bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of digital cardiovascular risk score (DiCAVA) in the United States All of Us dataset
Authors: Yao Z , Dolezalova N , Aral M , Albrecht G , Irving B , Blaha M J 
Published: October 2024

Abstract

Introduction
The cardiovascular disease (CVD) risk score DiCAVA was developed in 2021 using UK Biobank data with the aim to be used for population health screening by deriving its predictions only from variables readily available to every individual, omitting difficult-to-obtain measurements such as blood pressure and invasive blood tests for metrics like cholesterol or HbA1c, which are commonly used in clinical CVD risk assessment tools. The original set of variables was reduced to 30 in the DiCAVA Lite score to further improve usability in a digital solution accessible to the general population, while maintaining its discrimination ability.

Purpose
Like many countries, the US has a large burden of CVD and would benefit from easily accessible screening tools. However, to ensure generalisability of the UK-developed score, it is necessary to evaluate its performance in a population where the score is intended to be used.

Methods
Data from a large real-world modern observational study in the US, All of Us, was used to evaluate discrimination and calibration metrics of the risk score. Participants with pre-existing CVD and without available electronic health records were excluded from the study. Variables from the All of Us dataset were matched to the original variables and any missing values were imputed using multiple imputation.

Results
216,985 participants with a median follow-up time of 3.44 years were included in the study. The median age was 51 years and 63% of the population were female. Discrimination ability in the All of Us dataset (C-index 0.76) slightly surpassed the discrimination achieved at training with UK Biobank (C-index 0.73), and that of Framingham risk score calculated for the All of Us population (C-index 0.72), demonstrating the score’s usability in the US. The score showed very good discrimination in both males (C-index 0.74) and females (C-index 0.77), all ethnic groups and age groups, with the exception of the population over 65 years of age, where the C-index dropped to 0.65 as expected (similar to that observed in the UK Biobank). Calibration of the original model was assessed at 3 years and showed under-estimation of the predicted risk (calibration-in-the-large of 2.37%). Following re-calibration, the algorithm demonstrated excellent results with the average predicted 3-year risk showing 0.59% difference from the observed CVD rate (calibration plot in Figure).

Conclusions
Overall, the DiCAVA Lite score has shown very good discrimination in the US, showing its generalisability in different demographic populations. Its re-calibrated form is now validated for use in the US population and because of its ability to be utilised outside clinical settings, it can be deployed widely in the general population as an initial screening tool and potentially boost awareness of cardiovascular health in an effort to drive preventative care of CVD.Re-calibration of the DiCAVA Lite score
Evaluating myocardial involvement in patients with multiple myeloma at different stages a cardiac MR T1 mapping study
Authors: Guo P , Chen W , Wang Y U , Shi M , Gao F 
Published: October 2024

Abstract

Background
At present, the International criteria for diagnosis multiple myeloma（MM） do not specifically highlight the use of cardiac magnetic resonance (CMR) to detect abnormal myocardial infiltration in patients at different clinical stages of MM. Extracellular volume fraction (ECV) based on CMR T1 mapping indicates expansion of the extracellular space or deposition of material in infiltrative heart diseases.

Purpose
To detect whether myocardial involvement in patients with MM at different clinical stages based on CMR T1 mapping.

Methods
A cohort consisting of 20 patients with diagnosed MM and 15 sex- and age-matched controls (Cs) were recruited for this study. All participants underwent CMR examination to obtain native T1 and ECV. The patients with MM were stratified into three groups based on the International Staging System (ISS): Stage I (n=5), Stage II (n=7), and Stage III (n=8). Cardiac amyloidosis (CA) is diagnosed based on the patient's clinical presentation and tissue biopsy. The baseline biochemical indices were collected before CMR examination.

Result
Among patients with MM, there were a total of 9 patients diagnosed with CA, comprising 3 patients in stage II and 6 patients in stage III. The ECV in stage III patients (45.13±11.89%) was significantly higher compared to that in stage I (26.65±4.22%), stage II (34.09±8.90%), and controls (25.40±2.52%) (p &lt; 0.05). Furthermore, the ECV in stage II patients (34.09±8.90%) was higher compared to controls (25.40±2.52%), though not significantly different from stage I patients (26.65±4.22%). Correlation analysis revealed a positive correlation between brain natriuretic peptide (BNP) levels and ECV (r=0.606, p=0.013). Receiver operating characteristic (ROC) curve analysis demonstrated that ECV had good predictive value for CA, with an area under the curve (AUC) of 0.898 (p &lt; 0.01), and the optimal cutoff value for ECV was determined to be 33.7%.

Conclusions
ECV derived from CRM T1 mapping holds promise for identifying amyloid accumulation, which deteriorates progressively with the advancement of disease stages in patients with MM. It is recommended that patients diagnosed with Stage II and Stage III MM should undergo CMR to facilitate the early detection of myocardial infiltrative damage.
OSTEO18, a novel urinary proteomic signature, associated with osteoporosis in heart transplant recipients
Authors: Yu Y L , Huang Q F , An D W , Raad J , Martens D S , Latosinska A , Stolarz-Skrzypek K , Van Cleemput J , Feng Y Q , Mischak H , Allegaert K , Verhamme P , Janssens S , Nawrot T S , Staessen J A 
Published: October 2024

Abstract

Background
Immunosuppressive treatment in heart transplant (HTx) recipient causes osteoporosis. The urinary proteomic profile (UPP) includes peptide fragments derived from the bone extracellular matrix.

Purpose
Study aims were to develop and validate a multidimensional UPP biomarker for osteoporosis in HTx patients from single sequenced urinary peptides identifying the parent proteins.

Methods
A single-center HTx cohort was analyzed. Urine samples were measured by capillary electrophoresis coupled with mass spectrometry. Cases with osteoporosis and matching controls were randomly selected from all available 389 patients. In derivation case-control dataset, 1576 sequenced peptides detectable in ≥30% of patients. Applying statistical analysis on these, an 18-peptide multidimensional osteoporosis UPP biomarker (OSTEO18) was generated by support vector modeling. The 2 replication datasets included 118 and 94 patients. For further validation, the whole cohort was analyzed. Statistical methods included logistic regression and receiver operating characteristic curve (ROC) analysis.

Results
In derivation dataset, the AUC, sensitivity and specificity of OSTEO18 were 0.83 (95% CI: 0.76-0.90), 74.3% and 87.1%, respectively. In replication datasets, results were confirmatory. In the whole cohort (154 osteoporotic patients [39.6%]), the ORs for osteoporosis increased (p &lt; 0.0001) across OSTEO18 quartiles from 0.39 (95% CI: 0.25-0.61) to 3.14 (2.08-4.75). With full adjustment for known osteoporosis risk factors, OSTEO18 improved AUC from 0.708 to 0.786 (p = 0.0003) for OSTEO18 categorized (optimized threshold: 0.095) and to 0.784 (p = 0.0004) for OSTEO18 as continuously distributed classifier.

Conclusion
OSTEO18 is a clinically meaningful novel biomarker indicative of osteoporosis in HTx recipients and is being certified as in-vitro diagnostic.
ABO blood groups and platelet reactivity in patients with coronary artery disease undergoing percutaneous coronary intervention treated with clopidogrel
Authors: Liu M L , Li J W , Yan K L , Yuan J Q , Zhao X Y 
Published: October 2024

Abstract

Background
The association between ABO blood groups and the risk of thrombosis and bleeding in patients with coronary artery disease has been of interest for many years, but the mechanisms are not fully understood.

Aim
To investigate the relationship between the ABO blood groups and the platelet reactivity in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI) treated with clopidogrel.

Methods
We examined 10,724 consecutive PCI patients in China from January 2013 to December 2013.Among them, 6,740 patients had the results of thromborlastogram (TEG) and the ABO blood groups. Low on-treatment platelet reactivity (LTPR) was defined as adenosine diphosphate-induced platelet maximum amplitude of TEG&lt;31mm.

Results
A total of 6,740 PCI patients (mean age, 58.23±10.27; male, 77.6%) treated with clopidogrel were finally enrolled for analysis. There were 2560 (37.98%) patients in LTPR group. In this group, the multivariate logistic regression showed that the blood group A (OR: 0.885, 95%CI 0.789-0.993, p=0.038) was independent protective factor in the A/non-A model (model 1). Then, we further divided the non-A groups into B, O, AB groups to set the model 2. In model 2, compared to A, multivariate logistic regression showed that only the blood group B (OR: 1.157, 95%CI 1.015-1.320, p=0.030) was independent risk predictors for LTPR, representing a higher risk of bleeding.

Conclusions
In the large sample real-world study, we reported the relationship between ABO blood groups and platelet reactivityin PCI patients treated with clopidogrel for the first time. Blood group A was an independent protective factor for LTPR, representing a lower risk of bleeding, whereas blood group B was an independent risk factor for LTPR, representing a higher risk of bleeding. These results provide an interesting perspective on blood groups and individualized antithrombotic therapy in patients with coronary artery disease, and further elucidation of the mechanisms is still needed in the future.
Novel insights of phenylalanine in Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) and cardiovascular complications
Authors: Liu J , Chen Y , Qian J , Cui R , Demirkan A , Zheng Y 
Published: October 2024

Abstract

Background
Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to cardiovascular risk, necessitating an exploration of potential metabolic contributors, such as amino acids. While amino acids are implicated in metabolic disorders, their specific relationship with MASLD and subsequent cardiovascular complications is not well-defined. We aimed to delineate the association between circulating amino acids and MASLD, identifying amino acids that could potentially link MASLD to cardiovascular issues.

Methods
Utilizing UK Biobank data, we tested the association of ten amino acids with MASLD in a cohort of 72,626 MASLD cases and 128,102 controls. Afterwards, we performed Mendelian Randomization (MR) using genome-wide association study (GWAS) data from 8,434 MASLD cases and 770,180 controls, and GWAS of amino acids including 115,052 participants from UK Biobank. Multiple MR methods, including MR-Egger, Cochran's Q-test, and MR-PRESSO, were applied to assess pleiotropy and heterogeneity. Survival analysis in MASLD patients assessed the link between significant amino acid and incident severe cardiovascular outcomes, including stroke, heart failure, myocardial infarction, and mortality, using three different covariate combinations: Model 1 included age, sex, and fasting time; Model 2 included in addition smoking, alcohol use, education, physical activity, and Model 3 included body mass index (BMI) in addition to model 2.

Results
Nine out of the ten amino acids were statistically significantly associated with MASLD across all three models (p&lt;6.25×10^-3). Among them valine, leucine, isoleucine, total branched-chain amino acids, tyrosine, alanine, and phenylalanine were positively associated with MASLD, while glutamine and glycine were negatively associated with MASLD. The genetic predisposition of MASLD was significantly associated with increased phenylalanine (beta=0.05, p=4.0×10^-4) and tyrosine (beta=0.15, p=2.0×10^-3), suggesting that alterations in these amino acids may result from the progression of MASLD. We also detected heterogeneity (Cochran’s Q-test: p=8.4×10^-9) and pleiotropy (MR-Egger: p=0.02) for tyrosine, but not for phenylalanine. Furthermore, phenylalanine levels in MASLD patients were significantly (p&lt;6.25×10^-3) associated with the incidence of heart failure, stroke, and mortality, but not with myocardial infarction across all three models. We did not identify a significant association between baseline tyrosine levels and any cardiovascular complications or mortality across the three models (Figure 1).

Conclusion
Our findings indicate a strong association between certain amino acids and MASLD, with phenylalanine, in particular, emerging as a potential mediator of cardiovascular risk in MASLD patients. The absence of heterogeneity and pleiotropy for phenylalanine strengthens its candidacy as a biomarker for future cardiovascular complications in MASLD.
Prognostic implications of right and left atrial strain in diabetes mellitus without coronary artery diseases
Authors: Matshela M R 
Published: October 2024

Abstract

Background
2D- speckle-tracking echocardiography (2D-STE) has recently be used to assess subclinical myocardial dysfunction, however its utility in diabetes mellitus (DM) has been specifically focusing on the longitudinal systolic function of the left ventricle (LV).

Aim
To assess the prognostic relation between left (LA) and right (RA) systolic and diastolic strain parameters with clinical outcome in patients with DM.

Methods
Of the initial 1721 diabetic patients screened for this study only 502 consecutive patients with DM were eligible and retrospectively enrolled, and 2D-STE strain parameters assessed on the 2D-TTE images. All patients were prospectively followed for development of new outcome/cardiac events which included hospitalization for acute HF, CVS-related death, new onset AF/AFI, stroke, heart transplantation, or need for ventricular assist device implantation. The 2D-STE analysis was used to measure the peak LA (longitudinal, radial and circumferential) and RA (longitudinal) strain. The long-term outcomes were evaluated for all-cause CVS outcomes and recurrent hospitalization.

Results
For the 502 eligible patients [mean age:58±4; 58 % male sex], 221 reached the combined endpoint. Mean follow-up was 1.1±0.6years. Both LA and RA strain parameters were significantly impaired compared to normal standard references (p&lt;.0001), the RA was more impaired than LA strain parameters. The best performance parameters predictive of CVS (combined outcomes) events were for LA&gt;RA systolic and diastolic strain, global RA systolic and diastolic strain (AUC: 0.74 and 70) and global LA longitudinal systolic and diastolic strain (AUC: 0.86 and 0.77). The strongest association between the degree of atrial myocardial mechanical dysfunction and risk of cardiovascular events was more evident for LA strain (free wall &gt; global strain) and lesser extend to RA strain. More myocardial mechanical strain impairments were demonstrated in those with higher left atrial volume index (LAVI), NYHA ≥II class, significantly impaired diastolic function, lower strain values (LA, LV, RV), and tricuspid annular plane systolic excursion (TAPSE), p&lt;.001). The LA (free wall) strain impairment was the independent predictors of combined outcome (including survival) after multiple adjustments using different models.

Conclusion
Patients with DM, LA strain parameters are stronger predictors of outcome than RA and other conventional parameters and should be included for regular clinical screening DM patients as these parameters provide a stronger prognostic stratification.
Cardiovascular prevention with GLP1 agonists in high or very-high cardiovascular risk irrespective of diabetes
Authors: Del-Cuerpo-Salinas N , Cazorla-Morallon D , Perez-Ferrandiz A , Lopez-Ayala J M , Claramunt-Bayarri A M , Bodi-Beneito C , Monteagudo-Viana M , Frutos-Garcia M A 
Published: October 2024

Abstract

Introduction
Patients with established cardiovascular disease have an increased risk of stroke and myocardial infarction, even in the absence of atrial fibrillation. Several trials have analyzed the effect of glucagon-like peptide-1 receptor (GLP1) agonists in patients with high cardiovascular risk and lately this effect has been studied even in the absence of diabetes.

Methods
A meta-analysis of randomized clinical trials (RCT) comparing GLP1 agonists with placebo was performed. The primary objective of the study was to analyze the composite endpoint of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke (MACE). As secondary objectives, cardiovascular death, non-fatal myocardial infarction and non-fatal stroke have been studied separately. The meta-analysis was performed using the inverse variance method, using the fixed effects model when there was no heterogeneity and the random effects model when heterogeneity is significant. In the case of significant heterogeneity in the primary objective, a stratified analysis with exposure time have been performed to explain this outcome.

Results
A sum of 9 randomized controlled trials were included where a GLP1 agonist such as albiglutide, dulaglutide, exenatide, liraglutide, lixinatide or semaglutide was compared with placebo. 77684 patients were incorporated, while 39497 were treated with a GLP1 agonist. The mean age was of 63.7 years (SD ± 1.97 years), 60080 (77.3%) suffered from diabetes and 60552 (77.9%) from cardiovascular disease.
As showed in figure 1, the GLP1 agonists showed a reduction of 13% of the MACE (RR: 0.87, 95% CI 0.81-0.92; p&lt;0.001). Heterogeneity could be explained by exposure time and concentration in the blood, considering that it disappears within each group when applying this condition.
Treatment with GLP1 agonist also reduced cardiovascular death by 12% (RR: 0.88, 95% CI 0.82-0.94; p&lt;0.001), non-fatal strokes by 14% (RR: 0.86, 95%CI 0.79-0.95; p&lt;0.001) and non-fatal miocardial infarction by 13% (RR: 0.87, 95% CI 0.78-0.97; p&lt;0.001).

Conclusion
Treatment with a GLP1 agonist reduced the incidence of the MACE by 13% and cardiovascular death by 12%, as well as it decreased the incidence of nonfatal stroke by 14% and of nonfatal myocardial infarction by 13% in different RCTs involving patients with high or very-high cardiovascular risk with or without diabetes.
Estimated pulse wave velocity as a forefront indicator of developing metabolic syndrome
Authors: Kim H J , Kim B S , Shin J H 
Published: October 2024

Abstract

Background
The predictive value of estimated pulse wave velocity (ePWV) for the development of metabolic syndrome has not been extensively explored.

Purpose
This study aims to fill this gap by evaluating ePWV as a potential predictor for the development of metabolic syndrome in middle-aged adults.

Methods
Using prospective multi-center cohort database, participants aged between 40 and 69 years without metabolic syndrome at baseline were studied (enrolled from June 2001 to January 2003 and provided follow-up information spanning up to 18 years). ePWV was calculated using specific equations based on age and blood pressure. The primary outcome was the incidence of metabolic syndrome during a median follow-up period of 15.6 years (187 months).

Results
Of the 6,186 participants analyzed, 2,726 (44.1%) developed metabolic syndrome during the follow-up period. ePWV values were categorized into tertiles to assess their predictive value for the development of metabolic syndrome. An ePWV cut-off of 7.407 m/s was identified as a predictor of metabolic syndrome development, with a sensitivity of 0.743 and a specificity of 0.464 (Figure 1). Participants exceeding this cut-off, especially those in the third tertile (8.77–14.63 m/s), had a notably higher risk of developing metabolic syndrome. Specifically, the third tertile exhibited a 52.8% cumulative incidence compared with 30.8% in the first tertile as illustrated by Kaplan–Meier curves (Figure 2). After adjustments, participants exceeding the ePWV cut-off had a 1.425-fold increased independent risk of developing metabolic syndrome (HR, 1.425; 95% confidence interval [CI], 1.281–1.585). Furthermore, those in the third tertile showed an even higher risk with an HR of 1.530 (95% CI, 1.330–1.761) compared to first tertile, even after adjusting for multiple variables.

Conclusions
ePWV is a significant predictor of the development of metabolic syndrome. This finding underscores the potential of ePWV as a cardiometabolic risk assessment tool and can thus provide useful information for primary and primordial prevention strategies.Figure 1Figure 2
Parallel improvement of arterial stiffness with weight loss following intensification of antidiabetic treatment
Authors: Stampouloglou P , Bletsa E , Oikonomou E , Katsarou O , Tsigkou V , Ikonomidis I , Korakas E , Lambadiari V , Tentolouris N , Tousoulis D , Siasos G 
Published: October 2024

Abstract

Background
Arterial stiffness is a marker that can flag increased cardiovascular disease risk in patients with type 2 Diabetes Mellitus (T2DM), while weight management plays a crucial role for the management of glycemic control and prevention of complications in these patients.

Purpose
To investigate the effects of novel antidiabetic agents on arterial stiffness in T2DM patients as well as potential associations with their weight status before and after treatment.

Patients and Methods
We enrolled 118 consecutive patients under stable antidiabetic therapy. According to their physician they start treatment with an additional antidiabetic agent; either dipeptidyl peptidase-4 inhibitor (DPP-4i, n=19), or glucagon like peptide-1 receptor agonist (GLP-1RA, n=50) or sodium/glucose cotransporter-2 inhibitor (SGLT-2i, n=49). Body Mass Index (BMI) along with carotid-femoral pulse wave velocity (PWV) as a biomarker of arterial stiffness were measured at baseline and 3 months after treatment intensification.

Results
There were no differences between the study groups regarding their sex, age and other traditional risk factors or the values of PWV and BMI at baselined (p=NS for all). All groups achieved better glycemic control in terms of HbA1c values between baseline and follow-up; from 7.4±1.2% to 7.4±1.2% in the DPP4i group (p&lt;0.001 for all), from 8.6±0.7% to 6.7±0.8% in the GLP-1RA group (p=0.07) and from 7.7±1.1% to 6.7±0.7% in the SGLT-2i group (p&lt;0.001). PWV showed a decrease from 10.6±2.7 to 9.0±1.6 m/sec (p=0.001) in the DPP4-i group, from 11.2±2.5 to 9.3±2.2 m/sec (p&lt;0.001) in the GLP-1RA group and from 10.7±2.4 to 8.9±2.0 m/sec (p=0.001) in the SGLT-2i group as presented in Figure 1. Regarding BMI, a reduction in the values between groups from baseline to follow-up was also observed; from 27.4±5.3 to 26.1±5.0 kg/m2 for the DPP-4i group, from 33.6±4.9 to 31.5±4.6 kg/m2 for the GLP-1RA group, from 31.8±5.5 to 30.5±5.6 kg/m2 for the SGLT-2i group (p&lt;0.001 for all). Moreover, in the entire study population there was significant correlation between PWV and BMI improvement following treatment initiation (rho=0.247, p=0.007) (Figure 2).

Conclusion
Diabetes mellitus treatment intensification with GLP1-RA or SGLT-2i or DPP4i, ameliorated arteriosclerosis, improved PWV and BMI while there is significant association between BMI and PWV improvement.Changes in PWV values among the groupsCorrelation between deltaBMI & deltaPWV