Biomarkers of Renal Function in Acute Coronary Syndromes
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
The thesis aimed to investigate cystatin C and creatinine-based estimates of glomerular filtration rate (eGFR), both at admission and during follow-up, on the combined endpoint of cardiovascular death and myocardial infarction in patients with acute coronary syndrome (ACS). We also evaluated two cystatin C assays and assessed genetic determinants of cystatin C concentrations.
We used the PLATelet inhibition and Patient Outcomes study, where all types of ACS patients (n=18624) were randomized to ticagrelor or clopidogrel treatment. Multivariable Cox regression models, including clinical variables and biomarkers (troponin and NT-proBNP), and c-statistics were calculated.
Cystatin C and the creatinine-based CKD-EPI equation exhibited similar significant prognostic impact on the combined endpoint, with Area Under Curves (AUC) 0.6923 and 0.6941, respectively. Follow-up samples of renal biomarkers did not improve risk prediction.
Patients randomized to ticagrelor treatment were associated with a non-sustained larger increase in renal markers at discharge, but neither the change nor the difference between the randomized groups affected cardiovascular risk.
Two different cystatin C assays exhibited good correlation 0.86 (95% confidence interval 0.85-0.86), however moderate level of agreement. Risk prediction with a combination of creatinine and cystatin C did not outperform the creatinine-based CKD-EPI equation, AUC: 0.6913 and 0.6924, respectively (n=13050).
The genetic polymorphism rs6048952 independently affected the cystatin C concentration with mean levels of 0.85mg/L, 0.80mg/L and 0.73mg/L for the A/A, A/G, and G/G genotypes, respectively.
The genetic polymorphism did not affect outcome overall, however in the non-ST-elevation ACS subgroup a signal that genetic polymorphism may be associated with cardiovascular death was observed (p=0.002).
In conclusion: cystatin C or eGFR, irrespective of equation or assay, are important cardiovascular risk factors in ACS patients. Nonetheless, the incremental value of adding any renal variable, to a multivariable risk model, is small. Further research on the impact of cystatin C genetic polymorphism is warranted.
Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. , 74 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 891
cystatin C, glomerular filtration rate, GFR, creatinine, acute coronary syndrome, ACS, kidney, renal, mortality, death, myocardial infarction
Cardiac and Cardiovascular Systems
Research subject Cardiology; Medicine; Internal Medicine
IdentifiersURN: urn:nbn:se:uu:diva-197852ISBN: 978-91-554-8643-3OAI: oai:DiVA.org:uu-197852DiVA: diva2:614574
2013-05-24, Enghoffsalen, Ing 50, Akademiska Sjukhuset, Uppsala, 09:00 (Swedish)
Omland, Torbjörn, Professor
James, Stefan, DocentWallentin, Lars, Professor
PhD, i medicin.2013-05-032013-04-052013-08-30Bibliographically approved
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