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

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.

Heart Asia ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. e011142 ◽  
Author(s):  
Rugheed Ghadban ◽  
Tariq Enezate ◽  
Joshua Payne ◽  
Haytham Allaham ◽  
Ahmad Halawa ◽  
...  

BackgroundMorphine is widely used for pain control in patients with acute coronary syndrome (ACS). Several studies have questioned the safety of morphine in this setting with a concern of interaction with and reduced efficacy of antiplatelet agents.ObjectiveThis study aims to systematically review the safety of morphine use in ACS.MethodsMEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were queried from inception through April 2018. Studies comparing morphine to nonmorphine use in ACS were included. Study endpoints included: in-hospital myocardial infarction (MI), all-cause mortality, stroke, major bleeding, minor bleeding and dyspnoea.ResultsA total of 64 323 patients with ACS were included from eight studies, seven of which were observational studies and one was a randomised controlled trial. The use of morphine was associated with increased risk of in-hospital recurrent MI (OR 1.30, 95% CI 1.18 to 1.43, p < 0.00001). There was, however, no significant difference in terms of all-cause mortality (OR 0.87, 95% CI 0.62 to 1.22, p = 0.44), stroke (OR 0.81, 95% CI 0.39 to 1.66, p = 0.57), major bleeding (OR 0.49, 95% CI 0.24 to 1.00, p = 0.05), minor bleeding (OR 0.98, 95% CI 0.41 to 2.34, p = 0.97), or dyspnoea (OR 0.55, 95% CI 0.16 to 1.83, p = 0.33).ConclusionThe use of morphine for pain control in ACS was associated with an increased risk of in-hospital recurrent MI. Randomised clinical trials are needed to further investigate the safety of morphine in ACS.


2009 ◽  
Vol 55 (1) ◽  
pp. 93-100 ◽  
Author(s):  
Fred S Apple ◽  
Stephen W Smith ◽  
Lesly A Pearce ◽  
MaryAnn M Murakami

Abstract Background: Cardiac troponin is the preferred biomarker for detecting acute myocardial injury and infarction (MI). We studied whether multiple biomarkers of numerous pathophysiological pathways would increase the diagnostic accuracy for detecting MI. Methods: Seven biomarkers [myeloperoxidase, soluble CD40 ligand, placental growth factor, matrix metalloproteinase 9 (MMP-9), high-sensitivity C-reactive protein (hsCRP), cardiac troponin I (cTnI), N-terminal pro–B-type natriuretic peptide] and estimated glomerular filtration rate were measured in 457 patients presenting on admission with symptoms suggestive of acute coronary syndrome. Twenty-five patients (5.4%) received MI diagnoses. Clinical sensitivities and specificities were evaluated from 99th-percentile reference values. Forward and backward stepwise logistic regression modeling techniques were used to identify biomarkers that were independently predictive of MI. Results: Biomarker sensitivities ranged from 20% to 96%, and specificities ranged from 19% to 89%. MMP-9 had the highest sensitivity, but its specificity was 19%. cTnI demonstrated a sensitivity of 72% (95% CI, 51%–88%) and a specificity of 89% (95% CI, 85%–92%). In multivariate models, cTnI (P &lt; 0.001) and either hsCRP (P = 0.009) or MMP-9 (P = 0.03) were independently predictive of MI. Addition of hsCRP or MMP-9 increased the specificity to 95% (95% CI, 92%–97%) or 91% (95% CI, 88%–94%), respectively, but reduced the sensitivity to 56% (95% CI, 35%–76%) and 68% (95% CI, 47%–85%) relative to cTnI alone. Conclusions: Our findings indicate that the most clinically accurate biomarker for the early diagnosis of MI is the use of cTnI alone, rather than a multiple-biomarker approach, when an analytically robust cardiac troponin assay based on the 99th percentile is used.


2022 ◽  
Vol 21 (1) ◽  
Author(s):  
Yang Jiao ◽  
Yongkang Su ◽  
Jian Shen ◽  
Xiaoling Hou ◽  
Ying Li ◽  
...  

Abstract Background With the advancement of the world population aging, more attention should be paid to the prognosis of elderly patients with acute coronary syndrome (ACS). Triglyceride-glucose (TyG) index is a reliable indicator of insulin resistance (IR) and is closely related to traditional risk factors of cardiovascular disease (CVD). However, the effect of TyG index on the prognosis of long-term adverse events in elderly ACS patients has not been reported. This study evaluated the prognostic power of TyG index in predicting adverse events in elderly ACS patients. Methods In this study, 662 ACS patients > 80 years old who were hospitalized from January 2006 to December 2012 were enrolled consecutively and the general clinical data and baseline blood biochemical indicators were collected. The follow-up time after discharge was 40–120 months (median, 63 months; interquartile range, 51‒74 months). In addition, the following formula was used to calculate the TyG index: Ln [fasting TG (mg/dL) × FBG (mg/dL)/2], and patients were divided into three groups according to the tertile of the TyG index. Results The mean age of the subjects was 81.87 ± 2.14 years, the proportion of females was 28.10%, and the mean TyG index was 8.76 ± 0.72. The TyG index was closely associated with the traditional risk factors of CVD. In the fully-adjusted Cox regression model, the Hazard ratio (95% CI) of all-cause mortality (in tertile 3) was 1.64 (1.06, 2.54) and major adverse cardiac event (MACE) (in tertile 3) was 1.36 (1.05, 1.95) for each SD increase in the TyG index. The subgroup analyses also confirmed the significant association of the TyG index and long-term prognosis. Conclusion The TyG index is an independent predictor of long-term all-cause mortality and MACE in elderly ACS patients.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Michael Vavuranakis ◽  
Michael J Blaha ◽  
Steven R Jones ◽  
Thomas Schindler ◽  
Marlene S Williams ◽  
...  

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.


2009 ◽  
Vol 55 (5) ◽  
pp. 930-937 ◽  
Author(s):  
Fred S Apple ◽  
Lesly A Pearce ◽  
Stephen W Smith ◽  
Jason M Kaczmarek ◽  
MaryAnn M Murakami

Abstract Background: We sought to determine the diagnostic accuracy of the cardiac troponin I (cTnI) VITROS® Troponin I-ES assay for early detection of acute myocardial infarction (AMI) and for risk prediction of adverse events in patients with symptoms of acute coronary syndrome (ACS). Methods: cTnI was measured on admission and approximately 6 h postadmission in 381 patients. The 99th percentile cTnI concentration (0.034 μg/L) and change [delta (δ)] between admission and follow-up concentrations were evaluated in diagnostic sensitivity and specificity calculations. Risk of cardiac event or death within 60 days was evaluated by Cox proportional hazards regression. Results: AMI occurred in 52 patients. Diagnostic sensitivities (95% CI) of admission and follow-up cTnIs for AMI were 69% (55%–81%) and 94% (84%–99%), respectively. The corresponding specificities (95% CI) were 78% (73%–82%) and 81% (77%–85%), and ROC curve areas were 0.82 vs 0.96 (P &lt; 0.001). Deltas between admission and follow-up cTnI &gt;30% had a sensitivity of 75% (95% CI 61%–86%) and a specificity of 91% (95% CI 87%–94%). During follow-up, 1 cardiac death, 2 noncardiac deaths, 52 AMIs, 6 coronary artery bypass grafts, and 43 percutanous coronary interventions occurred in 62 patients. A δ cTnI &gt;30%, when added to either initial cTnI &gt;0.034 μg/L or follow-up cTnI &gt;0.034 μg/L, improved risk stratification for cardiac event or death (P &lt; 0.001). Conclusions: Admission cTnI measured by the VITROS ES assay is a sensitive biomarker for detection of AMI. Utilizing &gt;30% cTnI δ in addition to either the baseline or follow-up concentration improved both specificity and risk assessment in patients presenting with symptoms of ACS.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Sopova ◽  
G Georgiopoulos ◽  
M Mueller-Hennessen ◽  
M Sachse ◽  
N Vlachogiannis ◽  
...  

Abstract Background Blood-based biomarkers may be useful in the identification of residual risk for death or acute myocardial infarction (AMI) in patients with a previous acute coronary syndrome. Cathepsin S (CTSS) is a lysosomal cysteine protease with potent elastolytic and collagenolytic activity, which plays an important role in cardiovascular disease through extracellular matrix degradation, vasa vasorum development and atherosclerotic plaque rupture. The aim of the present study was to determine the prognostic and reclassification value of baseline circulating levels of CTSS after adjustment for the Global Registry of Acute Coronary Events (GRACE) score, which is widely recommended for risk stratification in non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Methods CTSS was measured in blood samples collected from 1,129 consecutive patients with adjudicated NSTE-ACS presenting at an acute chest pain unit for evaluation of a possible acute coronary syndrome. Cardiovascular (CV) death and a composite of all-cause mortality and AMI were evaluated as the primary and secondary endpoints of the study, respectively. The additive prognostic value of CTSS over the GRACE score was estimated by the Net Reclassification Index (NRI) that examines the net upward and downward reclassification into correct pre-defined risk categories. Results After a median follow-up of 21 months, 101 (8.95%) deaths were reported, of which 63 (5.6%) were of cardiac origin. The combined endpoint occurred in 176 (15.6%) patients. Patients with CTSS in the highest tertile presented the greatest risk for all-cause mortality (HR=1.84 for highest versus lowest tertile of CTSS distribution, 95% CI 1.1–3.08, P=0.02) and CV death (HR=2.5 for highest versus lowest tertile of CTSS distribution, 95% CI 1.24–5.05, P=0.011) after adjustment for age, gender, diabetes mellitus, hs-cTnT, hsCRP, revascularization and index diagnosis. Similarly, CTSS was associated with increased risk of cardiovascular death after adjusting for the GRACE Score (adjusted HR for highest versus lowest tertile of CTSS distribution=2.34, 95% CI 1.18–4.64, P=0.015). Further, CTSS predicted the combined endpoint of all-cause death or non-fatal MI independently of the GRACE Score (adjusted HR for highest versus lowest tertile of CTSS distribution=1.67, 95% CI 1.15–2.42, P=0.007). When CTSS was added over the GRACE Score, it conferred significant reclassification value for CV death (NRI=21.4%, P=0.008). Similarly, CTSS correctly reclassified risk for all-cause death or non-fatal MI (P=0.006) in 15.9% of the population. Conclusions Circulating CTSS predicts mortality and improves risk stratification of patients with NSTE-ACS over the GRACE score recommended by clinical guidelines. The clinical application of CTSS as a novel biomarker in NSTE-ACS should be further explored and validated.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Sato ◽  
Y Ogihara ◽  
T Kurita ◽  
H Mizutani ◽  
A Takasaki ◽  
...  

Abstract Background Right ventricular (RV) overload is associated with adverse outcome in patients with chronic heart failure. However, its prognostic value in acute coronary syndrome (ACS) patients remains unknown. Purpose The purpose of this study was to investigate the prevalence and prognostic impact of right ventricular overload in ACS patients. Methods We studied 2797 ACS patients from Mie ACS registry, a prospective and multicenter registry in Japan. They were divided into 4 subgroups according to the severity of RV overload and the extent of Left Ventricle Ejection Fraction (LVEF) assessed by echocardiography before hospital discharge. High RV overload was defined as trans-tricuspid pressure gradient (TRPG) ≥40mmHg and preserved LVEF was defined as ≥50%. The primary outcome was defined as 2-year all-cause mortality. Median follow up duration was 730 days (1–2215 days). Results High RV overload was detected in 76 patients (2.7%). In basic patients characteristics, high RV overload patients were significantly older and higher killip classification than low RV overload patients (P&lt;0.01, respectively). Laboratory data in high RV overload patients showed lower hemoglobin level and higher serum creatinine level than those in low RV overload patients (P&lt;0.01, respectively). Echocardiographic findings in high RV overload represented lower LVEF, higher rate of moderate or severe mitral regurgitation and left atrial enlargement than those in low RV overload patients (P&lt;0.01, respectively). During the follow-up periods (median 730 days), 260 (9.3%) patients experienced all-cause death. Multivariate cox hazard regression analysis for all-cause mortality demonstrated that high RV overload was an independent poor prognostic factor in the entire study population. Among patients with preserved LVEF, high RV overload resulted in an increased risk of all-cause mortality compared to low RV overload (P&lt;0.0001). Conclusion In ACS patients, high RV overload strongly contributes to worsening of prognosis regardless of the extent of LVEF. Kaplan-Meier survival curve Funding Acknowledgement Type of funding source: None


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
C Eyileten ◽  
J Jarosz-Popek ◽  
D Jakubik ◽  
M Wolska ◽  
A Fitas ◽  
...  

Abstract Background Acute coronary syndrome (ACS) remains a leading cause of mortality worldwide [1]. Patients who experienced ACS are at high risk of future cardiovascular events and death [2–4]. Identification of reliable predictive tools could potentially improve the risk stratification [5]. Numerous studies revealed that intestinal microbial organisms (microbiota) and its metabolites, as TMAO (trimethylamine-N-oxide) may play a pathogenic role in a cardiovascular disease (CVD) and ACS [6]. Elevated concentration of circulating TMAO has been associated with increased risk of CVD and major adverse cardiac events (MACE), including myocardial infarction (MI), stroke, major bleeding and all-cause mortality [7]. Purpose To investigate the association of liver metabolite TMAO with cardiovascular disease (CV)-related and all-cause mortality in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention. Methods Our prospective observational study enrolled 292 patients with ACS. Plasma concentrations of TMAO were measured during the hospitalization for ACS. Observation period lasted 7 years in the median. Adjusted Cox-regression analysis was used for prediction of mortality. Results ROC curve analysis revealed that increasing concentrations of TMAO levels assessed at the time point of ACS significantly predicted the risk of CV mortality (c-index=0.78, p&lt;0.001). The cut-off value of &gt;4 μmol/L, labeled as high TMAO level (23% of study population), provided the greatest sum of sensitivity (85%) and specificity (80%) for the prediction of CV mortality and was associated with a positive predictive value of 16% and a negative predictive value of 99%. A multivariate Cox regression model revealed that high TMAO level was a strong and independent predictor of CV death (HR=11.62, 95% CI: 2.26–59.67; p=0.003). High TMAO levels as compared with low TMAO levels were associated with the highest risk of CV death in a subpopulation of patients with diabetes mellitus (27.3% vs 2.6%; p=0.004). Although increasing TMAO levels were also significantly associated with all-cause mortality, their estimates for diagnostic accuracy were low. Conclusions High TMAO level is a strong and independent predictor of long-term CV mortality among patients presenting with ACS. TMAO concentration of 4 μmol/L may be a cut-off value for prognosis of ACS patients. FUNDunding Acknowledgement Type of funding sources: None. Figure 1. Kaplan-Meier curves Table 1


Author(s):  
Yong Yang ◽  
Haili Shen ◽  
Zhigeng Jin ◽  
Dongxing Ma ◽  
Qing Zhao ◽  
...  

AbstractThe association between metabolic syndrome (MetS) and survival outcome after acute coronary syndrome (ACS) remains controversial. This meta-analysis sought to examine the association of MetS with all-cause mortality among patients with ACS. Two authors independently searched PubMed and Embase databases (from their inception to June 27, 2020) for studies that examined the association of MetS with all-cause mortality among patients with ACS. Outcome measures were in-hospital mortality and all-cause mortality during the follow-up. A total of 10 studies involving 49 896 ACS patients were identified. Meta-analysis indicated that presence of MetS was associated with an increased risk of long-term all-cause mortality [risk ratio (RR) 1.25; 95% CI 1.15–1.36; n=9 studies] and in-hospital mortality (RR 2.35; 95% CI 1.40–3.95; n=2 studies), respectively. Sensitivity and subgroup analysis demonstrated the credibility of the value of MetS in predicting long-term all-cause mortality. MetS is associated with an increased risk of long-term all-cause mortality among patients with ACS. However, additional studies are required to investigate the association of MetS with in-hospital mortality.


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