Abstract 15287: Evolocumab Inhibits the Acute Rise in Lipoprotein(a) in Patients With Non-ST Elevation Myocardial Infarction (NSTEMI)- Results From the EVACS Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Michael Vavuranakis ◽  
Michael J Blaha ◽  
Steven R Jones ◽  
Thomas Schindler ◽  
Marlene S Williams ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Troponin I ◽  
Study Drug ◽  
Optimal Level ◽  
Distributed Data ◽  
Early Administration ◽  
Lipoprotein A ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
Normally Distributed

Introduction: Elevated Lipoprotein(a) [Lp(a)] is associated with an increased risk of coronary heart disease (CHD). Although Lp(a) is mostly heritable, and controlled by the apo(a) gene, acute increases are described in small studies following acute coronary syndrome (ACS). PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition modestly reduces Lp(a) in people with stable CHD but its effects during the early phase of an ACS are unknown. Hypothesis: Early administration of a PCSK9 inhibitor prevents a rise in Lp(a) following an ACS/NSTEMI. Methods: Participants from the EVACS trial (Evolocumab in Acute Coronary Syndrome; NCT03515304), all with a NSTEMI and a troponin-I of > 5 ng/ml were randomized to placebo or to evolocumab. Serum Lp(a) was obtained at study entry prior to study drug and at 30 days. Normally distributed data were summarized using means and standard deviations and non-normally distributed data using medians and interquartile ranges. Results: Fifty-six participants were randomized to placebo (27) or to evolocumab (29). Mean age was 55±13 years, 41% were women and 27% were African American. The Scatterplots (Fig.1) demonstrate for those with a baseline Lp(a) of ≤75 nmol/L (the previously described optimal level) there was no increase in Lp(a) over the 30-day study period in either group. However, for those with a baseline Lp(a) of >75 nmol/L there was a significant increase in the placebo group (Panel A), from a baseline of 176.5 nmol/L [131.5, 245.0] to 266 nmol/L [195.8, 302.5] at 30 days, p=0.02, but no increase in the evolocumab group (Panel B; baseline of 142 nmol/L [93, 177] to 137 nmol/L [96.8, 178.3], p=NS). The baseline values of those with Lp(a) of >75 nmol/L did not differ between the groups; at 30 days, however, Lp(a) was higher in the placebo than in the evolocumab group (p=0.02; Panel C). Conclusions: Early administration of evolocumab prevents the acute increase in Lp(a) in those with a baseline Lp(a) of over 75 nmol/L following an ACS/NSTEMI.

scholarly journals Multiple Biomarker Use for Detection of Adverse Events in Patients Presenting with Symptoms Suggestive of Acute Coronary Syndrome

2007 ◽  
Vol 53 (5) ◽  
pp. 874-881 ◽  
Author(s):  
Fred S Apple ◽  
Lesly A Pearce ◽  
Adrine Chung ◽  
Ranka Ler ◽  
MaryAnn M Murakami
Keyword(s):  
Acute Coronary Syndrome ◽  
Adverse Events ◽  
Cardiac Event ◽  
Troponin I ◽  
Mortality Rates ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Multiple Biomarkers ◽  
Event Rates

Abstract Background: We investigated multiple biomarkers of various pathophysiologic pathways to determine their relationships with adverse outcomes in patients presenting with symptoms of acute coronary syndrome. Methods: We obtained plasma specimens from 457 patients on admission and measured 7 biomarkers: myeloperoxidase (MPO), soluble CD40 ligand (CD40L), placental growth factor (PlGF), metalloproteinase-9 (MMP-9), high-sensitivity C-reactive protein (hsCRP), cardiac troponin I (cTnI), and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We used the Modification of Diet in Renal Disease formula to calculate the estimated glomerular filtration rate (eGFR). Endpoints were cardiac events (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, cardiac death) and all-cause mortality. We estimated cumulative event rates over a 4-month period with the Kaplan–Meier method and relative risk (RR) with the Cox proportional hazards model. Results: Patients with increased PlGF, NT-proBNP, hsCRP, or cTnI or decreased eGFR had 11% to 20% higher all-cause mortality rates than patients with concentrations within reference intervals: 20.4% (eGFR), 16.0% (PlGF), 15.8% (hsCRP), 12.7% (NT-proBNP), and 11.3% (cTnI; all P ≤0.03). No differences in mortality rates were observed between those with increased vs normal concentrations of MPO, CD40L, or MMP-9. Decreased eGFR (RR 3.4, P = 0.004) and increased NT-proBNP (RR 7.9, P = 0.04) were independently predictive of mortality, and PlGF (RR 2.0, P = 0.08) approached significance. Patients with increased NT-proBNP (12.3%) or cTnI (33.8%) had higher cardiac event rates (each P <0.02), with increased MPO (11.1%) showing a trend (P = 0.09). Patients in whom both cTnI and MPO were increased had a cardiac event rate of 43%. Conclusion: Multiple biomarkers that are likely indicative of different underlying pathophysiologic mechanisms are independently predictive of increased risk for adverse events in patients with acute coronary syndrome.

scholarly journals Clinical profile of patients with acute coronary syndrome and its association with biomarker troponin I

2018 ◽  
Vol 5 (2) ◽  
pp. 433
Author(s):  
Hemant S. Joshi ◽  
Samil Sajal ◽  
Nirmit V. Yagnik ◽  
Y. K. Bolya
Keyword(s):  
Acute Coronary Syndrome ◽  
Acute Coronary Syndromes ◽  
Troponin I ◽  
Clinical Profile ◽  
Prognostic Information ◽  
Risk Of Death ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
Acute Mi ◽  
Coronary Syndromes

Background: In patients with acute coronary syndromes, it is desirable to identify a sensitive serum marker that is closely related to the degree of myocardial damage, provides prognostic information, and can be measured rapidly. Author studied the clinical profile of patients with Acute MI and its relation with troponin I level.Methods: In this prospective study, 65 patients admitted with Acute MI were studied. Study patients were divided in Troponin I positive and Troponin I negative group. Patients were followed up to discharge or death in the hospital.Results: Most common symptom present in the patients with Acute Coronary Syndrome was chest pain (94%) and most common risk factor was dyslipidaemia (72.3%). Most common complication was recurrent angina (72.3%). Out of total patients with significant CAD, almost 70 % belong to Troponin I positive group and it is statistically highly significant (p<0.05). Total 30 patients (46.2%) have more than 10 episodes of angina in our study. There is statistically significant association between number of angina episode and Troponin I positivity (p<0.05). Out of total deaths, 73.3% have occurred among Troponin I positive study patients and it is statistically significant (p<0.05).Conclusions: In patients with acute coronary syndromes, cardiac troponin I levels provide useful prognostic information and permit the early identification of patients with an increased risk of death.  

scholarly journals Convalescent troponin and cardiovascular death following acute coronary syndrome

Heart ◽  
2019 ◽  
Vol 105 (22) ◽  
pp. 1717-1724 ◽  
Author(s):  
Philip D Adamson ◽  
David McAllister ◽  
Anna Pilbrow ◽  
John William Pickering ◽  
Katrina Poppe ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Prognostic Significance ◽  
High Sensitivity ◽  
Cardiovascular Death ◽  
Therapeutic Interventions ◽  
Coronary Syndrome ◽  
Increased Risk

ObjectivesHigh-sensitivity cardiac troponin testing is used in the diagnosis of acute coronary syndromes but its role during convalescence is unknown. We investigated the long-term prognostic significance of serial convalescent high-sensitivity cardiac troponin concentrations following acute coronary syndrome.MethodsIn a prospective multicentre observational cohort study of 2140 patients with acute coronary syndrome, cardiac troponin I concentrations were measured in 1776 patients at 4 and 12 months following the index event. Patients were stratified into three groups according to the troponin concentration at 4 months using the 99th centile (women>16 ng/L, men>34 ng/L) and median concentration of those within the reference range. The primary outcome was cardiovascular death.ResultsTroponin concentrations at 4 months were measurable in 99.0% (1759/1776) of patients (67±12 years, 72% male), and were ≤5 ng/L (median) and >99th centile in 44.8% (795) and 9.3% (166), respectively. There were 202 (11.4%) cardiovascular deaths after a median of 4.8 years. After adjusting for the Global Registry of Acute Coronary Events score, troponin remained an independent predictor of cardiovascular death (HR 1.4, 95% CI 1.3 to 1.5 per doubling) with the highest risk observed in those with increasing concentrations at 12 months. Patients with 4-month troponin concentrations >99th centile were at increased risk of cardiovascular death compared with those ≤5 ng/L (29.5% (49/166) vs 4.3% (34/795); adjusted HR 4.9, 95% CI 3.8 to 23.7).ConclusionsConvalescent cardiac troponin concentrations predict long-term cardiovascular death following acute coronary syndrome. Recognising this risk by monitoring troponin may improve targeting of therapeutic interventions.Trial registration numberACTRN12605000431628;Results.

scholarly journals Profile of copper-associated DNA methylation and its association with incident acute coronary syndrome

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Pinpin Long ◽  
Qiuhong Wang ◽  
Yizhi Zhang ◽  
Xiaoyan Zhu ◽  
Kuai Yu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Acute Coronary Syndrome ◽  
Methylation Level ◽  
Meta Analysis ◽  
Regulation Of Gene Expression ◽  
Density Lipoprotein ◽  
Blood Leukocytes ◽  
Coronary Syndrome ◽  
A Genome ◽  
Increased Risk

Abstract Background Acute coronary syndrome (ACS) is a cardiac emergency with high mortality. Exposure to high copper (Cu) concentration has been linked to ACS. However, whether DNA methylation contributes to the association between Cu and ACS is unclear. Methods We measured methylation level at > 485,000 cytosine-phosphoguanine sites (CpGs) of blood leukocytes using Human Methylation 450 Bead Chip and conducted a genome-wide meta-analysis of plasma Cu in a total of 1243 Chinese individuals. For plasma Cu-related CpGs, we evaluated their associations with the expression of nearby genes as well as major cardiovascular risk factors. Furthermore, we examined their longitudinal associations with incident ACS in the nested case-control study. Results We identified four novel Cu-associated CpGs (cg20995564, cg18608055, cg26470501 and cg05825244) within a 5% false discovery rate (FDR). DNA methylation level of cg18608055, cg26470501, and cg05825244 also showed significant correlations with expressions of SBNO2, BCL3, and EBF4 gene, respectively. Higher DNA methylation level at cg05825244 locus was associated with lower high-density lipoprotein cholesterol level and higher C-reactive protein level. Furthermore, we demonstrated that higher cg05825244 methylation level was associated with increased risk of ACS (odds ratio [OR], 1.23; 95% CI 1.02–1.48; P = 0.03). Conclusions We identified novel DNA methylation alterations associated with plasma Cu in Chinese populations and linked these loci to risk of ACS, providing new insights into the regulation of gene expression by Cu-related DNA methylation and suggesting a role for DNA methylation in the association between copper and ACS.

scholarly journals Circulating Levels of Dephosphorylated-Uncarboxylated Matrix Gla Protein in Patients with Acute Coronary Syndrome

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1108
Author(s):  
Admira Bilalic ◽  
Tina Ticinovic Kurir ◽  
Marko Kumric ◽  
Josip A. Borovac ◽  
Andrija Matetic ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Coronary Syndrome ◽  
High Risk ◽  
Hospital Mortality ◽  
Vascular Calcification ◽  
Matrix Gla Protein ◽  
St Elevation Myocardial Infarction ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
St Elevation

Vascular calcification contributes to the pathogenesis of coronary artery disease while matrix Gla protein (MGP) was recently identified as a potent inhibitor of vascular calcification. MGP fractions, such as dephosphorylated-uncarboxylated MGP (dp-ucMGP), lack post-translational modifications and are less efficient in vascular calcification inhibition. We sought to compare dp-ucMGP levels between patients with acute coronary syndrome (ACS), stratified by ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) status. Physical examination and clinical data, along with plasma dp-ucMGP levels, were obtained from 90 consecutive ACS patients. We observed that levels of dp-ucMGP were significantly higher in patients with NSTEMI compared to STEMI patients (1063.4 ± 518.6 vs. 742.7 ± 166.6 pmol/L, p < 0.001). NSTEMI status and positive family history of cardiovascular diseases were only independent predictors of the highest tertile of dp-ucMGP levels. Among those with NSTEMI, patients at a high risk of in-hospital mortality (adjudicated by GRACE score) had significantly higher levels of dp-ucMGP compared to non-high-risk patients (1417.8 ± 956.8 vs. 984.6 ± 335.0 pmol/L, p = 0.030). Altogether, our findings suggest that higher dp-ucMGP levels likely reflect higher calcification burden in ACS patients and might aid in the identification of NSTEMI patients at increased risk of in-hospital mortality. Furthermore, observed dp-ucMGP levels might reflect differences in atherosclerotic plaque pathobiology between patients with STEMI and NSTEMI.

Assessing the Performance of a Novel Point-of-Care Qualitative Assay for Early Diagnosis of Acute Coronary Syndrome

Cardiology ◽  
2020 ◽  
pp. 1-8
Author(s):  
Ronny Alcalai ◽  
Boris Varshisky ◽  
Ahmad Marhig ◽  
David Leibowitz ◽  
Larissa Kogan-Boguslavsky ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Chest Pain ◽  
Diagnostic Accuracy ◽  
Diagnostic Performance ◽  
Troponin I ◽  
Point Of Care ◽  
Final Diagnosis ◽  
Cardiac Biomarkers ◽  
Fatty Acid Binding ◽  
Coronary Syndrome

<b><i>Background:</i></b> Early and accurate diagnosis of acute coronary syndrome (ACS) is essential for initiating lifesaving interventions. In this article, the diagnostic performance of a novel point-of-care rapid assay (SensAheart<sup>©</sup>) is analyzed. This assay qualitatively determines the presence of 2 cardiac biomarkers troponin I and heart-type fatty acid-binding protein that are present soon after onset of myocardial injury. <b><i>Methods:</i></b> We conducted a prospective observational study of consecutive patients who presented to the emergency department with typical chest pain. Simultaneous high-sensitive cardiac troponin T (hs-cTnT) and SensAheart testing was performed upon hospital admission. Diagnostic accuracy was computed using SensAheart or hs-cTnT levels versus the final diagnosis defined as positive/negative. <b><i>Results:</i></b> Of 225 patients analyzed, a final diagnosis of ACS was established in 138 patients, 87 individuals diagnosed with nonischemic chest pain. In the overall population, as compared to hs-cTnT, the sensitivity of the initial SensAheart assay was significantly higher (80.4 vs. 63.8%, <i>p</i> = 0.002) whereas specificity was lower (78.6 vs. 95.4%, <i>p</i> = 0.036). The overall diagnostic accuracy of SensAheart assay was similar to the hs-cTnT (82.7% compared to 76.0%, <i>p</i> = 0.08). <b><i>Conclusions:</i></b> Upon first medical contact, the novel point-of-care rapid SensAheart assay shows a diagnostic performance similar to hs-cTnT. The combination of 2 cardiac biomarkers in the same kit allows for very early detection of myocardial damage. The SensAheart assay is a reliable and practical tool for ruling-in the diagnosis of ACS.

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