Cardiac Biomarkers and the Diagnosis of Myocardial Infarction in Women

PURPOSE OF REVIEW: Women with suspected acute coronary syndrome are less likely to undergo investigation or receive treatment than men, and women consistently have poorer outcomes. This review summarises how the latest development in cardiac biomarkers could improve both diagnosis and outcomes in women. RECENT FINDINGS: Novel high-sensitivity cardiac troponin assays have identified differences in the reference range and therefore diagnostic threshold for myocardial infarction in men and women. These differences are present across multiple populations with different ethnic backgrounds and for a range of assays. The use of a uniform threshold for cardiac troponin does not provide equivalent prediction in men and women, with lower thresholds needed for women to provide comparable risk stratification. SUMMARY: Sex differences in cardiac troponin concentrations are not widely recognised in clinical practice and may be contributing to the under-diagnosis of myocardial infarction in women and discrepancies in patient care and outcomes

Prognostic Value of Elevated Copeptin and High-Sensitivity Cardiac Troponin T in Patients with and without Acute Coronary Syndrome: The ConTrACS Study

Aims: We aimed to assess the prognostic role of copeptin in patients presenting to the emergency department with acute symptoms and increased high-sensitivity cardiac troponin T. Methods: A total of 3890 patients presenting with acute symptoms to the emergency department of Heidelberg University Hospital were assessed for increased hs-cTnT (>14 ng/L) from three cohorts: the Heidelberg Acute Coronary Syndrome (ACS) Registry (n = 2477), the BIOPS Registry (n = 320), and the ACS OMICS Registry (n = 1093). In a pooled analysis, 1956 patients remained, comprising of 1600 patients with ACS and 356 patients with non-ACS. Results: Median follow-up was 1468 days in the ACS cohort and 709 days in the non-ACS cohort. Elevated copeptin levels (>10 pmol/L) were found in 1174 patients (60.0%) in the entire cohort (58.1% in ACS and 68.5% in non-ACS, respectively) and mortality rates were significantly higher than in patients with normal copeptin levels (29.0% vs. 10.7%, p < 0.001). In a multivariate Cox regression, elevated copeptin was independently associated with all-cause death in the ACS (HR = 1.7, 1.3–2.3, p = 0.002) and non-ACS cohort (HR = 2.7, 1.4–5.0, p = 0.0018). Conclusion: Copeptin may aid in identifying patients at risk for adverse outcomes in patients with increased levels of hs-cTnT in ACS patients and in non-ACS conditions

High-sensitivity cardiac troponin T as an independent predictor of stroke in patients admitted to an emergency department with atrial fibrillation.

AimsElevated levels of high-sensitivity cardiac troponin T (hsTnT) are associated with adverse outcomes in numerous patient populations. Their value in prediction of stroke risk in patients with atrial fibrillation (AF) is in debate.MethodsThe study population included 2898 consecutive patients presenting with AF to the emergency department of the Department of Cardiology, Heidelberg University Hospital. Associations between hsTnT and stroke risk were assessed using multivariable Cox regression.ResultsElevated hsTnT levels (>14 ng/L) were associated with increased risk of stroke. Even after adjustment for various risk factors, elevated hsTnT remained independently associated with stroke risk in patients with AF, adjusted hazard ratio 2.35 [95% confidence interval (CI): 1.26-4.36] (P = 0.007). These results were consistent across important subgroups (age, renal function, ejection fraction, CHA2DS2-VASc score and main admission diagnosis). For hsTnT, area under the receiver-operating-characteristic curve (AUC) was 0.659 [95% CI: 0.575-0.742], compared to 0.610 [95% CI: 0.526-0.694] for the CHA2DS2-VASc score. Inclusion of hsTnT in the multivariable model for stroke risk prediction consisting of all variables of the CHA2DS2-VASc score was associated with a significant improvement of its discriminatory power.ConclusionElevated hsTnT levels are significantly associated with higher risk of stroke and provide prognostic information independent of CHA2DS2-VASc score variables. Measurement of hsTnT may improve prediction of stroke risk in patients presenting to an emergency department with AF as compared to risk stratification based only on clinical variables

Validation of two severity scores as predictors for outcome in Coronavirus Disease 2019 (COVID-19).

BackgroundAn established objective and standardized reporting of clinical severity and disease progression in COVID-19 is still not established. We validated and compared the usefulness of two classification systems reported earlier-a severity grading proposed by Siddiqi and a system from the National Australian COVID-19 guideline. Both had not been validated externally and were now tested for their ability to predict complications.MethodsIn this retrospective, single-centre observational study, patients hospitalized with confirmed COVID-19 across all severity stages were enrolled. The clinical severity was graded at admission and during hospitalization. Multivariate Cox regression was used to identify independent risk factors for mortality, a composite primary (mortality, incident acute respiratory distress syndrome, incident mechanical ventilation), a secondary endpoint (mortality, incident acute myocardial injury, incident venous thrombosis, pulmonary embolism or stroke) and progression of severity grades.ResultsOf 109 patients 17 died, 31 and 48 developed the primary and secondary endpoint, respectively. Worsening of the severity grade by at least one stage occurred in 27 and 28 patients, respectively. Siddiqi and Australian classification were identified as independent predictors for the primary endpoint (adjusted hazard ratio (aHR) 2.30, pConclusionsStandardized and objective severity grading is useful to unequivocally stratify patients presenting with COVID-19 for their individual risk of complications

Amyloid- (1-40) and Mortality in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome A Cohort Study

Background: Amyloid- (1-40) (A40) is implicated in mechanisms related to plaque destabilization and correlates with adverse outcomes in stable coronary artery disease. Objective: To determine the prognostic and reclassification value of baseline circulating levels of A40 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). Design: Retrospective cohort study using data from 2 independent prospective cohorts, the Heidelberg study (n = 1145) and the validation multicenter international APACE (Advantageous Predictors of Acute Coronary Syndrome Evaluation) study (n = 734). Setting: Academic hospitals in 7 European countries. Participants: Patients with adjudicated NSTE-ACS followed for a median of 21.9 and 24.9 months in the Heidelberg and APACE studies, respectively. Measurements: All-cause mortality was the primary end point. Results: Amyloid- (1-40) was associated with mortality after multivariate adjustment for age, sex, diabetes mellitus, high-sensitivity cardiac troponin T and C-reactive protein, revascularization, and ACS type (Heidelberg cohort hazard ratio [HR] for 80th vs. 20th percentiles, 1.66 [95% CI, 1.06 to 2.61; P = 0.026]; APACE cohort HR, 1.50 [CI, 1.15 to 1.96; P = 0.003]). It was also associated with mortality after adjustment for the GRACE score (Heidelberg cohort HR for 80th vs. 20th percentiles, 1.11 [CI, 1.04 to 1.18; P = 0.001]; APACE cohort HR, 1.39 [CI, 1.02 to 1.88; P = 0.036]). Amyloid- (1-40) correctly reclassified risk for death over the GRACE score (net reclassification index, 33.4% and 47.1% for the Heidelberg and APACE cohorts, respectively) (P < 0.05). Limitation: At low concentrations of A40, dose–response associations with mortality differed between cohorts, possibly because of varying blood preparations used to measure A40. Conclusion: Circulating A40 is a predictor of mortality and improves risk stratification of patients with NSTE-ACS over the GRACE score recommended by clinical guidelines. The clinical application of A40 as a novel biomarker in NSTE-ACS should be further explored and validated. © 2018 American College of Physicians. All rights reserved

Combined testing of copeptin and high-sensitivity cardiac troponin T at presentation in comparison to other algorithms for rapid rule-out of acute myocardial infarction

BACKGROUND: We aimed to directly compare the diagnostic and prognostic performance of a dual maker strategy (DMS) with combined testing of copeptin and high-sensitivity (hs) cardiac troponin T (cTnT) at time of presentation with other algorithms for rapid rule-out of acute myocardial infarction (AMI). METHODS: 922 patients presenting to the emergency department with suspected AMI and available baseline copeptin measurements qualified for the present TRAPID-AMI substudy. Diagnostic measures using the DMS (copeptin <10, <14 or < 20 pmol/L and hs-cTnT≤14 ng/L), the 1 h-algorithm (hs-cTnT<12 ng/L and change <3 ng/L at 1 h), as well as the hs-cTnT limit-of-blank (LoB, <3 ng/L) and -detection (LoD, <5 ng/L) were compared. Outcomes were assessed as combined end-points of death and myocardial re-infarction. RESULTS: True-negative rule-out using the DMS could be achieved in 50.9%-62.3% of all patients compared to 35.0%, 45.3% and 64.5% using LoB, LoD or the 1 h-algorithm, respectively. The DMS showed NPVs of 98.1%-98.3% compared to 99.2% for the 1 h-algorithm, 99.4% for the LoB and 99.3% for the LoD. Sensitivities were 93.5%-94.8%, as well as 96.8%, 98.7% and 98.1%, respectively. Addition of clinical low-risk criteria such as a HEART-score ≤ 3 to the DMS resulted in NPVs and sensitivities of 100% with a true-negative rule-out to 33.8%-41.6%. Rates of the combined end-point of death/MI within 30 days ranged between 0.2% and 0.3% for all fast-rule-out protocols. CONCLUSION: Depending on the applied copeptin cut-off and addition of clinical low-risk criteria, the DMS might be an alternative to the hs-cTn-only-based algorithms for rapid AMI rule-out with comparable diagnostic measures and outcomes

Amyloid- (1-40) and Mortality in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome A Cohort Study

Background: Amyloid- (1-40) (A40) is implicated in mechanisms related to plaque destabilization and correlates with adverse outcomes in stable coronary artery disease. Objective: To determine the prognostic and reclassification value of baseline circulating levels of A40 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). Design: Retrospective cohort study using data from 2 independent prospective cohorts, the Heidelberg study (n = 1145) and the validation multicenter international APACE (Advantageous Predictors of Acute Coronary Syndrome Evaluation) study (n = 734). Setting: Academic hospitals in 7 European countries. Participants: Patients with adjudicated NSTE-ACS followed for a median of 21.9 and 24.9 months in the Heidelberg and APACE studies, respectively. Measurements: All-cause mortality was the primary end point. Results: Amyloid- (1-40) was associated with mortality after multivariate adjustment for age, sex, diabetes mellitus, high-sensitivity cardiac troponin T and C-reactive protein, revascularization, and ACS type (Heidelberg cohort hazard ratio [HR] for 80th vs. 20th percentiles, 1.66 [95% CI, 1.06 to 2.61; P = 0.026]; APACE cohort HR, 1.50 [CI, 1.15 to 1.96; P = 0.003]). It was also associated with mortality after adjustment for the GRACE score (Heidelberg cohort HR for 80th vs. 20th percentiles, 1.11 [CI, 1.04 to 1.18; P = 0.001]; APACE cohort HR, 1.39 [CI, 1.02 to 1.88; P = 0.036]). Amyloid- (1-40) correctly reclassified risk for death over the GRACE score (net reclassification index, 33.4% and 47.1% for the Heidelberg and APACE cohorts, respectively) (P < 0.05). Limitation: At low concentrations of A40, dose–response associations with mortality differed between cohorts, possibly because of varying blood preparations used to measure A40. Conclusion: Circulating A40 is a predictor of mortality and improves risk stratification of patients with NSTE-ACS over the GRACE score recommended by clinical guidelines. The clinical application of A40 as a novel biomarker in NSTE-ACS should be further explored and validated