High dietary antioxidant intake linked to lower risk of myocardial infarction: a nested case-control study.

BACKGROUND: In developing nations, myocardial infarction (MI) remains a significant contributor to deaths from sudden cardiac arrest, with diet playing a key role in its incidence through oxidative stress mechanisms. Although the connection between the Dietary Antioxidant Index (DAI) and cardiovascular diseases has been demonstrated in some studies, the relationship between DAI and MI has not been extensively explored. Therefore, this research aims to investigate this association. METHODS: We conducted a nested case-control study involving 156 MI cases and 312 healthy controls, utilizing data from the Fasa Adults Cohort Study (FACS), a population-based study of individuals aged 35-70 residing in Fasa, Iran, with 11,097 participants included at baseline. The DAI was determined by normalizing the intake values of six dietary vitamins and minerals, adjusting by subtracting the global mean, and then dividing by the global standard deviation. MI diagnosis was established by an experienced cardiologist using electronic medical records. Conditional logistic regression was employed to examine the association between DAI and MI. RESULTS: There were no significant differences between the case and control groups in terms of age (P = 0.96), gender distribution (P = 0.98), and education level (P = 0.38). In a multiple conditional logistic regression analysis, after adjusting for key variables-including body mass index (BMI), smoking status, education level, and serum levels of triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), fasting blood sugar (FBS), saturated fatty acids (SFA), and polyunsaturated fatty acids (PUFA)-an inverse association was found between DAI and the risk of myocardial infarction (MI) [adjusted Odds Ratio (Adj OR) = 0.88, 95% Confidence Interval (CI): 0.85-0.92; P < 0.001]. CONCLUSIONS: This study highlights the crucial role of the DAI in reducing the risk of myocardial infarction. Promoting diets rich in antioxidants presents a straightforward and effective strategy for MI prevention and the promotion of cardiovascular health, underscoring the novelty and significance of this research in dietary approaches to disease prevention.

Serum BAFF level is associated with the presence and severity of coronary artery disease and acute myocardial infarction.

OBJECTIVE: The aim of this study was to investigate the relationship between circulating levels of B cell activating factor (BAFF) and the presence and severity of coronary artery disease (CAD) and acute myocardial infarction (AMI) in humans, as its biological functions in this context remain unclear. METHODS: Serum BAFF levels were measured in a cohort of 723 patients undergoing angiography, including 204 patients without CAD (control group), 220 patients with stable CAD (CAD group), and 299 patients with AMI (AMI group). Logistic regression analyses were used to assess the association between BAFF and CAD or AMI. RESULTS: Significantly elevated levels of BAFF were observed in patients with CAD and AMI compared to the control group. Furthermore, BAFF levels exhibited a positive correlation with the SYNTAX score (r = 0.3002, P < 0.0001) and the GRACE score (r = 0.5684, P < 0.0001). Logistic regression analysis demonstrated that increased BAFF levels were an independent risk factor for CAD (adjusted OR 1.305, 95% CI 1.078-1.580) and AMI (adjusted OR 2.874, 95% CI 1.708-4.838) after adjusting for confounding variables. Additionally, elevated BAFF levels were significantly associated with a high GRACE score (GRACE score 155 to 319, adjusted OR 4.297, 95% CI 1.841-10.030). BAFF exhibited a sensitivity of 75.0% and specificity of 71.4% in differentiating CAD patients with a high SYNTAX score, and a sensitivity of 75.5% and specificity of 72.8% in identifying AMI patients with a high GRACE score. CONCLUSION: Circulating BAFF levels serve as a valuable diagnostic marker for CAD and AMI. Elevated BAFF levels are associated with the presence and severity of these conditions, suggesting its potential as a clinically relevant biomarker in cardiovascular disease.

[Study on the procoagulant characteristics of microparticles in acute myocardial infarction].

OBJECTIVE: To investigate the characteristic of circulating microparticle in patients with acute myocardial infarction (AMI) and its possible mechanism of promoting coagulation. METHODS: A prospective case-control study was conducted. The patients with coronary heart disease admitted to the second department of cardiology in Harbin First Hospital from June to November 2023 were enrolled, and they were grouped according to whether the patients occurred AMI or not. On the day of admission, disseminated intravascular coagulation (DIC) score was calculated. At the same time, fasting venous blood was collected, and the levels of D-dimer, fibrin degradation product (FDP) and the activities of major coagulation factors were detected. The level of circulating microparticle was determined by microparticle trapping method. The microparticle carrying tissue factor (TF+MP) level was detected by tissue factor (TF) dependent F Xa production assay. Spearman correlation method was used to analyze the correlation among the indicators. RESULTS: A total of 52 patients with coronary heart disease were enrolled, including 26 patients in AMI group and 26 patients in non-AMI group. There was no significant difference in gender, age, body mass index (BMI), underlying diseases, smoking history, and pre-admission treatment of patients between the two groups, indicating that the baseline data of the two groups were balanced and comparable. Compared with the non-AMI group, the DIC score and D-dimer, FDP levels in the AMI group were significantly increased [DIC score: 3 (3, 4) vs. 3 (2, 3), D-dimer (mg/L): 8.80 (6.84, 15.66) vs. 2.13 (1.64, 3.86), FDP (mg/L): 30.13 (19.30, 52.54) vs. 20.00 (13.51, 28.37), all P < 0.01], indicating that the degree of coagulation activation in AMI patients was more severe. The consumption of major coagulation factors in the coagulation pathway in the AMI group was heavier than that in the non-AMI group [F II: 59.45% (49.65%, 71.25%) vs. 63.65% (49.98%, 73.22%), F V: 96.95% (73.50%, 112.78%) vs. 105.05% (73.48%, 131.48%), F VII: 42.30% (36.98%, 51.98%) vs. 53.40% (46.58%, 69.88%), F X: 60.90% (48.22%, 80.82%) vs. 73.50% (56.80%, 85.98%), F XI: 82.45% (62.90%, 99.10%) vs. 92.40% (73.90%, 114.25%), F XII: 29.90% (12.42%, 42.38%) vs. 34.65% (16.32%, 48.20%), all P < 0.05]. The circulating TF+MP level in the AMI group was significantly higher than that in the non-AMI group [nmol/L: 0.13 (0.06, 0.20) vs. 0.08 (0.04, 0.15), P < 0.05]. There was no significant difference in the level of circulating microparticle between AMI group and non-AMI group [nmol/L: 1.24 (0.71, 3.77) vs. 1.35 (0.73, 2.14), P > 0.05]. Correlation analysis showed that circulating TF+MP level in the patients with coronary heart disease was significantly positively correlated with coagulation indicator DIC score (r = 0.307, P = 0.027), D-dimer (r = 0.696, P < 0.001) and FDP (r = 0.582, P < 0.001), and there was a strong negative correlation with exogenous pathway factor F VII (r = -0.521, P < 0.001) and common pathway factor F X (r = -0.332, P = 0.016). CONCLUSIONS: The circulating TF+MP level in AMI patients was significantly higher than that in the non-AMI patients. TF+MP may play an important role in activating the extrinsic coagulation pathway, exacerbating coagulation factor consumption, and promoting clot formation during AMI occurrence.

Galectin-3 and Soluble CD146 Identify Cardiorenal Injuries in Severe Burn Patients: A Biomarker-Based Approach.

INTRODUCTION: Acute kidney injury (AKI) and myocardial injury (MI) are severe conditions in patients with severe burn injury, and combination of both is even worst and is called the cardiorenal syndrome (CRS). Identifying a distinct cardiorenal phenotype could significantly enhance the management of these patients. Galectin-3 (Gal3) and soluble CD146 (sCD146) are biomarkers for renal and cardiac injuries. This study aims to assess the occurrence and reliability of these biomarkers in recognizing CRS in individuals who have been severely burn. METHODS: This study is a single-center prospective proof-of-concept study involving patients with severe burn injuries. Plasma samples for Gal3 and sCD146 measurements were collected daily during the initial 7 days following admission. CRS was defined after 24 h of admission by the association of AKI stage 1 or more (KDIGO definition) and MI defined on high sensitive troponin (hsTnT) (variation >20% baseline value or absolute value >40 ng/mL). RESULTS: Forty patients met the inclusion criteria and were included in this study. Thirty-eight patients had CRS. The pooled values of Gal3 or combination of Gal3 and sCD146 values following 7 days after admission were associated with CRS with an odds ratio (OR) of 1.145 (95% CI: 1.081-1.211), p < 0.001, and 1.147 (95% CI: 1.085-1.212), p < 0.001, respectively. Gal3 values at admission (D0) had a predictive performance for CRS with an AUC of 0.78 (95% CI: 0.63-0.93), and this performance improved when using the combination of Gal3 and sCD146 values at admission (D0), with an AUC of 0.81 (95% CI: 0.66-0.96). Gal3 levels during the first 7 days were associated with patients experiencing AKI and no MI, with an OR of 1.129 (95% CI: 1.065-1.195), p < 0.001, and MI without AKI with an OR of 1.095 (95% CI: 1.037-1.167), p < 0.001. sCD146 alone was not associated with AKI without MI or MI without AKI and was poorly associated with CRS. CONCLUSION: In severely burned patients, CRS is a frequent and severe condition. Gal3 values during the first 7 days following admission were associated with CRS. The use of sCD146 with Gal3 improved prediction performance for CRS identification. The use of such biomarkers to identify CRS is important and needs to be confirmed in other studies.

Plasma proteomics implicate glutamic oxaloacetic transaminases as potential markers for acute myocardial infarction.

AIM: To provide a novel perspective on the pathogenesis of acute myocardial infarction (AMI) patients with respect to glutamic oxaloacetic transaminase (GOT). METHODS: The plasma proteome of 20 patients with AMI were matched for age and sex and compared with 10 healthy individuals. We analyzed the mass spectrum data and compared the signal intensity of the corresponding peptides which related to their corresponding proteins. A sample-specific protein database was constructed and a quality control analysis was conducted to screen out the key regulatory proteins under specific experimental conditions. The data from 37 new AMI patients and 13 healthy adults were subjected to parallel reaction monitoring (PRM) to verify the target proteins found. Finally, the survival status of the key genes (> 1.5-fold) in the PPI were analyzed. RESULTS: 2589 and 2162 proteins were identified and quantified, respectively, and 143 differentially expressed proteins (DEPs) (≥1.5-fold) were found between the AMI and control groups. Of these 90 and 53 were significantly up-regulated and down-regulated, respectively. Gene ontology, KEGG enrichment, protein domain and cluster analysis as well as PPI networks of the DEPs revealed a central role of acute inflammatory response processes in patients with AMI. A cluster of proteins were found to be related to cysteine, methionine, arginine, proline, phenylalanine and propanoate metabolism as well as the cAMP signaling pathway. PPI network analysis showed CHI3L1, COPB2, GOT2, MB, CYCS, GOT1, CKM, SAA1 and PRKCD and RPS3 were in key positions, but only MB, CKM, GOT1, PRKCD, CYCS and GOT2 were found in a cluster. PRM verified the high levels of MB, CKM, GOT1 and GOT2 in 37 AMI patients but there was no statistical difference in the survival status for patients with either high or low expression levels of these proteins. CONCLUSIONS: Our findings showed that acute inflammatory response processes play a central role in patients with AMI. Cysteine and methionine metabolism was also activated, in which GOT1 and GOT2 were key proteins. These pathways might be potential targets for diagnosis and novel therapies to improve the poor outcomes observed in patients with heart failure.

Association between C-reactive protein to albumin ratio and subclinical myocardial injury in the general population free from cardiovascular disease.

OBJECTIVE: The study aimed to examine the role of the C-reactive protein to albumin ratio (CAR) as an inflammatory biomarker in relation to subclinical myocardial injury (SC-MI), addressing the limited knowledge of their association. METHODS: The study included 5,949 individuals without cardiovascular disease (CVD) from the National Health and Nutrition Examination Survey. SC-MI was identified through a Cardiac Infarction Injury Score (CIIS) of ≥ 10 units based on a 12-lead electrocardiogram. The study used multivariate logistic regression models, adjusted for potential confounders, to evaluate the relationship between CAR and SC-MI. Subgroup analyses were conducted to substantiate the results, and the non-linear correlation was assessed via restricted cubic spline (RCS) regression. RESULTS: The RCS curve showed a significant positive correlation between CAR and SC-MI (P for nonlinear = 0.2496). When adjusted for all confounders, individuals in the highest tertile of CAR exhibited a higher likelihood of SC-MI compared to those in the lowest tertile, with an odds ratio (OR) of 1.21 (95% CI: 1.06-1.39, P for trend = 0.029). A 10-unit increment in CAR was linked to a 3.6% heightened risk of SC-MI [OR = 1.036 (95% CI: 1.006, 1.066)], with this association being more prominent among male adults, non-smokers, married individuals, those without diabetes mellitus, and those with no history of cancer. CONCLUSION: The findings of this study suggest a positive correlation between CAR and SC-MI among the US adult population, indicating the potential of CAR in enhancing SC-MI prevention strategies in the general population.

Lipoprotein(a) as a cardiovascular risk factor among patients with and without diabetes Mellitus: the Mass General Brigham Lp(a) Registry.

BACKGROUND: Diabetes mellitus (DM) and Lp(a) are well-established predictors of coronary artery disease (CAD) outcomes. However, their combined association remains poorly understood. OBJECTIVE: To investigate the relationship between elevated Lp(a) and DM with CAD outcomes. METHODS: Retrospective analysis of the MGB Lp(a) Registry involving patients ≥ 18 years who underwent Lp(a) measurements between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasms, and prior atherosclerotic cardiovascular disease (ASCVD). The primary outcome was a combination of cardiovascular death or myocardial infarction (MI). Elevated Lp(a) was defined as > 90th percentile (≥ 216 nmol/L). RESULTS: Among 6,238 patients who met the eligibility criteria, the median age was 54, 45% were women, and 12% had DM. Patients with DM were older, more frequently male, and had a higher prevalence of additional cardiovascular risk factors. Over a median follow-up of 12.9 years, patients with either DM or elevated Lp(a) experienced higher rates of the primary outcome. Notably, those with elevated Lp(a) had a higher incidence of the primary outcome regardless of their DM status. The annual event rates were as follows: No-DM and Lp(a) < 90th% - 0.6%; No-DM and Lp(a) > 90th% - 1.3%; DM and Lp(a) < 90th% - 1.9%; DM and Lp(a) > 90th% - 4.7% (p < 0.001). After adjusting for confounders, elevated Lp(a) remained independently associated with the primary outcome among both patients with DM (HR = 2.66 [95%CI: 1.55-4.58], p < 0.001) and those without DM (HR = 2.01 [95%CI: 1.48-2.74], p < 0.001). CONCLUSIONS: Elevated Lp(a) constitutes an independent and incremental risk factor for CAD outcomes in patients with and without DM.

Inflammatory biomarkers and long-term outcome in young patients three months after a first myocardial infarction.

BACKGROUND: Studies on predictive value of circulating inflammatory biomarkers after myocardial infarction (MI) have often been limited by blood sampling only in an acute setting and short follow-up time. We aimed to compare the long-term predictive value of nine inflammatory biomarkers, known to be involved in atherosclerosis, in young patients investigated three months after a first-time MI. METHODS: Nine biomarkers (high-sensitivity C-reactive protein, interleukin (IL)-6, IL-18, monocyte chemoattractant protein-1, matrix metalloproteinase (MMP)-1, MMP-3, MMP-9, serum amyloid A and tumor necrosis factor-alfa) were sampled in 382 young (<60 years) patients and in age and sex-matched controls, three months after a first-time MI between 1996 and 2000. Swedish national patient registers were used to determine cardiovascular (CV) outcomes during 20 years of follow-up. RESULTS: In cases, random forest models identified IL-6 as the most important predictor of the primary composite endpoint of death, heart failure (HF) or MI hospitalization, and the separate endpoints death and HF hospitalization. IL-18 was the most important predictor of MI hospitalization. In a Cox regression, the highest tertile of IL-6 was associated with the composite endpoint (HR (95% CI) 1.91 (1.31-2.79)), death (2.38 (1.42-3.98)) and HF hospitalization (2.70 (1.32-5.50)), when adjusting for age, sex and CV risk factors. The highest tertile of IL-18 was associated with MI hospitalization (2.31 (1.08-4.91)) when severity of coronary atherosclerosis was added to the same type of model. CONCLUSIONS: When nine inflammatory markers involved in atherosclerosis were analyzed three months after the acute event in young MI patients, IL-6 and IL-18 were the most important biomarkers to predict long-term CV outcomes during 20 years of follow-up.

LncRNA NEAT1/miR-211/IL-10 Axis Regulates Inflammation of Peripheral Blood Mononuclear Cells in Acute Myocardial Infarction.

This study aimed to explore the expression of long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) in patients with acute myocardial infarction (AMI) and its inflammatory regulation mechanism through miR-211/interleukin 10 (IL-10) axis.A total of 75 participants were enrolled in this study: 25 healthy people in the control group, 25 patients with stable angina pectoris (SAP) in the SAP group, and 25 patients with AMI in the AMI group. Real-time qPCR was used to detect mRNA expression levels of NEAT1, miR-211, and IL-10. The interaction between miR-211, NEAT1, and IL-10 was confirmed by dual-luciferase reporter assay, and protein expression was detected using western blot.High expression of NEAT1 in peripheral blood mononuclear cells (PBMCs) of patients with AMI was negatively related to serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), tumor necrosis factor-α (TNF-α), IL-6, and IL-1ß and was positively correlated with left ventricular ejection fraction (LVEF). In THP-1 cells, miR-211 was confirmed to target and inhibit IL-10 expression. NEAT1 knockdown and miR-211-mimic markedly decreased IL-10 protein levels, whereas anti-miR-211 markedly increased IL-10 protein levels. Importantly, miR-211 level was negatively related to NEAT1 and IL-10 levels, whereas IL-10 level was positively related to the level of NEAT1 expression in PBMCs of patients with AMI.LncRNA NEAT1 was highly expressed in PBMCs of patients with AMI, and NEAT1 suppressed inflammation via miR-211/IL-10 axis in PBMCs of patients with AMI.

Inflammatory Biomarkers to Predict Major Adverse Cardiovascular Events in Patients with Carotid Artery Stenosis.

Background and Objectives: Inflammatory proteins and their prognostic value in patients with carotid artery stenosis (CAS) have not been adequately studied. Herein, we identified CAS-specific biomarkers from a large pool of inflammatory proteins and assessed the ability of these biomarkers to predict adverse events in individuals with CAS. Materials and Methods: Samples of blood were prospectively obtained from 336 individuals (290 with CAS and 46 without CAS). Plasma concentrations of 29 inflammatory proteins were determined at recruitment, and the patients were followed for 24 months. The outcome of interest was a major adverse cardiovascular event (MACE; composite of stroke, myocardial infarction, or death). The differences in plasma protein concentrations between patients with vs. without a 2-year MACE were determined using the independent t-test or Mann-Whitney U test to identify CAS-specific prognostic biomarkers. Kaplan-Meier and Cox proportional hazards analyses with adjustment for baseline demographic and clinical characteristics were performed to assess the prognostic value of differentially expressed inflammatory proteins in predicting a 2-year MACE in patients with CAS. Results: The mean age of the cohort was 68.8 (SD 10.2) years and 39% were female. The plasma concentrations of two inflammatory proteins were significantly higher in individuals with a 2-year MACE relative to those without a 2-year MACE: IL-6 (5.07 (SD 4.66) vs. 3.36 (SD 4.04) pg/mL, p = 0.03) and CD163 (233.825 (SD 230.306) vs. 159.673 (SD 175.669) pg/mL, p = 0.033). Over a follow-up period of 2 years, individuals with elevated levels of IL-6 were more likely to develop MACE (HR 1.269 (95% CI 1.122-1.639), p = 0.042). Similarly, over a 2-year period, patients with high levels of CD163 were more likely to develop MACE (HR 1.413 (95% CI 1.022-1.954), p = 0.036). Conclusions: The plasma levels of inflammatory proteins IL-6 and CD163 are independently associated with adverse outcomes in individuals with CAS. These CAS-specific prognostic biomarkers may assist in the risk stratification of patients at an elevated risk of a MACE and subsequently guide further vascular evaluation, specialist referrals, and aggressive medical/surgical management, thereby improving outcomes for patients with CAS.

Association of Lipoprotein (a) and Standard Modifiable Cardiovascular Risk Factors With Incident Myocardial Infarction: The Mass General Brigham Lp(a) Registry.

BACKGROUND: Lipoprotein (a) [Lp(a)] is a robust predictor of coronary heart disease outcomes, with targeted therapies currently under investigation. We aimed to evaluate the association of high Lp(a) with standard modifiable risk factors (SMuRFs) for incident first acute myocardial infarction (AMI). METHODS AND RESULTS: This retrospective study used the Mass General Brigham Lp(a) Registry, which included patients aged ≥18 years with an Lp(a) measurement between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasm, and prior known atherosclerotic cardiovascular disease. Diabetes, dyslipidemia, hypertension, and smoking were considered SMuRFs. High Lp(a) was defined as >90th percentile, and low Lp(a) was defined as <50th percentile. The primary outcome was fatal or nonfatal AMI. A combination of natural language processing algorithms, International Classification of Diseases (ICD) codes, and laboratory data was used to identify the outcome and covariates. A total of 6238 patients met the eligibility criteria. The median age was 54 (interquartile range, 43-65) years, and 45% were women. Overall, 23.7% had no SMuRFs, and 17.8% had ≥3 SMuRFs. Over a median follow-up of 8.8 (interquartile range, 4.2-12.8) years, the incidence of AMI increased gradually, with higher number of SMuRFs among patients with high (log-rank P=0.031) and low Lp(a) (log-rank P<0.001). Across all SMuRF subgroups, the incidence of AMI was significantly higher for patients with high Lp(a) versus low Lp(a). The risk of high Lp(a) was similar to having 2 SMuRFs. Following adjustment for confounders and number of SMuRFs, high Lp(a) remained significantly associated with the primary outcome (hazard ratio, 2.9 [95% CI, 2.0-4.3]; P<0.001). CONCLUSIONS: Among patients with no prior atherosclerotic cardiovascular disease, high Lp(a) is associated with significantly higher risk for first AMI regardless of the number of SMuRFs.

Circulating miRNA-4701-3p as a predictive biomarker of cardiovascular disease which induces angiogenesis by inhibition of TOB2.

Angiogenesis is mainly regulated by the delivery of VEGF-dependent signaling to cells. However, the angiogenesis mechanism regulated by VEGF-induced miRNA is still not understood. After VEGF treatment in HUVECs, we screened the changed miRNAs through small-RNA sequencing and found VEGF-induced miR-4701-3p. Furthermore, the GFP reporter gene was used to reveal that TOB2 expression was regulated by miR-4701-3p, and it was found that TOB2 and miR-4701-3p modulation could cause angiogenesis in an in-vitro angiogenic assay. Through the luciferase assay, it was confirmed that the activation of the angiogenic transcription factor MEF2 was regulated by the suppression and overexpression of TOB2 and miR-4701-3p. As a result, MEF2 downstream gene mRNAs that induce angiogenic function were regulated. We used the NCBI GEO datasets to reveal that the expression of TOB2 and MEF2 was significantly changed in cardiovascular disease. Finally, it was confirmed that the expression of circulating miR-4701-3p in the blood of myocardial infarction patients was remarkably increased. In patients with myocardial infarction, circulating miR-4701-3p was increased regardless of age, BMI, and sex, and showed high AUC levels in specificity and sensitivity analysis (AUROC) (AUC = 0.8451, 95 % CI 0.78-0.90). Our data showed TOB2-mediated modulation of MEF2 and its angiogenesis by VEGF-induced miR-4701-3p in vascular endothelial cells. In addition, through bioinformatics analysis using GEO data, changes in TOB2 and MEF2 were revealed in cardiovascular disease. We suggest that circulating miR-4701-3p has high potential as a biomarker for myocardial infarction.

Clinical value of BRE-AS1 in myocardial infarction and its role in myocardial infarction-induced cardiac muscle cell apoptosis.

Objectives. The aim of this study was to investigate the expression of long non-coding RNA (lncRNA) brain and reproductive organ-expressed protein (BRE) antisense RNA 1 (BRE-AS1) in patients with acute myocardial infarction (AMI) and its effect on ischemia/reperfusion (I/R)-induced oxidative stress and apoptosis of cardiomyocytes. Methods. Serum BRE-AS1 levels in patients with AMI was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic and prognostic values of BRE-AS1 were evaluated. H9c2 cells were treated with hypoxia/reoxygenation to establish an in vitro myocardial infarction cell model. The levels of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA). Levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were determined by commercial kits. Cell counting kit-8 (CCK-8) and flow cytometry were used to evaluate the cell viability and cell apoptosis. Results. The expression of BRE-AS1 in serum of patients with AMI is upregulated, which shows the clinical diagnostic value for AMI. In the I/R injury cell model, the knockout of BRE-AS1 can significantly alleviate the increase in TNF-α, IL-1ß, and IL-6 levels, inhibit the production of LDH and MDA, increase the activities of SOD and GSH-Px, promote the cell viability and suppress cell apoptosis. Conclusions. Abnormally elevated BRE-AS1 has a high diagnostic value for AMI as well as a prognostic value for major adverse cardiovascular events (MACEs). The elevation of BRE-AS1 promoted oxidative stress injury and cell apoptosis in vitro.

Association of cardiac biomarkers with long-term cardiovascular events in a community cohort.

MATERIALS AND METHODS: The study assessed major adverse cardiac events (MACE) (myocardial infarction, coronary artery bypass graft, percutaneous intervention, stroke, and death. Cox proportional hazards models assessed apolipoprotein AI (ApoA1), apolipoprotein B (ApoB), ceramide score, cystatin C, galectin-3 (Gal3), LDL-C, Non-HDL-C, total cholesterol (TC), N-terminal B-type natriuretic peptide (NT proBNP), high-sensitivity cardiac troponin (HscTnI) and soluble interleukin 1 receptor-like 1. In adjusted models, Ceramide score was defined by from N-palmitoyl-sphingosine [Cer(16:0)], N-stearoyl-sphingosine [Cer(18:0)], N-nervonoyl-sphingosine [Cer(24:1)] and N-lignoceroyl-sphingosine [Cer(24:0)]. Multi-biomarker models were compared with C-statistics and Integrated Discrimination Index (IDI). RESULTS: A total of 1131 patients were included. Adjusted NT proBNP per 1 SD resulted in a 31% increased risk of MACE/death (HR = 1.31) and a 31% increased risk for stroke/MI (HR = 1.31). Adjusted Ceramide per 1 SD showed a 13% increased risk of MACE/death (HR = 1.13) and a 29% increased risk for stroke/MI (HR = 1.29). These markers added to clinical factors for both MACE/death (p = 0.003) and stroke/MI (p = 0.034). HscTnI was not a predictor of outcomes when added to the models. DISCUSSION: Ceramide score and NT proBNP improve the prediction of MACE and stroke/MI in a community primary prevention cohort.

In a community cohort, where a wide range of biomarkers were evaluated, Ceramide score provided additive value over traditional cardiac risk factors alone for predicting stroke/MI. NT ProBNP provided additive value in prediction of MACE/death. Other biomarkers failed to improve the discrimination of these models.

The relationship between levels of tumor necrosis factor-alpha, interleukin-6, and C-reactive protein in the serum of elderly and acute myocardial infarction.

This study aimed to explore the relationship between the serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and hypersensitive C-reactive protein (hs-CRP) and the prognosis of acute myocardial infarction (AMI) patients after percutaneous coronary intervention (PCI) treatment. A total of 118 early-onset AMI patients who successfully received PCI (in the PCI group, blood samples were collected before PCI, 12, 24, 48 h after PCI, and 90 d follow-up period) and 52 AMI patients who received only cardioangiography (CAG) (in the CAG group, blood samples were collected before CAG, 12, 24, 48 h after CAG, and 90 d follow-up period). The serum levels of IL-6, hs-CRP and TNF-α were detected, and the incidence of major adverse cardiac events (MACE) in the PCI group during follow-up was observed. The basic levels of IL-6, hs-CRP, and TNF-α between the PCI group and the CAG group were not statistically different (P>0.05); there was no statistically significant difference in changes of serum IL-6, hs-CRP, and TNF-α in the CAG group before and after CAG (P>0.05); IL-6, hs-CRP, and TNF-α in the PCI group were significantly higher than those before treatment (P<0.01); in the PCI group, the levels of IL-6, hs-CRP and TNF-α between the MACE group and the MACE-free group were statistically different (P<0.05). Serum IL-6, hs-CRP and TNF-α levels in AMI patients after PCI significantly increased in the short term, and PCI may induce an inflammatory response; the high levels of inflammatory cytokines, IL-6, hs-CRP, and TNF-α, in peripheral blood may have an important reference value for MACE and short-term prognosis in early-onset AMI patients after PCI.

Ticagrelor downregulates the expression of proatherogenic and proinflammatory miR125-b compared to clopidogrel: A randomized, controlled trial.

BACKGROUND: Platelet P2Y12 antagonist ticagrelor reduces cardiovascular mortality after acute myocardial infarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets release proatherogenic and proinflammatory microRNAs, including miR-125a, miR-125b and miR-223, we hypothesized that the expression of these miRNAs is lower on ticagrelor, compared to clopidogrel. OBJECTIVES: We compared miR-125a, miR-125b and miR-223 expression in plasma of patients after AMI treated with ticagrelor or clopidogrel. METHODS: After percutaneous coronary intervention on acetylsalicylic acid and clopidogrel, 60 patients with first AMI were randomized to switch to ticagrelor or to continue with clopidogrel. Plasma expression of miR-223, miR-125a-5p, miR-125b was measured using quantitative polymerase chain reaction at baseline and after 72 h and 6 months of treatment with ticagrelor or clopidogrel in patients and one in 30 healthy volunteers. Multiple electrode aggregometry using ADP test was used to determine platelet reactivity in response to P2Y12 inhibitors. RESULTS: Expression of miR-125b was higher in patients with AMI 72 h and 6 months, compared to healthy volunteers (p = 0.001), whereas expression of miR-125a-5p and miR-223 were comparable. In patients randomized to ticagrelor, expression of miR-125b decreased at 72 h (p = 0.007) and increased back to baseline at 6 months (p = 0.005). Expression of miR-125a-5p and miR-223 was not affected by the switch from clopidogrel to ticagrelor. CONCLUSIONS: Ticagrelor treatment leads to lower plasma expression of miR-125b after AMI, compared to clopidogrel. Higher expression of miR-125b might explain recurrent thrombotic events and worse clinical outcomes in patients treated with clopidogrel, compared to ticagrelor.

[Correlation between serum growth differentiation factor 11 level and severity of coronary artery disease in patients with acute myocardial infarction].

Objective: To investigate the correlation between serum growth differentiation factor 11 (GDF11) level and coronary artery lesions in patients with ST-segment elevation myocardial infarction (STEMI), and the predictive efficacy of nomogram risk prediction model based on GDF11 combined with traditional risk factors on the occurrence of STEMI. Methods: This study was a retrospective cross-sectional study. Patients hospitalized in the Department of Cardiology of the 904th Hospital of Joint Logistic Support Force of People's Liberation Army of China from 2016 to 2018 were selected and divided into control group and STEMI group. The demographic data, blood lipid level, laboratory indicators of blood and GDF11 level were collected. Logistic regression analysis screened out independent correlated factors for the occurrence of STEMI. Spearman correlation analysis clarified the correlation of each indicator with the SYNTAX or Gensini scores. A nomogram risk prediction model for the risk of STEMI occurrence and the receiver operating characteristic curve was used to compare the prediction efficiency of each model. Results: A total of 367 patients were enrolled, divided into control group (n=172) and STEMI group (n=195), age (66.5±11.8), male 222 (60.49%). The serum GDF11 level of STEMI group was significantly lower than that of the control group (36.20 (16.60, 70.75) µg/L vs. 85.00 (53.93, 117.10) µg/L, P<0.001). The results of multivariate logistic regression analysis showed serum GDF11(OR=0.98, 95%CI: 0.97-0.99) and traditional independent risk factors such as smoking, diabetes, C-reactive protein, homocysteine, lipoprotein (a) and apolipoprotein A1/B were independent correlate factors for the occurrence of STEMI (P<0.05). Spearman correlation analysis showed that serum GDF11 was negatively correlated with SYNTAX score and Gensini score (P<0.05). The nomogram model constructed by serum GDF11 combined with traditional independent risk factors (AUC=0.85, 95%CI: 0.81-0.89) had better predictive value for the occurrence of STEMI than the traditional nomogram model constructed by independent risk factors(AUC=0.80, 95%CI:0.75-0.84) or serum GDF11 (AUC=0.76, 95%CI: 0.72-0.81), all P<0.01. Conclusions: Serum GDF11 is an independent correlate factor in the occurrence of STEMI and is negatively correlated with the severity of coronary artery lesions in patients with STEMI. The nomogram model constructed based on GDF11 combined with traditional risk factors can be a good predictor for the occurrence of STEMI.

Derivation and Validation of Thresholds Using Synthetic Data Methods for Single-Test Screening of Emergency Department Patients with Possible Acute Myocardial Infarction Using a Point-of-Care Troponin Assay.

BACKGROUND: Single-sample (screening) rule-out of acute myocardial infarction (AMI) with troponin requires derivation of a single-test screening threshold. In data sets with small event numbers, the lowest one or two concentrations of myocardial infarction (MI) patients dictate the threshold. This is not optimal. We aimed to demonstrate a process incorporating both real and synthetic data for deriving such thresholds using a novel pre-production high-precision point-of-care assay. METHODS: cTnI concentrations were measured from thawed plasma using the Troponin I Next (TnI-Nx) assay (i-STAT; Abbott) in adults on arrival to the emergency department with symptoms suggestive of AMI. The primary outcome was an AMI or cardiac death within 30 days. We used internal-external validation with synthetic data production based on clinical and demographic data, plus the measured TnI-Nx concentration, to derive and validate decision thresholds for TnI-Nx. The target low-risk threshold was a sensitivity of 99% and a high-risk threshold specificity of >95%. RESULTS: In total, 1356 patients were included, of whom 191 (14.1%) had the primary outcome. A total of 500 synthetic data sets were constructed. The mean low-risk threshold was determined to be 5 ng/L. This categorized 38% (95% CI, 6%-68%) to low-risk with a sensitivity of 99.0% (95% CI, 98.6%-99.5%) and a negative predictive value of 99.4% (95% CI, 97.6%-99.8%). A similarly derived high-risk threshold of 25 ng/L had a specificity of 95.0% (95% CI, 94.8%-95.1%) and a positive predictive value of 74.8% (95% CI, 71.5%-78.0%). CONCLUSIONS: With the TnI-Nx assay, we successfully demonstrated an approach using synthetic data generation to derive low-risk thresholds for safe and effective screening.

[Effects of hemoglobin level on the risk of acute kidney injury in patients with acute myocardial infarction].

OBJECTIVE: To investigate the effect of preoperative hemoglobin (Hb) level on the risk of developing acute kidney injury (AKI) after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). METHODS: A retrospective study was conducted. The hospitalized patients diagnosed with AMI who underwent PCI from May 2015 to May 2020 in the department of cardiology in the Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University were enrolled. According to the serum creatinine (SCr) level before and after interventional therapy, the patients were divided into an AKI group and a non-AKI group. The difference in patients' Hb levels between the AKI and non-AKI groups was compared. Univariate and multivariate Logistic regression analyses were used to analyze the effects of Hb levels on the risk of AKI after interventional therapy in patients with AMI. Kaplan-Meier survival curve was used to evaluate the effects of Hb levels on patients with AMI in all-cause death in the hospital. RESULTS: A total of 922 AMI patients were enrolled in this study, of which 165 patients (17.9%) developed AKI. Compared with the non-AKI group, female patients in the AKI group had a higher proportion [35.8% (59/165) vs. 26.9% (204/757)], older (age: 69.78±14.56 vs. 66.61±13.44), with a lower rate of smoking [42.4% (70/165) vs. 51.7% (391/757)] and a higher prevalence of hypertension [73.3% (121/165) vs. 63.5% (481/757)], however, the patients in AKI group also had a worse cardiac function [the proportion of Killip grade 3 or above was higher: 33.9% (56/165) vs. 13.9% (105/757)], lower Hb level (g/L: 127.61±22.18 vs. 132.79±19.45), and there were less patients using angiotensin converting enzyme inhibitor/angiotensin II receptor blocker [ACEI/ARB, 60.0% (99/165) vs. 74.5% (564/757)] and more patients using diuretics [24.8% (41/165) vs. 17.7% (134/757)] in AKI group, the differences were statistically significant (all P < 0.05). Compared with non-AKI group, patients in AKI group had a longer operation time [operation time > 60 minutes: 4.2% (7/165) vs. 1.5% (11/757)] and received more contrast media during the operative procedure [contrast media > 100 mL: 16.4% (27/165) vs. 3.6% (27/757)], the individuals had a higher rate of intra-operative hypotension [16.4% (27/165) vs. 8.2% (62/757)], and more patients were implanted more than 2 stents [8.5% (14/165) vs. 3.6% (27/757), all P < 0.05]. Univariate Logistic regression analysis suggested that each 1 g/L increase in preoperative Hb level was associated with a 1.2% decrease in the risk of postoperative AKI [odds ratio (OR) = 0.988, 95% confidence interval (95%CI) was 0.980-0.996, P = 0.003]. Meanwhile, for every 1 standard deviation increase in preoperative Hb level, the risk of postoperative AKI decreased by 22.1% (OR = 0.779, 95%CI was 0.661-0.918, P = 0.003). The patients were divided into low, medium and high concentration groups according to Hb levels (Hb levels were < 110 g/L, 110-150 g/L, ≥ 150 g/L, respectively), and multivariate Logistic regression analysis showed that the risk of AKI was significantly reduced in the high concentration group compared with that in the low concentration group (OR = 0.463, 95%CI was 0.241-0.888, P = 0.020). The Kaplan-Meier survival curve analysis indicated that the short term survival after coronary intervention in AMI patients with low Hb concentration was significantly lower than that in patients with medium and high Hb concentration (Log-Rank: χ2 = 23.215, P < 0.001). CONCLUSIONS: Preoperative lower Hb level is an independent risk factor for postoperative AKI in AMI patients. AMI patients with lower Hb levels have an increased risk of all-cause mortality within 1 month after AMI.

High-Sensitivity Troponin I after Cardiac Surgery and 30-Day Mortality.

BACKGROUND: Consensus recommendations regarding the threshold levels of cardiac troponin elevations for the definition of perioperative myocardial infarction and clinically important periprocedural myocardial injury in patients undergoing cardiac surgery range widely (from >10 times to ≥70 times the upper reference limit for the assay). Limited evidence is available to support these recommendations. METHODS: We undertook an international prospective cohort study involving patients 18 years of age or older who underwent cardiac surgery. High-sensitivity cardiac troponin I measurements (upper reference limit, 26 ng per liter) were obtained 3 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We performed Cox analyses using a regression spline that explored the relationship between peak troponin measurements and 30-day mortality, adjusting for scores on the European System for Cardiac Operative Risk Evaluation II (which estimates the risk of death after cardiac surgery on the basis of 18 variables, including age and sex). RESULTS: Of 13,862 patients included in the study, 296 (2.1%) died within 30 days after surgery. Among patients who underwent isolated coronary-artery bypass grafting or aortic-valve replacement or repair, the threshold troponin level, measured within 1 day after surgery, that was associated with an adjusted hazard ratio of more than 1.00 for death within 30 days was 5670 ng per liter (95% confidence interval [CI], 1045 to 8260), a level 218 times the upper reference limit. Among patients who underwent other cardiac surgery, the corresponding threshold troponin level was 12,981 ng per liter (95% CI, 2673 to 16,591), a level 499 times the upper reference limit. CONCLUSIONS: The levels of high-sensitivity troponin I after cardiac surgery that were associated with an increased risk of death within 30 days were substantially higher than levels currently recommended to define clinically important periprocedural myocardial injury. (Funded by the Canadian Institutes of Health Research and others; VISION Cardiac Surgery ClinicalTrials.gov number, NCT01842568.).