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Background: Sex- and population-specific 99th percentiles of high-sensitivity cardiac troponin (hs-cTn) are recommended in guidelines although the evidence for a clinical utility is sparse. The DANSPOT trial will investigate the clinical effect of sex- and population-specific 99th percentiles of cTn. We report the 99th percentiles derived from this trial and their dependency on kidney function., Methods: We used samples from healthy Danish blood donors and measured hemoglobin A1c, N-terminal pro-brain natriuretic peptide and creatinine, and calculated an estimated glomerular filtration rate (eGFR). We compared 2 cutoffs for the eGFR of healthy participants (60 vs 90 mL/min/1.73 m2). The cTn assays investigated were Siemens Atellica and Dimension Vista hs-cTnI, Abbott hs-cTnI, and Roche hs-cTnT., Results: A total of 2287 participants were sampled, of which 71 (3.1%) were excluded due to a history of heart disease (n = 4), insufficient material (n = 7), or a screening biomarker (n = 60). Of the remaining 2216 participants, 1325 (59.8%) had an eGFR ≥90 mL/min/1.73 m2. Compared to a cutoff of 60 mL/min/1.73 m2 for eGFR, using 90 mL/min/1.73 m2 resulted in lower 99th percentiles for females; Siemens Vista (46 vs 70 ng/L), Abbott (14 vs 18 ng/L), and Roche cTnT (10 vs 13 ng/L), and decreased the number of measurements above the manufacturers' 99th percentiles for all assays., Conclusions: We present reference values for 4 cTn assays for eGFR cutoffs of 60 and 90 mL/min/1.73 m2. These cutoffs differ based on the eGFR threshold for inclusion indicating that any chosen cutoff is also valuable with moderately reduced kidney function., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Cardiac troponin (cTn) is key in diagnosing myocardial infarction (MI). After MI, the clinically observed half-life of cTn has been reported to be 7 to 20 hours, but this estimate reflects the combined elimination and simultaneous release of cTn from cardiomyocytes. More precise timing of myocardial injuries necessitates separation of these 2 components. We used a novel method for determination of isolated cTn elimination kinetics in humans., Methods: Patients with MI were included within 24 hours after revascularization and underwent plasmapheresis to obtain plasma with a high cTn concentration. After at least 3 weeks, patients returned for an autologous plasma retransfusion followed by blood sampling for 8 hours. cTn was measured with 5 different high-sensitivity cTn assays., Results: Of 25 included patients, 20 participants (mean age, 64.5 years; SD, 8.2 years; 4 women [20%]) received a retransfusion after a median of 5.8 weeks (interquartile range, 5.0-6.9 weeks) after MI. After retransfusion of a median of 620 mL (range, 180-679 mL) autologous plasma, the concentration of cTn in participants' blood increased 4 to 445 times above the upper reference level of the 5 high-sensitivity cTn assays. The median elimination half-life ranged from 134.1 minutes (95% CI, 117.8-168.0) for the Elecsys high-sensitivity cTnT assay to 239.7 minutes (95% CI, 153.7-295.1) for the Vitros high-sensitivity cTnI assay. The median clearance of cTnI ranged from 40.3 mL/min (95% CI, 32.0-44.9) to 52.7 mL/min (95% CI, 42.2-57.8). The clearance of cTnT was 77.0 mL/min (95% CI, 45.2-95.0)., Conclusions: This novel method showed that the elimination half-life of cTnI and cTnT was 5 to 16 hours shorter than previously reported. This indicates a considerably longer duration of cardiomyocyte cTn release after MI than previously thought. Improved knowledge of timing of myocardial injury may call for changes in the management of MI and other disorders with myocardial injury., Competing Interests: Dr Bundgaard received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Amgen, Sanofi, BMS, and MSD. Dr Bundgaard owns stock or stock options in Novo Nordic. Dr Kamstrup reported a grant from Gangsted Fonden outside the present work. P.R.K. reported consulting fees from Novartis and Silence Therapeutics. Dr Kamstrup reported payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Physicians’ Academy for Cardiovascular Education, Novartis, and PCSK9 Forum. Dr Frikke-Schmidt reported grants or contracts outside the present work from Lundbeck Foundation, The Danish Heart Foundation, and Sygeforsikringen Denmark Research Fund. Dr Kjærgaard reports a grant or contract from Novo Nordisk Foundation outside the present work. Dr Holmvang reported personal payment or honoraria for lectures from Boehringer Ingelheim and payment or honoraria to her institution for lectures from Bayer. Dr Holmvang reported receiving support for travel from Abbott to her institution. Dr Bor reported receiving honoraria for a lecture from Bristol-Myers. Dr Thygesen reported participation on the Data Safety Monitoring Board of DANBLOCK (Danish Trial of Beta Blocker Treatment After Myocardial Infarction Without Reduced Ejection Fraction) and REDUCE (Randomized Evaluation of Decreased Usage of Betablockers After Myocardial Infarction in the SWEDEHEART Registry). Dr Jaffe reported royalties or licenses and stock or stock options to RCE Technologies; consulting fees from Abbott, Roche, Beckman-Coulter, Radiometer, Siemens, Ortho Diagnostics, Spinship, and LuminaRx; and support for attending meetings and/or travel from the American Association for Clinical Chemistry. Dr Dahl reporting receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Grifols and Ciesi to himself and support for attending ERS Congress 2022 from Grifols.

Background: The influence of age on cardiac troponin is unclear and may vary between cardiac troponin T (cTnT) and I (cTnI). We aimed to compare the impact of age on the diagnostic and prognostic utility of cTnT and cTnI., Methods: This Danish nationwide, register-based cohort study included patients with at least one cardiac troponin (cTn) measurement from 2009 through June 2022, stratified into decades of age. We used peak cTn concentration during admission, dichotomized as positive/negative and normalized to the 99th percentile. Receiver operating characteristics for myocardial infarction (MI) and logistic regression were used to estimate the odds ratio (OR) for mortality at 1 year., Results: We included 541 817 patients; median age 66 years (interquartile range [IQR] 51-77) and 256 545 (47%) female. A total of 40 359 (7.4%) had an MI, and 59 800 (14.1%) patients died within 1 year of admission. The predictive ability of both cTns for MI were highest for patients 30 to 50 years. This was most pronounced for cTnT, the specificity of which fell from 83% among patients 40 to 49 years to 4% for patients ≥90 years. The prognostic ability of both cTns for 1-year mortality declined with age. cTnT had stronger prognostic ability for all age-groups; OR for a positive cTnT 28.4 (95% CI, 20.1-41.0) compared with 9.4 (95% CI, 5.0-16.7) for cTnI among patients <30 years., Conclusions: The predictive and prognostic ability of cTnT and cTnI declined with age. cTnT had a low specificity for MI in elderly patients. However, cTnT was the strongest prognostic marker among all age groups., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Cardiac troponins are the preferred biomarkers for the diagnosis of acute myocardial infarction. Although sex-specific 99th percentile thresholds of troponins are recommended in international guidelines, the clinical effect of their use is poorly investigated. The DANSPOT Study (The Danish Study of Sex- and Population-Specific 99th percentile upper reference limits of Troponin) aims to evaluate the clinical effect of a prospective implementation of population- and sex-specific diagnostic thresholds of troponins into clinical practice., Methods: This study is a nationwide, multicenter, stepped-wedge cluster-randomized trial of the implementation of population- and sex-specific thresholds of troponins in 22 of 23 clinical centers in Denmark. We established sex-specific thresholds for 5 different troponin assays based on troponin levels in a healthy Danish reference population. Centers will sequentially cross over from current uniform manufacturer-derived thresholds to the new population- and sex-specific thresholds. The primary cohort is defined as patients with symptoms suggestive of acute coronary syndrome having at least 1 troponin measurement performed within 24 hours of arrival with a peak troponin value between the current uniform threshold and the new sex-specific female and male thresholds. The study will compare the occurrence of the primary outcome, defined as a composite of nonfatal myocardial infarction, unplanned revascularization, and all-cause mortality within 1 year, separately for men and women before and after the implementation of the new sex-specific thresholds., Conclusions: The DANSPOT Study is expected to show the clinical effects on diagnostics, treatment, and clinical outcomes in patients with myocardial infarction of implementing sex-specific diagnostic thresholds for troponin based on a national Danish reference population., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05336435.

Aims: Guidelines do not differentiate between the available assays of cardiac troponin (cTn). We compared the prognostic and predictive ability of cTn assays., Methods and Results: This was a nationwide cohort study of patients with acute coronary syndrome (ACS) and ≥ 2 cTn measurements of one of four assays: Roche high-sensitivity cTnT (hs-cTnT), Abbott high sensitivity cTnI (hs-cTnI), Siemens Vista cTnI, and Siemens cTnI Ultra. Data were collected from Danish registries from 2009-18. Peak cTn concentration normalized to the 99th percentile was used. Outcomes were myocardial infarction (MI) during admission, one-year all-cause-, cardiovascular-, and non-cardiovascular mortality. Receiver operating characteristics and logistic regression calculating odds ratios (OR) were used. A total of 90 705 patients were included, of which 20 550 (23%) had MI. Siemens Vista cTnI was the strongest predictor of MI, Area under the curve (auc) 0.93 (95% CI 0.93-0.93). In 1 year 9012 (9.9%) of patients had died. An inverted U-shape relationship was observed between concentration of cTn and all-cause mortality. Hs-cTnT OR 21.3 (95% CI 18.4-24.8) at 2-5 times the 99th percentile and 12.1 (95% CI 10.3-14.1) for concentrations >100 times the 99th percentile. The inverted U-shape relationship was only present for non-cardiovascular mortality. The strongest predictor of cardiovascular mortality was hs-cTnT, OR 11.3 (95% CI 6.4-21.8) at 1-2 times the 99th percentile and 88.8 (95% CI 53.2-163.0) for concentrations >100 times the 99th percentile., Conclusion: Siemens Vista cTnI was the strongest predictor of MI and hs-cTnT was the strongest predictor of mortality. An inverted U-shape relationship was observed between cTn concentration and non-cardiovascular mortality., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: End-stage renal disease is associated with a high risk of cardiovascular disease. We compared the concentration and prognostic ability of high sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) and cardiac myosin-binding protein C (cMyC) among stable hemodialysis patients., Methods: Patients were sampled before and after hemodialysis. We measured hs-cTnI, hs-cTnT and cMyC and used Cox regressions to assess the association between quartiles of concentrations and all-cause mortality and a combination of cardiovascular events and all-cause mortality during follow-up., Results: A total of 307 patients were included, 204 males, mean age 66 years (SD 14). Before dialysis, 299 (99 %) had a hs-cTnT concentration above the 99th percentile, compared to 188 (66 %) for cMyC and 35 (11 %) for hs-cTnI. Hs-cTnT (23 %, p<0.001) and hs-cTnI (15 %, p=0.049) but not cMyC (4 %, p=0.256) decreased during dialysis. Follow-up was a median of 924 days (492-957 days); patients in the 3rd and 4th quartiles of hs-cTnT (3rd:HR 3.0, 95 % CI 1.5-5.8, 4th:5.2, 2.7-9.8) and the 4th quartile of hs-cTnI (HR 3.8, 2.2-6.8) had an increased risk of mortality. Both were associated with an increased risk of the combined endpoint for patients in the 3rd and 4th quartiles. cMyC concentrations were not associated with risk of mortality or cardiovascular event., Conclusions: Hs-cTnT was above the 99th percentile in almost all patients. This was less frequent for hs-cTnI and cMyC. High cTn levels were associated with a 3-5-fold higher mortality. This association was not present for cMyC. These findings are important for management of hemodialysis patients., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Materials extracted from atherosclerotic arteries can disclose data about the molecular pathology of cardiovascular disease, but obtaining such samples is complex and requires invasive surgery. To overcome this barrier, this study investigated whether angioplasty balloons inflated during standard percutaneous coronary interventions retain proteins from treated (dilated) atherosclerotic lesions and whether proteomic analysis of this material could provide data on lesion protein profiles and distinguish between patients with stable and unstable coronary artery disease., Methods: Patients with ST-segment-elevation myocardial infarction and stable angina pectoris were subjected to routine percutaneous coronary interventions. All angioplasty balloons inflated in a coronary artery were collected. Proteins retained on the balloons were extracted and analyzed using shotgun proteomic analysis., Results: Proteomics identified and quantified 1365 unique proteins captured on percutaneous coronary intervention balloons. Control balloons inflated in the ascending aorta showed minimal nonspecific protein binding, indicating specificity to the luminal region of atherosclerotic lesions of the diseased artery wall. Clustering and principal component analyses showed that ST-segment-elevation myocardial infarction and stable angina pectoris subjects could be separated by variations in protein content and abundance. We identified 206 proteins as differentially abundant between ST-segment-elevation myocardial infarction and stable angina pectoris subjects. Pathway analysis indicated several enriched processes in the ST-segment-elevation myocardial infarction group involved in neutrophil-mediated immunity and platelet activation., Conclusions: Disease-related proteins from coronary artery lesions adhere to angioplasty balloons and constitute a source of material for proteomic analysis. This approach can identify proteins and processes occurring in unstable coronary atherosclerotic lesions and suggest novel therapeutic approaches.

Objectives: Cardiac troponin (cTn) is the biochemical gold standard for diagnosing myocardial infarction (MI). We compared the Siemens ADVIA Centaur High-Sensitivity (hs-cTnI) assay with the Siemens Ultra assay (cTnI-U)., Methods: Over 3 months cTnI-U and hs-cTnI were measured simultaneously at Herlev-Gentofte Hospital. Acute myocardial injury was diagnosed using the 4th universal definition. Disputed cases were adjudicated using clinical data. We compared diagnostic accuracy using area under the curve (AUC) of the receiver operating characteristic. Outliers in between-assay differences were defined as a factor-5 difference and ≥1 measurement >40 ng/L. Patients with outlier differences were invited for re-sampling and tested with serial dilution and heterophilic blocking tubes., Results: From the 18th January to the 20th April 2019, 4,369 samples on 2,658 patients were included. cTnI-U measured higher concentrations than hs-cTnI (mean 23%, -52-213%), resulting in a higher frequency of acute myocardial injury, 255 (9.6%) vs. 203 (7.6%), p<0.001. This remained significant after adjudication, 212 vs 197, p<0.001. AUC for the prediction of MI for was 0.963 for cTnI-U and 0.959 for hs-cTnI, p=0.001. Outlier differences were seen in 35 (1.2%) patients, primarily with elevated hs-cTnI (n=33, 94%). On two re-samplings (median 144 and 297 days since inclusion), 16 of 20 (80%) and 11 of 11 had sustained elevation of hs-cTnI. The samples showed no signs of heterophilic antibodies., Conclusions: Using hs-cTnI resulted in a subset of patients with large, discrepant elevations in concentration. These patients still had elevated hs-cTnI 6-10 months post admission but no heterophilic antibodies., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: Acute STEMI is routinely treated by acute PCI. This treatment may itself damage the tissue (reperfusion injury). Conditioning with GLP-1 analogs has been shown to reduce reperfusion injury. Likewise, ischemic postconditioning provides cardioprotection following STEMI. We tested if combined conditioning with the GLP-1 analog liraglutide and ischemic postconditioning offered additive cardioprotective effect after reperfusion of 45 min coronary occlusion of left anterior descending artery (LAD)., Design: Fifty-eight non-diabetic female Danish Landrace pigs (60 ± 10kg) were randomly assigned to four groups. Myocardial infarction (MI) was induced by occluding the LAD for 45 min. Group 1 (n = 14) was treated with i.v. liraglutide after 15 min of ischemia. Group 2 (n = 17) received liraglutide treatment concomitant with ischemic postconditioning, after 45 min of ischemia. Group 3 (n = 15) recieved ischemic postconditioning and group 4 (n = 12) was kept as controls., Results: No intergroup differences in relative infarct size were detected (overall mean 57 ± 3%; p = 0.68). Overall mortality was 34% (CI 25-41%) including 26% post-intervention, with no intergroup differences (p = 0.99). Occurrence of ventricular fibrillation (VF) was 59% (CI 25-80%) including 39% postintervention with no intergroup differences (p = 0.65)., Conclusions: In our closed-chest pig-model, we were unable to detect any cardioprotective effect of liraglutide or ischemic postconditioning either alone or combined.

Background: Cardiac troponin T and I are important diagnostic and prognostic markers in patients with acute coronary syndrome (ACS). Troponin elevations in various non-ACS scenarios have been documented, but few studies have been conducted on the general hospitalized population, none compared the diagnostic performance of troponin I and T., Methods and Results: Patients aged >18years (n=1097), consecutively admitted to a district hospital, were included in the study. Blood samples were collected at admission and analysed with three different troponin assays. Serum was available in 92.2%, giving a study population of 1012 patients (mean age 61.6years, 510 (50.4%) female). ACS was diagnosed among 125 (12.4%) of the patients. Remaining patients were admitted with a broad spectrum of medical and surgical conditions. Of the total population, sc-cTnI was above the 99th percentile in 93 (9.2%), hs-cTnI was above the 99th percentile in 80 (7.9%) and hs-cTnT was above the 99th percentile in 400 (39.5%) of the patients (p<0.001 for all differences). Hs-cTnT was stronger correlated with estimated glomerular filtration rate (r [2]=0.13 vs r [2]=0.06) and haemoglobin (r [2]=0.1 vs r2=0.02) than with hs-cTnI, none were correlated with C-reactive protein (r [2]=0.04 vs r [2]=0.02). The correlation between ln(hs-cTnT) and ln(hs-cTnI) was better in ACS patients than in non-ACS patients (r [2]=0.79 vs r [2]=0.47, p<0.001)., Conclusion: Hs-cTnT was elevated above the 99th percentile in more than one third of the non-ACS patients, while hs-cTnI and sc-cTnI were elevated in approximately one tenth. The correlation between hs-cTnT and hs-cTnI concentrations was significantly stronger in ACS patients than in non-ACS patients., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: Patients with diabetes are at increased risk of experiencing myocardial infarction. The influence of the prevailing plasma glucose level on infarction and mortality after acute ischaemia is however unknown. The aim was to study the effect of the acute plasma glucose level on the myocardial infarction size in a closed-chest pig model., Design: 38 non-diabetic pigs were randomised to hypoglycaemic (1.8-2.2 mmol/l; n = 15), normoglycaemic (5-7 mmol/l; n = 12) or hyperglycaemic glucose clamping (22-23 mmol/l; n = 11). After 30 min within glucose target myocardial infarction was induced for 30 min followed by reperfusion for 120 min. Hereafter the heart was double-stained to delineate infarction from viable tissue within the area at risk., Results: Mean infarction size was 201 ± 35 mm(2) (mean ± SEM) in the hypoglycaemic group, 154 ± 40 mm(2) in the normoglycaemic group and 134 ± 40 mm(2) in the hyperglycaemic group, with no differences in infarction size, infarct/area at risk ratio or troponin T levels between the groups. There was no difference in incidence of ventricular fibrillation or mortality between the groups., Conclusion: No statistically significant associations were observed between the acute glycaemic level and measures of myocardial infarction, rates of ventricular fibrillation and subsequent premature death in the setting of acute ischaemia and reperfusion.

Background: Plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) predict mortality in several clinical settings, but the long-term prognostic importance of suPAR in chest pain patients admitted on suspicion of non-ST-segment elevation acute coronary syndrome (NSTEACS) is uncertain., Methods: suPAR concentrations were measured on admission in 449 consecutive chest pain patients in a single center between January 3, 2005, and February 14, 2006. Patients were followed for all-cause mortality from discharge until July 28, 2011., Results: The diagnoses at discharge comprised high-risk NSTEACS [non-ST elevation myocardial infarction or unstable angina with electrocardiogram (ECG) abnormalities] in 77 patients (17.2%) and low-risk NSTEACS without evidence of myocardial ischemia in 257 (57.2%) of patients. Another 115 (25.6%) of patients received other diagnoses. During a median follow-up of 5.7 years (range, 0.01-6.6 years) there were 162 (36.1%) deaths. suPAR was predictive of mortality independent of age, sex, smoking, final diagnosis for the hospitalization, comorbidities (diabetes, hypertension, previous myocardial infarction, and heart failure), and variables measured on the day of admission (renal function, inflammatory markers, and markers of myocardial ischemia) with a hazard ratio (95% CI) of 1.93 (1.48-2.51) per SD increase in log-transformed suPAR, P < 0.0001. The use of suPAR improved the predictive accuracy of abnormal ECG findings and increased troponin concentrations regarding all-cause mortality (c statistics, 0.751-0.805; P < 0.0001)., Conclusions: suPAR is a strong predictor of adverse long-term outcomes and improves risk stratification beyond traditional risk variables in chest pain patients admitted with suspected NSTEACS.

The plasma level of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is an independent predictor of cardiovascular disease and all-cause mortality in healthy subjects. The prognostic capability of suPAR, its temporal course, and its relation to plasma C-reactive protein (CRP) in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous intervention (PCI) is unknown. Therefore, the plasma suPAR and CRP levels were measured in 296 consecutive patients with ST-segment elevation myocardial infarction admitted for primary PCI at baseline and every 6 to 8 hours thereafter until the cardiac biomarker levels had peaked. The end points were all-cause mortality and fatal or nonfatal recurrent myocardial infarction (MI). During a median follow-up period of 5.75 years, 69 deaths and 48 nonfatal and 14 fatal recurrent MIs occurred. All-cause mortality increased significantly from 8.1% to 41.5% across increasing quartiles of suPAR levels at the end of follow-up (log-rank p <0.0001). After adjustment for other independent prognostic factors, a highly significant increase was seen in all-cause mortality (hazard ratio 1.45, 95% confidence interval, 1.19 to 1.76; p <0.001) and recurrent MI (hazard ratio 1.53, 95% confidence interval 1.16 to 2.01; p <0.01) for each standard deviation increment of suPAR levels). In contrast to plasma CRP, the suPAR levels remained stable after primary PCI. Furthermore, CRP did not predict mortality or reinfarction after adjustment for age and gender (p = 0.34). In conclusion, suPAR is a stable plasma biomarker after ST-segment elevation myocardial infarction treated with primary PCI that predicts all-cause mortality and recurrent MI., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Pregnancy associated plasma protein-A (PAPP-A) is a potential new marker for vulnerable plaques in the coronary arteries only examined in stable coronary disease (CAD) in patients undergoing coronary angiography. Here we address the prognostic value of serum PAPP-A in unselected stable CAD patients., Method: Blood samples were drawn at study entry. Serum PAPP-A values ≥4mIU/L were considered elevated. Mortality and non-fatal myocardial infarction was prospectively registered. The primary outcome was the composite outcome of myocardial infarction and all-cause mortality, secondary outcomes were all-cause mortality and myocardial infarction., Results: Patients (n=4243) were followed for a median of 2.8 years. In a Cox analysis, elevated PAPP-A was significantly related to the composite outcome of myocardial infarction and death (HR 1.99, 95% CI 1.62-2.45, p<0.0005), all-cause mortality (HR 2.42, 1.92-3.06, p<0.0005), and myocardial infarction (HR 1.40, 1.01-1.94, p=0.046). After Holm's correction, the latter significance disappeared. After adjustment for risk factors and medication at entry, elevated PAPP-A remained significantly related to the composite outcome (HR 1.51, 1.22-1.86, p<0.0005) and all-cause mortality (HR 1.68, 1.32-2.13, p<0.0005)., Conclusion: In patients with stable CAD elevated serum PAPP-A seems promising as aid in identifying patients at high risk for death., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

To investigate whether pregnancy-associated plasma protein-A (PAPP-A) is a prognostic marker in patients admitted with high-risk acute coronary syndrome. In patients admitted with high-risk non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and ST-segment elevation myocardial infarction (STEMI), risk stratification is primarily determined by the markers of myocardial necrosis and known demographic risk profiles. However, it has recently been proposed that the presence and extent of vulnerable plaques might influence the prognosis significantly. A marker for the vulnerable plaque could identify patients at high risk who would potentially benefit from intensive treatment and surveillance. Two populations of consecutive patients admitted with high-risk NSTE-ACS (n = 123) and STEMI (n = 314) were evaluated with serial measurements of PAPP-A. The incidence of mortality and nonfatal myocardial infarction was prospectively registered for 2.66 to 3.47 years. In the patients with high-risk NSTE-ACS, PAPP-A was related to the risk of nonfatal myocardial infarction (p = 0.02) and death (p = 0.03). This result was consistent on multivariate analysis of the combination of mortality or nonfatal myocardial infarction (odds ratio 2.65, 95% confidence interval 1.40 to 5.03) but not for mortality alone (p = NS). In patients with STEMI, PAPP-A was related to the risk of death (p = 0.01) but not the composite outcome of myocardial infarction and death. This was also true after adjustment for other univariate predictors of death (odds ratio 2.19, 95% confidence interval 1.16 to 4.16). In conclusion, PAPP-A seems to be valuable in predicting the outcomes of patients admitted with high-risk NSTE-ACS or STEMI.

Traditional biomarkers in acute coronary syndromes reflect myocardial necrosis but not the underlying arteriosclerotic disease. Pregnancy-associated plasma protein A (PAPP-A) is a new biomarker in acute coronary syndromes that detects vulnerable plaques in arteriosclerotic disease and identifies acute coronary syndromes earlier than traditionally used biomarkers. Information regarding circulating PAPP-A levels in patients with ST elevation myocardial infarctions (STEMIs) is limited and contradictory. The aim of the present study was to describe the presence and time-related pattern of circulating PAPP-A levels in patients with STEMIs. Consecutive patients (n = 354) referred for primary percutaneous intervention because of STEMI were included in the study. Blood samples for the analysis of PAPP-A, creatine kinase-MB (CKMB), and troponin T were drawn at admission and every 6 to 8 hours until biomarkers of myocardial necrosis were consistently decreasing. PAPP-A was measured using a newly developed sandwich enzyme-linked immunosorbent assay technique based on 2 monoclonal antibodies. In total, 1,091 PAPP-A, 1,049 troponin T, and 1,016 CKMB samples were analyzed. Mean PAPP-A values at admission were significantly higher in patients with STEMIs than in those with non-ST elevation myocardial infarctions or unstable angina pectoris (27.6 vs 12.2 mIU/L, p <0.01). In samples drawn <2 hours after admission, the sensitivity of PAPP-A was superior (93%) to that of CKMB (60%) and troponin T (61%). In conclusion, PAPP-A levels are elevated in >90% of patients presenting with STEMIs if measured <6 hours after the onset of symptoms or <2 hours of primary percutaneous coronary intervention. In the early stages of STEMI, PAPP-A seems to be a more sensitive marker of myocardial infarction than CKMB and troponin T.

Aims: To evaluate the importance of chronic obstructive pulmonary disease for prognosis and diagnosis of congestive heart failure in patients with acute myocardial infarction., Method and Results: Prospective registration of 6669 consecutive patients admitted with infarction and screened for a randomised controlled trial. A history of COPD was present in 765 (11.5%) patients. Thirty-day and 5-year survival in patients with chronic obstructive pulmonary disease was 86.3 and 42.9%. In patients without pulmonary disease the figures were 87.7 and 57.5%, respectively, giving a relative risk of 1.49 (1.35-1.65). In multivariate analysis the relative risk was 1.15 (1.04-1.28). The prevalence of congestive heart failure was 65.9% in patients with chronic obstructive pulmonary disease and 52.0% in patients without. This difference was most distinct in patients with normal or only slightly decreased left ventricular systolic function. In patients without congestive heart failure, chronic obstructive pulmonary disease was of prognostic importance [RR=1.44 (1.17-1.78)], but not in patients with congestive heart failure [RR=1.09 (0.96-1.23)]., Conclusion: Chronic obstructive pulmonary disease is a predictor of long-term mortality in patients with acute myocardial infarction without congestive heart failure, but is also a confounding factor for the diagnosis of congestive heart failure.

End-stage renal disease is associated with a high risk of cardiovascular disease. We compared the concentration and prognostic ability of high sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) and cardiac myosin-binding protein C (cMyC) among stable hemodialysis patients. Patients were sampled before and after hemodialysis. We measured hs-cTnI, hs-cTnT and cMyC and used Cox regressions to assess the association between quartiles of concentrations and all-cause mortality and a combination of cardiovascular events and all-cause mortality during follow-up. A total of 307 patients were included, 204 males, mean age 66 years (SD 14). Before dialysis, 299 (99 %) had a hs-cTnT concentration above the 99th percentile, compared to 188 (66 %) for cMyC and 35 (11 %) for hs-cTnI. Hs-cTnT (23 %, p<0.001) and hs-cTnI (15 %, p=0.049) but not cMyC (4 %, p=0.256) decreased during dialysis. Follow-up was a median of 924 days (492–957 days); patients in the 3rd and 4th quartiles of hs-cTnT (3rd:HR 3.0, 95 % CI 1.5–5.8, 4th:5.2, 2.7–9.8) and the 4th quartile of hs-cTnI (HR 3.8, 2.2–6.8) had an increased risk of mortality. Both were associated with an increased risk of the combined endpoint for patients in the 3rd and 4th quartiles. cMyC concentrations were not associated with risk of mortality or cardiovascular event. Hs-cTnT was above the 99th percentile in almost all patients. This was less frequent for hs-cTnI and cMyC. High cTn levels were associated with a 3-5-fold higher mortality. This association was not present for cMyC. These findings are important for management of hemodialysis patients. [ABSTRACT FROM AUTHOR]

MACE: Major adverse cardiovascular events Death might count differently in a patient aged 38 years as compared to the 82 years old patient - i.e. an age-adjusted weight might be relevant. This proposal may be an initial step for patients, patient organizations, funding parties and politicians together with the medical societies to re-think how to compose endpoints that more accurately reflect what patients prioritizes and are willing "to pay" for. [Extracted from the article]

Background:Cardiac-specific troponin T (cTnT) and troponin I (cTnI) are considered diagnostically equal in patients with acute coronary syndrome (ACS). The aim of this systematic review was to compare the prevalence and prognostic strength of elevations of cTnT and cTnI in patients with other conditions than ACS. Methods:A systemic review was conducted in concordance with the PRISMA guidelines. The studies were identified by searching PubMed, EMBASE and Cochrane Central Register, from May to August 2016. Studies measuring both cTnT and cTnI in populations without ACS were eligible. Results:Twenty-nine studies were included (n = 25,859). Seventeen studies reported on prognostic information with follow-up time ranging for 30 d–5 years. Elevation above the 99th percentile (reference value for a healthy population) in non-ACS population was reported to be 0–39% for cTnI and 40–100% for cTnT. Elevation of cTnT tends to be a superior predictor for all-cause mortality and elevation of cTnI tends to be a superior predictor for cardiovascular related mortality. Discussion:In the absence of ACS, elevation of cTnT is more frequent than elevation of cTnI. Conclusion:Both cTnT and cTnI elevations have important prognostic information regarding morbidity, cardiac mortality and all-cause mortality. [ABSTRACT FROM PUBLISHER]

Aims Evaluation of patients with primary mitral valve insufficiency (MI) is best supported by quantitative measures. Cardio- vascular magnetic resonance imaging (CMR) offers flow and cardiac chamber volume quantification. We studied cardiac remodelling with CMR to determine MI regurgitation volumes (MIVol) related to severe MI. Methods In total, 24, 20, and 28 patients determined to have mild, moderate, and severe primary MI, respectively, were studied. and results Combining cine stacks with phase-contrast velocity mapping across the ascending aorta, CMR-determined MIVol was reproducibly obtained as the difference between left ventricular (LV) stroke volume and aortic forward flow (Aoflow). With increasing MI severity, MIVol, left heart volumes, and pulmonary venous diameters increased (P, 0.01). Severe MI with LV end-systolic diameter of 40 mm was signified by MIVol >40 mL, MI regurgitant fraction >0.30, LV end-diastolic volume (LVEDV(i)) > 108 mL m-2, and a total left heart volume > 188 mL m-2 with dilated pulmonary veins and a LVEDV/right ventricular EDV ratio >1.2. In severe MI, LV ejection fraction was unaffected, but the Aoflow and the peak ejection rate indexed to LVEDV were lowered (P < 0.05). In surgical patients, the MIVol correlated to the decrease in LV dimension after valve surgery (P < 0.02). Conclusion CMR provides a reproducible quantitative technique for evaluation of MI, as MIVol and cardiac chamber volumes can be held against diagnostic cut-off values. The Aoflow and peak ejection rate indexed to LVEDV may reveal early LV systolic dysfunction in patients with severe MI. Severe MI is related to lower MI regurgitation volume and fraction than previously believed. [ABSTRACT FROM AUTHOR]

Objective: The aim was to assess serial measurements of high-sensitivity cardiac troponin T (hs-cTNT) post-exercise in patients with stable coronary artery disease (CAD). Methods: Twelve patients with positive coronary angiograms (CAD positives) and 12 controls performed an exercise stress test. Results: CAD positive had higher baseline and peak concentrations of hs-cTNT than controls. Significant increases in hs-cTNT were seen in both groups after exercise. In two-third of patients the peak in hs-cTNT was above the 99th percentile. Conclusion: hs-cTNT is higher in patients with stable coronary disease than in controls and exceeds the diagnostic cut-off value for myocardial infarction in a majority of patients with CAD after exercise. [ABSTRACT FROM AUTHOR]

Objective. Pregnancy-associated plasma protein A (PAPP-A) is expressed in eroded and ruptured atheromatous plaques, and circulating levels are elevated in acute coronary syndromes (ACS). Our objective was to investigate release patterns of PAPP-A in ACS and whether they differ among different types of ACS. Methods. In 40 patients, PAPP-A concentrations were measured in serially collected samples assessed by a novel ELISA technique. The patients were grouped according to type of ACS. Results. Release patterns for ST elevation myocardial infarction (STEMI) patients who underwent primary percutaneous coronary intervention (pPCI) showed a single substantial PAPP-A increase shortly after pPCI, followed by an abrupt return to normal levels without secondary peaks. STEMI, high-risk and low-risk non-ST elevation myocardial infarction/unstable angina pectoris (NSTEMI/UAP) patients without pPCI showed highly variable patterns with primary peaks followed by secondary PAPP-A increases. All patients with elevated PAPP-A levels reached the upper reference level within 24 h. There was a significant difference in median peak levels between STEMI (23.2 mIU/L) and low-risk ACS patients (6.35 mIU/L) (p = 0.004) and between high-risk (median = 15.3 mIU/L) and low-risk ACS patients (p = 0.01). Among high-risk ACS patients, NSTEMI patients had significantly higher peak levels than UAP patients (p = 0.003). Conclusion. PAPP-A serum levels increase above normal values within 24 h after onset of symptoms in ACS. There are significant differences in PAPP-A peak levels and release patterns across the spectrum of ACS patients. [ABSTRACT FROM AUTHOR]

Background: Cardiac troponins (cTns) are the cornerstone of diagnosing acute myocardial infarction. There is limited knowledge on the duration of ischemia necessary to induce a measurable release of cTns or the very-early-release kinetics of cTns after an ischemic event. Copeptin may have a supplementary role in ruling out myocardial infarction early. We investigated the release of cTns and copeptin in the first hours after experimental balloon-induced ischemia in humans.Methods: Thirty-four patients (median age, 60 years [interquartile range, 51-64]; 15 men, 43%) with angiographically normal coronary arteries were randomly assigned into 4 groups with different durations of induced myocardial ischemia (0, 30, 60, 90 s). Ischemia was induced by inflating a balloon in the left anterior descending artery between the first and second diagonal branch. Blood was collected before balloon inflation (baseline) every 15 minutes for the first 3 hours, and every 30 minutes for the next 3 hours. The cTns were analyzed by 3 high-sensitivity (hs) cTn assays: hs-cTnT (Roche), hs-cTnI (Siemens), and hs-cTnI (Abbott). Copeptin was analyzed by a sandwich immunoluminometric assay.Results: None of the patients had any complications. Increased cTn concentrations were detected by all 3 assays, and the magnitude of the increase was associated with the duration of ischemia. Increased hs-cTnI (Siemens) concentrations were first detectable 15 minutes after 90-s ischemia (median 43.7% increase) and increased more steeply and had a higher peak than the other assays. Copeptin levels did not significantly change. Using the cTnT, hs-cTnI (Siemens), and hs-cTnI (Abbott) concentrations at 0 and 180 minutes, 1 (11%), 0, and 0 patients from the 60-s ischemia group and 5 (63%), 2 (25%), and 1 (11%) from the 90-s ischemia group, respectively, fulfilled criteria for a biochemical myocardial infarction.Conclusions: This study is the first to report the early-release kinetics of cTn concentrations after different durations of experimental coronary balloon occlusion in humans. All assays detected a cTn increase after only 30 s of ischemia. hs-cTnI (Siemens) rose faster and reached a higher peak. Copeptin levels did not change significantly. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03203057. [ABSTRACT FROM AUTHOR]

• SuPAR was a strong prognostic biomarker of non-cardiac mortality after STEMI. • The suPAR level was independent of sampling time < 12 h after revascularization. • SuPAR may identify patients in risk of non-cardiac mortality prior to discharge. Identification of patients at high risk of non-cardiac mortality following ST-segment elevation myocardial infarction (STEMI) could guide clinicians to identify patients who require attention due to serious non-cardiac conditions after the acute phase of STEMI. The purpose of this study was to evaluate if the non-specific and prognostic biomarker of inflammation and comorbidity, soluble urokinase receptor (suPAR), could predict non-cardiac mortality in a cohort of STEMI patients. SuPAR was measured in 1,190 STEMI patients who underwent primary percutaneous coronary intervention (pPCI). The primary endpoint was non-cardiac mortality, secondary endpoints were cardiac mortality, all-cause mortality, reinfarction and periprocedural acute kidney injury. Backwards elimination of potential confounders significantly associated with the respective outcome was used to adjust associations. Patients were followed for a median of 3.0 years (interquartile range 2.5– 3.6 years). Multivariate cox regression revealed that a plasma suPAR level above 3.70 ng mL−1 was associated with non-cardiac and cardiac mortality at hazard ratios 3.33 (95% confidence interval 1.67–6.63, p = 0.001, adjusted for age) and 0.99 (0.18–5.30, p = 0.98, adjusted for previous myocardial infarction and left ventricular ejection fraction), respectively. In patients with pPCI treated STEMI, suPAR was an independent prognostic biomarker of non-cardiac but not cardiac mortality and may identify patients with high risk of non-cardiac mortality. [ABSTRACT FROM AUTHOR]