scholarly journals Plasma Levels of Bactericidal/Permeability-Increasing Protein Correlate with Systemic Inflammation in Acute Coronary Syndrome

Author(s):  
Shicheng Yu ◽  
Zheng Li ◽  
Miaonan Li ◽  
Pan Xu ◽  
Nana Zhang ◽  
...  

Abstract Background: Neutrophils play important roles in atherosclerosis and atherothrombosis. Bactericidal/permeability-increasing protein (BPI) is mainly expressed in the granules of human neutrophils in response to inflammatory stress. This observational, cross-sectional study investigated the plasma level of BPI in patients with acute coronary syndrome (ACS) and its correlation with blood neutrophil counts and circulating inflammatory biomarkers.Methods: A total of 367 patients who had acute chest pain and who were admitted to our hospital for coronary angiography (CAG) and/or percutaneous coronary intervention (PCI) from May 1, 2020 to August 31, 2020 were recruited. Among them, 256 had a cardiac troponin value above the 99th percentile upper reference limit and were diagnosed with ACS. The remaining patients (n = 111) were classified as non-ACS. The TIMI and GRACE scores were calculated at admission. The Gensini score based on CAG was used to determine atherosclerotic burden. Plasma levels of interleukin (IL)-1β, myeloperoxidase-DNA (MPO-DNA), high sensitivity C-reactive protein (hs-CRP), S100A8/A9, and BPI were measured using enzyme-linked immunosorbent assays. Correlations of plasma BPI levels with examination scores and levels of circulating inflammatory biomarkers were explored. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic efficacy of BPI for ACS and myocardial infarction. Results: Patients in the ACS group showed significantly higher plasma BPI levels compared to the non-ACS group (46.42 ± 16.61 vs. 16.23 ± 13.19 ng/mL, p < 0.05). Plasma levels of IL-1β, MPO-DNA, hs-CRP, and S100A8/A9 in the ACS group were also significantly higher than those in the non-ACS group (all p < 0.05). In addition, plasma BPI levels were positively correlated with the TIMI, GRACE, and Gensini scores (r = 0.176, p = 0.003; r = 0.320, p < 0.001; r = 0.263, p < 0.001, respectively) in patients with ACS. Plasma BPI levels were also positively correlated with blood neutrophil counts (r = 0.266, p < 0.001) and levels of circulating inflammatory biomarkers (IL-1β, r = 0.512; MPO-DNA, r = 0.452; hs-CRP, r = 0.554; S100A8/A9, r = 0.434; all p < 0.001) in patients with ACS. ROC curve analysis revealed that the diagnostic efficacy of BPI for ACS was not inferior to that of IL-1β, MPO-DNA, hs-CRP, S100A8/A9, or blood neutrophil counts. ROC analysis also showed that the diagnostic efficacy of BPI for myocardial infarction was not inferior to that of creatine kinase (CK)-MB or cardiac troponin I.Conclusion: BPI is associated with systemic inflammation in ACS and may be involved in the process of atherosclerosis and atherothrombosis. The potential of BPI as a prognostic and diagnostic biomarker for ACS should be investigated in clinical settings.

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Danielle M Gualandro ◽  
Gisela B Llobet ◽  
Pai C Yu ◽  
Daniela Calderaro ◽  
Andre C Marques ◽  
...  

Introduction: Isolated high sensitive cardiac troponin T (hsTnT) elevations after vascular surgery are frequent and may lead to over diagnosis of myocardial infarction (MI). The aim of our study was to determine the accuracy of the current hsTnT cut-off value in the setting of acute coronary syndrome (ACS) after vascular surgery. Methods: Between August 2012 and March 2014, we included 337 consecutive patients submitted to arterial vascular surgery for which cardiac perioperative evaluation was requested. Perioperative surveillance included 12-lead electrocardiogram and hsTnT measurements on the three days following surgery. Patients were followed-up by cardiologists until hospital discharge and monitored for ACS. A receiver operating characteristics (ROC) curve analysis was performed to determine the hsTnT cut-off value with better accuracy for the diagnosis of perioperative ACS. Results: Of the 337 patients included, 240 (71.2%) presented hsTnT elevation above the manufacturer-provided cut-off value (0.014 ng/ml), whereas 22 (6.5%) fulfilled criteria for ACS. Median post-operative peak hsTnT of ACS patients were 0.215 ng/ml (IQR 0.043-0.493 ng/ml), versus 0.02 ng/ml (IQR 0.012-0.038 ng/ml) in patients that did not have events (P<0.001). After performing a ROC curve analysis (AUC = 0.876), we found that the manufacture-provided cutoff hsTnT value yielded a sensitivity of 100% and specificity of only 35% for diagnosis of perioperative ACS. A new hsTnT cutoff value of 0.0415 ng/ml was obtained with 86.4% sensitivity and 77% specificity for the diagnosis of perioperative ACS. Ninety-two patients (27.3%) had hsTnT elevations above the proposed new cutoff. Conclusion: A different hsTnT cutoff value of 0.0415 ng/ml is proposed and could be more useful for the diagnosis of perioperative ACS.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D Bongiovanni ◽  
K Mayer ◽  
N Schreiner ◽  
V Karschin ◽  
I Wustrow ◽  
...  

Abstract Introduction Reticulated or immature Platelets are pro-thrombotic RNA-rich young platelets, which have been reported to correlate with adverse events in several pathological settings including coronary artery disease. However, the predictive value of this subgroup of platelets in patients with acute coronary syndrome treated with the potent novel P2Y12 inhibitors prasugrel or ticagrelor has not been investigated yet. Moreover, their role as predictors of major bleeding is unclear. Purpose The primary aim of this prespecified reticulated platelet ISAR-REACT-5 substudy was to evaluate the immature platelet fraction (IPF%) in peripheral blood as a predictor of the composite primary endpoint consisting of death, myocardial infarction, or stroke at one year after randomization in patients with acute coronary syndrome. Methods IPF was assessed in the first 24h after randomization using a fully automated system and correlated to the incidence of the primary endpoint. All patients with available IPF values were included. The Sysmex system uses two fluorescent dyes to stain platelet RNA and a computer algorithm (Sysmex IPF Master) discriminates immature from mature platelets by the intensity of forward scattered light and fluorescence. The immature platelet fraction is displayed as percentage of the total optical platelet count (IPF%). Results IPF values within the first 24h after randomization were available in a total of 506 randomized patients. Baseline characteristics and IPF (median [IQR]) values did not differ between the 2 study groups (IPF: prasugrel 3.9% [2.7–5.8] ticagrelor 3.4% [2.5–5.6] p=0.56). Significantly higher IPF values were observed in patients reaching the primary endpoint (n=55 of 506) independent from the study group (p for interaction= 0.28). ROC-curve analysis revealed a cut-of value of IPF 3.6% for the prediction of death, myocardial infarction or stroke with a Hazard ratio (HR) according to cox-regression analysis of 1.98 (95% CI, 1.15–3.44), P=0.01 (Figure 1A). Interestingly, we also detected a trend for higher major bleedings (BARC 3–5) in patients with elevated IPF values above IPF&gt;4.8% according to ROC-curve analysis (Figure 1B). Conclusion IPF was significantly associated with the primary endpoint in the ISAR-REACT 5 substudy independent from the treatment group and therefore is a promising novel biomarker for the prediction of adverse cardiovascular events in patients with acute coronary syndrome. Figure 1 Funding Acknowledgement Type of funding source: None


2021 ◽  
Vol 6 (3) ◽  
pp. 146-152
Author(s):  
Andreea Buicu ◽  
Răzvan-Andrei Licu ◽  
Emil Blîndu ◽  
Diana Opincariu ◽  
Roxana Hodas ◽  
...  

Abstract Introduction: Systemic inflammation plays a key role in the pathophysiology of acute coronary syndrome (ACS), having a direct effect in promoting the progression and rupture of vulnerable coronary plaques. The aim of this study was to investigate the association between inflammatory biomarkers and the type of ACS (ST-elevation myocardial infarction – STEMI, non-ST-elevation myocardial infarction – NSTEMI, or unstable angina – UA) in patients with confirmed heart failure. Material and Methods: This study included a total of 266 patients admitted to the Clinical Department of Cardiology of the County Emergency Clinical Hospital of Târgu Mureș – Cardiac Intensive Care Unit (CICU) for ACS of various types (UA, NSTEMI or STEMI) between January 1, 2017 and December 31, 2020, in whom the diagnosis of heart failure was established based on clinical and paraclinical data. From the total number of patients, 36 were hospitalized for UA and 230 for MI, of which 165 were STEMI and 65 were NSTEMI. Results: Only hs-CRP and IL-6 were significantly higher in MI compared to UA. Mean hs-CRP was 4.9 ± 4.5 mg/mL in patients with UA vs. 20.4 ± 42.2 mg/mL in patients with MI (p = 0.001), and mean IL-6 was 7.2 ± 13.8 pg/mL in UA vs. 31.6 ± 129.2 pg/mL in MI (p <0.0001). ICAM seems to have had a greater discriminating power between STEMI and other types of ACS in those with heart failure, having a value more than double in those with STEMI (216.1 ± 149.6 ng/mL vs. 448.2 ± 754.4 ng/mL, p <0.0001). Conclusions: In patients with heart failure, the increase of inflammatory biomarkers such as hs-CRP is associated with the development of an acute myocardial infarction but not with its type. Adhesion molecules, especially ICAM, are elevated in patients with STEMI compared to other types of ACS, indicating a potential role of endothelial alteration in the development of an ACS when it adds to systemic inflammation linked to heart failure.


2011 ◽  
Vol 57 (10) ◽  
pp. 1452-1455 ◽  
Author(s):  
Evangelos Giannitsis ◽  
Tzveta Kehayova ◽  
Mehrshad Vafaie ◽  
Hugo A Katus

BACKGROUND Two recent clinical trials showed that adding copeptin to a conventional cardiac troponin assay improved diagnostic performance for patients with chest pain early after symptom onset. We prospectively tested whether copeptin adds information to that provided by a high-sensitivity cardiac troponin T (hscTnT) assay in the early evaluation of patients with suspected acute myocardial infarction, particularly non–ST-segment elevation myocardial infarction (non-STEMI). METHODS We enrolled 503 patients with suspected acute coronary syndrome and onset of chest pain occurring within the previous 12 h. Copeptin was measured on presentation, and hscTnT was measured serially at baseline and after 3 and 6 h. We used ROC curve analysis and likelihood ratio χ2 statistics for nested models. Diagnostic sensitivities, specificities, positive predictive values (PPVs), and negative predictive values (NPVs) were calculated for admission values of copeptin alone, hscTnT alone, and the combination of both markers. RESULTS For ruling out non-STEMI (after excluding STEMI), an hscTnT concentration &lt;14 ng/L (99th percentile) plus a copeptin concentration &lt;14 pmol/L yielded a diagnostic sensitivity of 97.7% (95% CI, 91.9%–99.7%), an NPV of 99.03% (95% CI, 96.6%–99.9%), a diagnostic specificity of 55.9% (95% CI, 50.6%–61.0%), and a PPV of 34.4% (95% CI, 28.5%–40.7%). ROC curve analysis of the continuous biomarker values on admission demonstrated no added value of using this marker combination for ruling out non-STEMI when hscTnT was used as the standard for diagnosing non-STEMI. CONCLUSIONS A strategy using copeptin with hscTnT at prespecified cutoffs improves the ruling out of non-STEMI, compared with using hscTnT alone; thus, this strategy could help to obviate a prolonged stay in the emergency department.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S El-Deek ◽  
A.R Meki ◽  
A Hassan ◽  
M Gaber ◽  
O Mohamed

Abstract Introduction Acute coronary syndrome (ACS) is a leading cause of mortality and morbidity worldwide. Despite being the gold standard biomarkers, cTn and CK-MB have a major drawback as they are less sensitive in the first 3 hours of the onset of symptom. So, there is still a need for novel biomarkers, which can reliably rule in or rule out this disease immediately on admission. Aim of the work To evaluate the role of copeptin, miRNA-499 and miRNA-208 as novel biomarkers for early detection of unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI) Patients and Methods: A total of 65 patients presenting within 4 h of onset of chest pain suggestive of ACS were enrolled in the study. They included 23 UA, 42 NSTEMI. Also 25 apparently healthy controls were included. Blood samples (first set within the first 3 hours and second set at 6 hours) were taken for estimation of copeptin by ELISA and miRNA-499 and miRNA-208 expression levels by real time PCR. Results Copeptin, miRNA-499 and miRNA-208 expression levels were significantly increased in UA and NSTEMI patients compared to controls (P&lt;0.001 each). Also these biomarkers were significantly increased in NSTEMT compared to UA (P&lt;0.001 each). They also significantly elevated in UA and NSTEMI patient in the first 3 hours who had negative cardiac troponin (p&lt;0.001 each). ROC curve analysis revealed that the area under curve (AUC) for prediction of ACS was 0.96 for copeptin, 0.97 for miRNA-499 and 0.0.97 for miRNA-208. Interestingly, combining copeptin with miRNA-499 and miRNA-210 significantly improved the diagnostic value by increasing the AUC to 0.98, P&lt;0.001. The sensitivity and specificity within the first 3 hours were 90%, 86% for copeptin, 95%, 94% for miRNA-499 and 93%, 98% for miRNA-208. The sensitivity and specificity were 81% and 86% for cardiac troponin within 6 hours. There was a positive correlation between copeptin and miRNA-499 and miRNA-208 (r=0.75, P&lt;0.001 and r=0.76, P&lt;0.001 respectively) Also, there was a positive correlation between these biomarkers and cTn (r=0.7. P&lt;0.001, r=0.64, P&lt;0.001 and r=0.68, P&lt;0.001 respectively). Conclusions Copeptin, miRNA-499 and miRNA-208 expression might be novel biomarkers as they are associated with UA and NSTEMI presented in the first 3 hours of onset of pain. The combination of copeptin and miRNA with cTn accelerate the diagnosis of ACS and avoiding the gray zone of cTn. Copeptin and miRNAs representing a potential aid in early diagnosis as they have different pathogenesis and site of liberation. Funding Acknowledgement Type of funding source: None


Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 733
Author(s):  
Admira Bilalic ◽  
Tina Ticinovic Kurir ◽  
Josip A. Borovac ◽  
Marko Kumric ◽  
Daniela Supe-Domic ◽  
...  

The “Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines” (CRUSADE) score emerged as a predictor of major bleeding in patients presenting with the acute coronary syndrome. On the other hand, previous studies established the association of dephosphorylated-uncarboxylated Matrix Gla protein (dp-ucMGP) and vitamin K, as well as their subsequent impact on coagulation cascade and bleeding tendency. Therefore, in the present study, we explored if dp-ucMGP plasma levels were associated with CRUSADE bleeding score. In this cross-sectional study, physical examination and clinical data, including plasma dp-ucMGP levels, were obtained from 80 consecutive patients with acute myocardial infarction (AMI). A significant positive correlation was found between CRUSADE bleeding score and both dp-ucMGP plasma levels (r = 0.442, p < 0.001) and risk score of in-hospital mortality (r = 0.520, p < 0.001), respectively. In comparing the three risk groups of risk for in-hospital bleeding, the high/very high-risk group had significantly higher dp-ucMGP levels from both very low/low group (1277 vs. 794 pmol/L, p < 0.001) and the moderate group (1277 vs. 941 pmol/L, p = 0.047). Overall, since higher dp-ucMGP levels were associated with elevated CRUSADE score and prolonged hemostasis parameters, this may suggest that there is a biological link between dp-ucMGP plasma levels and the risk of bleeding in patients who present with AMI.


2011 ◽  
Vol 69 (2) ◽  
pp. 175-180 ◽  
Author(s):  
Mabrouka El Oudi ◽  
Chaker Bouguerra ◽  
Zied Aouni ◽  
Chakib Mazigh ◽  
Ridha Bellaaj ◽  
...  

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Niket Nathani ◽  
Monika M Safford ◽  
Christopher Gamboa ◽  
Mallika Mundkur ◽  
Shannon Preston ◽  
...  

Background: Studies have shown increased mortality after myocardial infarction (MI) with low level elevations of cardiac troponin (“microsize MI”) and subsequent risk reduction with intensive medical management. However, non-standard reporting and highly sensitive assays of cardiac troponin can make the clinical recognition of microsize MI difficult, creating barriers to the implementation of appropriate secondary prevention. Methods: REGARDS follows 30,239 community-dwelling participants of the 48 continental states age ≥45 years recruited from 2003-7; 41% of the sample was African American and 55% female by design. Following national consensus guidelines, experts adjudicated cases of acute coronary syndrome (ACS), defined as an admission for acute signs or symptoms of ischemia, and MI from hospital records. We studied first cases of ACS, classified as: 1) ACS without MI, 2) ACS+microsize MI (peak troponin <0.5), and 3) ACS+usual MI (peak troponin ≥0.5), to compare whether secondary prevention medications were prescribed at hospital discharge among these 3 groups. We used multivariable logistic regression to examine odds ratios for receipt of medications at discharge associated with microsize MI and no MI relative to usual MI. Results: The 1,238 cases of ACS were mean age 68.0+/-8.7 years, 59% male, and 66% white. Of these, 917 had discharge medications available. Compared to those with ACS+usual MI, individuals with ACS+microsize MI had lower odds of receiving beta-blockers and statins at discharge in a similar range as those without MI ( Table ). Conclusion: Individuals hospitalized for ACS and microsize MI were less likely to receive guideline appropriate secondary prevention measures than those with usual MI.


2019 ◽  
Vol 65 (3) ◽  
pp. 484-489 ◽  
Author(s):  
Atul Anand ◽  
Anoop S V Shah ◽  
Agim Beshiri ◽  
Allan S Jaffe ◽  
Nicholas L Mills

Abstract BACKGROUND The universal definition of myocardial infarction (UDMI) standardizes the approach to the diagnosis and management of myocardial infarction. High-sensitivity cardiac troponin testing is recommended because these assays have improved precision at low concentrations, but concerns over specificity may have limited their implementation. METHODS We undertook a global survey of 1902 medical centers in 23 countries evenly distributed across 5 continents to assess adoption of key recommendations from the UDMI. Respondents involved in the diagnosis and management of patients with suspected acute coronary syndrome completed a structured telephone questionnaire detailing the primary biomarker, diagnostic thresholds, and clinical pathways used to identify myocardial infarction. RESULTS Cardiac troponin was the primary diagnostic biomarker at 96% of surveyed sites. Only 41% of centers had adopted high-sensitivity assays, with wide variation from 7% in North America to 60% in Europe. Sites using high-sensitivity troponin more frequently used serial sampling pathways (91% vs 78%) and the 99th percentile diagnostic threshold (74% vs 66%) than sites using previous-generation assays. Furthermore, high-sensitivity institutions more often used earlier serial sampling (≤3 h) and accelerated diagnostic pathways. Fewer than 1 in 5 high-sensitivity sites had adopted sex-specific thresholds (18%). CONCLUSIONS There has been global progress toward the recommendations of the UDMI, particularly in the use of the 99th percentile diagnostic threshold and serial sampling. However, high-sensitivity assays are still used by a minority of sites, and sex-specific thresholds by even fewer. Additional efforts are required to improve risk stratification and diagnosis of patients with myocardial infarction.


Author(s):  
Paul Simpson ◽  
Rosy Tirimacco ◽  
Penelope Cowley ◽  
May Siew ◽  
Narelle Berry ◽  
...  

Background The management of patients presenting with symptoms suggestive of acute coronary syndrome is a significant challenge for clinicians. Guidelines for the diagnosis of acute myocardial infarction require a rise and/or fall of cardiac troponin, along with other criteria. Knowing what constitutes a significant delta change from baseline is still unclear and the literature is varied. Methods We compared three methods for determining cardiac troponin delta changes (relative, absolute and z-scores) for detecting acute myocardial infarction in 806 patients presenting to an emergency department with symptoms suggestive of acute coronary syndrome. Blood specimens were collected at admission and 2, 3, 4 and 6 h postadmission and tested on the Roche Elecsys high-sensitivity troponin T assay. Results A positive diagnosis for acute myocardial infarction was found in 39 (4.8%) patients. ROC AUC showed better performance for the absolute and z-score delta change (0.959–0.988 and 0.956–0.988, respectively) compared with relative delta change (0.921–0.960) at all time points in the diagnosis of acute myocardial infarction. Optimal timing for the second sample was at 4–6 h postadmission. Conclusions Although not statistically significant, the results show a trend of absolute and z-score delta change performing better than relative delta change for the diagnosis of acute myocardial infarction. The z-score approach allows for a single cut-off value across multiple high-sensitivity assays which could be useful in the clinical setting. Our study also highlighted the importance of interpreting cardiac troponin changes in the clinical context with a combination of the patient’s clinical history and electrocardiogram.


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