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Cystatin C- and Creatinine-based Estimates of Renal Function and Their Value for Risk Prediction in Patients with Acute Coronary Syndrome: Results from the PLATelet Inhibition and Patient Outcomes (PLATO) Study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
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2013 (English)In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 59, no 9, 1369-1375 p.Article in journal (Refereed) Published
Abstract [en]

Background: The estimated glomerular filtration rate (eGFR) independently predicts cardiovascular (CV) death or myocardial infarction (MI), and can be estimated by creatinine and cystatin C concentrations. We evaluated two different cystatin C assays, alone or combined with creatinine, in patients with acute coronary syndromes.

Methods: Plasma cystatin C, measured with assays from Gentian and Roche, and serum creatinine was analyzed in 16279 patients from the PLATelet inhibition and patient Outcomes trial. Pearson’s correlation and agreement (Bland–Altman) between methods was evaluated. Prognostic value in relation to CV death or MI during one year of follow up was evaluated by multivariable logistic regression analysis including clinical variables and biomarkers, c-statistics and relative Integrated Discrimination Improvement (IDI).

Results: Median cystatin C concentrations (interquartile intervals) were 0.83 (0.68 - 1.01) mg/L (Gentian) and 0.94 (0.80 - 1.14) mg/L (Roche). Overall correlation was 0.86 (95% confidence interval 0.85-0.86). The level of agreement was ±0.39mg/L (±2 standard deviations) (n=16279).

The area under curve (AUC) in the multivariable risk prediction model with cystatin C (Gentian, Roche) or Chronic Kidney Disease - Epidemiology (CKD-EPI) added was 0.6914, 0.6913 and 0.6932. Corresponding relative IDIs were 2.96%, 3.86% and 4.68%, respectively (n=13050). Addition of eGFR by the combined creatinine-cystatin C equation yielded AUC of 0.6923(Gentian) and 0.6924(Roche) with relative IDIs of 3.54% and 3.24% respectively.

Conclusions: Despite differences in cystatin C concentrations, overall correlation between the Gentian and Roche assays was good while agreement was moderate.  The combined creatinine-cystatin C equation did not outperform risk prediction compared to CKD-EPI.

Place, publisher, year, edition, pages
2013. Vol. 59, no 9, 1369-1375 p.
Keyword [en]
cystatin C, creatinine, glomerular filtration rate, myocardial infarction, acute coronary, syndrome, death, assay
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
URN: urn:nbn:se:uu:diva-197704DOI: 10.1373/clinchem.2012.200709ISI: 000325398600015OAI: oai:DiVA.org:uu-197704DiVA: diva2:614514
Available from: 2013-04-04 Created: 2013-04-02 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Biomarkers of Renal Function in Acute Coronary Syndromes
Open this publication in new window or tab >>Biomarkers of Renal Function in Acute Coronary Syndromes
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 891
Keyword
cystatin C, glomerular filtration rate, GFR, creatinine, acute coronary syndrome, ACS, kidney, renal, mortality, death, myocardial infarction
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology; Medicine; Internal Medicine
Identifiers
urn:nbn:se:uu:diva-197852 (URN)978-91-554-8643-3 (ISBN)
Public defence
2013-05-24, Enghoffsalen, Ing 50, Akademiska Sjukhuset, Uppsala, 09:00 (Swedish)
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Note

PhD, i medicin.

Available from: 2013-05-03 Created: 2013-04-05 Last updated: 2013-08-30Bibliographically approved

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Åkerblom, AxelWallentin, LarsSiegbahn, AgnetaJames, Stefan K.

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