There is a clinical need for early and accurate diagnosis of acute myocardial infarction (AMI). Current European Society of Cardiology (ESC) guidelines recommend diagnosis of non-ST-elevation AMI based on serial troponin measurements. We aimed to challenge the ESC guidelines using 1) a high-sensitivity troponin I (hs-TnI) baseline cutoff, 2) an absolute hs-TnI change after 1 hour and 3) additional application of an ischemic ECG.

Our aims were to evaluate the distribution of troponin I concentrations in population cohorts across Europe, to characterize the association with cardiovascular outcomes, to determine the predictive value beyond the variables used in the ESC SCORE, to test a potentially clinically relevant cut-off value, and to evaluate the improved eligibility for statin therapy based on elevated troponin I concentrations retrospectively.

Stroke is a common cause of death and a leading cause of disability and morbidity. Stroke risk assessment remains a challenge, but circulating biomarkers may improve risk prediction. Controversial evidence is available on the predictive ability of troponin concentrations and the risk of stroke in the community. Furthermore, reports on the predictive value of troponin concentrations for different stroke subtypes are scarce.

The introduction of modern troponin assays has facilitated diagnosis of acute myocardial infarction due to improved sensitivity with corresponding loss of specificity. Atrial fibrillation (AF) is associated with elevated levels of troponin. The aim of the present study was to evaluate the diagnostic performance of troponin I in patients with suspected acute coronary syndrome and chronic AF.

: High-sensitivity troponin has proven to be a promising biomarker for the prediction of future adverse cardiovascular events. We aimed to assess the prognostic value of high-sensitivity troponin I (hs-TnI) on admission in patients with suspected acute myocardial infarction (AMI) analyzed by a novel (Singulex Clarity cTnI) and established hs-TnI assay (ARCHITECT STAT hs-TnI, Abbott). Hs-TnI was measured in a total of 2332 patients from two prospective cohort studies presenting to the emergency department with suspected AMI. The prognostic impact for overall and cardiovascular mortality of both hs-TnI assays was assessed in the total patient cohort as well as in the subgroups of patients with AMI (n = 518) and without AMI (non-AMI) (n = 1814). Patients presenting with highest hs-TnI levels showed higher overall and cardiovascular mortality rates compared to those with lower troponin levels, irrespective of the assay used. Both hs-TnI assays indicated association with overall mortality according to adjusted hazard ratio (HR) among the entire study population (HR for Singulex assay: 1.16 (95% CI 1.08-1.24) and HR for Abbott assay: 1.17 (95% CI 1.09-1.25)). This finding was particularly pronounced in non-AMI patients, whereas no association between hs-TnI and overall mortality was found in AMI patients for either assay. In non-AMI patients, both assays equally improved risk prediction for cardiovascular mortality beyond conventional cardiovascular risk factors. Hs-TnI is independently predictive for adverse outcomes in patients with suspected AMI, especially in the subset of patients without confirmed AMI. There was no difference between the established and the novel assay in the prediction of mortality.

Common ECG criteria such as ST-segment changes are of limited value in patients with suspected acute myocardial infarction (AMI) and bundle branch block or wide QRS complex. A large proportion of these patients do not suffer from an AMI, whereas those with ST-elevation myocardial infarction (STEMI) equivalent AMI benefit from an aggressive treatment. Aim of the present study was to evaluate the diagnostic information of cardiac troponin I (cTnI) in hemodynamically stable patients with wide QRS complex and suspected AMI.

Cardiac troponin blood levels are frequently elevated in patients with impaired renal function. Their predictive value for the severity of stable coronary artery disease (CAD) remains unclear in these cases. Therefore, we aimed to evaluate the blood levels of high-sensitivity troponin T and I (hsTnT/I) and their association with the severity of stable CAD in patients with chronic kidney disease.

Cardiac troponin and B-type natriuretic peptide (BNP) concentrations are associated with adverse cardiovascular outcome in primary prevention populations. Whether statin therapy modifies this association is poorly understood.

The soluble urokinase-type plasminogen activator receptor (suPAR) is a new marker for immune activation and inflammation and may provide diagnostic value on top of established biomarkers in patients with suspected acute myocardial infarction (AMI). Here, we evaluate the diagnostic potential of suPAR levels on top of high-sensitivity troponin I (hs-TnI) in a cohort of patients with suspected AMI. A total of 1220 patients presenting to the emergency department with suspected AMI were included, of whom 245 were diagnosed with AMI. Median suPAR levels at admission were elevated in subjects with AMI compared to non-AMI (3.8 ng/mL vs 3.3 ng/mL, p = 0.001). In C-statistics, the area under the curve (AUC) regarding the diagnosis of AMI was low (0.57 at an optimized cut-off of 3.7 ng/mL). Moreover, baseline suPAR levels on top of troponin values at admission and hour 1 reduced the number of patients who were correctly ruled-out as non-AMI, and who were correctly ruled-in as AMI. Our study shows that circulating levels of suPAR on top of high-sensitivity troponin I do not improve the early diagnosis of AMI.

Background The association between high-sensitivity troponin T (hsTnT) and high-sensitivity troponin I (hsTnI) and outcome when adjusted for confounders including the angiographical severity of coronary artery disease (CAD) remains largely unknown. We therefore aimed to explore whether hsTnT and hsTnI blood levels increase with CAD severity and add independent predictive information for future major adverse cardiovascular events and all-cause mortality in stable patients. Methods and Results Patients from the INTERCATH cohort with available coronary angiography and hsTnT and hsTnI concentrations were included. Troponin concentrations were quantified via hsTnT (Roche Elecsys) and hsTnI (Abbott ARCHITECT STAT). To investigate the association of hsTnT and hsTnI with outcome, a multivariable analysis adjusting for classical cardiovascular risk factors, low-density lipoprotein cholesterol, estimated glomerular filtration rate, hs-CRP (high-sensitivity C-reactive protein), NT-proBNP (N-terminal pro-brain natriuretic peptide), and Gensini score was carried out. Of 1829 patients, 27.9% were women, and the mean age was 68.6±10.9 years. Troponin blood concentrations were higher in patients with diagnosed CAD compared with those without. Using a linear regression model current smoking, arterial hypertension, estimated glomerular filtration rate, hs-CRP, NT-proBNP, and CAD severity as graded by the Gensini and SYNTAX scores were associated with high-sensitivity troponin levels. Patients were followed for 4.4 years (25th and 75th percentiles: 4.3, 4.4). After multivariable adjustment, all-cause mortality was predicted by hsTnT (hazard ratio [HR], 1.7 [95% CI, 1.5-2.2], P<0.001) as well as hsTnI (HR, 1.5 [95% CI, 1.2-1.8], P<0.001). However, only hsTnI (HR, 1.2 [95% CI, 1.0-1.4], P=0.032) remained as an independent predictor of major adverse cardiovascular events after adjusting for most possible confounders, including CAD severity (hsTnT: HR, 1.0 [95% CI, 0.9-1.2], P=0.95). Conclusions After adjusting for classical cardiovascular risk factors, low-density lipoprotein cholesterol, estimated glomerular filtration rate, hs-CRP, NT-proBNP, and CAD severity, hsTnT and hsTnI were independently associated with all-cause mortality, but only hsTnI was associated with major adverse cardiovascular events in stable patients undergoing coronary angiography. Registration URL: https://clinicaltrials.gov/; Unique identifier: NCT04936438.

Risk stratification among patients with coronary artery disease (CAD) is of considerable interest to potentially guide secondary preventive therapies. Cardiac troponins as well as C-reactive protein (hsCRP) and natriuretic peptides have emerged as biomarkers for risk stratification. The question remains if one of these biomarkers is superior in predicting adverse outcomes. Thus, we perform a head-to-head comparison between high-sensitivity troponin I (hsTnI), hsCRP, and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with CAD. Plasma levels were measured in a cohort of 2193 patients with documented CAD. The main outcome measures were cardiovascular (CV) death and/or nonfatal myocardial infarction (MI). During a median follow-up of 3.8 years, all three biomarkers were associated with cardiovascular death and/or MI. After adjustments for conventional cardiovascular risk factors, the hazard ratio (HR) per standard deviation (SD) for the prediction of CV death and/or nonfatal MI was 1.39 [95% CI: 1.24-1.57, p < 0.001] for hsTnI, 1.41 [95% CI: 1.24-1.60, p < 0.001] for hsCRP, and 1.64 [95% CI: 1.39-1.92, p < 0.001] for NT-proBNP. However, upon further adjustments for the other two biomarkers, only NT-proBNP was still associated with the combined endpoint with an HR of 1.47 [95% CI: 1.19-1.82, p < 0.001]. Conclusively, NT-proBNP is reliably linked to CV death and MI in patients with CAD and provides incremental value beyond hsCRP and hsTnI.

Background High-sensitivity cardiac troponin (hs-cTn)-based diagnostic algorithms are recommended for the management of patients with suspected myocardial infarction (MI) without ST elevation. Although mirroring different phases of myocardial injury, falling and rising troponin patterns (FPs and RPs, respectively) are equally considered by most algorithms. We aimed to compare the performance of diagnostic protocols for RPs and FPs, separately. Methods and Results We pooled 2 prospective cohorts of patients with suspected MI and stratified patients to stable, FP, and RP during serial sampling separately for hs-cTnI and hs-cTnT and applied the European Society of Cardiology 0/1- and 0/3-hour algorithms comparing the positive predictive values to rule in MI. Overall, 3523 patients were included in the hs-cTnI study population. The positive predictive value for patients with an FP was significantly reduced compared with patients with an RP (0/1-hour: FP, 53.3% [95% CI, 45.0-61.4] versus RP, 76.9 [95% CI, 71.6-81.7]; 0/3-hour: FP, 56.9% [95% CI, 42.2-70.7] versus RP, 78.1% [95% CI, 74.0-81.8]). The proportion of patients in the observe zone was larger in the FP using 0/1-hour (31.3% versus 55.8%) and 0/3-hour (14.6% versus 38.6%) algorithms. Alternative cutoffs did not improve algorithm performances. Compared with stable hs-cTn, the risk for death or MI was highest in those with an FP (adjusted hazard ratio [HR], hs-cTnI 2.3 [95% CI, 1.7-3.2]; RP adjusted HR, hs-cTnI 1.8 [95% CI, 1.4-2.4]). Findings were similar for hs-cTnT tested in 3647 patients overall. Conclusions The positive predictive value to rule in MI by the European Society of Cardiology 0/1- and 0/3-hour algorithms is significantly lower in patients with FP than RP. These are at highest risk for incident death or MI. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02355457, NCT03227159.

To examine the long-term predictive value of 28 biomarkers for subsequent non-ischaemic congestive heart failure (CHF) and separately for other cardiovascular outcomes (myocardial infarction (MI) and stroke).

Background Risk stratification among patients with coronary artery disease (CAD) is of considerable interest due to the potential to guide secondary preventive therapies. Thus, we evaluated the predictive value of soluble urokinase-type plasminogen activator receptor (suPAR) levels for cardiovascular mortality and nonfatal myocardial infarction in patients with CAD. Methods and Results Plasma levels of suPAR were measured in a cohort of 1703 patients with documented CAD as evidenced by coronary angiography-including 626 patients with acute coronary syndrome and 1077 patients with stable angina pectoris. Cardiovascular death and/or nonfatal myocardial infarction were defined as main outcome measures. During a median follow-up of 3.5 years, suPAR levels reliably predicted cardiovascular death or myocardial infarction in CAD, evidenced by survival curves stratified for tertiles of suPAR levels. In Cox regression analyses, the hazard ratio for the prediction of cardiovascular death and/or myocardial infarction was 2.19 (P<0.001) in the overall cohort and 2.56 in the acute coronary syndrome cohort (P<0.001). Even after adjustment for common cardiovascular risk factors, renal function and the biomarkers C-reactive protein, N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin I suPAR still enabled a reliable prediction of cardiovascular death or myocardial infarction with a hazard ratio of 1.61 (P=0.022) in the overall cohort and 2.22 (P=0.005) in the acute coronary syndrome cohort. Conclusions SuPAR has a strong and independent prognostic value in secondary prevention settings, and thereby might represent a valuable biomarker for risk estimation in CAD.

The atypical presentation of women with acute coronary syndrome (ACS) has been related to delayed diagnosis and treatment, which may explain worse outcome compared with men.

Background Patients with chronic kidney disease ( CKD ) are at high risk of myocardial infarction. Cardiac troponins are the biomarkers of choice for the diagnosis of acute myocardial infarction ( AMI ) without ST -segment elevation ( NSTE ). In patients with CKD , troponin levels are often chronically elevated, which reduces their diagnostic utility when NSTE - AMI is suspected. The aim of this study was to derive a diagnostic algorithm for serial troponin measurements in patients with CKD and suspected NSTE - AMI . Methods and Results Two cohorts, 1494 patients from a prospective cohort study with high-sensitivity troponin I (hs- cTnI ) measurements and 7059 cases from a clinical registry with high-sensitivity troponin T (hs- cTnT ) measurements, were analyzed. The prospective cohort comprised 280 CKD patients (estimated glomerular filtration rate <60 mL/min/1.73 m2). The registry data set contained 1581 CKD patients. In both cohorts, CKD patients were more likely to have adjudicated NSTE - AMI than non- CKD patients. The specificities of hs- cTnI and hs- cTnT to detect NSTE - AMI were reduced with CKD (0.82 versus 0.91 for hs- cTnI and 0.26 versus 0.73 for hs- cTnT ) but could be restored by applying optimized cutoffs to either the first or a second measurement after 3 hours. The best diagnostic performance was achieved with an algorithm that incorporates serial measurements and rules in or out AMI in 69% (hs- cTnI ) and 55% (hs- cTnT ) of CKD patients. Conclusions The diagnostic performance of high-sensitivity cardiac troponins in patients with CKD with suspected NSTE - AMI is improved by use of an algorithm based on admission troponin and dynamic changes in troponin concentration.

Variations in cardiac troponin concentrations by age, sex and time between samples in patients with suspected myocardial infarction are not currently accounted for in diagnostic approaches. We aimed to combine these variables through machine learning to improve the assessment of risk for individual patients.

Long-term sequelae may occur after SARS-CoV-2 infection. We comprehensively assessed organ-specific functions in individuals after mild to moderate SARS-CoV-2 infection compared with controls from the general population.

Background: Several cardiovascular biomarkers have regulatory functions in perinatal physiology. Aim: This study aimed to analyze the feto-maternal distribution pattern of biomarkers in samples of amniotic fluid, umbilical arterial blood, umbilical venous blood, and maternal blood samples, and to establish reference values. Each linked sample set consisted of the combined samples obtained in an individual pregnancy. Study design: We performed a prospective, observational, cross-sectional, single-center study. Subjects: The sample cohort included 189 neonates who were born to 170 mothers. A total of 162/189 neonates were full term and 129/189 were delivered by elective cesarean section. Outcome measures: Midregional pro-adrenomedullin (MRproADM [nmol/L]), midregional pro-atrial natriuretic peptide (MRproANP [pmol/L]), brain natriuretic peptide (BNP [pg/mL]), N-terminal pro-brain natriuretic peptide (NTproBNP [pg/mL]), copeptin [pmol/L], and high-sensitive troponin I (hsTnI [pg/mL]) levels were measured. Results: In singleton, full-term, primary cesarean deliveries (n = 91), biomarker levels (median, [IQR]) at delivery were as follows. MRproADM levels in umbilical arterial blood/umbilical venous blood/amniotic fluid/maternal blood were 0.88 (0.20)/0.95 (0.18)/2.80 (1.18)/1.10 (0.54), respectively. MRproANP levels were 214.23 (91.38)/216.03 (86.15)/0.00 (3.82)/50.67 (26.81), respectively. BNP levels were 14.60 (25.18)/22.08 (18.91)/7.15 (6.01)/6.20 (18.23), respectively. NTproBNP levels were 765.48 (555.24)/816.45 (675.71)/72.03 (55.58)/44.40 (43.94), respectively. Copeptin levels were 46.17 (290.42)/5.54 (9.08)/9.97 (7.44)/4.61 (4.59), respectively. Levels of hsTnI were 6.20 (4.25)/5.60 (5.01)/0.45 (1.73)/2.50 (2.40), respectively. Conclusion: We determined reference values for biomarkers in term neonates delivered by primary cesarean section in amniotic fluid, umbilical arterial and venous blood, and maternal blood. Biomarkers in the fetal circulation appear to be of primary fetal origin, except for MRproADM.

Iron is essential in terms of oxygen utilization and mitochondrial function. The liver-derived peptide hepcidin has been recognized as a key regulator of iron homeostasis. Since iron metabolism is crucially linked to cardiovascular health, and low hepcidin was proposed as potential new marker of iron metabolism, we aimed to evaluate the prognostic value of hepcidin in a large cohort of patients with coronary heart disease (CHD). Serum levels of hepcidin were determined at baseline in patients with angiographically documented CHD. The main outcome measure was non-fatal myocardial infarction (MI) or cardiovascular death. During a median follow-up of 4.1 years, 10.3% experienced an endpoint. In Cox regression analyses for hepcidin the hazard ratio for future cardiovascular death or MI was 1.03 (95% confidence interval (CI) 0.91⁻1.18, p = 0.63) after adjustment for sex and age. This association virtually did not change after additional adjustment for body mass index (BMI), smoking status, hypertension, diabetes, dyslipidemia, and surrogates of cardiac function (NT-proBNP), size of myocardial necrosis (troponin I), and anemia (hemoglobin). In this study, by far the largest evaluating the predictive value of hepcidin, hepcidin levels were not associated with future MI or cardiovascular death. This implicates a limited, if any, role for hepcidin in secondary cardiovascular risk prediction.