bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cystatin C predicts cardiovascular events in patients with coronary artery disease both among patients with and among those without type 2 diabetes
Authors: Plattner T , Larcher B , Mader A , Vonbank A , Leiherer A , Muendlein A , Drexel H , Saely C H 
Published: October 2024

Abstract
Cystatin C is an established biomarker for renal function, and, given the close association of chronic kidney disease and cardiovascular disease might indicate new-onset or deteriorating cardiovascular disease. However, evidence for cystatin C as a predictor of cardiovascular events is limited and controversial. We therefore aimed at investigating the role of cystatin C as a predictor of future cardiovascular events in a high risk-cohort of patients with established coronary artery disease (CAD).
We prospectively recorded cardiovascular events in 1053 patients with angiographically verified CAD over a mean follow-up of 9.5±5.3 years. At baseline, 352 patients had type 2 diabetes mellitus (T2DM) and 701 did not have T2DM.
During follow-up, 560 (53.2%) of our patients suffered cardiovascular events. Cystatin C proved to be a strong and independent predictor for cardiovascular events in the total study cohort (standardized adjusted HR 1.22 [1.12-1.33], p&lt;0.001). When T2DM status was taken into account, cystatin C significantly predicted cardiovascular events both in patients with T2DM (HR 1.18 [1.04-1.35], p=0.011) and in non-diabetic patients (HR 1.23 [1.09-1.38], p&lt;0.001).
We conclude that cystatin C predicts cardiovascular events in CAD patients both among those with and among those without T2DM.
Remnant cholesterol is associated with platelet reactivity for patients with coronary artery disease underwent percutaneous coronary intervention
Authors: Liu M L , Li J W , Yan K L , Yuan J Q , Zhao X Y 
Published: October 2024

Abstract

Background
In recent years, remnant cholesterol has received increasing attention and has been shown to be associated with thrombotic and bleeding events in coronary clinical research, but the mechanisms are not fully understood.

Aim
To investigate the relationship between the remnant cholesterol (RC) and the platelet reactivity in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI) who were receiving the dual antiplatelet therapy (DAPT).
Methods: A total of 10,724 consecutive PCI patients in China from January 2013 to December 2013 were enrolled, among whom 6212 patients had the results of thromborlastogram (TEG) with DAPT for analysis. Low on-treatment platelet reactivity (LTPR) and high on-treatment platelet reactivity (HTPR) were defined as adenosine diphosphate-induced platelet maximum amplitude of TEG&lt;31mm and &gt;47mm, respectively.
Results: A total of 6,212 PCI patients (mean age, 58.24±10.27 years;male, 77.5%) were finally enrolled for analysis. There were 2362 (38.02%) patients in LTPR group, and 1900 (30.59%) patients in HTPR group. For LTPR,when the RC is used as a continuous variable, the multivariate logistic regression showed that RC concentration was independently and negatively associated with LTPR (OR: 0.769, 95%CI 0.610-0.968, p=0.025). For quartiles of RC, the quartile 3 of RC was also associated with LTPR, compared with the lowest quartile (Q1) (OR: 0.854, 95%CI 0.732-0.996, p=0.044). For HTPR, when the RC is used as a continuous variable, the multivariate logistic regression showed that RC concentration was independently and positively associated with HTPR (OR: 1.492, 95%CI 1.162-1.916, p=0.002). For quartiles of RC, compared with the lowest quartile (Q1), the higher quartile of RC (Q2, Q3, Q4) was also associated with HTPR (ORQ2: 1.211, 95%CI 1.024-1.431, p=0.025; ORQ3: 1.380, 95%CI 1.165-1.634, p＜0.001; ORQ4: 1.391, 95%CI 1.143-1.692, p=0.001).
Conclusions: In this large sample real-world study, we firstly reported that the lower RC concentration was an independent risk factor for LTPR, representing a higher risk of bleeding, whereas the higher RC concentration was an independent risk factor for HTPR, representing a higher risk of ischemic. These results suggest that higher or lower RC may increase the potential risk of bleeding or ischemia in patients with PCI, which provides new perspectives on individualized lipid-lowering and antithrombotic treatment strategies for patients with coronary artery disease.
Serum metabolomics improve risk stratification for incident heart failure
Authors: Oexner R R , Ahn H , Theofilatos K , Shah R A , Schmitt R , Chowienczyk P , Zoccarato A , Shah A M 
Published: October 2024

Abstract

Background
The prediction and early detection of heart failure (HF) is vital to reduce its substantial impact on quality of life, survival and healthcare expenditure. Current incident HF risk stratification strategies achieve only modest performance. Moreover, state-of-the-art risk scores focus on commonly acknowledged clinical risk factors, thus necessitating the integration of heterogenous data sources and prioritizing individuals with obvious risk constellations.

Purpose
Here, we explored the predictive value of serum metabolomics (168 metabolites detected by proton nuclear magnetic resonance (1H-NMR) spectroscopy) for incident HF.

Methods
Leveraging data of n = 68,311 individuals and &gt; 0.8 million person-years of follow-up from the UK Biobank (UKB) cohort, we (I) evaluated the association of individual metabolites with incident HF via fitting of per-metabolite COX proportional hazards models and (II) trained and validated elastic net (EN) models to predict incident HF using the serum metabolome. Discriminative performance was benchmarked against a comprehensive, well-validated clinical risk score (Pooled Cohort Equations to Prevent HF, PCP-HF). External validation was conducted in the independent FINRISK study.

Results
Several metabolites were independently associated with incident HF (90/168 adjusting for age and sex, 48/168 adjusting for PCP-HF). Performance-optimized risk models effectively retained key predictors representing highly correlated clusters (≈ 80 % feature reduction). The addition of metabolomics to PCP-HF improved predictive performance (Harrel’s C: 0.768 vs. 0.755, ΔC = 0.013 (95% confidence interval (CI) 0.004 – 0.022), continuous net reclassification improvement (NRI) = 0.287 (95% CI 0.200 – 0.367), relative integrated discrimination improvement (IDI): 17.47 % (95% CI 9.463 - 27.825)). Simplified models only including age, sex and metabolomics performed almost as well as the PCP-HF model (Harrel’s C: 0.745 vs. 0.755, ΔC = 0.010 (95% CI -0.004 - 0.027), continuous NRI: 0.097 (95% CI -0.025 - 0.217), relative IDI: 13.445 % (95% CI -10.608 - 41.454)). Risk and survival stratification was improved by integrating metabolomics. External validation within FINRISK revealed similar patterns using the original model coefficients.

Conclusions
Serum metabolomics improve the prediction of incident HF risk. Scores obtained from the combination of age, sex and metabolomics exhibit similar predictive power as clinical risk models. Offering serum metabolomics to a middle-aged cohort might significantly improve HF risk stratification, thus facilitating preventive efforts. Via a single blood draw, serum metabolomics displays a highly cost- and time-effective, standardizable, and scalable alternative to clinical risk scores involving physical measurements and history taking in addition to clinical chemistry.Relative performance (test split)ROC & DCA plots (test split)
A sex-related analysis on the influence of lipoprotein(a) on primary cardiovascular disease prevention and its interplay with traditional lipid markers: results from a 20-year cohort study
Authors: Giannakopoulou S P , Chrysohoou C , Antonopoulou S , Damigou E , Barkas F , Vlachopoulou E , Dalmyras D , Adamidis P S , Kyrili K , Kravvariti E , Tsioufis C , Pitsavos C , Liberopoulos E , Sfikakis P P , Panagiotakos D 
Published: October 2024

Abstract

Introduction
Elevated lipoprotein(a) [Lp(a)] levels is an established risk factor mediating cardiovascular disease.

Purpose
The relationship between Lp(a) and the first fatal/non-fatal CVD incident over a 20-year period in males and females without CVD was assessed.

Methods
A longitudinal prospective study was conducted during 2002–2022. In 2002, a total of 3,042 CVD-free adults (1,514 males and 1,528 females) were enrolled. A follow-up was carried out after 20 years, in 2022, which included 2,169 participants. Out of these, 1,988 had comprehensive data for the occurrence of CVD. The recommended threshold of 50mg/dL was used to define abnormal Lp(a) status (≥50mg/dL).

Results
During the 2002-2022 period, 718 (i.e. 36%) of participants had a fatal or non-fatal CVD event. Twenty-year CVD-event rate was 35.8% and 40.0% in participants with normal and abnormal Lp(a) levels, respectively. For every mg/dL increase in Lp(a), the odds of having a CVD event within 20 years increases by approximately 0.36% (Hazard ratio (HR) = 1.0036, 95% confidence interval (CI) 1.001,1.007, p=0.048). When stratified by sex the relationship remained significant only in females (HR= 1.006, 95% confidence interval (CI) 1.001,1.011, p=0.023). In the multivariate analysis, significance was lost after adjusting for low- and high-density lipoprotein (LDL-C, HDL-C) and triglycerides (HR= 1.0017, 95% confidence interval (CI) 0.998,1.005, p=0.348).

Conclusion
Elevated Lp(a) levels are linked to higher CVD risk, particularly in females. Despite growing efforts to clarify Lp(a) as a risk-predicting marker in CVD, clinical guidelines still require definitive evidence, particularly from a sex-focused perspective.
False-positive cardiac troponin I values in healthy athletes post COVID-19 Infection: concerning insights from a prospective cohort study
Authors: Kaplan E , Kissel C K , Bernasconi L , Lopez-Ayala P , Wittfooth S , Neyer P , Hure G , Sanzone A , Manka R , Noack P , Hof D , Hammarsten O , Hammerer-Lercher A , Mueller C 
Published: October 2024

Abstract

Background
Cardiac troponin I and T (cTnI, cTnT) are cardiac-specific biomarkers that detect and quantify cardiomyocyte injury. In patients with symptoms possibly indicating acute myocardial infarction (AMI), detection of elevated cTnT or cTnI concentrations usually mandates invasive coronary angiography. Accordingly, false-positive cTnT or cTnI concentrations could have detrimental consequences. Unfortunately, little is known about the prevalence and triggers of false-positive cTnI concentrations. Based on two index cases seen by one of us, we hypothesized that false-positive cTnI values may be common after COVID-19 infection and that macrotroponin, a complex formed between endogenous cTn autoantibodies and circulating cTn, may be the underlying cause.

Purpose
We aimed to test these hypotheses in a prospective cohort study.

Methods
We prospectively investigated professional athletes coming to the mandatory return to sports investigation at least 10 days after COVID-19 infection between 2022 and 2023 in an observational study. The presence of false-positive cTnI was centrally adjudicated in individuals that had elevated cTnI concentrations with one (or two) high-sensitivity cTnI assays, but normal high-sensitivity cardiac troponin T concentrations and normal electrocardiography (ECG), normal echocardiography, and normal cardiac magnetic resonance imaging (CMR). Divergences in hs-cTn concentrations were investigated using sex-specific upper limits of normal (ULN) of 4 different assays (hs-cTnI: Alinity/Abbott Diagnostic, hs-cTnI: Atellica/Siemens Healthineers, hs-cTnI: Access Beckman Coulter; hs-cTnT: Cobas/Roche Diagnostics). Athletes were instructed to cease training 48 hours before blood testing. Athletes with divergent hs-cTn assay results underwent further analysis for macrotroponin using sucrose gradient ultracentrifugation.

Results
Among 35 enrolled athletes (median age 24 years, 19 women and 16 men), 18 athletes had normal hs-cTn concentrations with all four hs-cTnT/I assays. In 17 athletes (48.6%), hs-cTn concentration was increased in at least one assay above the ULN, mostly one hs-cTnI method (hs-cTnI, Alinity) with normal concentrations of the other assays and normal cardiac imaging results. In contrast, two athletes had elevations in all hs-cTnI/T assays. Sucrose gradient ultracentrifugation provided evidence of macrotroponin in 15 of the 17 athletes (88%).

Conclusions
False-positive cTnI values are common after COVID-19 infection and should be considered in the differential diagnosis. Assay interference by macrotroponin seems to be the underlying mechanisms in most individuals. Documentation of normal hs-cTnT concentrations helps in the early detection of false-positive cTnI values.
AI-enabled automated cardiac chambers volumetry in non-contrast ECG-gated cardiac scans vs. non-contrast non-gated lung scans
Authors: Naghavi M , Reeves A P , Atlas K , Zhang C , Budoff M J , Henschke C , Yankelevitz D 
Published: October 2024

Abstract

Introduction
We have developed an AI-enabled automated volume measurement of cardiac chambers (AutoChamber) that works on ECG-gated coronary artery calcium scans and correlates well with contrast enhanced coronary CT angiography scans. We have recently reported that increased left atrial volume measured by AutoChamber is a strong predictor of new onset atrial fibrillation (AF) in asymptomatic individuals of Multi-Ethnic Study of Atherosclerosis (MESA). In this study, we compare the volumetry results in ECG- gated CAC scans with those of non-gated full-chest lung cancer screening scans in the same individuals.

Methods
We have studied 169 cases of paired ECG-gated cardiac CT scans and non-gated lung scans obtained from Harbor UCLA. Mean±SD for age was 62.1±10.0 years with 52% female participants. All cases were asymptomatic and were scanned for preventive health assessment. AutoChamber was run on all cases by an independent operator who was not involved in data analysis. P value was calculated using a two-tailed test of significance with α=0.05.

Results
AutoChamber in cardiac scans vs lung scans reported volume (Mean±SD) for left atrium (LA) was 63.8 ± 18.5 vs. 65.5 ± 19.4, left ventricle (LV) 102.8 ± 25.3 vs. 105.5 ± 25.2, right atrium (RA) 81.9 ± 20.5 vs. 85.7 ± 21.9 right ventricle (RV), 140.7 ± 34.2 vs. 134.2 ± 33.7, left ventricle wall (LVW) 113.0 ± 26.6 vs. 109.7 ± 27.0 respectively (P &lt; 0.0001). Strong correlation was shown between cardiac and lung scans for each cardiac chamber: LA (R = 0.92), LV (R = 0.93), RA (R = 0.91), RV (R = 0.92), and left ventricular wall (LVW) R = 0.95.

Conclusions
AutoChamber volumetry results are similar in ECG-gated cardiac scans vs non-gated full-chest lung scans. This AI-enabled automated tool is promising as it can provide added value to patients undergoing coronary calcium and lung cancer screening scans flagging enlarged cardiac chambers at risk of AF and heart failure.
Opportunistic screening of coronary artery calcification on non-gated conventional CT scans using artificial intelligence
Authors: Aviv Y , Awesat J , Abitbol M , Tamir T , Hermann D , Hudadi N , Shiyovich A , Weissman M , Shafir G , Nachmias K , Mizrahi N , Kimmel Y , Kornowski R , Hamdan A 
Published: October 2024

Abstract

Background
Recent advancements in artificial intelligence (AI) led to the development of automatic Coronary artery calcification (CAC) analysis based on chest CT scans. The objective of this study is to assess the impact of AI-based CAC evaluation on improving the allocation of add-on therapies and further evaluation.

Methods
We used a novel propriety AI software to estimate CAC from non-gated, non-contrast chest CT scans. Patients were categorized into groups: low CAC 0-99 Agatston unit (AU), moderate CAC 100-399AU, and high CAC ≥ 400 AU. Exclusion criteria included prior myocardial infarction, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), and life expectancy &lt; 2 years. Patients classified as high CAC were invited to a dedicated clinic to perform a risk factor and clinical assessment, initiate appropriate medication, and refer to further testing as needed. For low-moderate CAC, referring physicians were informed of CAC status, encouraging guideline-based optimal preventive management.

Results
1272 eligible patients between January 1th, 2023 to February 29th, 2024 were evaluated for inclusion. 641/1272 (50.3%) were excluded. Out of 631 enrolled patients, 84 (13%) patients were classified as high CAC, 163 (26%) as moderate and 348 (61%) as low CAC. At the dedicated clinic, appropriate low-density lipoprotein (LDL) goals were assigned and statins were initiated or dose adjusted where necessary. Twenty patients were referred to myocardial perfusion imaging, of which 2 were referred for invasive coronary angiography, one of them underwent PCI (Figure), and the other was referred for CABG.

Conclusion
This ongoing study indicates routine CAC quantification using AI software on chest CT scans can identify patients who may benefit from preventive cardiology services and lead them to appropriate cardiac treatment pathway. Further follow-up is required to assess its clinical impact.
Left ventricular flow dynamics and energetics derived from 4D flow CMR in patients with low gradient severe aortic stenosis
Authors: Wang Y S , Shan Y , Li J , Wu B T , Lu F W , Shu X H , Ge J B 
Published: October 2024

Abstract

Background
Up to 40% of patients with severe aortic stenosis (SAS) determined by current guidelines present with discordant Doppler echocardiography findings and demonstrate divergent prognosis. Differentiation of true SAS who generally benefits from aortic valve intervention among this subset of patients is important albeit challenging for clinical management.

Purpose
Left ventricular (LV) 3-dimentional flow characterization was analyzed to illustrate altered intracardiac hemodynamics in different types of low gradient SAS and to investigate its application for the identification of true SAS in comparison with LV stroke volume index (LVSVI) and transaortic flow rate.

Methods
Four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) was performed in 126 patients with low gradient SAS and 30 age- and gender-matched controls. All patients were categorized into 3 groups according to left ventricular ejection fraction (LVEF) and LVSVI as follows: classical low-flow low-gradient (CLFLG, n=37), paradoxical low-flow low-gradient (PLFLG, n=41), and normal-flow low-gradient (NFLG, n=48). Left ventricular flow was partitioned into 4 components: direct flow, retained inflow, delayed ejection flow, and residual volume. Average kinetic energetic parameters indexed to end-diastolic volume (KEiEDV) throughout the systolic phase were analyzed.

Results
Patients with CLFLG and PLFLG SAS had reduced LV direct flow proportion (CLFLG vs. control: 10±5% vs. 35±5%, P&lt;0.001; PLFLG vs. control: 29±6% vs. 35±5%, P&lt;0.001, Figure 1) and systolic ejection-flow KEiEDV (CLFLG vs. control: median, 5.3μJ/ml vs 8.7μJ/ml, P&lt;0.001; PLFLG vs. control: median, 6.0μJ/ml vs. 8.7μJ/ml) compared with controls. Reduced systolic ejection-flow KEiEDV correlated with decreased LVSVI (R=0.47, P&lt;0.001) and transaortic flow rate (R=0.72, P&lt;0.001). Among 126 patients in the study cohort, 74 (59%) were determined as true SAS according to standardized criteria based on flow-independent parameters and demonstrated elevated systolic ejection-flow KEiEDV than patients with pseudo-SAS (median, 6.5μJ/ml vs 5.6μJ/ml, P&lt;0.001). Systolic ejection-flow KEiEDV≥6.1μJ/ml demonstrated an optimal positive predictive value of 90% for distinguishing true SAS from pseudo-SAS among patients with low gradient SAS (Figure 2).

Conclusion
Alterations in LV flow components and kinetic energy were associated with the presence and type of low gradient SAS. LV systolic outflow energetic markers responsible for aortic valve opening could aid the evaluation of AS severity with Doppler-based parameters.Comparison of LV flow componentsROC analysis for discriminating true SAS
Age-dependent associations with the risk of mental disorders in patients with myocardial infarction: a UK Biobank cohort study
Authors: Lee H , Rhee T M , Park J B , Choi S Y 
Published: October 2024

Abstract

Background
Despite an overall decrease in cardiovascular mortality in recent decades due to effective preventive strategies, a concerning trend is emerging among young adults, with a rising incidence of myocardial infarction (MI) and its poor prognosis. Previous studies report that a significant association between mental disorders and the incidence and prognosis of MI. However, a detailed age-specific information is still lacking.

Purpose
We aimed to determine whether the risk of developing mental disorders after MI differs based on age and to stratify individuals at a higher risk.

Methods
From the UK Biobank prospective database (n=502,386), we collected data on patients with a prior MI (n=10,840) and compared them to age- and sex-matched controls (n=54,197) in a 1:5 ratio. Diagnoses of mental disorders were ascertained through linked hospital admission and mortality data, using the appropriate ICD-10-CM codes. Mental disorders were defined by at least two inpatient or outpatient claims within 1 year. The primary outcome was a composite of incident mental disorders, including depression, anxiety, stress-related, and somatoform disorders. Follow-up was done until the first diagnosis of mental disorders or the end of 2022.

Results
During a median follow-up of 13.7 years (interquartile range 12.8-14.5 years), the incidence rate of the primary outcome was 9.28 vs. 5.37/1,000 person-years among patients with MI and controls, respectively (p&lt;0.001). A prior MI history demonstrated an independent association with the risk of incident mental disorders, yielding an adjusted hazard ratio (aHR) of 1.41 (95% confidence interval [CI], 1.29–1.54; p&lt;0.001) after adjusting for confounders. This was comparable to heavy drinking and family history of depression. Notably, the risk of mental disorders attributed to previous MI was more prominent in younger individuals aged &lt;55 years than their older counterpart (aHR 1.61 vs. 1.33) (p-for-interaction 0.020). Similar results were observed in the analysis of two important components: depression and anxiety disorder. Furthermore, in younger patients with MI (&lt;55 years), mental disorders significantly increased the risk of mortality, while not in older patients.

Conclusion
MI was associated with a higher risk of incident mental disorders, resulting in poor prognosis, particularly in young individuals. Active surveillance and prevention for incident mental disorders after young MI may be beneficial.Cumulative Incidence of Mental Disorders