Browsing by Author "Ziegler, André"

Now showing 1 - 3 of 3
  • Thumbnail Image
    ItemOpen Access
    Bone morphogenetic protein 10: a novel risk marker of ischaemic stroke in patients with atrial fibrillation.
    (European heart journal, 2023-01) Hijazi, Ziad; Benz, Alexander P; Lindbäck, Johan; Alexander, John H; Connolly, Stuart J; Eikelboom, John W; Granger, Christopher B; Kastner, Peter; Lopes, Renato D; Ziegler, André; Oldgren, Jonas; Siegbahn, Agneta; Wallentin, Lars

    Aims

    Biomarkers specifically related to atrial tissue may increase the understanding of the pathophysiology of atrial fibrillation (AF) and further improve risk prediction in this setting. Bone morphogenetic protein 10 (BMP10) is a protein expressed in the atrial myocardium. We evaluated the association between BMP10 and the risk of ischaemic stroke and other cardiovascular events in large cohorts of patients with AF, treated with and without oral anticoagulation (OAC).

    Methods and results

    BMP10 was measured in plasma samples collected at randomisation in patients with AF without OAC in the ACTIVE A and AVERROES trials (n = 2974), and with OAC in the ARISTOTLE trial (n = 13 079). BMP10 was analysed with a prototype Elecsys immunoassay. Associations with outcomes were evaluated by Cox-regression models adjusted for clinical characteristics, kidney function, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Median concentrations of BMP10 were 2.47 and 2.44 ng/mL, in the non-OAC and OAC cohort, respectively. Increasing BMP10 was associated with lower body mass index, older age, female sex, kidney dysfunction, and AF rhythm. BMP10 was consistently associated with ischaemic stroke. In the non-OAC cohort, BMP10 increased the concordance index of the multivariable model from 0.713 to 0.733 (P = 0.004) and in the OAC cohort from 0.673 to 0.694 (P < 0.001). Additionally, BMP10 maintained a significant prognostic value after additionally adjusting for NT-proBNP. BMP10 was not independently associated with bleeding or with death.

    Conclusion

    The novel atrial biomarker BMP10 was independently associated with ischaemic stroke in patients with AF irrespective of OAC treatment. BMP10 seems to be more specifically related to the risk of ischaemic stroke in AF.

    One-sentence summary

    In this study, BMP10 may be a novel specific biomarker of ischaemic stroke in patients with atrial fibrillation, irrespective of oral anticoagulation.
  • No Thumbnail Available
    ItemOpen Access
    The 99th percentile upper reference limit for the 5th generation cardiac troponin T assay in the United States.
    (Clinica chimica acta; international journal of clinical chemistry, 2020-05) Fitzgerald, Robert L; Hollander, Judd E; Peacock, W Frank; Limkakeng, Alexander T; Breitenbeck, Nancy; Rivers, E Joy; Ziegler, André; Laimighofer, Michael; deFilippi, Christopher
    BACKGROUND:Determining diagnostic thresholds for cardiac troponin assays is key to interpreting their clinical performance. We describe the calculation of 99th percentile upper reference limits (URLs) for the Elecsys® Troponin T Gen 5 (TnT Gen 5) assay. METHODS:Plasma and serum samples from healthy US participants were prospectively evaluated using TnT Gen 5 Short Turn Around Time and 18-min assays on cobas e 411 and cobas e 601 analyzers (Roche Diagnostics); with, up to 8 TnT Gen 5 results per participant. RESULTS:A total of 10,402 TnT Gen 5 results from 1301 participants were included (50.4% female). Across 9 calculation methods, overall 99th percentile URL was 19.2 ng/l (females, 13.5-13.6 ng/l; males, 21.4-22.2 ng/l). Across different sample/assay/analyzer combinations, overall 99th percentile URLs ranged from 18.4-20.2 ng/l. Median TnT Gen 5 results increased with age, were higher in males, and ranged from 3.0-3.7 ng/l across races/ethnicities and from 3.0-3.6 ng/l across body mass index (BMI) classes. Applying additional exclusion criteria (N-terminal pro-brain natriuretic peptide, BMI and estimated glomerular filtration rate) resulted in lower 99th percentile URLs (overall, 16.9 ng/l; females, 11.8 ng/l; males, 18.5 ng/l). CONCLUSION:Our findings facilitate the interpretation of TnT Gen 5 results in US clinical practice.
  • No Thumbnail Available
    ItemOpen Access
    Using Sex-specific Cutoffs for High-sensitivity Cardiac Troponin T to Diagnose Acute Myocardial Infarction.
    (Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 2020-07-29) Peacock, W Frank; Baumann, Brigitte M; Rivers, E Joy; Davis, Thomas E; Handy, Beverly; Jones, Christopher W; Hollander, Judd E; Limkakeng, Alexander T; Mehrotra, Abhi; Than, Martin; Cullen, Louise; Ziegler, André; Dinkel-Keuthage, Carina
    High-sensitivity cardiac troponin (hs-cTn) assays facilitate early decision-making in acute myocardial infarction (AMI).1 The accuracy of these assays now allow sex-specific differences in levels to be detected within healthy populations. It is thought that differences in plasma levels of cardiac troponin (cTn) are due to sex-specific variations in body composition and cardiac physiology,2 and that estrogen may also play a part.3 However, the clinical relevance of this remains unclear.4 Women presenting with suspected acute coronary syndrome (ACS) are less frequently diagnosed, have poorer outcomes,5 and are more likely to have atypical symptoms than men.6 The requirement for sex-specific cutoffs may vary depending on the troponin assay, intended use, AMI type, and clinical performance estimate being assessed. Previously proposed sex-specific hs-cTnT assay cutoffs (females, 14 ng/L; males, 22 ng/L) did not alter sensitivity for AMI versus the overall cutoff (19 ng/L), but resulted in slightly lower specificity for AMI in females and higher specificity in males.4 However, it is uncertain whether sex-specific cutoffs improve hs-cTnT assay diagnostic performance.