bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of SCORE and SCORE 2 risk prediction tools in contemporary very high risk european population
Authors: Boskovic N , Giga V , Djordjevic-Dikic A , Beleslin B , Stojkovic S , Nedeljkovic I , Aleksandric S , Tesic M , Dedic S , Burazor I , Karadzic T , Paunovic I , Jovanovic I 
Published: October 2022

Abstract

Background
New SCORE 2 algorithm overperformed SCORE algorithm in population with decreasing prevalence of cardiovascular (CV) morbidity and mortality. However, there is limited data in risk stratification with SCORE 2 model in contemporary populations from very high risk countries.

Aim
The aim of this study was to compare risk prediction using SCORE 2 and SCORE model and to compare the proportions of patients requiring statin treatment in primary prevention.

Methods
Our study included 1317 patients (511, 38.8% male gender, average age 54±8) without known CV disease aged 40 to 70 years. Data on CV risk factors were prospectively collected in 20 primary care centers throughout the Serbia from January 2020. to December 2020. Based on the CV risk profile, patients were stratified into 4 categories: low, moderate, high and very high risk according to SCORE model and into 3 categories: low to moderate, high and very high risk according to SCORE 2 model. The number of patients requiring statin treatment was assessed according to the risk category and value of LDL cholesterol in SCORE model and the value of non-HDL cholesterol in SCORE 2 model.

Results
Overall, 589 patients (44.7%) were smokers, mean value of total cholesterol was 6.2±1.1 mmol/L, LDL 3.9±1.1, HDL 1.4±0.5, non HDL 4.8±1.2 mmol/L. Systolic blood pressure was 138.6±19.6, diastolic blood pressure was 85.3±10.4 mmHg and was BMI 26.9±5.2. Based on the SCORE model 166 patients (12.6%) were classified into low risk category, 658 (49.9%) into moderate, 276 (20.9%) into high risk and 217 (16.6%) into very high risk category. Based on the SCORE 2 model 30 (2.8%) patients were classified into low to moderate, 273 (18%) and 1014 (79.2%) into very high risk category. There was significantly less patients in low to moderate group in SCORE 2 model compared to SCORE model (30, 2.8% vs 824, 62.6%, p&lt;0.001 respectively) and significantly more patients with very high risk (1014, 79.2% vs 217, 16.6%, p&lt;0.001), but without significance difference in the high risk group (Figure 1). The use of SCORE 2 model resulted in significantly higher proportion of patients requiring statin treatment 93% vs. 43% using SCORE model (p&lt;0.001).

Conclusion
The use SCORE 2 risk prediction tool, in comparison to SCORE model, results in significant higher proportion of patients being classified as very high risk category with the increase number of patients requiring statin treatment in primary prevention.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Krka Farma
Net clinical benefit of NOAC in Korean atrial fibrillation patients with low to intermediate stroke risk
Authors: Shin S Y , Jung M , Kang K , Byeon K 
Published: October 2022

Abstract

Background
The balance of stroke risk reduction and potential hemorrhagic risk associated with anti-thrombotic treatment (ATT) remain unclear in Korean atrial fibrillation (AF) patients with low to intermediate stroke risk, defined as non-gender CHA2DS2-VASc score 0–1.

Purpose
The net clinical benefit (NCB) analysis of ATT may be helpful to guide stroke prevention strategy in AF patients with non-gender CHA2DS2-VASc score 0–1.

Methods
This Korean multi-center cohort study retrospectively evaluated the clinical outcomes with single antiplatelet (SAPT), vitamin K antagonist (VKA), and non-vitamin K antagonist oral anticoagulant (NOAC) in non-gender CHA2DS2-VASc score 0–1 and further stratified by biomarker-based ABCD score (Age [≥60 years], B-type natriuretic peptide [BNP] or N-terminal pro-BNP [≥300 pg/ml], Creatinine clearance [&lt;50 ml/min/1.73 m2], and Dimension of the left atrium [≥45 mm]). The primary outcome was the NCB of ATT including thromboembolic and major bleeding events.

Results
We included 2465 patients (56.2±9.5 years; female, 665 [27.0%]) followed-up for 4.0±2.8 years, of whom 661 (26.8%) were treated with SAPT; 423 (17.2%) with VKA; and 1040 (42.2%) with NOAC. In comparison with no treatment, only NOAC demonstrated a positive tendency for stroke prevention (NOAC, NCB 0.47, 95% confidence interval [CI] −0.40 to 2.10; SAPT, NCB −0.31, 95% CI −1.48 to 1.40; and VKA, NCB −1.26, 95% CI −2.97 to 0.67). With detailed risk stratification with ABCD score, NOAC showed a significant NCB for stroke prevention compared with SAPT and VKA (SAPT vs. NOAC, NCB 1.6, 95% CI 0.26–3.50; VKA vs. NOAC, NCB 1.96, 95% CI 0.47–4.16) in patients with ABCD score ≥1. ATT failed to show NCB in patients with truly low stroke risk defined as ABCD score=0.

Conclusion
Korean AF cohort with low to intermediate stroke risk indicates that, in comparison with no ATT, only ATT with NOAC showed marginal NCB. With further risk stratification by ABCD score, NOAC showed significant advantages over other ATTs (VKA or SAPT) in patients with ABCD ≥1.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Korean Disease Control and Prevention Agency
A Genetic Risk Score englobing variants associated with coronary artery disease is a good marker for prognosis in an asymptomatic population
Authors: Santos M , Mendonca M I , Sa D , Temtem M , Sousa A C , Freitas S , Rodrigues M , Henriques E , Borges S , Freitas A I , Guerra G , Ornelas I , Drumond A , Palma Dos Reis R 
Published: October 2022

Abstract

Genome-wide association studies have identified several loci linked to coronary artery disease, and coronary atherosclerosis progression. However, the impact of the genetic contribution to MACE occurrence in sub-clinical atherosclerosis is unknown.

Purpose
This study intended to assess the relationship between a set of single nucleotide popymorphism (SNP) associated with CAD by GWAS and the MACE occurrence in an asymptomatic population. After that evaluate whether a wGRS englobing these variants is useful to estimate the prognostic.

Methods
Prospective study performed in an asymptomatic cohort from GENEMACOR population-based sample of 1114 subjects aged 51.7±8.3, 74.2 male, without prior coronary artery disease. Coronary Artery Calcium (CAC) score was assessed by coronary computed tomography (Agatston method), and two categories were considered 1–99 and &gt;100. 33 SNP were evaluate to assess the significantly associated with prognostic. A weighted (wGRS) was constructed as the sum of the risk alleles weighted by the corresponding effect size (HR). Cox regression analysis adjusted for the main risk factors, calcium score (CAC) and wGRS to assess the risk of MACE during follow-up. Kaplan Meier assessed the survival.

Results
Of the studied 33 SNPs previously associated with CAD (GWAS), only 4 presented the significant association with MACE occurrence: CDKN2B-AS1 rs4977574, HNF4A rs1884613,
APOE rs7412/rs429358A and GJA4A rs 618675. After Cox regression analysis the wGRS remained in the equation (HR=2.834); p=0.012, together with CAC score (HR 3.35); p=0.012; diabetes (HR=2.398); p=0.032 and age (HR=1.056; p=0.049. WGRS above the median presented a worst survival rate (p=0.006).

Conclusion
The wGRS englobing: CDKN2B-AS1 rs4977574, HNF4A rs1884613, APOE rs7412/rs429358A and GJA4A rs 618675 is independently associated with cardiovascular events in an asymptomatic population. CDKN2B-AS1 rs4977574 gene expression modulates the progression and severity of vascular calcification in vascular smooth muscle cells (VSMCs), HNF1α-AS1 is an important regulatory molecule in cancer biology and cardiovascular disease (its expression may regulate VSMCs, and high expression promotes atheroprotection). More research is crucial for understand prognosis in asymptomatic population.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): SESARAM EPE
High-sensitivity troponin (hs-cTn) for cardiovascular risk prognostication: a systematic review and meta-analysis
Authors: Sagris M S , Antonopoulos A A , Antoniades C A , Tsioufis K T , Tousoulis D T 
Published: October 2022

Abstract

Background
Chronic low-grade inflammation is involved in coronary atherosclerosis progression whereas recent research efforts suggest that preventative methods should be tailored to the “residual inflammatory risk”. As such, modalities for the early identification of the risk have to be investigated.

Methods
We performed a systematic review and meta-analysis according to the PRISMA guidelines. Any study that presented the prognostic value of high sensitivity troponin (hs-cTn) of vascular inflammation in stable patients without known cardiac heart disease was considered to be potentially eligible. The Medline (PubMed) database was searched up to April 22, 2021. The main endpoint was the difference in c-index (Δ[c-index]) with the use of hs-cTn for major adverse cardiovascular events (MACEs), cardiovascular and all-cause mortality. We calculated I2 to test heterogeneity.

Results
In total, 44 studies and 112,288 stable patients without known coronary heart disease were included in this meta-analysis. The mean follow-up duration of the whole cohort was 6.8±1.1 years. 77,004 (68.5%) of the patients presented in low cardiovascular risk while 35,284 (31.5%) in high. The overall pooled estimated of Δ[c-index] for MACE was 1.4% (95% CI: 0.7–2.1, I2=0%) and for cardiovascular death 1.3% (95% CI: 0.3–2.3, I2=0%). Finally, the overall pooled estimate of Δ[c-index] for all-cause mortality was 3% (95% CI: 1.9–3.9, I2=86%), while high heterogeneity was observed between the studies.

Conclusion
The predictive usefulness of changes in hs-cTn measures in stable individuals with either high or low cardiovascular risk, demonstrating that assessing vascular inflammation in addition to clinical risk factors enhances risk prediction for cardiovascular events and all-cause mortality. Further prospective studies are necessary to confirm these findings and assist clinical decision-making regarding the most optimal prevention strategy.

Funding Acknowledgement
Type of funding sources: None.
Ultra-sensitive troponin-I and incident coronary heart disease, stroke, heart failure, cardiac arrhythmias, arterial aneurysms and venous thromboembolism hospitalizations
Authors: Empana J P , Lerner I , Perier M C , Jabre P , Andrieu M , Climie R E , Van Sloten T , Vedie B , Geromin D , Marijon E , Danchin N , Thomas F , Boutouyrie P , Jouven X 
Published: October 2022

Abstract

Background
Cardiac troponin I (cTnI) as measured by high-sensitive assays has been related to incident cardiovascular disease events (CVD) in the community. With the advent of ultra-sensitive assays, it is now possible to detect troponin I at very low concentration, far below the classical threshold of 1.9 pg/mL. However, the clinical relevance of these low concentrations for predicting CVD is largely unknown.

Purpose
To examine the association of cTnI as low as 0.013 pg/mL with incident cardiovascular disease events (CVDs) in the primary prevention setting.

Methods
cTnI was analyzed in the baseline plasma (2008–2012) of CVD free volunteers from the Paris Prospective Study III using for the first time a novel ultra-sensitive immunoassay (Simoa Troponin-I 2.0 Kit, Quanterix, Lexington) with a limit of detection (LOD) of 0.013 pg/mL. Incident CVD hospitalizations for coronary heart disease, stroke, arrhythmias, venous thromboembolism, arterial aneurysms and heart failure were validated by critical review of the hospital records. Hazard ratios were estimated per log-transformed standard deviation (SD) increase of cTnI in Cox models using age as the time scale. The added value (gain in discriminatory capacity) of cTnI for CVD risk prediction was examined by calculating the Harell's C-index boostraped difference of the SCORE 2 risk model with and without cTnI.

Results
There were 9503 CVD free participants (40% women) aged 59.6 (6.3) years at baseline. cTnI was detected in 99.6% of the participants (median value = 0.63 pg/mL, interquartile range [IQR] 0.39–1.09). After a median follow-up of 8.34 years (IQR, 8.0–10.07), 516 participants suffered 612 events. In fully-adjusted analysis, higher cTnI (per 1 SD increase of log cTnI) was significantly associated with CVD events combined (n=516, HR= 1.21; 1.06; 1.39). In univariate Cox analysis and compared to each single established risk factor, cTnI had the highest discrimination capacity for incident CVD events (C-index=0.6349) (Figure 1). Adding log cTnI to the SCORE 2 algorithm increased significantly albeit moderately discriminatory capacity (C-index 0.698 vs. 0.685; boostraped C index difference: 0.0135 (95% CI: 0.0131; 0.0138)).

Conclusion
cTnI concentrations as measured by a novel ultra-sensitive immunoassay is associated with a significant increased risk of incident CVD events in the primary prevention setting.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): ANR: French National Research AgencyEurope: Horizon 2020
Invasive validation of pressure-volume loops derived from cardiovascular magnetic resonance imaging and brachial blood pressure in heart failure patients
Authors: Arvidsson P , Green P G , Watson W D , Shanmuganathan M , Heiberg E , De Maria G L , Arheden H , Herring N , Rider O J 
Published: October 2022

Abstract

Introduction
Left ventricular (LV) pressure-volume (PV) loops provide gold-standard physiological information but require invasive measurements of ventricular intracavity pressure, limiting clinical and research applications. Recent development has seen the introduction of non-invasively computed PV loops from cardiovascular magnetic resonance (CMR) volumetry and a brachial blood pressure measurement. The approach combines LV volumes with a time-varying elastance function to compute time-resolved LV pressures and was validated on invasive pressure data from a porcine model. The method is readily implemented using standard CMR sequences and provides measures of hemodynamic parameters including stroke work, myocardial efficiency, and contractile state. However, the method remains to be validated in patients using invasive left ventricular pressure recordings.

Purpose
To validate for the first time in human patients the performance of non-invasively computed PV loops against invasive measures.

Methods
Four heart failure patients underwent two subsequent sessions of CMR cine imaging and simultaneous brachial blood pressure measurement, with intravenous administration of two different vasoactive drugs, resulting in two different haemodynamic states for each patient. LV catheterization was then conducted with repeat administration of the same infusions. Pressure-volume loops were computed from CMR volumes combined with 1) a time-varying elastance function scaled to brachial blood pressure and temporally stretched to match volume data, and 2) invasive pressures averaged from multiple sampled beats. Method comparison was conducted using linear regression and Bland-Altman analysis.

Results
Figure 1 shows non-invasively derived PV loop parameters compared to invasive data. The non-invasive method demonstrated strong correlations and low bias for stroke work (R2=0.97, bias 4.6%, p&lt;0.0001), potential energy (R2=0.83, bias 1.5%, p=0.001), end-systolic pressure-volume relationship (R2=0.90, bias 5.4%, p=0.0003), energy per ejected volume (R2=0.93, bias 3.5%, p=0.0001), ventricular efficiency (R2=0.99, bias 1.1%, p&lt;0.0001), arterial elastance (R2=0.87, bias −7.8%, p=0.0006), and mean external power (R2=0.89, bias 4.6%, p=0.0005).

Conclusions
Pressure-volume loops can be precisely and accurately computed from cardiovascular magnetic resonance imaging and brachial cuff blood pressure in humans, and is ready for use in research applications.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Swedish Heart Lung Foundation
The effect of ziltivekimab on the neutrophil-lymphocyte ratio: analysis from RESCUE
Authors: Adamstein N , Cornel J , Davidson M , Libby P , De Remigis A , Jensen C , Rajan S , Ridker P 
Published: October 2022

Abstract

Background
The neutrophil-lymphocyte ratio (NLR), derived from the complete blood count, independently predicts atherosclerotic events and is a potential biomarker for residual inflammatory risk. A previous study showed that interleukin (IL)-1β inhibition reduces the NLR, but whether inhibition with IL-6, a cytokine downstream of IL-1, also lowers the NLR is unknown.

Purpose
To evaluate whether ziltivekimab, a monoclonal antibody targeting the IL-6 ligand, dose-dependently lowers the NLR compared to placebo.

Methods
The phase II RESCUE trial randomized 264 patients with moderate to severe chronic kidney disease (CKD) and high-sensitivity CRP (hsCRP) &gt;2mg/L in a 1:1:1:1 ratio to placebo or ziltivekimab 7.5 mg, 15 mg, and 30 mg subcutaneously once every four weeks. As previously reported, the trial met its primary endpoint as demonstrated by hsCRP reductions of 4% in the placebo group as compared to 77%, 88%, and 92% at 12 weeks in the ziltivekimab 7.5, 15, and 30 mg groups, respectively. Using RESCUE trial data, we further evaluated the percent change from baseline in the NLR at 12 weeks and sought evidence of correlation between any observed changes in the NLR with changes in other measured biomarkers.

Results
Ziltivekimab dose-dependently reduced the NLR starting at week one and sustained through week 12 (Table). The median change in the NLR at 12 weeks, the primary pre-specified endpoint, was −13.5% in the 7.5 mg group, −14.3% in the 15 mg group, and −22.4% in the 30 mg group compared to 1.56% in the placebo group. The estimated treatment difference was −14.6% (p=0.004), −15.3% (p=0.004), and −23.6% (p&lt;0.0001) in the ziltivekimab 7.5, 15, and 30 mg groups respectively. These changes were driven largely by reductions in the absolute neutrophil count with minimal change in lymphocyte count. The change in NLR with ziltivekimab correlated modestly with the changes in hsCRP (R=0.26, p=0.0006), fibrinogen (R=0.18, p=0.02), and haptoglobin (R=0.17, p=0.03), but not serum amyloid A, ApoA1, ApoB, ApoB/ApoA ratio, or traditional risk markers.

Conclusions
IL-6 inhibition with ziltivekimab lowers the NLR. The ongoing ZEUS cardiovascular (CV) outcomes trial will assess whether ziltivekimab can reduce CV event rates among individuals with stage 3 to 4 CKD, known atherosclerotic disease, and elevated hsCRP. If ziltivekimab reduces CV risk, it would provide further evidence for critical inter-relationships between bone marrow function and atherothrombosis.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Novo Nordisk
Increased arterial stiffness predict major adverse cardiovascular events in post-infarcted patients. Do parameters and methods matter?
Authors: Gaszner B , Simor T , Van Der Geest R J , Farkas N , Meiszterics Z 
Published: October 2022

Abstract

Introduction
According to recent 2021 ESC prevention guidelines arterial stiffness (aortic pulse wave velocity – PWV, augmentation index - Aix) predicts future major adverse cardiovascular events (MACE). Both parameters have a prognostic relevance, however due to the various technical approaches the level of high stiffness values show significant differences and resulting an argue against widespread use.

Purpose
We evaluated the cut-off PWV and Aix values for MACE prediction using cardiac magnetic resonance imaging (CMR) and oscillometric methods for validating the prognostic value of high stiffness parameters in post-infarcted patients.

Methods
CMR phase contrast imaging (Siemens Avanto, 1,5 T CMR device) and an invasively validated oscillometric based Arteriograph (AG) method were compared in this 6 years follow-up study, including 49 patients suffered previous ST-elevation myocardial infarction (STEMI). Patients received follow-up for MACE comprising all-cause death, non-fatal MI, ischemic stroke, hospitalization for heart failure and coronary revascularization.

Results
49 patients (37 male, average age: 57±8 years) were investigated. An acceptable agreement and significant correlation (Spearman's rho: 0.332, p&lt;0,01) was found between AG and CMR derived PWV values. Bland Altman plot was created to test for methods' agreement. The bias showed that in general the mean difference between the two measures was 3.6 m/s (upper and lower limit of agreement: –0.2 and 7.5 m/s). The coefficient of variation was 43.9%. Totally 51 MACE events occurred during the 6 years follow-up period. Hospitalisation for coronary revascularisation (55%), all-cause death (15%), non-fatal MI (12%), heart failure (12%) exposed the majority of MACE events. Optimized PWV and Aix cut-off values for MACE prediction were calculated (PWVCMR: 6,47 m/s; PWVAG: 9,625 m/s; AixAG: 34,22%) by receiver operating characteristic analysis (Figure 1). Kaplan-Meier analysis in all parameters showed a significantly lower event-free survival in case of high PWV and Aix values (Figure 2). Multivariate Cox regression analysis revealed PWV and Aix as a predictor of MACE (PWVCMR hazard ratio (HR): 1.31 (CI: 1.1–1.7), PWVAG HR: 1.24 (CI: 1.0–1.5), AixAG HR: 1,043 (CI: 1,01–1,08), p&lt;0,05 respectively).

Conclusions
Arterial stiffness, particularly elevated PWV predicts MACE in postinfarcted patients. Our study showed both CMR and oscillometric techniques are feasible for MACE prediction, however, adjusted cut-off values of PWV are recommended for different methods to improve individual risk stratification. All these findings emphasize the clinical relevance for the future measurement of arterial stiffness might contribute to improved risk stratification after MI, which is crucial for the assessment of prognosis and guidance of secondary prevention treatment.

Funding Acknowledgement
Type of funding sources: None.
Clinical significance of undetectable high sensitivity cardiac troponin I (hs-TnI) in Thai individuals with low cardiovascular risk
Authors: Sabkaewyod P , Vathesatogkit P , Stitara P 
Published: October 2022

Abstract

Introduction
The long term prognosis of individuals who has undetectable hs-TnI is poorly defined in low cardiovascular risk. We aim to examine whether undetectable hs-TnI individuals have better cardiovascular outcomes in low cardiovascular risk population.

Methods
Data of low cardiovascular risk population (&lt;7.5%) who has no established of atherosclerosis cardiovascular disease (ASCVD) was derived from the Electricity Generating Authority of Thailand (EGAT) study in 2007–2009 survey. High sensitivity cardiac troponin I was measured by using the Abbott ARCHITECT i2000 SR assay. We categorized level of hs-TnI into undetectable hs-TnI (&lt;1.9 ng/L), low hs-TnI, intermediate and more hsTnI by gendered specific cut-off. The low cardiovascular risk population was classified into extremely low risk (&lt;5%) and low risk (5–7.5%). Major cardiovascular event (MACE) and all-cause mortality were collected until 31st December 2019. Survival analysis and subgroup analysis were performed.

Results
A total of 3,442 participants were eligible. Mean age was 43.6 years-old, 65.5% male, hs-TnI was detected 79.8%, median hs-cTnI was 2.6 ng/L (2,3.6). During median time followed-up 10.3 years, 52 events (1.5%) of MACE and 60 events (1.7%) of all-cause mortality occurred. After adjusted for conventional risk factors, hs-cTnI significantly associated with incidence of MACE (HR 1.03 95% CI 1.02–1.04, p-value &lt;0.001). Compared with intermediate and more hs-TnI group, undetectable hs-TnI and low hs-TnI had 79% and 52% lower incidence of MACE (HR 0.21, 95% CI (0.05–0.79) and HR 0.48, 95% CI (0.23–1.0), p-value for trend 0.04. Subgroup analysis, incidence of MACE remained higher either extremely low or low CV risk compared with those undetectable hs-TnI. (P for interact 0.83)

Conclusion
Among individuals with low cardiovascular risk, hs-TnI testing can provide risk prognostication. Undetectable hs-TnI could be as a negative risk marker for adverse cardiovascular events.

Funding Acknowledgement
Type of funding sources: None.