Search

Trimethylamine N -oxide (TMAO) and phenylacetylglutamine (PAGln) are associated with acute myocardial infarction (AMI) and type 2 diabetes mellitus (T2DM). This study developed and validated a simple method firstly for simultaneously quantifying serum TMAO and PAGln using liquid chromatography-tandem mass spectrometry (LC–MS/MS). Serum samples from patients with T2DM, AMI, and healthy subjects were analyzed using a new LC–MS/MS method to evaluate TMAO and PAGln levels. Statistical analyses were performed to evaluate TMAO and PAGln distributions among different groups. Retention and separation of the two metabolites were achieved within 5 min. For both analytes, the assay was linear in a 0.02–10 µg/mL range, with >0.99 average linear correlation coefficients, and quantification limit values of approximately 0.010 µg/mL. The average recoveries of TMAO and PAGln were 96.3 % and 96.4 %, respectively. The intra-run and total coefficient variations were 3.5–4.8 % and 3.9–5.7 % respectively for TMAO; and 4.0–5.1 % and 4.6–6.3 % respectively for PAGln. TMAO and PAGln showed a moderate correlation (P < 0.001) and their levels in patients with T2DM were significantly higher than those in healthy individuals (P < 0.001). TMAO levels were higher in patients with T2DM than in patients with AMI (P < 0.01). Patients with AMI had higher PAGln levels than healthy individuals (P < 0.05). After adjusting for sex and age, the top tertile of PAGln was positively correlated with T2DM and AMI while that of TMAO was positively correlated with T2DM. Overall, a robust isotope dilution LC–MS/MS method was established, which may be beneficial for assessing the association between two metabolites with AMI and T2DM. [ABSTRACT FROM AUTHOR]

• Well-supported cognitively unimpaired plasma NfL reference intervals were determined. • Observed 97.5th percentile NfL concentrations increased at a rate of 3.1% per year of age. • Decade-wide reference intervals will aid in the evaluation of potential neurodegeneration. Neurofilament light chain (NfL) is an emerging biomarker of neurodegenerative disease progression. As plasma NfL increases with age, characterization of NfL concentrations in an age-stratified cognitively unimpaired population was assessed. EDTA-plasma samples were measured using the Simoa® NF-light™ Advantage Kit assay. One-sided reference intervals were established from 1100 cognitive normal individuals (588 male, 512 female) aged 20 to 95 years. Of those, 927 samples were obtained from the Mayo Clinic Study of Aging cohort (age > 50 years), and the remainder (age < 50 years) were obtained from individuals without known neurological conditions. All samples were from individuals without known chronic kidney disease, stroke or myocardial infarction, and a body mass index < 30 kg/m2. The 97.5th percentile limits for the following age ranges (in years) were (pg/mL): 20 s: ≤8.4, 30 s: ≤11.4, 40 s: ≤15.4, 50 s: ≤20.8, 60 s: ≤28.0, 70 s: ≤37.9, 80+: ≤51.2. Sex had no significant effect on reference intervals. Observed NfL concentrations increased at a rate of 3.1 % per year of age. Characterization of the rate of NfL concentration increase and decade-wide reference intervals from a neurologically well-characterized patient population will aid in interpretation of NfL during the clinical evaluation of a potential neurodegenerative disease. [ABSTRACT FROM AUTHOR]

• De Ritis ratio predicts 3-year all-cause mortality after acute myocardial infarction. • De Ritis ratio predicts 3-year cardiac mortality after acute myocardial infarction. • De Ritis ratio predicts 30-day risk of bleeding after percutaneous coronary intervention. • De Ritis ratio has a moderate sensitivity regarding prediction of mortality. The association between aspartate aminotransferase to alanine aminotransferase ratio (De Ritis ratio) and prognosis of patients with acute myocardial infarction (AMI) remains poorly investigated. This study included 3000 patients with AMI undergoing percutaneous coronary intervention. Patients were categorized in groups according to tertiles of the De Ritis ratio: tertile 1 (De Ritis ratio < 1.11; 905 patients), tertile 2 (De Ritis ratio 1.11 to 1.95; 1003 patients) and tertile 3 (De Ritis ratio > 1.95; 1002 patients). The primary endpoint was 3-year all-cause mortality. At 3 years, all-cause deaths occurred in 487 patients: 119 deaths (13.2%) in patients of 1st tertile, 164 deaths (17.8%) in patients of 2nd tertile and 204 deaths (21.9%) in patients of 3rd tertile of the De Ritis ratio (adjusted hazard ratio [HR] = 1.16, 95% confidence interval [CI] 1.02 to 1.31], P = 0.023 per unit increment in the logarithmic scale of the De Ritis ratio); cardiac deaths occurred in 328 patients: 76 deaths (8.2%) in patients of 1st tertile, 110 deaths (12.0%) in patients of 2nd tertile and 142 deaths (15.4%) in patients of 3rd tertile of the De Ritis ratio (adjusted HR = 1.20 [1.04–1.40], P = 0.014 per unit increment in the logarithmic scale of De Ritis ratio). The C-statistic of the multivariable model(s) with baseline data without and with De Ritis ratio was 0.822 [0.805–0.839] and 0.823 [0.805–0.840], (P = 0.419) for all-cause mortality and 0.831[0.811–0.852] and 0.832 [0.811–0.853], P = 0.621) for cardiac mortality. In patients with AMI, elevated De Ritis ratio was associated with increased risk of 3-year mortality. [ABSTRACT FROM AUTHOR]

• Tenascin-C is expressed in diseased hearts, not in normal hearts. • Clinical utility of Tenascin-C in diseased heart is unclear. • Tenascin-C was independently associated with acute myocardial infarction, cardiomyopathy, diabetic retinopathy. • Tenascin could predict cardiovascular outcomes in patient with stable coronary heart disease. We investigated the prognostic value of tenascin-C in patients with stable coronary heart disease. A total of 666 patients were enrolled and followed for 72 months. The primary outcome was a composite of cardiac events. The secondary outcomes were all-cause death, cardiovascular death, acute myocardial infarction (AMI), and heart failure hospitalization. Results: The area under the curve of tenascin-C to discriminate the occurrence of composite cardiac events was 70 % (95 % CI: 64.2 % to 75.8 %), and the corresponding optimal cutoff value was 19.91 ng/ml. A higher concentration of tenascin-C was associated with a greater risk of composite cardiac events (P trend < 0.001). Similar results were observed in all-cause death, AMI, and heart failure hospitalization. Tenascin-C was found to be an independent predictor of total cardiovascular events in patients with stable coronary heart disease at 72 months, and also for all-cause death, AMI, and heart failure hospitalization. [ABSTRACT FROM AUTHOR]

• MAp19 did not demonstrate diagnostic ability in distinguishing between patients with and without functional coronary artery disease. • A·MAp19 concentrations were associated with the risk of non-fatal myocardial infarction. • The concentration of MAp19 increased at peak exercise and subsequently decreased within two hours, demonstrating that physical activity may influence the blood concentration of MAp19. • The concentration of MAp19 was found to be weakly associated with age, cholesterol and eGFR levels. This study aimed to evaluate the diagnostic and prognostic potential of MAp19, a regulating component of the lectin pathway of the complement system, in patients with suspected functionally relevant coronary artery disease (fCAD) as well as the determinants of MAp19 levels. The presence of fCAD was adjudicated using myocardial perfusion imaging with single-photon emission tomography and, where available, coronary angiography. MAp19 levels were measured in participants at rest, at peak stress tests, and two hours after the stress. The study also tracked major cardiovascular events, including non-fatal myocardial infarction and cardiovascular death, over a five-year follow-up period. Among the 1,571 patients analyzed (32.3 % women), fCAD was identified in 462 individuals (29.4 %). MAp19 demonstrated no diagnostic significance, yielding an area under the curve (AUC) of 0.51 (0.47–0.55). Throughout the five-year follow-up, 107 patients (6.8 %) experienced non-fatal myocardial infarctions, 99 (6.3 %) had cardiovascular death, 194 (12.3 %) experienced all cause death and 50 (3.1 %) suffered a stroke. Cox and Kaplan-Meier analysis confirmed prognostic value of MAp19 for myocardial infarction, but not for cardiovascular death. Significant increases in the concentration of MAp19 were observed during bicycle (p = 0.001) and combined stress tests (p = 0.001). MAp19 demonstrated an association with the risk of myocardial infarction. Increases in MAp19 concentration were observed during bicycle and combined stress-tests. [ABSTRACT FROM AUTHOR]

[Display omitted] • Review of the most specific cardiac biomarker, troponin I and T. • Introduction of SPR biosensors to detection the cardiac troponin I and T biomarker. • Immunosensor, aptasensor, and imprinting SPR based biosensor was introduced. • Expressing the SPR biosensors as a useful platform for early detection of troponin. Acute myocardial infarction (AMI) is one of the life-threatening causes that decrease blood flow to the heart, leading to increased mortality and related complications. Recently, the measure of blood concentration of cardiac biomarkers has been suggested to overcome the limitations of electrocardiography (ECG) analyses for early diagnosis of this disease. Troponins, especially cardiac troponin I and cardiac troponin T, with high sensitivity and specificity, are considered the gold standards in myocardial diagnosis. Recently, the use of new biosensors such as surface plasmon resonance (SPR) for early detection of these biomarkers has been greatly appreciated. Due to the rapid, sensitive, real-time, and label-free detection of SPR-based biosensors, they can be applied for selective and nonspecific absorption that is intended to be used as an in situ cardiac biosensor. Here, we exclusively discussed the updated developments of these valuable predictors for the possible occurrence of AMI detected by SPR. [ABSTRACT FROM AUTHOR]

• The cardiac damage biomarkers troponin T and troponin I are regarded as interchangeable. • In patients with COVID-19 troponin T was higher than troponin I. • In patients with myocardial infarction troponin I was higher than troponin T. • Our data indicate that troponin was elevated by cardiac stress in COVID-19. • The troponin I / troponin T ratio may distinguish cardiac stress from necrosis. Although cardiac troponin T (cTnT) and troponin I(cTnI) are expressed to similar amount in cardiac tissue, cTnI often reach ten-times higher peak levels compared to cTnT in patients with myocardial necrosis such as in acute myocardial infarction (MI). In contrast, similar levels of cTnT and cTnI are observed in other situations such as stable atrial fibrillation and after strenuous exercise. Examine cTnT and cTnI levels in relation to COVID-19 disease and MI. Clinical and laboratory data from the local hospital from an observational cohort study of 27 patients admitted with COVID-19 and 15 patients with myocardial infarction (MI) that were analyzed with paired cTnT and cTnI measurement during hospital care. Levels of cTnI were lower than cTnT in COVID-19 patients (TnI/TnT ratio 0.3, IQR: 0.1–0.6). In contrast, levels of cTnI were 11 times higher compared to cTnT in 15 patients with MI (TnI/TnT ratio 11, IQR: 7–14). The peak cTnI/cTnT ratio among the patients with MI following successful percutaneous intervention were 14 (TnI/TnT ratio 14, IQR: 12–23). The 5 COVID-19 patient samples collected under possible necrotic events had a cTnI/cTnT ratio of 5,5 (IQR: 1,9–8,3). In patients with COVID-19, cTnT is often elevated to higher levels than cTnI in sharp contrast to patients with MI, indicating that the release of cardiac troponin has a different cause in COVID-19 patients. [ABSTRACT FROM AUTHOR]

• In our reference population of 763 individuals over 64 years of age without diagnoses of heart or kidney diseases, both age and gender had a clear association with cTnT and proBNP levels. • Age-specific reference limits for cTnT and proBNP are needed for more precise evaluation of cardiac symptoms of older population. • Elevated proBNP was statistically significantly associated with future AMIs in subjects with and without a previous heart disease. Our aim was to define reference limits for cardiac troponin T (cTnT) and N-terminal pro B-type natriuretic peptide (proBNP) that would better reflect their concentrations in older people. In addition, the incidence of acute myocardial infarctions (AMIs) was studied using these reference limits in an older population with and without previous heart diseases. A population-based study with a ten-year follow-up. The reference population was formed by 763 individuals aged over 64 years, with no diagnoses of heart or kidney diseases. There was a significant increase in cTnT and proBNP concentrations with age. The 99 % reference limits for cTnT were 25 ng/L, 28 ng/l, 38 ng/l, and 71 ng/l for men in five-year-intervals starting from 64 to 69 years to 80 years and older, and 18 ng/L, 22 ng/l, 26 ng/l, and 52 ng/L for women, respectively. The 97.5 % reference limits for proBNP were 272 ng/L, 287 ng/l, 373 ng/l and 686 ng/L for men, and 341 ng/L, 377 ng/l, 471 ng/l, and 794 ng/L for women, respectively. Elevated proBNP was statistically significantly associated with future AMIs in subjects with and without a previous heart disease. Age-specific reference limits for cTnT and proBNP are needed to better evaluate cardiac symptoms. [ABSTRACT FROM AUTHOR]

• Serum microbiome composition differed significantly between patients with acute myocardial infarction (AMI) and unstable angina (UA), as revealed by 16S rDNA sequencing. • Specific bacterial genera showed distinct abundance patterns, with Ralstonia, Faecalibaculum, Bacteroides, Sphingomonas, Haemophilus, Serratia, Bifidobacterium, and Chloroplast being identified as potential discriminative markers. • A diagnostic model based on random forest analysis demonstrated high accuracy in distinguishing between AMI and UA, suggesting that blood microbiome analysis holds promise as a novel diagnostic biomarker for acute myocardial infarction. It is difficult to distinguish between acute myocardial infarction (AMI) and unstable angina (UA) due to their similar clinical features. In recent years, studies have shown that microbiomes have great potential in distinguishing diseases. The purpose of this study is to describe the composition of serum microbiome in the AMI and UA by 16S rDNA sequencing. Based on the high-throughput detection platform and 16S rDNA amplification sequencing technology, this study detected the blood microbial composition of 55 patients with AMI and 62 patients with UA. Alpha diversity and Beta diversity analysis were used to compare the differences in microbial composition and bacterial colony structure between AMI and UA groups. We perform PCoA (Principal Co-ordinates Analysis) based on Unweighted Unifrac distance. In addition, various statistical methods were employed to examine the significance of differences in microbial composition and genus between the two groups. PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) was employed to predict KEGG (Kyoto Encyclopedia of Genes and Genomes) function from 16S sequencing data. Random forest was applied to identify biomarkers and construct the diagnostic model. Subsequently, the stability of the model was verified by 10-fold cross and the diagnostic effectiveness was evaluated through ROC (Receiver Operating Characteristic). In this study, we found that alpha diversity index of serum microbiome in AMI group was significantly higher than in UA group. T-test analysis demonstrated that the UA group presented a higher abundance of Ralstonia, Faecalibaculum and Gammaproteobacteria, while Bacteroides, Sphingomonas, Faecalibaculum, Haemophilus, Serratia, Bifidobacterium and Chloroplast were more abundant in the AMI group. The LefSe (LDA Effect Size) analysis showed that the Gammaproteobacteria, Proteobacteria, Ralstonia pickettli, Ralstonia, Burkholderiaceae and Burkholderiales were enriched in UA group, and Bacteroidales, Bacteroidia, Bacteroidota, Clostridia and Firmicutes were more abundant in the AMI group. Ten bacterial diagnostic models were constructed in the random forest. The area under the curve (AUC) in the training set was 88.01%, and the AUC value in the test set was 95.04%. In this study, the composition of blood microorganisms in the groups of patients with AMI and UA has been analyzed, providing novel insights for understanding the pathogenesis of AMI; Blood microbiome may serve as novel diagnostic biomarkers of AMI. [ABSTRACT FROM AUTHOR]

• Neutrophil count is the independent risk factors of in-hospital MACEs for post-MI HF. • TFF3 might be a new biomarker for predicting the severity of HF after AMI. • Regulating inflammation might become a new target for controlling heart failure. Acute myocardial infarction (AMI) still has a high incidence of varying degrees of heart failure (HF). The aim of this study is to identify new molecular markers for predicting the severity of HF after AMI. We analyzed demographic indicators, past medical history, clinical indicators, major adverse cardiac events (MACEs) and molecular markers in patients with different Killip classifications after AMI. Olink proteomics was used to explore new molecular markers for predicting different severity of HF after AMI. Neutrophil count was the independent risk factors for in-hospital MACEs. Nineteen differentially expressed proteins (DEPs) increased significantly with increasing Killip classification. Five DEPs were also found to have an AUC (95 % CI) value greater than 0.8: GDF-15, NT-pro BNP, TNF-R2, TNF-R1 and TFF3. Neutrophil count, GDF-15, TNF-R2, TNF-R1 and TFF3 were closely related to the Killip classification of HF after AMI, which suggests that the inflammatory response plays an important role in the severity of HF after AMI and that regulating inflammation might become a new target for controlling HF. [ABSTRACT FROM AUTHOR]

• The low proportion of T2MI coronary imaging and the lack of guidelines for managing T2MI patients have resulted in difficulty in diagnosis. • OCT was used to identify the types of MI. • NALL, FFA(15:1), TTP, MevPP, and five unknown function oligopeptides are potential metabolic biomarkers for distinguishing T2MI from T1MI. • The metabolic characteristics of these two types of MI differ considerably. • An operable T2MI subclassification method based on its causes/triggers could reduce disease heterogeneity. It is difficult to distinguish type 2 myocardial infarction (T2MI) from type 1 myocardial infarction (T1MI), although their management varies. Using optical coherence tomography (OCT) and pseudo-targeted metabolomics to identify biomarkers, investigate metabolic differences, and establish a T2MI subclassification. Among 1519 patients with MI, 97 T2MI patients are identified who are 1:1 matched with 97 T1MI patients after considering age, gender, ST-segment elevation, time from onset to coronary angiography, and hs-cTnI on admission by propensity score matching. Plasma pseudo-targeted metabolomics at baseline was determined. The clinical characteristics of the two groups were comparable, while the T1MI showed more severe coronary lesions than T2MI according to OCT imaging. 90 differential metabolites were identified between the two groups, among 1027 endogenous metabolites in 20 classes. N-Acetyl-L-Leucine, free fatty acid (15:1), Thymidine-5′-triphosphate, Mevalonic acid 5-pyrophosphate, and five oligopeptides were candidate biomarkers (AUC ≥ 0.85) distinguishing T2MI from T1MI. 12 KEGG pathways showed significant differences, mainly involving amino acid, nucleotide, and their derivatives metabolism, and signaling pathways such as mTOR, cGMP-PKG, and cAMP. Other differences were observed in TCA cycle (P = 0.08) and ROS (P = 0.05). Proteolysis and coronary heart disease risk lipid level were lower in T2MI. T2MI had a decrease of differential abundance score in almost all the KEGG enrichment pathways. Furthermore, T2MI can be subdivided into three subtypes by hierarchical cluster analysis of AUCs with causes/triggers of T2MI. There are significant metabolic profile differences between T1MI and T2MI. Several candidate metabolic biomarkers can effectively distinguish the two groups. Clinical trial registration: ClinicalTrials. gov NCT03297164. [ABSTRACT FROM AUTHOR]

• Through the joint analysis of omics, we can understand the pathophysiological mechanism of MI more systematically. • Omics technology promotes the clinical diagnosis of MI. • The integration and analysis of MI-related joint pathways furnish a theoretical basis for MI therapeutic development. Myocardial infarction (MI), a prevalent cardiovascular disease, is fundamentally precipitated by thrombus formation in the coronary arteries, which subsequently decreases myocardial perfusion and leads to cellular necrosis. The intricacy of MI pathogenesis necessitates extensive research to elucidate the disease's root cause, thereby addressing the limitations present in its diagnosis and prognosis. With the continuous advancement of genomics technology, genomics, proteomics, metabolomics and transcriptomics are widely used in the study of MI, which provides an excellent way to identify new biomarkers that elucidate the complex mechanisms of MI. This paper provides a detailed review of various genomics studies of MI, including genomics, proteomics, transcriptomics, metabolomics and multi-omics studies. The metabolites and proteins involved in the pathogenesis of MI are investigated through integrated protein-protein interactions and multi-omics analysis by STRING and Metascape platforms. In conclusion, the future of omics research in myocardial infarction offers significant promise. [ABSTRACT FROM AUTHOR]

• We investigated the association between Lp-PLA2 activity and CAD and MI from a genetic standpoint. • This is the first Mendelian Randomization study to investigate the causal association of Lp-PLA2 activity with the risk of CAD and MI. • High genetically determined Lp-PLA2 activity had causal effects on the increased risks of CAD and MI. • Further studies are needed to investigate whether targeting Lp-PLA2 activity can decrease the incidence of CAD and MI in the population. Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity has been reported to be associated with coronary artery disease (CAD) and myocardial infarction (MI). However, whether Lp-PLA2 is a causal risk factor for CAD and MI remains unclear. Herein, we performed a two-sample mendelian randomization (MR) study to assess the causal effect of Lp-PLA2 activity on CAD and MI. We selected 7 single-nucleotide polymorphisms (SNPs) associated with Lp-PLA2 activity as instrumental variables based on the data from Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium with 13,664 European individuals. Summary data about CAD and MI were obtained from Coronary Artery Disease Genome-wide Replication and Meta-analysis plus the Coronary Artery Disease Genetics (CARDIOGRAMPLUSC4D) consortium with 60,801 CAD cases and 43,676 MI cases (mostly European). The inverse-variance weighted method was applied to assess the causal associations of Lp-PLA2 activity with CAD and MI in the main analysis. The main inverse-variance weighted (IVW) MR analysis showed that 1-SD increment in genetically determined LP-PLA2 activity was associated with increased risks of CAD (odds ratio, 5.93; 95% CI, 2.91–12.07; p value = 9.43 × 10-7) and MI (odds ratio, 4.71; 95% CI, 2.49–8.90; p value = 1.86 × 10-6). MR-Egger regression showed no evidence of pleiotropic bias. The causal associations were consistent in sensitivity analyses with multiple MR methods, in which showed Lp-PLA2 activity was causally associated with an increased risk of CAD and MI. In this two-sample MR study, high Lp-PLA2 activity was a causal risk factor for CAD and MI, indicating that Lp-PLA2 activity may be a promising intervention target in reducing the risk of CAD and MI. [ABSTRACT FROM AUTHOR]

• This article focus on the progress of sestrin2 in regulating the pathogenesis of atherosclerosis. • The results show that sestrin2 can become a novel target for the prevention and treatment of atherosclerosis. Atherosclerosis (AS) is the pathological basis of numerous lethal diseases, such as myocardial infarction, heart failure, and stroke. As we know, almost twenty million people worldwide die of the arterial diseases annually. Sestrin2 is a stress-inducing protein, which serves as a guardian by activating AMPK, inhibiting mTOR, and maintaining redox balance beneath various stress environments. A large number of studies show that Sestrin2 would shield the body from injury by stress. Moreover, it has been demonstrated that Sestrin2 is closely connected with AS. Here, this article reviewed the involvement of Sestrin2 in the pathogenesis of AS from four aspects: cellular mechanism, oxidative stress, inflammation, and lipid metabolism. Current evidence reveals that Sestrin2 is a novel target for the prevention and treatment of AS. [ABSTRACT FROM AUTHOR]

• H-FABP is a potential biomarker for the detection of ACS and AKI. • This study is the first URL determination for H-FABP in a healthy U.S. population. • H-FABP differences were found between sexes but not with age. • H-FABP may be affected by regional differences in diet and obesity. Heart-type fatty acid binding protein (H-FABP), a low molecular weight protein found primarily in myocardial tissue, has been identified as a potential biomarker in the detection of acute coronary syndrome and acute kidney injury. To further investigate clinical utility, we sought to establish an upper reference limit (URL) of H-FABP within a healthy U.S. population. Serum samples of healthy donors were acquired from the AACC Universal Sample Bank. We analyzed 355 samples for H-FABP concentration using the Randox Laboratories immunoturbidimetric assay on the Roche Cobas 8000 series analyzer. The final sample population consisted of individuals aged 18–74 y, with 170 males and 185 females. The distribution of the population exhibited a strong positive skew, affecting outlier analysis and URL determination. The 97.5th-percentile URL was found to be 7.4 ng/ml (95% CI: 6.3–9.2), while the 99th-percentile URL was 12.1 ng/ml (8.6–14.9). As the URL for H-FABP is highly affected by population distribution and outlier removal, final determination for an assay cutoff should be made in the context of clinical utility, either as a standalone assay or in conjunction with other biomarkers, and the desired clinical sensitivity and specificity. [ABSTRACT FROM AUTHOR]

• Cockcroft-Gault creatinine clearance and EKFC equations predict mortality better than MDRD-4 and CKD-EPI equations. • Cockcroft-Gault creatinine clearance and EKFC equations predict bleeding better than MDRD-4 and CKD-EPI equations. • All four eGFR equations failed to improve risk prediction for myocardial infarction. It remains unknown which equation used to assess the glomerular function is better for risk stratification in patients with acute coronary syndrome (ACS). This study included 3985 patients with ACS. Glomerular function was assessed using 4 equations: the Cockcroft-Gault creatinine clearance (C-G CrCl), Modification of Diet in Renal Disease-4 (MDRD-4), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and European Kidney Function Consortium (EKFC) equations. The primary outcome was one-year all-cause mortality. For each 30 ml/min decrement, the adjusted hazard ratio [HR] with 95% confidence interval [CI] for one-year mortality was 1.67 [1.27–2.25] for C-G CrCl , 1.45 [1.16–1.81] for MDRD-4, 1.76 [1.35–2.30] for CKD-EPI and 1.94 [1.44–2.63] for EKFC equation. Area under the receiver operating characteristic curve (AUC) for one-year mortality was 0.748 [0.709–0.788] for C-G CrCl , 0.670 [0.621–0.718] for estimated glomerular filtration rate (eGFR) calculated by MDRD-4 equation, 0.725 [0.684–0.765] for eGFR calculated by CKD-EPI equation and 0.741 [0.703–0.779] for eGFR calculated by EKFC equation (P = 0.342 for C-G CrCl , vs. EKFC equation and P ≤ 0.009 for all other AUC comparisons). In patients with ACS, C-G CrCl and EKFC equations showed a similar discriminatory power regarding prediction of one-year mortality. Both equations were better than MDRD-4 and CKD-EPI equations for risk discrimination for mortality. Clinical Trial Registration: NCT01944800. [ABSTRACT FROM AUTHOR]

Sphingosine 1-phosphate (S1P), a metabolite of sphingolipids, is mainly derived from red blood cells (RBCs), platelets and endothelial cells (ECs). It plays important roles in regulating cell survival, vascular integrity and inflammatory responses through its receptors. S1P receptors (S1PRs), including 5 subtypes (S1PR1-5), are G protein-coupled receptors and have been proved to mediate various and complex roles of S1P in atherosclerosis, myocardial infarction (MI) and ischemic stroke by regulating endothelial function and inflammatory response as well as immune cell behavior. This review emphasizes the functions of S1PRs in atherosclerosis and ischemic diseases such as MI and ischemic stroke, enabling mechanistic studies and new S1PRs targeted therapies in atherosclerosis and ischemia in the future. [ABSTRACT FROM AUTHOR]

• The agreement between hs-cTn T (Roche) and hs-cTn I (Abbott) is weak. • This disagreement is in favor of underdiagnosis with hs-cTn I and overdiagnosis with hs-cTn T. • The use of sex-specific 99th percentile reduces significantly this disagreement. • No impact was seen for circadian rhythm on the agreement while the disagreement increased with decreasing renal function. Many reports noted a disagreement between High sensitivity cardiac Troponin (hs-cTn) assays on the diagnosis of Acute Coronary Syndrome (ACS). We conducted a retrospective study aiming to assess the agreement between hs-cTn T (Roche) and hs-cTn I (Abbott) in patients presenting with a suspected ACS to the emergency department at Hotel-Dieu hospital between September 2017 and October 2019 using overall, sex-specific, and age-adjusted sex-specific cut-off values. This was measured using Cohen's Kappa. We explored whether renal function, circadian rhythm, age and sex influenced the discordance. And we analyzed the trend of agreement between baseline and repeated measurements. 4856 patients who had simultaneous hs-cTn I and T values were retained for the analysis. 53.5% had a hs-cTn T above the overall 99th percentile, compared to 19.9% for hs-cTn I. The numbers were significantly reduced when applying age-adjusted sex-specific 99th percentile. A disagreement was seen in 34% of cases using overall 99th percentile. Using sex-specific cut off values did not impact this discordance; however, age-adjusted sex-specific cut-off values reduced the percentage of discrepancies to 15.8%. The decreased renal function had a negative effect on the agreement while the circadian rhythm had minimal effect. This initial discordance was carried forward into repeated measurements. The disagreement between hs-cTn T and I assays could be imputed to the choice of cut-off values. The use of age-adjusted sex specific 99th percentile reduced majorly these discordances. Further studies are needed in order to evaluate their clinical utility in patients presenting with ACS. [ABSTRACT FROM AUTHOR]

• Accurate etiological classification of stroke is the basis of treatment choice. • Studies have shown that plasma combined with cardiac markers is valuable for the diagnosis of cardioembolic stroke. • It is the first study to demonstrate that serum LRG1 might be a promising indicator to predict cardioembolic stroke. • Serum LRG1 was associated with the severity and prognosis of cardioembolic stroke patients. • The combined predictive model, including LRG1, BNP, and LAD, significantly improved the prediction effect. In recent years, LRG1 was found to be closely related to atrial fibrillation, heart failure, and myocardial remodeling after myocardial infarction. While its role in cerebral infarction was still controversial. We aimed to explore the value of LRG1 to identify the cardioembolic stroke. 283 acute ischemic stroke(AIS) patients and 169 controls were enrolled. The AIS patients were divided into a CE(cardiogenic embolism) group and a non-CE group. Serum LRG1 levels were quantified by ELISA. The serum LRG1 levels were decreased in the AIS patients. CE group had higher serum LRG1 levels than the non-CE group. LRG1 was an independent risk factor for cardioembolic stroke. The area under the curve (AUC) was 0.768 with a sensitivity of 72.5% and specificity of 69.5%, which was not second to BNP and LAD. The combined predictive model we designed, including LRG1, BNP, and LAD, greatly improved the prediction effect. A positive correlation was shown between LRG1 and stroke severity in the CE group. Those who experienced poor outcomes had higher serum LRG1 levels compared with good ones. Serum LRG1 was a promising indicator to predict cardioembolic stroke, as well as stroke severity and the 3-month prognosis of it. [ABSTRACT FROM AUTHOR]

• The Ortho hs-cTnI assay demonstrated excellent analytical performances. • Ortho hs-cTnI showed good correlation with Roche hs-cTnT and Abbott hs-cTnI assays. • Ortho hs-cTnI assay provided an acceptable diagnostic performance. • Ortho hs-cTnI assay may be used in the clinical practice using 0/3-hour algorithm. Recently, Ortho Clinical Diagnostics have launched a high sensitivity cardiac troponin I assay adapted on Vitros3600 / 5600. We aimed at evaluating the analytical and clinical performances using the 0/3-hour algorithm, of the Ortho hs-cTnI assay on the Vitros 3600® (Ortho Clinical Diagnostics, Illkirch, France) analyzer with comparison to Roche hs-cTnT assay on the Cobas8000/e801® module (Roche diagnostics, Meylan, France) and the Abbott STAT hs-cTnI assay on the Alinity i® (Abbott, Rungis, France) analyzer. Imprecision studies, linearity, limit of detection, and the interference to hemolysis were performed for Ortho hs-cTnI assay. The concordance study was based on results of troponin obtained from 160 patients with chest pain to the emergency department. Testing was performed simultaneously measuring the Roche hs-cTnT and the Ortho hs-cTnI, then on remaining sample the concentration of Abbott hs-cTnI (n = 150). We applied the 0/3h algorithm to rule out/rule in, in acute myocardial infarction. Analytical performances were acceptable and in accordance with manufacturer's data. For late presenters 100, 92.8 and 88.8% patients could be rule-out with Roche, Ortho and Abbott assay, respectively with one NSTEMI missed with both hs-TnI assays. Applying the hs-cTn cut-offs from 0/3-hour algorithm, 107 (66.8%) could be rule out with Roche hs-cTnT with no AMI missed (sensitivity 100% [95%CI : 90.5 to 100] and NPV 100%); 89 with Ortho hs-cTnI (sensitivity 97.3% [95%CI : 85.8–99.9] and NPV 98.8% [95%CI :92.7–99.8]); and 61 with Abbott hs-cTnI (sensitivity 97% [95%CI : 84.2–99.9] and NPV 98.4% [95%CI : 89.8–99.7]). For rule-in, 23.7% (n = 37) from the total population would be designated in this group, with a specificity of 86.9% (95%CI: 79.7–92.4) and PPV of 69.8% (95%CI: 59.4–78.5) vs specificity of 72.3% (95%CI:63.5–80.0) and PPV of 51.4% (95%CI: 44.1–58.2) with Roche hs-cTnT vs Ortho hs-cTnI respectively; and with Abbott, 33 patients had constitued this group with a specificity of 52.1% (95%CI:42.7–61.4) and PPV of 36.4% (95%CI: 32.0–41.0). In conclusion, according to ESC guidelines, our results indicate that the Ortho hs-cTnI assay for the Vitros 3600 instrument is a method that may be used in the clinical practice using 0/3-hour algorithm. [ABSTRACT FROM AUTHOR]

• Efferocytosis involves the clearance of apoptotic cells by phagocytes to suppress atherosclerosis. • ABCA1 promotes not only cholesterol efflux but also efferocytosis. • ABCA1 promotes efferocytosis by regulating "find-me" ligands and "eat-me" ligands expression. • ABCA1 has an efferocytosis pathway similar to that of TG2, which is an "eat-me" ligand. • ABCA1 can form several regulatory feedback axes with ANXA1, MEGF10, GULP1, TNFα, IL-6. Atherosclerosis, a disease process characterized by lipid accumulation and inflammation, is the main cause of coronary heart disease (CHD) and myocardial infarction (MI). Efferocytosis involves the clearance of apoptotic cells by phagocytes. Successful engulfment triggers the release of anti-inflammatory cytokines to suppress atherosclerosis. ABCA1 is a key mediator of cholesterol efflux to apoA-I for the generation of HDL-C in reverse cholesterol transport (RCT). Intriguingly, ABCA1 promotes not only cholesterol efflux but also efferocytosis. ABCA1 promotes efferocytosis by regulating the release of "find-me" ligands, including LPC, and the exposure, release, and expression of "eat-me" ligands, including PtdSer, ANXA1, ANXA5, MEGF10, and GULP1. ABCA1 has a pathway similar to TG2, which is an "eat-me" ligand. ABCA1 has the highest known homology to ABCA7, which controls efferocytosis as the engulfment and processing ligand. In addition, ABCA1 can form several regulatory feedback axes with ANXA1, MEGF10, GULP1, TNFα, and IL-6. Therefore, ABCA1 is the central factor that links cholesterol efflux and apoptotic cell clearance. Several drugs have been studied or approved for apoptotic cell clearance, such as CD47 antibody and PD1-/PD-L1 antibody. In this article, we review the role and mechanism of action of ABCA1 in efferocytosis and focus on new insights into the ABCA1-efferocytosis axis and its potential as a novel therapeutic target in atherosclerosis. [ABSTRACT FROM AUTHOR]

• We have developed a double-antibody sandwich-based chemiluminescent immunoassay to determine the plasma concentration of S100A1. • S100A1 is a sensitive and specific cardiac biomarker for early diagnosis of acute myocardial infarction. • S100A1 may provide prognostic information for acute myocardial infarction after PCI. A member of the S100 family of Ca2+-binding proteins, S100A1 is highly expressed in cardiac muscle tissue. Although this protein is considered an indicator of acute myocardial infarction (AMI), high-throughput and sensitive detection methods are still urgently needed. We constructed a rapid and sensitive method for detecting S100A1 and to investigate the clinical utility of S100A1 as a biomarker for the early diagnosis of AMI and subsequent prognostic assessments. We developed an automated chemiluminescent immunoassay to detect S100A1. We then analyzed the performance of the newly developed assay including evaluation of the analytical sensitivity, analytical selectivity, linear range, accuracy and repeatability. We recruited 87 patients with AMI or angina pectoris to explore the value of this marker for the early diagnosis and prognostic assessment. The chemiluminescent-immune-based S100A1 assay had functional analytical sensitivity with a detection limit of 0.13 ng/ml, and a wide linear range of 0.13–31.66 ng/ml. It also exhibited good repeatability with intra-assay and inter-assay findings of <5% and <15%, respectively. Plasma S100A1 was found to have a higher diagnostic sensitivity than conventional cardiac biomarkers (creatine kinase-MB and cardiac troponin T). The survival analysis showed that a higher concentration of plasma S100A1 (>1.02 ng/ml) was notably associated with the poor prognosis of AMI patients after first PCI. Measurement of circulating S100A1 concentrations with our newly developed chemiluminescent-immune-based assay shows potential for use in the clinic. This assay could enable early identification and prognostic assessment of AMI. [ABSTRACT FROM AUTHOR]

• There is no review summarizing biomarkers in MINOCA. • We summarized the non-atherosclerotic biomarkers, including traditional markers, potential markers, and imaging markers. • Biomarkers of MINOCA are of great significance for diagnosis, treatment, prognosis and mechanism research. Myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) is an important subtype of myocardial infarction. Although comprising less than 50% stenosis in the main epicardial coronary arteries, it constitutes a severe health risk. A variety of approaches have been recommended, but definitive diagnosis remains elusive. In addition, the lack of a comprehensive understanding of underlying pathophysiology makes clinical management difficult and unpredictable. This review highlights ongoing efforts to identify relevant biomarkers in MINOCA to improve diagnosis, individualize treatment and better predict outcomes. [ABSTRACT FROM AUTHOR]

• H-ficolin at rest, at peak exercise, and 2 h after exercise did not demonstrate diagnostic ability in distinguishing between patients with fCAD versus patients without fCAD. • H-ficolin was not a predictor of cardiovascular death and non-fatal myocardial infarction in the overall cohort. • H-ficolin slightly increased during bicycle exercise stress, and decreased to baseline levels 2 h after bicycle stress. Similarly, H-ficolin slightly decreased during pharmacological (adenosine) or combined stress, and returned to baseline levels at 2 h. • H-ficolin was weakly correlated with systolic and diastolic blood pressure. We aimed to test the diagnostic and prognostic ability of H-ficolin, an initiator of the lectin pathway of the complement system, for functionally relevant coronary artery disease (fCAD), and explore its determinants. The presence of fCAD was adjudicated using myocardial perfusion imaging single-photon emission tomography and coronary angiography. H-ficolin levels were measured by a sandwich-type immunoassay at rest, peak stress-test, and 2 h after stress-test. Cardiovascular death and non-fatal myocardial infarction were assessed during 5-year follow-up. Among 1,571 patients (32.3 % women), fCAD was detected in 462 patients (29.4 %). H-ficolin concentration at rest was 18.6 (15.3–21.8) µg/ml in patients with fCAD versus 17.8 (15.4–21.5) µg/ml, p = 0.33, in patients without fCAD, resulting in an AUC of 0.53 (95 %CI 0.48–0.56). During follow-up, 107 patients (6.8 %) had non-fatal myocardial infarction and 99 patients (6.3 %) experienced cardiovascular death. In Cox regression analysis, H-ficolin was not a predictor of events in the overall cohort. Subgroup analysis suggested a potential link between H-ficolin and non-fatal myocardial infarction in patients without fCAD (adjusted HR 1.03, 95 % CI 1.02–1.15, p = 0.005). H-ficolin concentration showed a weak positive correlation with systolic (r = 0.069, p < 0.001) and diastolic blood pressure (r = 0.111, p < 0.001). H-ficolin concentration did not have diagnostic and/or prognostic value in patients referred for fCAD work-up. [ABSTRACT FROM AUTHOR]

• AIM2 inflammasome can be activated in the context of cardiovascular diseases. • Mitochondrial dysfunction and cGAS- STING pathway activate AIM2 inflammasome. • AIM2 promotes atherosclerotic plaque instability via AIM2 inflammasome activation. • AIM2 has close links to myocardial infarction, heart failure, abdominal aortic aneurysm. Absent in melanoma 2 (AIM2) is a member of the PYHIN (pyrin and HIN domain-containing protein) family with important roles in sensing double-stranded DNA (dsDNA) and assembling the AIM2 inflammasome, which has wide-ranging, pro-inflammatory and pro-pyroptotic properties. The AIM2 inflammasome can become activated in atherosclerotic plaque, abdominal aortic aneurysm wall and injured myocardium, and its activation is tightly regulated by a variety of atherogenic factors. Activation of the AIM2 inflammasome has close links to the progression of several cardiovascular diseases. This review will summarize the current knowledge of AIM2 biology, providing the latest insights into the mechanisms and contributions of atherogenic factors to AIM2 inflammasome activation. In addition, we will also explore crosstalk between AIM2 and the pathologies of atherosclerosis, abdominal aortic aneurysm, myocardial infarction and heart failure. A better understanding of the pathological roles of AIM2 in these disorders will be helpful in developing novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

• To evaluate whether it is possible to harmonize two hs-cTnI methods by means of a recalibration procedure. • A two-step approach using both quality control and clinical samples was used. • A significant bias reduction between the two hs-cTnI methods was found after recalibration procedure. • A recalibration procedure can be used to improve harmonization between the results of hs-cTnI methods. The study aim was to evaluate whether is possible to harmonize the results of two hs-cTnI methods using a recalibration procedure based on linear regression models and measured values of external quality assessment (EQA) and clinical samples. A two-step experimental approach was used. The preliminary step was performed using 16 EQA samples. The harmonization procedure was then validated by using 2530 heparinized plasma samples collected by 12 Italian University and Regional Hospitals from apparently healthy volunteers and patients admitted to emergency department with cardiac diseases. Two hs-cTnI methods were tested: Architect Stat High Sensitive Troponin-I, and the Access hs-cTnI using DxI platform. Linear regression models based on mean values measured with the two hs-cTni methods were used. A significant reduction in the measurement bias between the two methods was found after recalibration procedure. The agreement between-methods improved of about 2.5 folds after recalibration, as assessed by reduction in mean CV values from 38.4% (SD 25.9%) before recalibration to 15.0% (SD 10.6%) after recalibration for hs-cTnI values ≤ 500 ng/L (n = 13, P = 0.0111 by non-parametric test for paired data). A recalibration procedure based on means of measured concentrations with hs-cTnI methods, which use monoclonal antibodies with similar binding characteristics, can be used to significantly reduce systematic bias and so to improve harmonization between methods. The results of this study can aid laboratorians and clinicians to better compare the concentrations respectively measured with the Architect and Access hs-cTnI methods. [ABSTRACT FROM AUTHOR]

• Analytical performance specifications for hs-cTn assays should be based clinical use. • Outcome studies suggest performance is sufficient for rapid identification of NSTEMI. • Biological variation may guide performance when hs-cTn are used for risk prediction. • Further improvement in analytical performance is likely to be clinically useful. Concurrent with the introduction of cardiac troponin measurements into the diagnostic definition of myocardial infarction (MI), clinicians and laboratory professionals signaled a clear clinical need for improved analytical quality. This was an important precipitant for developing high-sensitivity cardiac troponin (hs-cTn) assays, currently used in rapid algorithms guiding investigations of patients presenting to the emergency department with possible MI. The hs-cTn assays were also important for the detection and monitoring of low-grade chronic myocardial injury, a condition that has been linked to increased long-term risk of cardiovascular morbidity and mortality. This review summarizes the general recommendations for defining analytical performance specifications while providing relevant clinical situations related to analytical performance. Importantly, outcome studies suggest analytical quality performance for hs-cTn is sufficient for early discharge of patients investigated for possible MI. However, bias due to change in calibrators or reagents may significantly affect the percentage of patients discharged. Biological variation data is suitable for defining performance specifications when hs-cTn measurements are used for diagnosing and monitoring chronic myocardial injury. Further improvement in analytical performance for hs-cTn testing may result in even faster decision making in the emergency setting; while also identifying those with chronic injury at risk for an adverse cardiac event. [ABSTRACT FROM AUTHOR]

• In NSTEMI patients there was considerable variation in the kinetic profiles of cTn concentrations. • cTnI concentrations increased at a much more rapid rate than cTnT concentrations. • Concentrations of 33% of patients took 3 h from symptom onset to exceed rule-out thresholds. The early concentration kinetic profiles of cardiac troponin in patients with non-ST-elevated myocardial infarction (NSTEMI) measured by high-sensitivity cardiac troponin I (hs-cTnI) and T (hs-cTnT) assays have not been described. In intermediate-to-high-risk of NSTEMI patients we measured serial cTn concentrations on ED arrival, at 1, 2, 3, 6–12, 24 and 48-hours with hs-cTnI and hs-cTnT assays. Log-normal curves were fitted to concentrations from time from symptom onset, and the time to rule-out decision thresholds estimated (hs-cTnI: 2 ng/L and 5 ng/L; hs-cTnT: 5 ng/L). Among 164 patients there were 58 NSTEMI. The hs-cTnI to hs-cTnT ratio increased linearly over the first 6–12 h following symptom onset. The estimated times from symptom onset to the 2 ng/L and 5 ng/L thresholds for hs-cTnI were 1.8 (0.1–3.1) and 1.9 (1.1–3.5) hours, and to the 5 ng/L threshold for hs-cTnT 1.9 (1.1–3.8) hours. The estimated time to exceed 5 ng/L was ≥3 hours in 32.6% (95%CI: 20.0% to 48.1%) cases for hs-cTnI and 33.3% (19.6% to 50.0%) for hs-cTnT. cTnI concentrations increased at a much more rapid rate than cTnT concentrations in patients with NSTEMI. Concentrations of a high proportion of patients took longer than 3 hours from symptom onset to exceed the 5 ng/L rule-out decision threshold. [ABSTRACT FROM AUTHOR]

• Validation of 99th percentile URL for TnT Gen 5 assay in a healthy US population. • TnT Gen 5 results were higher in healthy males vs females and increased with age. • The findings facilitate interpretation of TnT Gen 5 results in US clinical practice. Determining diagnostic thresholds for cardiac troponin assays is key to interpreting their clinical performance. We describe the calculation of 99th percentile upper reference limits (URLs) for the Elecsys® Troponin T Gen 5 (TnT Gen 5) assay. Plasma and serum samples from healthy US participants were prospectively evaluated using TnT Gen 5 Short Turn Around Time and 18-min assays on cobas e 411 and cobas e 601 analyzers (Roche Diagnostics); with, up to 8 TnT Gen 5 results per participant. A total of 10,402 TnT Gen 5 results from 1301 participants were included (50.4% female). Across 9 calculation methods, overall 99th percentile URL was 19.2 ng/l (females, 13.5–13.6 ng/l; males, 21.4–22.2 ng/l). Across different sample/assay/analyzer combinations, overall 99th percentile URLs ranged from 18.4–20.2 ng/l. Median TnT Gen 5 results increased with age, were higher in males, and ranged from 3.0–3.7 ng/l across races/ethnicities and from 3.0–3.6 ng/l across body mass index (BMI) classes. Applying additional exclusion criteria (N-terminal pro-brain natriuretic peptide, BMI and estimated glomerular filtration rate) resulted in lower 99th percentile URLs (overall, 16.9 ng/l; females, 11.8 ng/l; males, 18.5 ng/l). Our findings facilitate the interpretation of TnT Gen 5 results in US clinical practice. [ABSTRACT FROM AUTHOR]

• Patients show a unique cTnT release profile after CABG surgery. • Latent class mixed models can uncover subgroups of patients based on cTnT profiles. • 4 unique classes were found, depicted by: normal, high, low or rising cTnT profiles. • A rising cTnT profile is more accurate to diagnose PMI than a single cut-off value. Diagnosis of perioperative myocardial infarction (PMI) after coronary artery bypass grafting (CABG) is fraught with complexity since it is primarily based on a single cut-off value for cardiac troponin (cTn) that is exceeded in over 90% of CABG patients, including non-PMI patients. In this study we applied an unsupervised statistical modeling approach to uncover clinically relevant cTn release profiles post-CABG, including PMI, and used this to improve diagnostic accuracy of PMI. In 624 patients that underwent CABG, cTnT concentration was serially measured up to 24 h post aortic cross clamping. 2857 cTnT measurements were available to fit latent class linear mixed models (LCMMs). Four classes were found, described by: normal, high, low and rising cTnT release profiles. With the clinical diagnosis of PMI as golden standard, the rising profile had a diagnostic accuracy of 97%, compared to 83% for an optimally chosen cut-off and 21% for the guideline recommended cut-off value. Clinically relevant subgroups, including patients with PMI, can be uncovered using serially measured cTnT and a LCMM. The LCMM showed superior diagnostic accuracy of PMI. A rising cTnT profile is potentially a better criterion than a single cut-off value in diagnosing PMI post-CABG. [ABSTRACT FROM AUTHOR]

• cfDNA is a biomarker for diagnosis and prognosis of cardiovascular disease. • cfDNA is released from living cells via exosomes, NETosis, or vesicular transport. • cfDNA activates immune cells and increases cytokines, chemokines, and MMPs. • Future studies should be focused on optimizing sample preparation to increase reliability of cfDNA analysis. Release of cell free DNA (cfDNA) from damaged or dead cells routinely occurs in normal physiology. Recently, cfDNA has emerged as an essential biomarker in cardiovascular disease (CVD) of potential prognostic and diagnostic significance. Within the last decade, significant research efforts have been devoted to uncovering the mechanisms mediating cfDNA release and its outcome-predicting ability. The current review focuses on the pathways for cfDNA release in myocardial infarction, heart failure and hypertension, and discusses implementation of cfDNA monitoring to assess the overall development of these disease states and predict future complications. [ABSTRACT FROM AUTHOR]

• Lipoprotein(a) interacts with LDL-C on myocardial infarction. • Lipoprotein(a) lowering may be an option for those with inadequate LDL-C control. • Risk of AMI from exposure of both Lp(a) and LDL-C is greater than the sum of the risks from that of both alone. To evaluate the interaction effects between lipoprotein (a) (Lp(a)) and low-density lipoprotein cholesterol (LDL-C) on first incident acute myocardial infarction (AMI) among Chinese Han population. 1522 cases and 1691 controls were retrospectively analyzed. All subjects were grouped by Lp(a) or LDL-C level. Compared with reference group (LDL-C < 2.6 mmol/L and in the 1st quintile of Lp(a)), multivariable-adjusted analysis revealed that OR(95%CI) of first incident AMI for higher LDL-C alone is 2.66(1.78–3.98); that ORs(95%CI) for higher Lp(a) alone are 1.51(1.07–2.15), 1.84(1.28–2.64), 1.86(1.30–2.67) and 2.66(1.88–3.76) across the Lp(a) quintiles; and that ORs(95%CI) for both higher LDL-C and higher Lp(a) are 3.95(2.64–5.92), 3.20(2.21–4.64), 5.64(3.80–8.36) and 7.48(4.90–11.44) which were greater than the sum of the risks of both alone across the Lp(a) quintiles. Relative excess risks due to interaction were 1.78(95% CI, 0.12–3.44, P = 0.036) and 3.01(0.58–5.44, P = 0.015) at the 4th and 5th quintile of Lp(a), confirming the presence of additive interaction between Lp(a) and LDL-C on initial AMI. Lp(a) interacts with LDL-C in first incident AMI on additive scale in Chinese Han population. The risk of initial AMI from exposure of elevated Lp(a) combined with elevated LDL-C is much greater than the sum of the risks from that of both alone. [ABSTRACT FROM AUTHOR]

The study aim is to compare cTnI values measured with three high-sensitivity (hs) methods in apparently healthy volunteers and patients admitted to emergency department (ED) with acute coronary syndrome enrolled in a large multicentre study. Heparinized plasma samples were collected from 1511 apparently healthy subjects from 8 Italian clinical institutions (mean age: 51.5 years, SD: 14.1 years, range: 18–65 years, F/M ratio:0.95). All volunteers denied chronic or acute diseases and had normal values of routine laboratory tests. Moreover, 1322 heparinized plasma sample were also collected by 9 Italian clinical institutions from patients admitted to ED with clinical symptoms typical of acute coronary syndrome. The reference study laboratory assayed all plasma samples with three hs-methods: Architect hs-cTnI, Access hs-cTnI and ADVIA Centaur XPT methods. Principal Component Analysis (PCA) was also used to analyze the between-method differences among hs-cTnI assays. On average, a between-method difference of 31.2% CV was found among the results of hs-cTnI immunoassays. ADVIA Centaur XPT method measured higher cTnI values than Architect and Access methods. Moreover, 99th percentile URL values depended not only on age and sex of reference population, but also on the statistical approach used for calculation (robust non-parametric vs bootstrap). Due to differences in concentrations and reference values, clinicians should be advised that plasma samples of the same patient should be measured for cTnI assay in the same laboratory. Specific clinical studies are needed to establish the most appropriate statistical approach to calculate the 99th percentile URL values for hs-cTnI methods. • The evaluation of the 99th URL value is a very difficult task that is usually beyond the capacity of a single laboratory. • A multicenter study was promoted in Italy to evaluate and compare reference values of three hs-cTnI methods. • 1511 apparently healthy subjects from 8 clinical institutions were enrolled (51.5± 14.1 years, 18-65 years, F/M 0.95). • Due to between-method systematic differences, cTnI measurement should assayed in the same laboratory. • Further studies are needed to establish the appropriate statistical approach to calculate the 99th percentile URL values for hs-cTnI methods. [ABSTRACT FROM AUTHOR]

We report the analytical performance of the Elecsys® Troponin T Gen 5 STAT (TnT Gen 5 STAT; Roche Diagnostics) assay. Measuring limits/ranges were determined in lithium-heparin plasma samples per Clinical and Laboratory Standards Institute (CLSI) EP17-A2. Precision was evaluated per CLSI EP05-A2 using lithium-heparin plasma/quality control samples on cobas e 411/cobas e 601 analyzers; two duplicated runs per day for 21 days (n = 84). Cross-reactivity with other troponin forms and interference from endogenous substances/drugs was tested; recovery criterion for no cross-reactivity was within ±10%. Coefficients of variation (CV) for repeatability/intermediate precision were 0.7–5.6%/1.4–10.3% (cobas e 411; mean cardiac troponin T [cTnT]: 7.3–9341 ng/L) and 0.7–3.0%/1.5–6.4% (cobas e 601; mean cTnT: 7.4–9455 ng/L). There was no cross-reactivity with skeletal muscle troponin T (≤ 10,000 ng/L), skeletal muscle troponin I (≤ 100,000 ng/L), cardiac troponin I (≤ 10,000 ng/L), or human troponin C (≤ 80,000 ng/L). No interference was observed with biotin (≤ 20 ng/mL) or 34 drugs. The TnT Gen 5 STAT assay demonstrated a CV of <10% at the 99th percentile upper reference limit, meeting precision requirements (Fourth Universal Definition of Myocardial Infarction) for high-sensitivity troponin assays. • The Elecsys® Troponin T Gen 5 assay demonstrated excellent analytical precision. • No reactivity with skeletal muscle troponin (Tn) T/I, cardiac TnI, or human TnC. • No interference was observed from 34 therapeutic drugs or biotin up to 20 ng/L. [ABSTRACT FROM AUTHOR]

CXC chemokine ligand 12 (CXCL12) is a specific chemokine ligand and plays a significant role in cell chemotaxis. Upon binding to CXC chemokine receptor 4 (CXCR4) or CXCR7, CXCL12 can activate different signaling cascades to regulate cell proliferation, migration, and metabolism. CXCL12 exerts a pro-atherogenic action by aggravating multiple pathogenesis of atherogenesis, including dyslipidemia, inflammation, neointima hyperplasia, angiogenesis, and insulin resistance. Serum CXCL12 levels are also markedly increased in patients with atherosclerosis-associated disease. The present review focuses on recent advances in CXCL12 research in the pathogenesis of atherosclerosis together with its clinical values. This may provide insight into potential novel therapies for atherosclerosis. • CXCL12 involves the multiple pathogenesis of atherosclerosis. • CXCL12 serves as predictive and prognostic markers for myocardial infarction and ischemic stroke. • The inhibition of CXCL12 production and activity that contributes to prevention of athrosclerosis [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is a group of risk factors that increase the risk for heart disease. Little is known about the role of IL-10 in the severity of coronary artery disease (CAD) in patients with MetS. We investigated plasma levels of IL-10 and other pro-inflammatory cytokines in patients with MetS with or without severe CAD. Cross-sectional study with healthy and MetS individuals. IL-10 and other pro-inflammatory interleukins were analyzed in 90 subjects divided into 3 groups: group 1 (n = 30), patients with MetS without severe CAD; group 2 (n = 30), patients with MetS and severe CAD (history of myocardial infarction or revascularization performed through surgery or percutaneous transluminal coronary angioplasty with or without stent placement); and group 3 (n = 30), healthy individuals. Levels of IL-12 (p =.018), TNF-α (p =.007) and IL-6 (p =.010) were significantly higher in group 1 when compared to group 3 (p =.003; p =.002; p =.001, respectively). In addition, group 1 presented significantly higher levels of IL-12 (p =.019), TNF-α (p =.026) and IL-6 (p =.020) when compared to group 2. IL-10 levels were significantly higher in group 1 (p =.003) when compared to group 2 (p =.014) and group 3 (p <.001). Only the level of IL-10 was significant to explain the presence of severe CAD, as a protective factor (OR: 0.896; 95%CI: 0.818–0.981) in the logistic regression model. Higher IL-10 levels in patients with MetS are associated with lower incidence of severe CAD, suggesting a protective effect through its anti-inflammatory activity even in the presence of higher levels of pro-inflammatory cytokines. • Higher IL-10 levels in patients with MetS are associated with lower incidence of severe CAD. • IL-10 anti-inflammatory activity show a protective effect for MetS population. • Patients with lower levels of IL-10 increase by 4.9 the risk for severe CAD. [ABSTRACT FROM AUTHOR]

Chest pain and its clinical manifestations are the most common reasons for presentation to the emergency department (ED). Given that the prevalence of chest pain due to acute myocardial infarction (AMI) in the ED is modest, clinicians should use cardiac troponins to safely and rapidly rule out AMI, avoiding the delayed release of low risk patients. The study aims to develop and validate an algorithm to early rule-out of non-ST elevation myocardial infarction (NSTEMI) in subjects admitted to the ED with symptoms of myocardial infarction. High sensitivity cardiac Troponin T (hs-cTnT) serial measurements (baseline, T0; after 1 h, T1; after 3 h, T3) were used to develop and validate the algorithm, respectively, in 6403 and 773 consecutive admissions suggestive of AMI. Patients were classified as having or not having NSTEMI according to clinical assessment, diagnostic imaging, and serial measurements ofhs-cTnT; ROC curve analysis allowed to find changes in consecutive hs-cTnT associated with diagnostic sensitivity close to 100%. Only patients with hs-cTnTat T0 lower than 14 ng/L resultedto be eligible for the safe rule-out of NSTEMI. Although some points remain to be improved, the results obtained indicate that algorithms for fast NSTEMI rule-out are feasible and safe. • AMI should be rapidly excluded in low risk patients. • Laboratory is pivotal in the diagnostic work-up of AMI. • A universal Δ change between consecutive troponin measurements for rapid NSTEMI rule-out is not reliable. • Serial hs-cTnT measurements allowed to develop an algorithm for rapid NSTEMI rule-out. • Patients with T0 hs-cTnT <14 ng/L are candidates for rapid NSTEMI rule-out strategy. [ABSTRACT FROM AUTHOR]

• •In this study, 92 proteins were detected in healthy control (HC) group, unstable angina (UA) group and acute myocardial infarction (AMI) group, based on Olink platform. • •25 proteins were differentially altered by the AMI compared to HC group and UA group. • • AGRP, TGM2, IL6, GH1 and CA5A might serve as potential biomarkers for AMI diagnosis. Both pathological and normal processes depend on proteins. In this study, plasma protein profiles were analyzed by a novel proximity extension assay (PEA) to identify potential pathogenic mechanisms and diagnostic biomarkers in patients diagnosed with acute myocardial infarction (AMI). In this study, we identified a total of 92 plasma proteins using the Olink Target 96 Cardiovascular III panel in a cohort consisting of 30 healthy controls (HC), 28 patients with unstable angina (UA) and 30 patients with AMI. Subsequently, we conducted a differential expression analysis to identify protein molecules that were specifically expressed in patients with AMI. To gain insights into the potential functional mechanisms of these differentially expressed molecules, we performed Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Following that, the utilization of least absolute shrinkage and selection operator (LASSO) regression facilitated the identification of potential protein biomarkers, enabling the differentiation between AMI and UA. A diagnostic model was subsequently developed through logistic regression, and the effectiveness of these markers was assessed using receiver operating characteristic (ROC) analysis. Ultimately, the diagnostic capabilities of these potential biomarkers were validated in an independent validation cohort consisting of 30 UA cases and 30 AMI cases. In this study, a comprehensive analysis of plasma proteins identified a total of 92 proteins. Further analysis using analysis of variance revealed that 25 proteins exhibited specific expression in the AMI group compared to the HC and UA groups. Additionally, KEGG enrichment analysis indicated that these differentially expressed proteins were primarily associated with the activation of cytokine-cytokine receptor interaction, PI3K-Akt signaling pathway, and GnRH signaling pathway. AGRP, TGM2, IL6, GH1, and CA5A were identified through LASSO regression as prospective protein biomarkers for distinguishing between UA and AMI. The diagnostic model comprising these five proteins exhibited exceptional performance in both the discovery and validation datasets, surpassing AUC values of 0.9. The findings of our study provide additional insights into the involvement of the inflammatory response and AKT cascade response in the development of AMI. Moreover, we have identified potential protein markers that could be utilized for the accurate diagnosis of AMI. These results offer a fresh perspective for clinical decision-making in the context of AMI. [ABSTRACT FROM AUTHOR]

The Italian Society of Clinical Biochemistry (SIBioC) and the Italian Section of the European Ligand Assay Society (ELAS) have recently promoted a multicenter study (Italian hs-cTnI Study) with the aim to accurately evaluate analytical performances and reference values of the most popular cTnI methods commercially available in Italy. The aim of this article is to report the results of the Italian hs-cTnI Study concerning the evaluation of the 99th percentile URL and reference change (RCV) values around the 99th URL of the Access cTnI method. Heparinized plasma samples were collected from 1306 healthy adult volunteers by 8 Italian clinical centers. Every center collected from 50 to 150 plasma samples from healthy adult subjects. All volunteers denied the presence of chronic or acute diseases and had normal values of routine laboratory tests (including creatinine, electrolytes, glucose and blood counts). An older cohort of 457 adult subjects (mean age 63.0 years; SD 8.1 years, minimum 47 years, maximum 86 years) underwent also ECG and cardiac imaging analysis in order to exclude the presence of asymptomatic cardiac disease. The results of the present study confirm that the Access hsTnI method using the DxI platform satisfies the two criteria required by international guidelines for high-sensitivity methods for cTn assay. Furthermore, the results of this study confirm that the calculation of the 99th percentile URL values are greatly affected not only by age and sex of the reference population, but also by the statistical approach used for calculation of cTnI distribution parameters. • 99th percentile URL is considered as the cut-off for detection of myocardial injury and diagnosis of myocardial infarction. • The evaluation of 99th percentile URL is affected by age, sex and the experimental approach used for calculation. • An accurate evaluation of 99th percentile URL and reference change values of a high-sensitivity cTnI method is reported. • The results of this study should be taken into consideration by clinicians for clinical interpretation of cTnI assay. [ABSTRACT FROM AUTHOR]

We investigated the prognostic value of fibrinogen-albumin ratio (FAR) in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) based on inflammation and hemorheology alterations and to determine whether FAR can supplement incremental predictive information to the Global Registry of Acute Coronary Events (GRACE) score. We retrospectively analyzed 475 STEMI patients undergoing pPCI. Kaplan-Meier curve, Cox proportional hazards regression model, and Hosmer-Lemeshow test were used to evaluate the prognostic value of FAR in the patients. Patients were assigned to groups of high FAR (≥0.080) vs low FAR (<0.080) based on the optimal cutoff value of 0.080. In all, 59 patients (12.4%) died; the mortality rate was higher in high FAR patients than in low FAR patients (20.5% vs. 8.6%, p <.001). FAR positively correlated with C-reactive protein, GRACE score, and Gensini score (p <.001). On multivariate analysis, FAR was an independent prognostic factor in STEMI patients undergoing pPCI. Accordingly, adding FAR to the GRACE score improved the C-index, net reclassification index, and integrated discrimination improvement. Preoperative FAR is an independent prognostic factor in STEMI patients undergoing pPCI and might improve risk stratification in STEMI. Unlabelled Image • Inflammation and hemorheology play important roles in the origin and development of STEMI. • Combining two opposing indicators could improve comprehensive clinical evaluation. • FAR is a promising biomarker for predicting prognosis and improving risk stratification in STEMI. [ABSTRACT FROM AUTHOR]

Abstract Plasminogen activator inhibitor 1 (PAI-1) is the main regulator of endogenous fibrinolysis, overriding the impact of other constituents of fibrinolysis. In plasma, it can be found in three forms: active, latent and inactive. There are numerous commercially available tests, analysing the activity of PAI-1 or the antigen level, with variable correlations between the two. PAI-1 has been extensively studied regarding incidence and outcomes of acute coronary syndromes, and showed positive association with both in numerous studies. Higher PAI-1 has been associated with worse short- and long-term outcomes. Studies are more consistent in the primary percutaneous coronary intervention era. Higher rise of PAI-1 within the first 24 h of acute myocardial infarction has been linked to some of its high-risk features. The circadian pattern of PAI-1 kinetics has been previously described, and the mechanisms behind this phenomenon and its impact on the incidence of acute coronary syndromes are well known. Further investigations are needed to test the safety and efficacy of PAI-1 as a pharmacological target in cardiovascular diseases. Highlights • PAI-1 analysis is complex, with various tests, equivocal correlations • Related to incidence, worse outcome of acute coronary syndromes • Related to high-risk features of myocardial infarction • Responsible for circadian pattern of myocardial infarction symptom onset [ABSTRACT FROM AUTHOR]