer's (v 7.4.0) subregion segmentation module and Sequence Adaptive Multimodal SEGmentation from brain MRI in 1,736 pts. Detailed neurocognitive assessments in pts at baseline and follow up periods were performed. We used mixed-effect linear regression models to determine the association of n-3 FAs and HV. For conversion to cognitive impairment (defined as MoCA score < 26), we performed cox-proportional hazards regression model. Two adjustment models were applied as described in the figures. Results Patients with AF (mean age, 73 years old [±8.5 SD]; 157 women [27%]) with 9569 cognitive evaluations (mean follow-up, 3.6 years [±2.3 SD]) were assessed. At baseline, we observed statistically significant associations between total n-3 FAs levels (EPA + DHA + ALA + DPA) and individual n-3 FAs (EPA, DHA, DPA) with increased HV after adjustment for ICV and other covariates (Fig1A, 1B). After all adjustments, EPA remained associated with both bilateral HV and right HV. Furthermore, we observed a significant association between HV and neurocognitive assessments, as measured both in global (MoCA, CoCo) and specific tests (TMT-A, TMT-B, DSST, SF) (Fig1C). Over time, quartile 4 (Q4, highest n-3) compared to quartile 1 (Q1, lowest), had a 16% lower risk of cognitive impairment (HR, 0.84 [CI 0.75-0.93]; P=0.001) for total n-3 FAs and even 30% lower specifically for EPA (HR, 0.7 [CI 0.63-0.78]; P<0.001). The risk of cognitive impairment was 47% lower (HR, 0.53 [CI 0.45-0.63]; P<0.001) when the highest HV Q4 was compared to lowest HV Q1 (Fig2A). In combination, the highest quartile of bilateral HV and EPA demonstrated an increased probability of being cognitive impairment-free and they had a 72% lower (HR, 0.28 [0.18-0.43]; P<0.001) risk of cognitive impairment (Fig2B). Conclusions 1. Red cell n-3 FAs levels are associated with higher HV in AF pts. 2. Higher baseline levels of n-3 FAs, particularly of EPA, are associated with both an increased HV and a decreased risk of cognitive impairment after 7 years follow up.

Elevated GDF-15 is associated with stroke severity, myocardial injury and poor clinical outcome in patients after acute ischemic stroke

Abstract Background GDF-15 is emerging as a biomarker of cardiometabolic risk and disease burden. Increased concentrations of circulating GDF-15 are associated with increased mortality in patients with acute coronary syndromes or heart failure. Purpose We aimed to describe relation between GDF-15 elevation with stroke severity, myocardial injury and poor clinical outcome in patients after acute ischemic stroke (AIS). Methods Patients after AIS were enrolled in our study. Blood samples were obtained from patients at the time of admission, 24 and 48 hours later to determine the plasma levels of GDF-15 and high-sensitive troponin I (hs-cTnI). Receiver-operating characteristic (ROC) curve analysis was used to determine the diagnostic accuracy and optimal elevation cut-off values of GDF-15 on day 1 for the severity of acute stroke defined by NIHSS score. The optimal cut off in our group was 1776 pg/ml (Sensitivity 0,8, Specificity 0,52). Myocardial injury was defined by fourth universal definition of myocardial infarction using hs-cTnI. Demographic characteristics, clinical data, functional outcome, and all-cause mortality at 1 year were compared between groups according to GDF-15 levels. National Institutes of Health Stroke Scale (NIHSS) at the time of admission and the modified Rankin Scale (mRS) 90 days following the patient’s discharge from the hospital were used to assess stroke severity and clinical outcome. All analyses were performed with SPSS 29.0 (SPSS Inc). Results Between August 2020 and August 2022, 177 patients after AIS were enrolled. Elevated GDF-15 was observed in 71 patients (40,1%). Most common comorbidities included arterial hypertension, dyslipidemia, type 2 DM and atrial fibrillation. In analysis, we observed a connection between elevated GDF-15 with unfavourable outcome evaluated by mRS at 90 days (HR 2.57, 95% CI 1,44 to 4,57, p=0.001) and with all-cause death at 1 year (HR 4.479, 95% CI 1,81 to 11,09, p=0.001). GDF-15 elevation was associated with myocardial injury (Figure 1C). Moreover, individuals with moderate to severe and severe strokes (NIHSS 16-42) displayed higher GDF-15 levels compared to those with minor to moderate stroke (Figure 1D). The Kaplan-Meier survival curve accentuated a significantly elevated all-cause mortality among patients with increased GDF-15 (p < 0.001) (Figure 2). In multivariate regression analysis elevated GDF-15 was associated with atrial fibrillation and high-sensitive troponin I elevation. Conclusion The conclusions drawn suggest that heightened GDF-15 is associated with increased stroke severity, myocardial injury and unfavourable outcome.

Baseline C-reactive protein as a predictor of non-ischemic LGE in myocarditis

Abstract Background Identifying reliable early indicators of myocardial injury in myocarditis is a pressing concern in cardiology. Despite their established role in detecting myocardial necrosis, traditional markers like high-sensitivity cardiac troponin (hs-cTn) may not fully capture the extent of myocardial damage identified by non-ischemic late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) Purpose To identify early admission biomarkers associated with non-ischemic LGE in patients with myocarditis, offering the potential for improved risk stratification and therapeutic targeting. Methods In this retrospective study, we analyzed 59 myocarditis patients admitted to a high-volume medical center from 2017 to 2023, who underwent CMR to evaluate LGE. 41 patients (69.5%) exhibited non-ischemic LGE and 18 (30.5%) did not. We assessed baseline laboratory and echocardiographic parameters, employing Pearson correlation, logistic regression, and ROC curve analyses to elucidate the potential association of baseline biomarkers with non-ischemic LGE, while also discerning subepicardial from midwall patterns. Results Baseline C-reactive Protein (CRP) levels were significantly correlated with non-ischemic LGE (Pearson's r=0.301, p<0.05). Logistic regression analysis substantiated CRP as a predictor of non-ischemic LGE (OR=1.41, p<0.05), corroborated by a multivariate approach even after accounting for age and sex (OR=1.33; p<0.05). Among non-ischemic patterns, subepicardial LGE exhibited the strongest correlation with CRP (Pearson's r=0.321, p<0.05). In contrast, hs-cTn levels showed no significant association with non-ischemic LGE. The ROC analysis revealed that while both CRP and hs-cTn provide valid predictive values for non-ischemic LGE, with AUCs of 0.7333 and 0.6898 respectively, CRP demonstrated a higher discriminative performance, indicating that CRP may offer a more reliable assessment in this clinical context. Additionally, diabetic status emerged as the most significant condition associated with increased CRP levels, with diabetic patients presenting a substantial elevation in baseline CRP compared to non-diabetic patients (8.75 mg/dl vs 3.21 mg/dl; p<0.05). Conclusion CRP appears as a key early biomarker for non-ischemic LGE in myocarditis, with its predictive value being particularly evident in the subepicardial pattern and notably more pronounced among diabetic patients who demonstrate an increased inflammatory burden. These findings suggest a critical role for CRP in risk stratification right from the point of hospital admission and underline the potential for tailored therapeutic approaches that warrant further investigations. Figure 1: ROC curves comparison for CRP and hs-cTn in predicting non-ischemic LGE in myocarditis patients. Figure 2: Patients with diabetes (DM) exhibit significantly higher CRP levels (mean 8.75 mg/dl, SE = 5.54 mg/dl) than those without DM (mean 3.21 mg/dl, SE = 0.49 mg/dl).ROC curves comparisonCPR in patients with and without DM

Characterization of individuals with atherosclerotic cardiovascular disease, with and without chronic kidney disease: results from a UK electronic health record database

Abstract Introduction Elevated C-reactive protein (CRP) levels are often present in individuals with atherosclerotic cardiovascular disease (ASCVD), including in those who also have chronic kidney disease (CKD), and are associated with an increased risk of major adverse cardiovascular events (MACE). To understand unmet needs in the identification and management of at-risk individuals, we characterized patients with ASCVD in a UK database, according to CKD stage and CRP levels. Methods This study comprised separate retrospective cross-sectional and longitudinal cohort analyses of patients in the Clinical Practice Research Datalink (CPRD) Aurum database, a representative UK database of anonymized primary care records. In the cross-sectional analysis, CPRD Aurum was linked with Hospital Episode Statistics (HES) and Index of Multiple Deprivation data to assess patient characteristics on 1 Jan 2021 (defined as index date). In the cohort analysis, CPRD Aurum was linked with HES and Office for National Statistics mortality data to determine the incidence of 3-point MACE (3P-MACE) over approximately 5 years of follow-up (index date: 1 Jan 2016). Both analyses included individuals ≥ 18 years old with an ASCVD diagnosis in both primary and secondary care in the 5 years pre-index. Data were analysed using descriptive statistics. Patient characteristics were assessed by CKD stage; for individuals with CKD stage 3–4, characteristics were also assessed by CRP levels. Results In total, 225,767 and 230,055 individuals were included in the cross-sectional and cohort analyses, respectively. The prevalence of CKD stage 3–4 among individuals with ASCVD was 24.3% (Table 1). The proportion of individuals with elevated CRP (CRP ≥ 2 mg/L) and anaemia increased for successively higher CKD severity groups; in addition, glycated haemoglobin (HbA1c) ≥ 7% and elevated blood pressure were generally more frequently observed in individuals with CKD than in those without (Table 1). Individuals with ASCVD, CKD stage 3–4 and elevated CRP had higher HbA1c and total cholesterol levels and a greater proportion had obesity, anaemia and elevated blood pressure, compared with individuals with CRP < 2 mg/L (Table 2). Over 5 years’ follow-up, the incidence of 3P-MACE increased with CKD severity (Table 1) and with increasing CRP levels in individuals with ASCVD and CKD stage 3–4 (Table 2). However, only 28% of individuals with ASCVD and CKD stage 3–4 had CRP measurements. Conclusion Adults with ASCVD, CKD and elevated CRP identified from primary and secondary UK care records had a higher disease burden than individuals with CRP levels < 2 mg/L. In the UK, testing CRP levels is not routinely recommended, resulting in a high proportion of missing CRP measurements in this study. Routine testing of CRP may help in identifying patients with residual cardiovascular risk and has the potential to support risk assessment and management of patients with ASCVD and CKD.

6.G. Scientific session: The importance of using country-specific severity distributions in burden of disease indicators

Abstract One of the most commonly used health gap summary measures in the field of public health is the Disability-adjusted life year (DALY). It has become the key metric for quantifying the burden of disease (BoD) and is used as an information source for setting priorities for health care and health service planning. The DALY metric quantifies gaps between a theoretical population in perfect health and the current health status related to both morbidity and mortality. It is the sum of the number of healthy life years lost due to disability (YLD) and death (YLL). The YLD summarises the loss of healthy life time using the frequency of diseases differentiated by severities or related health states (including sequelae). Depending on each health state, it converts the time spent with diseases into YLD by weighting each year with health limitation with so-called disability weights. This allows the two indicators YLL and YLD to be added to the DALY. Consequently, severity distributions are a means of describing the range of health loss along specific health states, which enables an accurate mapping with disability weights. For most of the diseases, these distributions are usually categorised as mild, moderate, severe, or no health loss (asymptomatic). Conditions with higher severity levels contribute more to the YLD and thus, to the overall disease specific BoD. The severity distributions are highly dependent on utilization at the individual level, but also on available health care services at the society level, which indicates that differences by settings are to be expected. Changes over time in the share of severe cases, for instance, may reflect the effectiveness of health interventions and policies. This underlines the importance of severity distributions, as they also reflect information about the quality of healthcare for those affected. The Global Burden of Disease (GBD) study applies for a significant proportion of their considered diseases uniform severity distributions across countries and broader regions. They acknowledge concerns over applying estimates of severity distributions based on limited data, noting that it is the only available information that they were able to use. As the YLD estimates are often utilized to develop and prioritize health policy interventions, there is a necessity for country-specific estimates that are evidence based and less susceptible to model assumptions. In most cases, the estimation of severity distributions involves complex methodology as data for such assessments are very limited or hardly reliable. In the following workshop, general concepts and country cases from Germany, Scotland, and Belgium will be presented covering a variety of diseases. The examples underline the importance of estimating national and even regional severity distributions when identifying the importance of diseases or comparing the health conditions of populations across time. Key messages • As the Burden of disease indicators are predominantly used to prioritize health interventions and allocate resources, it is crucial to use accurate information in the severity levels of disease. • Severity distributions reflect the health care services and vary across different settings. Utilising country-specific severity distributions when estimating Burden of Disease indicators is essential.

Diastolic shock index: a novel prognostic parameter unveiling insights into vasodilatory cardiogenic shock

Abstract Introduction Systemic vasodilation is an increasingly acknowledged feature in cardiogenic shock (CS), defining a subset of patients with low systemic vascular resistances and higher vasopressor requirements. While a diastolic shock index (DSI) above 2.0 predicts vasoplegia and mortality in septic shock, its cut-off and prognostic significance in CS remain unclear. Our study aimed to characterize vasoplegia in CS using the DSI and assess its impact on prognosis. Methods Single-center retrospective cohort study on Cardiac Intensive Care Unit (CICU) admissions for CS from January 2017 to October 2023. Data included patient variables, CS features, vasoactive drugs, mechanical circulatory support, and 30-day mortality. DSI (heart rate (HR) to invasive diastolic blood pressure (DBP) ratio) impact on 30-day all-cause mortality was assessed with univariate Cox regression. Optimal DSI cut-off for adverse outcomes was determined through ROC curve analysis, and survival based on this cut-off was analyzed using Kaplan-Meier curves. Results 185 patients (mean age 59 ± 12 years, 63% male) were included. Acute myocardial infarction-related CS (47%) and heart failure-related CS (29%) were predominant. According to SCAI classification, 86% were class C, 22% class D, and 4% class E, with 26% experiencing previous cardiac arrest. Median Vasoactive-Inotropic Score (VIS) was 48 (IQR 21-85), and 25% used mechanical circulatory support. At admission, median HR was 105 bpm (IQR 90-125), DBP was 60 mmHg (IQR 55-65), and DSI was 1.71 (IQR 1.31-2.18). Thirty-day all-cause mortality was 36% (n=67), with median time to death of 4 days (IQR 1-10). DSI at 30 days predicted mortality (OR 1.42, 95%CI 1.06-1.91, p=0.020). DSI showed fair discriminative power for 30-day mortality (C-Statistic 0.60, 95% CI 0.51-0.68, p=0.031) with a cut-off of 2.2. Patients with DSI >2.2 exhibited heightened likelihood of prior cardiac arrest (38% vs. 20%, p=0.032), and higher serum lactate (5.5 vs. 3.9 mmol/L, p=0.008), and serum creatinine (2.64 vs. 1.88 mg/dL, p=0.003) at admission. Despite higher VIS at 48 hours (120±136 vs. 65±93.9, p=0.04), MCS need did not significantly differ. This group had superior 30-day mortality risk (log-rank p=0.011). Conclusion In our cohort, the admission Diastolic Shock Index (DSI) emerged as a promising identifier for CS vasoplegic patients and was a predictor of a higher risk for mortality. A DSI above 2.2 identified a subset of patients with previous cardiac arrest and higher lactate levels, enlightening possible risk factors associated with vasoplegia. Further studies are warranted to establish the robustness of this novel prognostic parameter in CS patients and its therapeutic implications.

Signature of diabetic cardiomyopathy progression using high-fat diet and streptozotocin mouse model: from subclinical to clinical with three-hit mouse model

Abstract Background Diabetic cardiomyopathy (DbCM) is a pre-heart failure (pre-HF) condition that usually exhibits early diastolic dysfunction and evolving systolic dysfunction, along with left ventricular (LV) remodelling. Although DbCM shows distinct pathophysiology, the transition from the subclinical to the symptomatic stage is not straightforward and usually involves multifaceted processes which are not fully understood. Purpose To define the signature of DbCM progression in a novel mouse model using longitudinal echocardiography and multi-omics approaches. Methods Male mice (C57BL/6) were fed with high-fat diet (HFD) or control diet (CD) for 24 weeks, with single dose of streptozotocin (STZ) or vehicle injection at 8 weeks (n=10 each). Serial functional and metabolic parameters were measured prior to endpoint single nuclei RNA sequencing (snRNA-seq) and mass spectrometry-based proteomics analysis with comparison to cardiac remodelling to define detailed mechanisms underlying DbCM progression. Results HFD/STZ mice developed type 2 diabetes mellitus (T2DM) based on higher fasting blood glucose and HbA1C levels, insulin resistance and decreased beta-cell function (HOMA-IR and HOMA-beta, respectively) compared to controls. Progressive diastolic dysfunction was evident in HFD/STZ mice compared to CD mice based on enlarged LVPW;d from 12 weeks (P<0.05), reduced MV E/A ratio (P<0.01) and IVRT (P<0.05) from 16 weeks, and increased cardiac filling pressure (Left atrial (LA) area and LA volume) at 24 weeks, with preserved systolic function. This was paralleled by elevated collagen deposition (Picrosirius red), myocyte cross-sectional area and Col1a1 expression in HFD/STZ versus CD mice (all P<0.05). snRNA-seq analysis indicated preferential monocyte migration into diabetic hearts (P<0.01) whilst inflammatory pathways were activated across all cardiac cell types. Proteomics analysis revealed elevated expression of the established inflammation marker, plasma C-reactive protein (CRP), in HFD/STZ versus CD mice (P<0.05), which was correlated with worsening diastolic function (MV E/A ratio: r=-0.839, P<0.01) and LV hypertrophy (LVPW;d: r=0.861, P<0.01). Conclusion Our HFD/STZ mouse model offers a ‘three-hit’ approach which effectively captures key stages of clinical DbCM progression: 1) T2DM with insulin resistance, 2) progressive diastolic dysfunction with elevated chronic filling pressure and cardiac remodelling, and 3) systemic inflammation. This improved HFD/STZ mouse model is therefore appropriate to support a detailed study of mechanisms underlying DbCM progression and subsequent translation.

Sex-specific associations between remnant cholesterol and cardiovascular risk in patients undergoing percutaneous coronary intervention: a 5-year large-sample study from the real world

Abstract Background Differences in the pathophysiological characteristics and cardiovascular risk between female and male patients with coronary artery disease (CAD) are well-established. Recent studies on the relationship between remnant cholesterol (RC) and cardiovascular risk in coronary artery disease patients have gained popularity. To date, little is known about the RC-related cardiovascular risk disparities between males and females. Purpose The aim is to investigate sex-specific differences in the association between RC and cardiovascular risk among CAD patients undergoing percutaneous coronary intervention (PCI). Methods A prospective cohort study was conducted among 10,724 CAD patients undergoing PCI from January to December in 2013. RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. The primary outcome was major adverse cardiovascular and cerebrovascular events (MACCE, including cardiac mortality, revascularization and ischemic stroke) and the secondary outcomes were each component of MACCE. Results Among 9,587 PCI patients included (the average age was 58.43 ± 10.26 years and 2,181 (22.70%) were female), 1,864 (19.4%) MACCEs were recorded during the 5-year follow-up. For primary outcome, a significant interaction was observed between RC levels and sex (P for interaction = 0.007 and 0.011, for continuous and categorical RC variables, respectively). Specifically, in male patients, no significant MACCE risk was observed at any RC level (both P > 0.05) (Figure 1). However, in female patients, both continuous RC levels (hazard ratio [HR] 1.412, 95% confidence interval [CI] 1.103-1.807) and the upper two quartiles of RC relative to the lowest quartile (Q3: HR 1.458, 95% CI 1.062-2.001; Q4: HR 1.496, 95% CI 1.081-2.070) were associated with higher MACCE risk. For secondary outcomes, higher RC levels were linked to an increased risk of cardiac mortality and revascularization in female patients but not in males (Table 1). Conclusions In a large-scale 5-year follow-up study from the real world, we are the first to demonstrate that RC-related cardiovascular risk is specifically observed in female CAD patients undergoing PCI, suggesting that female patients merit closer surveillance and more aggressive RC management to reduce cardiovascular risk.

Race/Ethnicity, Education, and All-Cause Mortality in US Adults: Mediation by Telomere Length

Abstract Background Racial/ethnic inequities in mortality risk are pervasive in the United States even after controlling for socioeconomic status indicators such as educational attainment. Although the mechanisms underlying these inequities remain unclear, telomere length (TL) has emerged as a potential mediator. We aimed to investigate the joint association of race/ethnicity and education with all-cause mortality risk, and the contribution of TL to this relationship. Methods We used data from the U.S. National Health and Nutrition Examination Survey, 1999 to 2002, and 2019 Linked Mortality File (n = 6,526 non-institutionalized adults aged 25 years or older, including 2,166 deaths), a retrospective cohort study with a follow-up period to December 31, 2019. Cox proportional hazards regression and causal mediation analysis were used to address these aims. We reported hazard ratios (HR) and 95 % confidence intervals (CI). Furthermore, for the mediation analysis, we reported the total, direct, and indirect effects measured as HR and 95 % CI. Results After adjusting for age and sex, among White individuals, those with less than a high school education had a 2.26 times higher (95% CI: 1.93, 2.65) rate of all-cause mortality compared to those with some college or higher education. When compared with White adults with at least a college degree, Black adults with at least a college degree had a 1.38 higher rate of dying (95% CI: 1.04, 1.84). There was no significant joint association of race/ethnicity and education on all-cause mortality in Mexican Americans. In the mediation analysis, TL did not significantly contribute to the joint association of race/ethnicity and education with all-cause mortality risk. Discussion These findings underscore the need for a better understanding of the joint relationship of race/ethnicity and education on mortality risk inequities and their potential mechanisms to improve population health ultimately. Key messages • Lower educational attainment was associated with higher mortality rates among White individuals, disparities persisted among the Black population, despite higher education levels. • Our analysis did not find a significant mediation effect of telomere length on the joint effect of race/ethnicity and education-mortality relationship.

Prognostic impact of composite lipid indices in patients with acute coronary syndrome undergoing percutaneous coronary intervention

Abstract Background Composite lipid indices have been reported to have associations with several cardiovascular diseases and their negative adverse events. Among these, there are four novel indices that can be easily calculated, namely, triglyceride-glucose index (TyG, calculated from fasting plasma glucose [FPG] and triglyceride [TG]), lipid accumulation product (LAP, calculated from waist circumference [WC] and TG), visceral adiposity index (VAI, calculated from WC, TG, body mass index [BMI], and high-density lipoprotein [HDL]), and atherogenic index of plasma (AIP, calculated from TG and HDL). Herein, we aimed to investigate the impact of these indices on the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Methods All the patients with ACS who underwent PCI at our institution during the 2015-2022 period were included in the analyses. Patients were divided based on each of the TyG, VAI, LAP, and AIP indices quartiles (Q). The median follow-up was 378 days and the outcome assessed was MACCE composed of all-cause mortality, myocardial infarction, stroke, target vessel revascularization, target lesion revascularization, and coronary artery bypass grafting surgery. Results There was a total of 13,682 patients with ACS undergoing PCI with a mean age of 62.67 ± 11 years and 72.61% male predominance. Regarding the TyG index, patients in Q4 had a higher incidence of MACCE, compared to those in Q1 (adjusted HR [aHR] 1.271, 95% CI 1.067 – 1.513], p-value < 0.01). While in the crude model, patients in Q2, Q3, and Q4 of LAP had significantly higher rates of MACCE, compared to Q1, this association was not observed in the age- and sex-adjusted model and fully-adjusted model. Similarly, there was no difference among the quartiles of VAI and AIP regarding the incidence of MACCE. Kaplan-Meier curves also show that there were significant differences among TyG and LAP quartiles (p-value = 0.0049 and p-value = 0.035, respectively). Conclusion As our findings suggest, patients with higher TyG levels, as a surrogate marker of insulin resistance, had a higher incidence of MACCE. LAP could also play an important role in the incidence of adverse events after PCI. These novel lipid indices could help clinicians in determining the risks of patients with ACS undergoing PCI in order to provide better care to them.Risk of MACCE in different quartilesKaplan Meier Curves for risk of MACCE

Performance variables and nutritional status analysis from Moroccan professional and adolescent football players during the competition period: a descriptive study

IntroductionNutrition plays an integral role in optimizing football players’ performance during training sessions and matches and maintaining their overall health throughout the season. This study aimed to evaluate how well the dietary practices of professional and adolescent football players in Morocco during the competitive period met international macronutrient recommendations, and to explore the relationship between their nutritional status and aerobic performance, as measured by the Yo-Yo IRL1 test.MethodsA total of 277 footballers from Morocco's professional league, “Botola-Pro”, were monitored over a seven-day (training microcycle) during the competitive period. The dietary intake was assessed through self-reported methods and 24-hour recalls. Relevant body composition was measured with bioelectrical impedance (BI), and aerobic performance was evaluated using the Yo-Yo IR test.ResultsThe results indicated significant variations in performance and nutritional status across different categories and age groups. The nutritional status of the players didn't match the UEFA recommendations (p < 0.001). We found that higher intake levels of carbohydrates and proteins were positively correlated with the total distance covered by the players (p < 0.001, r = 0.63, R2 = 0.4 for carbohydrates; p < 0.001, r = 0.59, R2 = 0.35 for proteins). Conversely, a higher proportion of energy derived from fats in the diet was negatively correlated with the distance covered (p < 0.001, r = −0.64, R2 = 0.41).ConclusionThese findings suggest that optimizing carbohydrates and protein intake while managing fat consumption is crucial for enhancing sporting performance. This information is essential for tailoring training programs and nutritional regimens based on the competition level.

High-sensitivity troponin T and risk of stroke in persons with suspected acute coronary syndrome

Abstract Background Serial high-sensitivity troponin (hsTn) concentrations are associated with the risk of recurrent ischemic events and death from any cause. Higher hsTn levels may suggest greater infarct size and possibly, a more pronounced risk of non-coronary atherosclerotic events. Purpose To examine the association between single and serial hsTnT levels and the risk of incident stroke in individuals presenting with suspected acute coronary syndrome. Methods In this Danish nationwide registry-based study, we identified individuals without a history of stroke who presented for myocardial infarction, unstable angina, suspected myocardial infarction, or chest pain from 2013 through 2019, and who underwent serial hsTnT (Roche Diagnostics, Rotkreuz, Switzerland; 99th percentile upper reference limit: 13.5 ng/l) measurements 1-7 hours apart. Subjects were stratified according to their hsTnT level pattern from first to second measurement (main groups: normal, rising, persistently elevated, or falling) and the magnitude of hsTnT level change (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, 10-16 ng/l, 17-68 ng/l, >=69 ng/l). The standardized risk of stroke was computed using multivariable logistic regression with average treatment effect modeling. Results The final study sample consisted of 26867 persons, of whom 10407 (38.7%) were diagnosed with myocardial infarction, 1404 (5.2%) with unstable angina, and 15056 (56.0%) with suspected myocardial infarction or chest pain. Median age was 64.3 years, and 40.1% were women. The prevalences of known cardiovascular disease were as follows: coronary artery disease, 20.2%; prior coronary revascularization, 8.4%; heart failure, 6.4%; and atrial fibrillation, 8.9%. At 30 days, 69 individuals had been diagnosed with a stroke, and an additional 185 individuals were diagnosed from days 31 through 365. The standardized risk of stroke at 30 days was <=0.31% in all main groups and did not meaningfully differ from each other. The risk remained low between days 31-365 (<=0,79%), with no significant between-group difference. The magnitude of hsTnT change within each group did not affect stroke risk, nor did hsTnT quartile based on the first measurement. Conclusions Persons with suspected acute coronary syndrome had a very low overall risk of incident stroke. Single or serial hsTnT levels at presentation did not seem helpful in identifying individuals at an increased risk of stroke.