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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]

Abstract Background Heart-type fatty acid-binding protein (H-FABP) is a cytoplasmic protein and is released form necrotic cardiac myocytes, as well as ischemic cardiac myocytes. In this study, we compared creatine kinase MB (CK-MB), H-FABP, and cardiac troponin T (cTnT) after coronary artery bypass grafting (CABG), heart valve surgery, or septal defect surgery to evaluate the difference in detecting myocardial injury between three markers. Methods A total of 69 patients (CABG, 32; valve surgery, 27; and septal defect surgery, 10) were prospectively enrolled. Blood samples were taken at specific intervals. Results Mean amount (AUC 0-72h) of CK-MB and cTnT released for 72 h in the patients with valve surgery were 2446 h·ng/ml and 93.2 h·ng/ml, which were significantly larger than those in the patients with CABG or septal defect surgery (p <.05). Mean amount (AUC 0-72h) of H-FABP released for 72 h in the patients with CABG was 1939 h·ng/ml, which was significantly larger than that in the patients with septal defect surgery (700.1 h·ng/ml) (p <.05). Conclusion H-FABP would be a more useful marker for detecting myocardial ischemic injury than CK-MB and cTnT. CK-MB and cTnT would be more sensitive to myocardial injury with surgical trauma than with ischemic injury in the patients with cardiac surgery. Highlights • Mean amounts of CK-MB and cTnT released in the patients with CABG was similar to septal defect surgery. • Mean amount of H-FABP released in the patients with CABG was significantly larger than septal defect surgery. • H-FABP would be a more useful marker for detecting myocardial ischemic injury than CK-MB and cTnT. [ABSTRACT FROM AUTHOR]

Abstract Autosomal dominant hypercholesterolemia, being referred to as familial hypercholesterolemia (FH), is mainly due to defective LDL receptor (LDLR) function, but is also associated with variants in genes encoding APOB (LDLR ligand) and PCSK9, the catabolic regulator of LDLR. The signal-transducing adaptor family member 1 (STAP1) gene has been recently linked to FH. We describe the case of a 56-year-old male patient found to have hypercholesterolemia at age 34, but who did not continue follow-up nor received treatment with lipid-lowering drugs. At age 55 he suffered a myocardial infarction. A systematic NGS analysis did not show point mutations in the LDLR , APOB , LDLRAP1 , or PCSK9 genes, nor large rearrangements of the LDLR gene, but revealed the heterozygous missense variant rs199787258 of STAP1 (c.526C > T; p.Pro176Ser). This variant was also found in heterozygosis in the two siblings of the index case, who also had hypercholesterolemia, but did not cosegregate in his progeny. A bioinformatics analysis and available structural information predicts p.Pro176Ser as the most damaging of all STAP1 missense variants associated with familial hypercholesterolemia. Our findings confirm and extend the linkage between STAP1 variants and FH, and point to an important role of this adaptor protein within a signaling pathway that affects cholesterol homeostasis. [ABSTRACT FROM AUTHOR]

Abstract Background International recommendations on high-sensitivity cardiac troponin (hs-cTn) testing recommend that laboratories select only one sample type for testing. We evaluated the Siemens ADVIA Centaur hs-cTnI assay in serum and thereby provide information on imprecision, long-term storage stability, freeze-thaw stability, method comparison to other hs-cTnI assays, and clinical performance. Methods Patients with chest pain onset <6 h who already had Roche hs-cTnT, Beckman hs-cTnI and Abbott hs-cTnI results recorded and had non-thawed and frozen serum aliquots formed the study population (n = 134 patients with 305 serum aliquots obtained at either 0, 3 or 6 h stored below -70 °C since 2003) for measurement with the Siemens hs-cTnI assay in 2018. Receiver-operating characteristic curve analyses for myocardial infarction (MI) using the highest obtained hs-cTn concentration was performed. Additional comparison testing on serum samples stored frozen (at -70 °C for <1 month in 2018) for the Siemens and Abbott hs-cTnI assays were performed, as well as precision testing in serum pools and freeze-thaw stability testing. Results The Siemens hs-cTnI assay had an area under the curve (AUC) of 0.978 (95%CI: 0.937–0.996) for MI in the study cohort (Roche hs-cTnT AUC = 0.965 and Abbott AUC = 0.973). The Siemens hs-cTnI assay yielded higher cTnI concentrations than the other hs-cTn assays, with the same proportional bias (slope = 1.4) between the Siemens and Abbott hs-cTnI assays obtained from serum samples collected in 2003 and 2018. Over 3 months, a low serum pool of 3.5 ng/l achieved a CV of 20% (SD = 0.7, n = 42) and a high serum pool of 820 ng/l achieved a CV of 2.3% (SD = 20, n = 42). Three different serum pools recovered within 10% from baseline concentration after 5 freeze-thaw cycles for the Siemens hs-cTnI assay. Conclusions In serum, the Siemens ADVIA Centaur hs-cTnI assay had excellent clinical performance for MI in an early chest pain onset population, acceptable precision at normal and highly elevated cTnI concentrations, long-term storage stability (15 y storage below -70 °C) and acceptable freeze-thaw stability, all of which supports serum as an acceptable sample type to use in clinical studies and in clinical practice. Highlights • Siemens ADVIA Centaur hs-cTnI assay had excellent clinical performance for MI • Precision in serum exceeds expert laboratory recommendations • Long-term storage (15 years below -70 °C) or freeze thaw cycles did not alter results [ABSTRACT FROM AUTHOR]

Background Elevated triglyceride to high density lipoprotein cholesterol (TG/HDL-C) ratio has been identified as a surrogate marker of insulin resistance and an independent predictor for cardiovascular events in the general population. However, the prognostic value of TG/HDL-C ratio in revascularized ST-elevation myocardial infarction(STEMI) patients remains unclear. We examined the association between TG/HDL-C ratio and clinical outcome of revascularized STEMI patients in the Chinese population. Methods 464 STEMI patients who underwent successful revascularization were enrolled to determine the relationship between TG/HDL-C ratio and major adverse coronary events(MACEs) with a 30-month follow-up. The Kaplan-Meier analysis and Cox regression proportional hazard model were applied to assess the prognostic value of TG/HDL-C ratio. Results TG/HDL-C ratio was found to be significantly associated with age (p = 0.017), history of diabetes(p = 0.017), heart rate(p = 0.011), TG(p < 0.001), HDL-C(p < 0.001) and Gensini score(p = 0.034). The multivariate Cox regression analysis revealed that elevated TG/HDL-C ratio was an independent prognostic factor for MACE in female patients (HR = 2.624,95%CI = 1.211–5.687,p = 0.014) but not in male patients(HR = 0.756, 95%CI = 0.484–1.179,p = NS) after adjustment with other MACE-related prognostic factors. Conclusion The TG/HDL-C ratio may be independently associated with MACEs in female revascularized STEMI patients in the Chinese population. [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]

Background Though lipoprotein (a) (Lp (a)) has been considered as a risk factor for coronary artery disease, there is a lack of cutoff values of Lp (a) for Chinese Han ethnicity. Methods We included 1 population for health check-ups. Lp (a) percentile distributions were analyzed and its cutoff for Chinese Han ethnicity was also proposed according to the its relative risk of myocardial infarction. Results Lp (a) distributions differed between sexes, and were highly skewed towards low concentrations with a long tail towards the highest ones. The relative risks of elevated Lp (a) concentrations for myocardial infarction had an inflection in Chinese Han ethnic at the 8th decile, corresponding to 167 mg/l, where the risk was prone to be increased. In terms of Lp (a) median concentrations, per higher age quantile (5-y interval) was associated with a significant increase of 3.2 mg/l and females were on average 19.75 mg/l higher than males with a significant difference. Conclusions We proposed Lp (a) < 170 mg/l after rounding as cut-off values for Chinese Han ethnicity. Effects of age and sex on Lp (a) concentrations were also noted. Prospective validation of these cutoff values is critically important in Chinese Han ethnicity. [ABSTRACT FROM AUTHOR]

Background High level of red blood cell distribution width (RDW) has been associated with adverse outcomes in coronary artery disease patients. We aimed to investigate the relationship between RDW and the risk of myocardial injury in chest pain patients. Methods and Results We retrospectively reviewed 2078 chest pain patients with suspected acute myocardial infarction. Myocardial injury was defined as high-sensitivity cardiac troponin T (hs-cTnT) >14 ng/L. RDW was associated with hs-cTnT (r = 0.607) and the risk of myocardial injury stepwise increased across increasing RDW quartiles in all subgroups based on age and sex. The receiver operating characteristic curve analysis was calculated to assess the elevated RDW to predict myocardial injury, with the cutoff value of 13.25%. RDW had a high sensitivity (78.10%), specificity (87.44%), as well as positive predictive value (77.48%). The area under the curve (AUC) for all patients was 0.88 (95%CI 0.87, 0.90) and there is no statistical significant in AUCs for all subgroups. Conclusions Elevated RDW was significantly associated with a higher risk of myocardial injury in chest pain patients with potential acute myocardial infarction. The RDW may be helpful to identify myocardial injury in such patients. [ABSTRACT FROM AUTHOR]

Background Clinicians regularly observe increased high-sensitivity cardiac troponin (hs-cTn) concentrations in patients with low estimated glomerular filtration rate (eGFR). The challenge is to differentiate acute coronary syndrome (ACS) from increased hs-cTn results across a range of eGFR. The objective of this study was to determined the optimal hs-cTn concentrations for acute myocardial infarction (MI) and a composite cardiovascular outcome across different eGFR ranges and to assess the utility of a low hs-cTn cutoff to rule-out events. Methods We undertook an observational study in the emergency department of patients ( n  = 1212) with symptoms suggestive of ACS who had an eGFR and at least one Roche hs-cTnT and one Abbott hs-cTnI result. The 7-day outcomes were MI or a composite of MI, unstable angina, congestive heart failure, serious ventricular cardiac arrhythmia, or death. The maximum hs-cTn concentration was assessed across different eGFR ranges (<30,30–59,60–89,≥90 ml/min/1.73m 2 ) by spearman correlation, ROC-curve analyses, and sensitivity and negative predictive value (NPV) for the proposed rule-out hs-cTn cutoffs (hs-cTnI<5 ng/l and hs-cTnT<6 ng/l) for the outcomes. Results Both hs-cTnI and hs-cTnT concentrations were negatively correlated with eGFR. The lower the eGFR, the lower the AUC and the higher the optimal hs-cTn cutoffs for both MI and the composite outcome. The highest combined sensitivity (100%), NPV (100%) and proportion of low-risk for MI (45% of group) was observed for patients with hs-cTnT<6 ng/l with an eGFR≥90. Conclusion The test performance for hs-cTn for diagnosing or ruling-out an acute cardiac event varies per the eGFR. Accurate risk stratification requires knowledge of the eGFR. [ABSTRACT FROM AUTHOR]

Despite the advances in medicine and in science of diagnosis, cardiovascular diseases (CVD) remain the number one cause of morbidity and mortality worldwide. Apart from the modifiable risk factors, genetic factors are believed to also influence the outcome of this umbrella of diseases. Under the genetic factors, miRNA polymorphisms, namely miR-146a (rs2910164), miR-196 (rs11614913) and miR-499 (rs3746444), have become an important tool to study the mechanism that underlie the pathogenesis of this disease. In this review, we analyze the advances made through various research studies and the evidence provided by them in the area of miRNA polymorphisms by comparing the allelic frequencies and genotyping patterns. Interestingly, these studies have contradicting results even those conducted in same set of population. We also highlight the gap in literature search as majority of these studies have been conducted in Chinese population and data gaps are evident in Caucasian population, along with developing countries like, India, where no such data is available. This makes the daunting task of presenting a global picture and of the extent these polymorphisms play a role in CVD progression, even more difficult. Therefore, we suggest that more work needs to be done by taking various geographical domains in to consideration. Also, larger sample size calculated through statistical tools is the key to progress in establishing the genetic co-relation of miRNA polymorphisms and CVDs. [ABSTRACT FROM AUTHOR]

Background The transport of lipids from the artery wall is one of the most essential anti-atherogenic functions of high-density lipoprotein (HDL). Recent reports of changes in the HDL composition, during myocardial infarction (MI), suggest that this function may be altered. Methods Forty-one consecutive patients with ST-segment elevation MI enrolled at the Brasilia Heart Study were selected. The following HDL-related measures were determined upon admission (D1) and on the fifth day (D5) after MI: C-reactive protein, CETP and PLTP activity, HDL composition, efflux of cholesterol from J774 macrophages to HDL, and transfer of unesterified and esterified cholesterol, triglycerides and phospholipids from a donor nanoemulsion to HDL. Results From D1 to D5, the activity of CETP decreased by 25%, but PLTP activity remained unchanged. Esterified cholesterol (− 23%) and phospholipid (− 9.5%) contents of HDL decreased. Transfer of triglycerides (− 36.5%) and esterified cholesterol (− 14.7%) to HDL from nanoemulsions was reduced, but other lipids transfers were unchanged. Cholesterol efflux to HDL was also diminished by 8.5% ( p = 0.04) on D5 compared to D1. It was more pronounced in patients above the 75th percentile of C-reactive protein. Conclusions After an MI, a simultaneous decrease in lipid transfer to HDL and in the capacity of HDL to efflux cholesterol from cells occurs. Thus, HDL with inferior atheroprotective properties may be generated in the acute post-MI period. [ABSTRACT FROM AUTHOR]

Background To evaluate the association of serum albumin (SA) with long-term all-cause, cardiovascular, and cardiac mortality in patients with first-onset acute myocardial infarction (AMI). Methods The cohort study enrolled 2305 patients with first-onset AMI. The median follow-up was of 1088 days (3 years). Impacts of SA on long-time mortality after AMI were determined using multivariate Cox proportional hazard regression analysis with backward selection. Results The patients were divided into three categories by SA tertiles (≤ 3.62, 3.63–4.08, > 4.08 g/dl). High tertile group was used as reference, the adjusted HRs for all-cause death were 1.21 (P = 0.338) and 1.74 (P = 0.003) for intermediate and low tertile, respectively (p-for-trend = 0.001); The equivalent values for cardiovascular death were 1.13 (P = 0.588) and 1.64 (P = 0.022), respectively (p-for-trend = 0.009); The corresponding values for cardiac death were 1.07 (P = 0.806) and 1.59 (P = 0.048), respectively (p-for-trend = 0.022). Moreover, adjusted HRs per 1-g/dl decrease in SA concentrations were 1.66 (P = 0.001) for all-cause death, 1.47 (P = 0.024) for cardiovascular death, and 1.61 (P = 0.012) for cardiac death. Conclusions Low SA level (≤ 3.62 g/dl) on admission was an independent predictor of long-term all-cause, cardiovascular, and cardiac mortality in patients with first-onset AMI. There was a dose–response relationship between decreased SA concentrations and increased long-term all-cause, cardiovascular, and cardiac mortality. [ABSTRACT FROM AUTHOR]

• Myocardial infarction-derived exosomes are involved in cellular damage repair. • miRNAs expression levels in exosomes are correlated with MI outcomes in patients. • Conditioning maneuvers promote cardiosomes release involved in cardioprotection. Cardiosomes, exosomes released in cardiospheres by cardiomyocytes and progenitor cells, communicate locally and at a distance from different tissues, promoting beneficial cellular changes. For example, miRNAs have emerged as regulators of intercellular communication via transport by extracellular vesicles in general and cardiosomes specifically. Although cardiosomes are considered biomarkers owing to their immense biomedical application in various clinical fields, their role in cardiovascular diseases remains unclear. This mini-review examines the experimental and clinical evidence for cardiosomes as non-invasive diagnostic, treatment and prognostic tools in acute myocardial infarction, the novelty of which is often lost in medical practice. In addition, we discuss the potential role of cardiosomes in physiologic mechanisms and cell signaling in cardiac conditioning strategies against reperfusion injury. [ABSTRACT FROM AUTHOR]

• In people with acute myocardial infarction (AMI), we found a progressive increase in the incidence of post-myocardial infarction heart failure (post-MI HF) with increasing levels of metabolic acid load. • We confirmed by mediation analysis that deteriorating renal function and high inflammatory status partially mediated the relationship between metabolic acid load and the incidence of post-MI HF. • These findings are of important clinical value for early identification of people at risk for post-MI HF at different stages and for improving the prognosis of patients with AMI specifically. There is scant evidence on a relationship between metabolic acid load and acute myocardial infarction (AMI). We evaluated the relationship between serum albumin corrected anion gap (ACAG), a metabolic acid load biomarker, and post-myocardial infarction heart failure (post-MI HF) in patients with AMI. This prospective, single-center study enrolled 3,889 patients with AMI. The primary endpoint was the incidence of post-MI HF. Serum ACAG levels were calculated with the following formula: ACAG = AG + (40 - [albuminemia in g/l]) × 0.25. After correction for multiple confounding factors, patients in the fourth quartile of ACAG (highest serum ACAG levels) showed 33.5% higher risk of out-of-hospital HF [hazard ratio (HR) = 1.335, 95% CI = 1.034–1.724, p = 0.027], and 60% higher risk of in-hospital HF [odds ratio (OR) = 1.600, 95% CI = 1.269–2.017, p < 0.001] than those in the first quartile of ACAG (lowest serum ACAG levels). Altered levels of eGFR mediated 31.07% and 37.39% of the association between serum ACAG levels with out-of-hospital HF and in-hospital HF, respectively. Furthermore, altered levels of hs-CRP mediated 20.85% and 18.91% of the association between serum ACAG levels with out-of-hospital and in-hospital HF, respectively. Our study showed that higher metabolic acid load was associated with increased incidences of post-MI HF in the AMI patients. Furthermore, deterioration of renal function and the hyperinflammatory state partially mediated the association between metabolic acid load and the incidence of post-MI HF. [ABSTRACT FROM AUTHOR]

• Muscle damage leads to increased serum creatine kinase (CK) levels in diseases such as acute myocardial infarction. Still, many individuals have abnormal serum CK levels lacking muscle-related diagnoses. • The current study hypothesized that failed or overactivated CK clearance by non-muscle organs/tissues might be responsible for increased or decreased CK levels in blood circulation. Analyzing over 37,081 independent CK test results in 36 human diseases during the past five years, we found that 33 out of 36 diseases were associated with decreased median CK levels compared to healthy controls. • Besides muscle damage-related conditions, the highest mean CK levels were observed in hepatitis and cirrhosis. In contrast, six blood cell-related illnesses had the lowest mean CK values. ROC analysis showed that CK levels were the best biomarkers (AUC: 0.80–0.94) for the six blood-related diseases, especially myeloproliferative disorders. • The principal component analysis revealed that the same category of diseases, such as liver-, blood -, kidney-, cancers, and vascular-related diseases, had clustered CK distributions. • We proposed that the liver and blood cells were mainly responsible for CK clearance in blood circulation based on overall results. The testable mechanisms were presented and discussed. Muscle damage leads to increased serum creatine kinase (CK) levels in diseases such as acute myocardial infarction. Still, many individuals have abnormal serum CK activities lacking muscle-related diagnoses. The current study hypothesized that failed or overactivated CK clearance by non-muscle organs/tissues might be responsible for increased or decreased CK activities in blood. We analyzing 37,081 independent CK test results in 36 human diseases during the past 5 y. We found that 33 out of 36 diseases were associated with decreased median CK activities compared to healthy controls. Besides muscle damage-related conditions, the highest mean CK activities were observed in hepatitis and cirrhosis. In contrast, 6 blood cell-related illnesses had the lowest mean CK values. ROC analysis showed that CK activities were the best biomarkers (AUC: 0.80–0.94) for the 6 blood-related diseases, especially myeloproliferative disorders. The principal component analysis revealed that the same category of diseases, such as liver-, blood -, kidney-, cancers, and vascular-related diseases, had clustered CK distributions. We proposed that the liver and blood cells were mainly responsible for CK clearance in blood circulation based on overall results. The testable mechanisms were presented and discussed. [ABSTRACT FROM AUTHOR]

Background The association between blood vitamin D levels and the risk of myocardial infarction (MI) is controversial. This meta-analysis aimed to describe the relationship between MI risk and blood vitamin D levels. Methods Online databases were searched in PubMed, EMBASE and Web of science till February 2017 for observational studies in relation to reporting the vitamin D levels in MI cases and non-MI controls. The weighted mean difference (WMD) or odds ratio (OR), with 95% confidence interval (CI), were calculated to evaluate the relationship between MI risk and blood vitamin D levels. Results Eight observational studies with 9913 individuals, consisted of 3411 MI patients and 6502 non-MI controls, were included in our study. The pooled results revealed that blood vitamin D levels were significantly lower in MI patients when compared with non-MI controls (WMD = − 3.40; 95% CI: − 5.87 to − 0.92, P = 0.007). Subgroup analyses indicated MI patients were also associated with lower levels of blood vitamin D in America and Asia. Furthermore, when compared to non-MI controls, sufficient blood vitamin D appeared to protect against the occurrence of MI (OR = 0.44; 95% CI: 0.25 to 0.76, P = 0.004) in MI patients. Subgroup analyses also showed that sufficient blood 25(OH)D levels was a protective factor for MI in America and Asia. Conclusions Present study suggested that the levels of blood 25(OH)D were significant lower in MI patients, especially in America and Asia, and sufficient blood vitamin D levels might protect against the occurrence of MI. [ABSTRACT FROM AUTHOR]

Background We explored the impact of glycemic variability on the occurrence of periprocedural myocardial infarction and major adverse cardiovascular events (MACE) after coronary intervention in patients with stable angina pectoris (SAP) at 6 months follow-up. Methods From May 2015 to April 2016, a total of 746 patients with SAP were divided to high glycemic variability group (H group) ( n = 261) and low glycemic variability group (L group) ( n = 485). The primary end point was incidence of periprocedural myocardial infarction and MACE at 6 months follow-up. Results The occurrence of periprocedural myocardial infarction occurred in 18.8% of patients in H group and in 12.4% in L group (P = 0.03). The incidence of MACE at 6 months follow-up was 9.6% in H group and 4.5% in L group (P = 0.01). Multivariable analysis suggested that high glycemic variability conferred a 53% risk increment of 6 months follow-up MACE (odds ratio 2.13, 95% confidence interval 1.85–5.38; P = 0.01). Conclusions The trial shows that higher blood glucose variability was correlated with higher incidence of periprocedural myocardial infarction and MACE at 6 months follow-up. [ABSTRACT FROM AUTHOR]

The initial clinical manifestation of ischemic heart disease (IHD) i.e. unheralded myocardial infarction (MI) versus chronic angina pectoris (AP) is statistically associated with adverse or mild disease progression respectively in the long-term follow-up. Here, we subjected AP and MI patients to blood proteomic analysis by Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS) in order to investigate putative new prognostic biomarkers of IHD manifestation. We found several differentially expressed peaks but four of them (4176, 4475, 14,158 m / z and 8922 m / z for AP and MI, respectively) were most reliable. Two of them were identified; 14,158 m / z peak was the double-charged form of Apolipoprotein A-I and its vasoprotective action accords with prominence in AP. The 4176 m / z peak was related to FAM83C protein, while neither the 4475 m / z peak nor the MI-linked 8922 m / z peak could be identified. We conclude that SELDI-TOF-MS analysis may yield a panel of molecular signals able to retrospectively classify patients according to their clinical and molecular features, exploitable for predicting the natural course of IHD. [ABSTRACT FROM AUTHOR]

Background We evaluated whether a low high-sensitivity cardiac troponin (hs-cTn) cutoff combined with glucose, red cell distribution width (RDW), and the estimated glomerular filtration rate (eGFR) can be used to rule-out a serious cardiac outcome or death in patients presenting with symptoms suggestive of acute coronary syndrome (ACS). Methods This was a prospective observational emergency department (ED) study enrolling consecutive patients presenting with symptoms suggestive of ACS ( ClinicalTrials.gov : NCT01994577 ). The primary outcome was a 7-day composite of myocardial infarction, unstable angina, decompensated congestive heart failure, serious ventricular cardiac arrhythmia, or death. A laboratory score combining glucose, RDW, eGFR with hs-cTnT (Roche) or hs-cTnI (Abbott) was compared to hs-cTn alone using the limit of detection (LoD; hs-cTnT < 5 ng/l/hs-cTnI < 2 ng/l) as the cutoff. A benchmark of > 99% sensitivity was used to assess the laboratory panel with hs-cTn versus the LoD alone to identify low-risk patients suitable for discharge. Results A total of 1095 patients (n = 267 composite-outcomes) had measurements of glucose, RDW, eGFR, hs-cTnT, and hs-cTnI at presentation. Applying the hs-cTn LoD alone as the cutoff missed 5 composite-outcomes (sensitivity = 98.1%), however the addition of the laboratory panel to the hs-cTn LoD increased the sensitivity to > 99% with approximately 10% of the population identified as low-risk. The percentage of low-risk patients was increased to 15% (1 composite-outcome missed) when employing a low measurable hs-cTnI cutoff with the laboratory panel (laboratory score < 2 points). Conclusion A laboratory score with hs-cTn may identify low-risk patients suitable for ED discharge at presentation. [ABSTRACT FROM AUTHOR]

Background IL-37 emerges as a natural suppressor of inflammatory responses. The potential role of IL-37 in the pathology of atherosclerosis is unclear. The purpose of this study was to assess IL-37 profile in acute coronary syndrome (ACS) and the prognostic role of this cytokine in patients with ST-segment elevation acute myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Methods In a case-control study, we prospectively enrolled 216 patients undergoing the first coronary angiography, which consisted of 5 groups: normal (n = 57), stable angina (SAP, n = 36), unstable angina (UAP, n = 42), non-STEMI (n = 36), STEMI (n = 45). Plasma IL-37, IL-6 and serum amyloid A (SAA) were measured using a commercially ELISA kit. Besides, in a prospective cohort study, 125 patients with STEMI of onset < 12 h undergoing PPCI were enrolled and divided into 2 groups according to the concentrations of IL-37 (< 341.1 pg/ml or ≥ 341.1 pg/ml). In-hospital major adverse cardiac event (MACE) including nonfatal myocardial infarction (MI), target lesion revascularization, acute heart failure, and cardiac death were estimated for prognosis. Results IL-37 was gradually increased in accordance with the severity of coronary artery disease. The circulating concentration of IL-37 was remarkably higher in the ACS patients than in either of the normal or SAP patients ( p < 0.05), and especially higher in the AMI patients including STEMI and non-STEMI than in the angina pectoris subjects no matter SAP or UAP ( p < 0.05). There was no statistical difference of IL-37 between normal and SAP patients, STEMI and non-STEMI patients ( p > 0.05). The trend of the change of IL-37 was consistent with that of SAA or IL-6. A higher circulating concentration of IL-37 before PPCI was accompanied with the decreased LVEF and the increased NT-proBNP concentrations, and independently predictive of in-hospital MACE rate in patients with STEMI undergoing PPCI (OR = 3.652, 95% CI = 1.113–11.983, p < 0.05). Conclusions We demonstrated the IL-37 profile in patients with acute coronary syndrome and the increased IL-37 concentration was associated with a worse clinical in-hospital outcome in STEMI patients undergoing PPCI. [ABSTRACT FROM AUTHOR]

Apelin is the endogenous ligand of the G protein-coupled receptor APJ. Both Apelin and APJ receptor are widely distributed in various tissues such as heart, brain, limbs, retina and liver. Recent research indicates that the Apelin/APJ system plays an important role in pathological angiogenesis which is a progress of new blood branches developing from preexisting vessels via sprouting. In this paper, we review the important role of the Apelin/APJ system in pathological angiogenesis. The Apelin/APJ system promotes angiogenesis in myocardial infarction, ischemic stroke, critical limb ischemia, tumor, retinal angiogenesis diseases, cirrhosis, obesity, diabetes and other related diseases. Furthermore, we illustrate the detailed mechanism of pathological angiogenesis induced by the Apelin/APJ system. In conclusion, the Apelin/APJ system would be a promising therapeutic target for angiogenesis-related diseases. [ABSTRACT FROM AUTHOR]

Backgrounds The relation between serum total bilirubin (TBi) and mortality in patients with established coronary artery disease (CAD) remains undefined. We try to investigate the role of the subtypes of CAD in the association. Methods A total of 3013 patients with angiographically obstructive CAD were enrolled. A retrospective analysis was conducted. Patients were divided into 3 groups as follows: stable CAD (SCAD), unstable angina pectoris (UAP) and acute myocardial infarction (AMI). The predictive values of TBi for 30-day and long-term mortality were assessed using logistic and Cox regression, respectively. Results Higher initial serum TBi levels were significantly associated with increased risk of short-term mortality (OR 2.35, 95% CI 1.15–4.77) in AMI group. However, the association was absent among patients with SCAD and UAP. Serum TBi was able to independently predict the long-term mortality in SCAD (HR 0.34, 95% CI 0.16–0.70) and UAP (HR 0.49, 95% CI 0.31–0.78) groups. However, there was no significant relation between TBi and long-term mortality in AMI groups. Conclusion The different subtypes of CAD affected the relation between serum TBi and clinical prognosis. Initial serum TBi was positively correlated with short-term mortality of AMI patients, and negatively correlated with long-term mortality in SCAD or UAP patients. [ABSTRACT FROM AUTHOR]

• cTnT is present in the blood of MI patients as 23 proteolytic fragments. • Two major and several minor sites of cTnT degradation were identified. • Fraction of free cTnT central fragments increased in the first ∼ 30 h after MI. Blood measurement of cardiac troponin T (cTnT) is one of the most widespread methods of acute myocardial infarction (MI) diagnosis. cTnT degradation may have a significant influence on the precision of cTnT immunodetection; however, there are no consistent data describing the level and sites of cTnT proteolysis in the blood of MI patients. In this study, we bordered major cTnT fragments and quantified their relative abundance in the blood at different times after MI. Serial heparin plasma samples were collected from 37 MI patients 2–37 h following the onset of MI. cTnT and its fragments were studied by western blotting and immunofluorescence analysis using monoclonal antibodies specific to various cTnT epitopes. cTnT was present in the blood of MI patients as 23 proteolytic fragments with an apparent molecular mass of ∼ 8–37 kDa. Two major sites of cTnT degradation were identified: between amino acid residues (aar) 68 and 69 and between aar 189 and 223. Analysis of the abundance of cTnT fragments showed an increase in the fraction of free central fragments in the first few hours after MI, while the fraction of the C-terminal fragments of cTnT remained almost unchanged. cTnT progressively degrades after MI and appears in the blood as a mixture of 23 proteolytic fragments. The cTnT region approximately bordered by aar 69–158 is a promising target for antibodies used for measurement of total cTnT. [ABSTRACT FROM AUTHOR]

• Lp(a) was closely associated with LVH. • Association between Lp(a) and LVH persisted in most subgroups. • Lp(a) remained significantly associated with LVH in sensitivity analyses. The association of lipoprotein(a) [Lp(a)] with echocardiography-estimated left ventricular hypertrophy (LVH) in high-risk population remains uncertain, so we assessed the association between Lp(a) with echocardiography-derived LVH in patients with new-onset acute myocardial infarction (AMI). In this large, single-center, cross-sectional observational study, we enrolled 2,096 patients with new-onset AMI. Lp(a) was used as the independent variable and LVH was used as the dependent variable. Logistic regression, subgroup and sensitivity analysis were performed to test the association of Lp(a) with LVH. The concentration of Lp(a) was higher in LVH group compared with the non-LVH group (P < 0.001). Multivariate logistic regression analysis showed that higher Lp(a) was strongly associated with higher risk of LVH, independently of traditional cardiovascular risk factors (Fully adjusted model, Q4 vs Q1, OR: 1.941, 95% CI: 1.343–2.803, P < 0.001). Subgroup analysis showed that the association of Lp(a) with LVH persisted in the subgroups of age (<60 and ≥60 years), sex (male and female), smoking (yes and no), diabetes (yes), hypertension (yes), hyperlipidemia (yes), and chronic kidney diseases (yes and no). Further sensitivity analysis indicated that Lp(a) remained significantly associated with LVH after further adjusting for high-sensitivity C-reactive protein or excluding patients with estimated glomerular filtration rate < 30 ml/min/1.73 m2 or dividing Lp(a) into multiple dichotomous variables. Lp(a) was closely associated with LVH in patients with new-onset AMI. [ABSTRACT FROM AUTHOR]

• Lp(a) was closely associated with coronary severity. • Lp(a) was associated with Gensini score, left main disease and three-vessel disease. • Lp(a) was nonlinearly associated with Gensini score and three-vessel disease. Although current evidence suggests a causal association between lipoprotein(a) [Lp(a)] and cardiovascular disease, there is still no consensus on its association with coronary severity in new-onset acute myocardial infarction (AMI). We explored the association of Lp(a) with coronary severity. In this large cross-sectional study, we enrolled 2,740 patients with new-onset AMI from the Zhongda Hospital affiliated to Southeast University. Lp(a) was considered as an exposure variable. Gensini score, left main disease and three-vessel disease were used to assess coronary severity. Multivariate logistic regression, restricted cubic spline (RCS) models and threshold effects were used to analyze the association of Lp(a) with coronary severity. Multivariate adjusted models showed that Lp(a) was independently associated with Gensini score (≥100), left main disease and three-vessel disease [Q4 vs Q1, OR (95 % CI), P value: 2.301 (1.770, 2.992), P < 0.001; 1.743 (1.174, 2.587), P = 0.006; 1.431 (1.128, 1.816), P = 0.003; respectively], and the associations persisted in sensitivity analyses and most subgroups (P < 0.05). Additionally, the RCS showed that Lp(a) was nonlinearly associated with Gensini score (continuous variable), Gensini score (≥100) and three-vessel disease (P for nonlinearity < 0.05). Threshold effects analysis showed that Lp(a) above the inflection point was positively associated with Gensini score (continuous variable) as well as the risk of Gensini score (≥100) and three-vessel disease. Lp(a) was closely associated with coronary severity represented by Gensini score, left main disease and three-vessel disease in patients with new-onset AMI. [ABSTRACT FROM AUTHOR]

• Circulating miRNAs and ncRNAs are promising biomarkers of myocardial infarction (MI). • Circulating miRNAs and ncRNAs have more specificity and sensitivity than standard MI biomarkers. • Circulating miRNAs and ncRNAs are promising biomarkers of different cardiovascular conditions other than MI. Non-coding RNAs (ncRNAs) encompass a family of ubiquitous RNA molecules that lack protein-coding potential and have tissue-specific expression. A significant body of evidence indicates that ncRNA's aberrant expression plays a critical role in disease onset and development. NcRNAs' biochemical characteristics such as disease-associated concentration changes, structural stability, and high abundance in body fluids make them promising prognostic and diagnostic biomarkers. Myocardial infarction (MI) is a leading cause of mortality worldwide. Acute myocardial infarction (AMI), the term in use to describe MI's early phase, is generally diagnosed by physical examination, electrocardiogram (ECG), and the presence of specific biomarkers. In this regard, compared to standard MI biomarkers, such as the cardiac troponin isoforms (cTnT & cTnI) and the Creatinine Kinase (CK), ncRNAs appears to provide better sensitivity and specificity, ensuring a rapid and correct diagnosis, an earlier treatment, and consequently a good prognosis for the patients. This review aims to summarize and discuss the most promising and recent data on the potential clinical use of circulating ncRNAs as MI biomarkers. Specifically, we focused primarily on miRNAs and lncRNAs, highlighting their significant specificity and sensitivity, discussing their limitations, and suggesting possible overcoming approaches. [ABSTRACT FROM AUTHOR]

The effect of invasive percutaneous coronary procedures on complement activation has not been elucidated. We enrolled stable angina patients with elective percutaneous coronary intervention (SA-PCI, n = 24), diagnostic coronary angiography (CA, n = 52) and 23 patients with ST segment elevation myocardial infarction and primary PCI (STEMI-PCI). Complement activation products (C1rC1sC1inh, C3bBbP and SC5b-9) were measured on admission, 6 and 24 h after coronary procedures. The alternative pathway product, C3bBbP significantly and reversibly increased 6 h after elective PCI (baseline: 7.81 AU/ml, 6 h: 16.09 AU/ml, 24 h: 4.27 AU/ml, p < 0.01, n = 23) and diagnostic angiography (baseline: 6.13 AU/ml, 6 h: 12.08 AU/ml, 24 h: 5.4 AU/ml, p < 0.01, n = 52). Six hour C3bBbP values correlated with post-procedural CK, creatinine level and the applied contrast material volume (r = 0.41, r = 0.4, r = 0.3, p < 0.05, respectively). In STEMI-PCI, baseline C3bBbP level was higher, compared to SA-PCI or CA patients (11.33 AU/ml vs. 7.81 AU/ml or 6.13 AU/ml, p < 0.001). Similarly, the terminal complex (SC5b-9) level was already elevated at baseline compared to SA-PCI group (3.49 AU/ml vs. 1.87 AU/ml, p = 0.011). Complement pathway products did not increase further after primary PCI. Elective coronary procedures induced transient alternative complement pathway activation, influenced by the applied contrast volume. In STEMI, the alternative complement pathway is promptly activated during the atherothrombotic event and PCI itself had no further detectable effect. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (AMI) is defined as a dynamic change in cardiac troponin (cTn) with at least one cTn value exceeding the 99th percentile of a reference population in combination with typical clinical symptoms. In hemodialysis (HD) patients, a broad range of cTn concentrations is found, partially due to patient-specific comorbidities. Therefore, the 99th percentile cannot be used in HD patients and decision algorithms to diagnose AMI should be based on temporal variations of troponin. In this study, relative and absolute variations of cTn in a large population of asymptomatic hemodialysis patients were established during a period of 15 months. Patients were stratified according to their history of coronary artery disease (CAD). An intra-individual long term variation of 23% for cTroponin I (cTnI) and 12% for cTroponin T (cTnT) was found for patients without a history of CAD. The corresponding reference change values (RCVs) were 69% and 39% respectively. For patients with a history of CAD this variation was 29% for cTnI and 10% for cTnT, with RCVs of 86% and 35% respectively. During follow up, 27 HD patients developed an acute myocardial infarction (AMI). During these events, irrespective of CAD history, cTnI increased > 172% and cTnT increased > 97% above baseline cTn as measured during clinically stable periods three months separate to the event. Therefore, if a HD patient has symptoms of an acute event and a cTn increase that exceeds the RCVs described here, AMI may be suspected. If the troponin increase exceeds 172% for cTnI or 97% for cTnT, AMI is likely. [ABSTRACT FROM AUTHOR]

Background The aim of this study is to evaluate whether it is possible to reduce the between-methods variability of troponin I (cTnI) immunoassays using mathematical algorithms calculated from the results of both patients' samples and quality control materials distributed in an external quality assessment (EQA) scheme. Methods We collected 122 heparinized plasma samples of patients admitted to the emergency department with thoracic pain or supraventricular tachyarrhythmia. Moreover, we also analyzed 20 control samples distributed in an EQA and 26 plasma pools prepared from healthy subjects and patients with myocardial infarction. We evaluated 4 different methods for cTnI assay: STAT Architect High Sensitive TnI (Abbott Diagnostics), ADVIA Centaur Troponin I Ultra (Siemens Healthcare Diagnostics), ST AIA-Pack cTnI Third Generation (Tosoh Bioscience), and Access AccuTnI + 3 (Beckman Coulter Diagnostics). Results Systematic differences between cTnI methods were observed. However, correlation coefficients (R from 0.976 to 0.990) between the log-transformed cTnI values measured in all 168 samples were significantly better (p = 0.0037) than those obtained considering only the 122 patients' samples. cTnI values measured in EQA and pool samples were included within the 95% prediction intervals of linear regressions calculated with those of patients' samples. After the recalibration of cTnI values based on the robust principal component analysis approach the between-methods variability decreased significantly (about 40% around the cut off values). Conclusions Our pilot study suggests that EQA schemes for cTnI immunoassay methods, based on both quality control samples with tested commutability and robust statistical analyses, are able to evaluate between-methods variability as well as allow a reliable recalibration and harmonization of results. [ABSTRACT FROM AUTHOR]

Aim Cardiovascular disease (CVD) is a major cause of morbidity and mortality in developed countries. This study aimed to confirm the effect of common putative CVD-associated gene variants ( FTO rs17817449, KIF6 rs20455, 9p21 rs10757274 and 2q36.3 rs2943634) on CVD manifestation, and determine whether this effect differs between younger (< 50 years) and older CVD patients. Methods 1191 controls and 1889 MI patients were analyzed. All participants were Caucasian Czech males aged < 65 years (532 were < 50 years) who were examined at cardiology clinics in Prague, Czech Republic. Variants of FTO , 9p21 , 2q36.3 , and KIF-6 were genotyped using PCR-RFLP or TaqMan assay. Results Variants of FTO (OR 1.48; 95% CI, 1.19–1.84 in a TT vs. GG comparison, p = 0.0005); 9p21 (OR 1.74; 95% CI, 1.41–2.14 in an AA vs. GG comparison, p = 0.0001); and 2q36.3 (OR 1.34; 95%CI, 1.09–1.65 in an AA vs. + C comparison, p = 0.006) were significantly associated with MI in the male Czech population. In contrast, genotype frequencies of KIF-6 (rs20455) were the same in patients and controls (P = 1.00). Nearly identical results were observed when a subset of young MI patients (N = 532, aged < 50 years) was analyzed. Conclusion We confirmed the importance of determining FTO , 9p21 , and 2q36.3 variants as part of the genetic determination of MI risk in the Czech male population. [ABSTRACT FROM AUTHOR]

Background The data regarding low serum albumin (LSA) concentrations as a risk factor of CAD have been inconsistent and previous studies also have not considered the potential presence of multicollinearity among covariates. Additionally, there has been to date no reports about the association of LSA with first incident acute myocardial infarction (AMI) in Chinese Han ethnic population. Methods Cross-sectional study of 1552 cases and 6680 controls was performed for identifying the association of LSA with first incident AMI and its possible interactions with risk factors on first incident AMI. Results On a continuous scale, 1SD (~ 5 g/l) decrease in serum albumin concentrations was significantly associated with a fully adjusted odds ratio of 1.79, 95% CI (1.54–2.04) for first incident AMI in women, 1.53, (1.41–1.69) in men, and 1.61, (1.49–1.72) in total. On a categorical scale, the association of LSA with risk of first incident AMI was stepwise significantly strengthened with the increased albumin quintiles in age categories in both sexes, without a threshold effect found. A significant interaction was found between LSA and primary hypertension, ischemic stroke and hematocrit on the risk of first incident AMI. Conclusions LSA concentrations were significantly associated with first incident AMI in a dose–response manner in age categories in both sexes in Chinese Han ethnic population. Primary hypertension and hematocrit could modify this association. Whether the albumin transfusion for first incident AMI will improve patients' outcome deserves further studies. [ABSTRACT FROM AUTHOR]

Background Fibrosis is a pivotal event in infarct repair and progressive remodeling after myocardial infarction (MI). Biomarkers may be used to monitor fibrosis, and therefore we evaluated the predictive value of galectin-3 and sST2 for cardiac remodeling after MI. Methods Plasma galectin-3 and sST2 were measured in patients admitted with primary percutaneous coronary intervention (PCI) for acute MI, at baseline and at 4 months. Left ventricular ejection fraction (LVEF) and infarct size were measured after 4 months with cardiac MRI (CMR). Results In total, 247 patients had blood samples and CMR data available (mean age 57.7 ± 11.6 years; 79.8% male). Increased baseline galectin-3 (≥ 17.8 ng/mL) identified patients with lower LVEF (50.3% (± 9.1) vs. non-elevated galectin-3 55.0% (± 8.0); P < 0.001), and larger infarct size (13.8 g. (± 12.9) vs. 8.6 g. (± 8.7); P = 0.002) after 4 months. Elevated sST2 (≥ 35.0 ng/mL) did not predict decreased LVEF or larger infarct size. Furthermore we showed that at baseline, galectin-3 was an independent predictor for LVEF (β = − 0.18; P = 0.005) and infarct size (β = 0.18; P = 0.004). We repeated the analyses using median values of galectin-3 (13.4 ng/mL) and sST2 (30.3 ng/mL) as a cut point, and this validated our results. Conclusion The fibrosis biomarker galectin-3, but not sST2, taken immediately after MI, predicts LVEF and infarct size after 4 months. We hypothesize that galectin-3 may play a role in the pathophysiology of cardiac remodeling after acute MI. [ABSTRACT FROM AUTHOR]

The study aims are to evaluate the analytical performance and the clinical results of the chemiluminescent Access AccuTnI + 3 immunoassay for the determination of cardiac troponin I (cTnI) with DxI 800 and Access2 platforms and to compare the clinical results obtained with this method with those of three cTnI immunoassays, recently introduced in the European market. The limits of blank (LoB), detection (LoD), and quantitation (LoQ) at 20% CV and 10% CV were 4.5 ng/L and 10.9 ng/L, 17.1 and 30.4 ng/L, respectively. The results of STAT Architect high Sensitive TnI (Abbott Diagnostics), ADVIA Centaur Troponin I Ultra (Siemens Healthcare Diagnostics), ST AIA-Pack cTnI third generation (Tosoh Bioscience), and Access AccuTnI + 3 (Beckman Coulter Diagnostics) showed very close correlations (R ranging from 0.901 to 0.994) in 122 samples of patients admitted to the emergency department. However, on average there was a difference up to 2.4-fold between the method measuring the highest (ADVIA method) and lowest cTnI values (AccuTnI + 3 method). The consensus mean values between methods ranged from 6.2% to 29.6% in 18 quality control samples distributed in an external quality control study (cTnI concentrations ranging from 29.3 ng/L to 1557.5 ng/L). In conclusion, the results of our analytical evaluation concerning the AccuTnI + 3 method, using the DxI platform, are well in agreement with those suggested by the manufacturer as well as those reported by some recent studies using the Access2 platform. Our results confirm that the AccuTnI + 3 method for the Access2 and DxI 800 platforms is a clinically usable method for cTnI measurement. [ABSTRACT FROM AUTHOR]

Aims Assessment of patients with suspected non-ST elevation myocardial infarction (NSTEMI) is based on cardiac troponin (cTn) levels with the 99th percentile as cut-off. However, cardiovascular risk starts already at lower troponin concentrations. We therefore, aimed to investigate the utility of 2-hour algorithms using the high-sensitivity cardiac troponin I (hs-cTnI) 97.5th percentile as cut-off which corresponds to the standard URL for most biomarkers. Methods Hs-cTnI was measured at presentation and 2 h in 1624 chest pain patients. Diagnostic algorithms were developed applying hs-cTnI levels dichotomized at the 99th and 97.5th percentiles combined with hs-cTnI changes and/or ECG findings. Results The prevalence of NSTEMI was 13.9%. The adjusted odds ratios for 1-year mortality were 2.7 (95% CI 1.4–5.1) for the 99th percentile and 3.1 (95% CI 1.6–5.9) for the 97.5th percentile. The best-performing 99th percentile-based algorithms provided a positive predictive value (PPV) of 86.3% and a negative predictive value (NPV) of 99.3%. Using 97.5th percentile-based algorithms to define NSTEMI resulted in few reclassifications and yielded similar diagnostic estimates (PPV 85.4%, NPV 99.4%). Conclusion The hs-cTnI 97.5th percentile integrated into 2-hour algorithms provided high diagnostic estimates and could, due to better prognostic properties serve as an alternative to the 99th percentile. [ABSTRACT FROM AUTHOR]

Ventricular remodeling occurs progressively in untreated patients after large myocardial infarction and in those with cardiomyopathy. The pathologic changes of increased left ventricular (LV) volume and perturbation in the LV chamber geometry involve not only the myocytes, but also the non-myocyte cells and the extracellular matrix. Inflammation, fibrosis, neuro-hormonal activation, and ongoing myocardial damage are the mechanisms underlying remodeling. The detection of an ongoing remodeling process by means of biomarkers such as cytokines, troponins, neurohormones, metalloproteinases, galectin-3, ST-2 and others, may hold a clinical value and could, to some extent, drive the therapeutical strategy in patients after a myocardial infarction or with heart failure. For this reason, there is an increasing interest in the development of new biomarkers and a great number of laboratory tests have been recently proposed, whose clinical usefulness, however, is not fully established yet. [ABSTRACT FROM AUTHOR]

Interferon-γ (IFN-γ), the sole member in type II IFN predominantly secreted by macrophages and T cells, is a critical regulator of immune function and provides a robust first line of defense against invading pathogens. Binding of IFN-γ to its receptor complex can activate a variety of downstream signaling pathways, particularly the Janus kinase (JAK)/signal transducer and activator of transcription (STAT), to induce gene transcription within the target cells. This pro-inflammatory mediator is highly expressed in atherosclerotic lesions and promotes foam cell formation, but its effects on the atherogenesis are complex, with both pro- and anti-atherogenic properties. IFN-γ also contributes to the development of myocardial infarction and stroke, the two main atherosclerotic diseases. Inhibition of IFN-γ signaling may prevent the development of atherosclerosis and help treat atherosclerotic diseases. Since IFN-γ may also exert anti-atherogenic effects, the safety and efficacy of anti-IFN-γ treatment still require careful evaluation in the clinical setting. In the current review, we summarize recent progression on regulation and signaling pathways of IFN-γ, and highlight its roles in foam cell formation, atherosclerosis, myocardial infarction as well as stroke. An increased understanding of these processes will help to develop novel IFN-γ-centered therapies for atherosclerotic diseases. [ABSTRACT FROM AUTHOR]

Early experimental and clinical reports on glycogen phosphorylase BB (GPBB) kinetics following myocardial ischemic injury suggested that it could be a useful diagnostic marker for early detection of acute myocardial infarction (AMI). After more than two decades of investigation, there is now overwhelming body of evidence that do not support the use of GPBB measurement in diagnosis of acute AMI in patients presenting with acute chest pain. Currently, GPBB cannot be recommended as a diagnostic marker of AMI either as a stand-alone test or as an addition to (high-sensitive) troponin testing. It should be noted that these considerations apply to the early diagnosis of AMI, not to the prognostic stratification, which is also suggested but it warrants further investigation. The aim of this review is to summarize available evidence of GPBB measurement in early diagnosis of myocardial infarction. [ABSTRACT FROM AUTHOR]

Atherosclerotic plaques are the main cause of life threatening clinical endpoints like myocardial infarction and stroke. To prevent these endpoints, the improved early diagnosis and treatment of vulnerable atherosclerotic vascular lesions are essential. Although originally applied for anticancer treatment, recent advances have also showed the considerable potential of nanotechnology for atherosclerosis. Otherwise, one domain of laboratory medicine is the investigation of new biomarkers. Recent research activities have identified the usability of biomarker-targeted nanoparticles for molecular imaging and pharmacologic modification of vulnerable atherosclerotic lesions leading to myocardial infarction or stroke. These investigations have established a new research interface between laboratory medicine, nanotechnology, cardiology/neurology, and radiology. In this review, we discuss inflammatory pathophysiologic mechanisms and biomarkers associated with a vulnerable atherosclerotic plaque phenotype. Further, we will emphasize cardiovascular relevant functionalized nanoparticle biomarker constructs which were developed within the cooperation interface between Laboratory Medicine (anti-inflammatory biomarkers), Nano-Medicine (nanoparticle development), and Radiology (molecular imaging). [ABSTRACT FROM AUTHOR]

Objective The European Federation of Laboratory Medicine (EFLM) and the Union of European Medical Specialists (UEMS) joint Working Group on guidelines recently proposed a checklist to help standardize the description of laboratory investigations in clinical practice guidelines (CPG). Methods Nine CPGs or consensus documents published from 2011 to 2013 describing the investigation of chest pain, diagnosis of acute coronary syndrome, or myocardial infarction were evaluated against the published checklist. Results Clinical use of troponin analysis are commonly dealt with but the publications present variable, vague and sometimes conflicting information regarding this laboratory test being very much relied on upon making a diagnosis of acute coronary syndrome. Most of the laboratory related checklist items are not considered or need to be updated e.g. suggested analytical quality goals are not applicable for the high sensitive assays and important interferences that may lead to false positive or negative diagnoses are commonly not mentioned. Conclusion The current paper sums up important analytical and biological issues related to troponin assays and gives suggestions for analytical quality goals that could be included in CPG's. [ABSTRACT FROM AUTHOR]

Abstract: Background: Intrinsic functional properties of high density lipoproteins (HDL) are considered to be physiologically important for atheroprotection. We compared the HDL anti-inflammatory capacity between patients with acute myocardial infarction (MI) and patients with non-cardiac chest pain, and prospectively determined the association of new major adverse cardiovascular events (MACE) with this metric of HDL function. Methods: A prospective study was carried out in 93 patients referred for acute chest pain (65 patients with acute MI). The HDL anti-inflammatory capacity was determined as the ability to suppress tumor necrosis factor-α-induced vascular cell adhesion molecule-1 mRNA expression in endothelial cells in vitro. Results: Acute MI at admission was associated with impaired HDL anti-inflammatory capacity (p =0.001), even after adjustment for HDL cholesterol and apolipoprotein A-I (p =0.003). Twenty nine MACE were ascertained during a median follow-up of 1210 (910–1679) days. New MACE was associated with impaired HDL anti-inflammatory capacity (hazard ratio: 1.80 (1.17–2.77) per SD change, p =0.007) in age, sex, HDL cholesterol and apolipoprotein-AI adjusted analysis. Conclusions: The ability of HDL to attenuate endothelial inflammation is impaired in acute MI, and this metric of HDL function may serve as a predictor of new MACE, even independent of HDL cholesterol and apolipoprotein A-I. [Copyright &y& Elsevier]

Abstract: High-density lipoproteins (HDL) are inversely related with coronary artery disease (CAD) and HDL-cholesterol is the only standardized and reproducible parameter available to estimate plasma concentration of these lipoproteins. However, pharmacological interventions intended to increase HDL-cholesterol have not been consistently associated to an effective CAD risk reduction. Among patients with a myocardial infarction, 43 and 44% of men and women, respectively, had normal plasma levels of HDL-cholesterol, whereas genetic studies have failed to show a causal association between HDL-cholesterol and CAD risk. Instead, HDL functionality seems to be the target to be evaluated, but the existing methods are still poorly reproducible and far to be adapted to the clinical laboratory. HDL subclasses rise as a potential alternative for the evaluation of CAD risk; HDL subclasses are a surrogate of intravascular metabolism of these lipoproteins and probably of their functionality. Low levels of large HDL and increased proportions of small particles are the most remarkable features associated to an increased risk of type 2 diabetes mellitus (T2DM) or CAD. However, inflammation and other environmental factors are related with abnormal HDL structure, and, as a consequence, more prospective studies are needed to better support the clinical usefulness of HDL subclasses. New insights from proteome and lipidome profiles of HDL will provide potential HDL-related biomarkers in the coming years. [Copyright &y& Elsevier]

Abstract: Background: Since Pakistanis have high prevalence of hypovitaminosis-D as well as acute myocardial infarction (AMI), the objective of the study was to investigate the relationship between vitamin-D deficiency and risk of AMI in a hospital-based population and to identify major risk factors for this disease. Methods: Fasting serum samples from 66 consecutive AMI patients [age 30–70y] and 132 gender and age-matched (within 5y) healthy controls were analyzed for concentrations of glucose, total-cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, calcium, inorganic phosphate, alkaline phosphatase (ALP), bone-ALP, parathyroid hormone (PTH), 25(OH) vitamin-D (25(OH)D) and alanine aminotransferase. Results: Mean concentrations of serum 25(OH)D, PTH, total-ALP, bone-ALP, LDL-cholesterol, HDL-cholesterol and glucose were significantly different compared to healthy controls (p<0.05). Percent vitamin-D deficiency/insufficiency (levels<30ng/ml) was significantly greater in AMI patients compared to controls (93.9% vs.75.8%; p=0.001). Multiple conditional logistic regression analysis revealed that increased levels of 25(OH)D were associated with decreased risk of AMI [MAOR (95% CI)=0.821 (0.718, 0.940); p=0.004]. Hypertension and smoking were positively associated with AMI. Conclusions: Increased vitamin-D levels were associated with decreased risk of AMI, while serum glucose, bone-ALP, hypertension and smoking were positively associated with it. Association of bone-ALP with AMI in hypovitaminosis-D is a novel finding of this study. [Copyright &y& Elsevier]