TY - JOUR
T1 - Contribution of cystatin C- and creatinine-based definitions of chronic kidney disease to cardiovascular risk assessment in 20 population-based and 3 disease cohorts
T2 - the BiomarCaRE project
AU - BiomarCaRE Consortium
AU - Rothenbacher, Dietrich
AU - Rehm, Martin
AU - Iacoviello, Licia
AU - Costanzo, Simona
AU - Tunstall-Pedoe, Hugh
AU - Belch, Jill J. F.
AU - Söderberg, Stefan
AU - Hultdin, Johan
AU - Salomaa, Veikko
AU - Jousilahti, Pekka
AU - Linneberg, Allan
AU - Sans, Susana
AU - Padró, Teresa
AU - Thorand, Barbara
AU - Meisinger, Christa
AU - Kee, Frank
AU - McKnight, Amy Jayne
AU - Palosaari, Tarja
AU - Kuulasmaa, Kari
AU - Waldeyer, Christoph
AU - Zeller, Tanja
AU - Blankenberg, Stefan
AU - Koenig, Wolfgang
N1 - Funding Information:
This work was supported by Seventh Framework Programme collaborative project [grant agreement no. HEALTH-F2-2011-278913]. The MORGAM project has been funded through several grants from the EU, the latest ones being from the Seventh Framework Programme (FP7/2007-2013) under grant agreement no. HEALTH-F2-2011-278913, BiomarCaRE, FP7/2007-2013 [HEALTH-F4-2007-201413, ENGAGE and HEALTH-F3-2010-242244, CHANCES], and the Medical Research Council London [G0601463, No 80983: Serum Biomarkers in the MORGAM Populations]. This has supported central coordination, workshops, and part of the activities of the MORGAM Data Centre, at THL in Helsinki, Finland, and the MORGAM Biomarker Laboratory at Johannes Gutenberg University in Mainz, Germany. MORGAM Participating Centres are funded by regional and national governments, research councils, charities, and other local sources. Dr. Zeller was supported by the German Center of Cardiovascular Research (DZHK e.V.) under the grant number 81Z1710101. Stefan Blankenberg reports grants from Abbott Diagnostics, during the conduct of the study. Open access funding provided by Projekt DEAL. Acknowledgements
Funding Information:
Outside the submitted work, S.B. reports personal fees from Lumira Diagnostics, ThermoFisher, Siemens, Abbott Diagnostics, and Roche Diagnostics and grants from ThermoFisher, Siemens, and Abbott Diagnostics. S.S. reports personal fees from Actelion Ltd.; V.S. reports personal fees from Novo Nordisk and Sanofi and grants from Bayer AG. W.K. reports personal fees from AstraZeneca, Novartis, Pfizer, The Medicines Company, DalCor, Kowa, Amgen, Corvidia, Berlin-Chemie, Sanofi, and Daichii-Sankyo, in addition to grants and non-financial support from Beckmann, Singulex, Abbott, and Roche Diagnostics. D.R., M.R., J.J.F.B., J.H., P.J., A.L., S.Sa., T.Pad., B.T., C.M., F.K., A.J.M., H.T.P., L.I., S.C., C.W., and T.Pal. declare no conflict of interest.
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/11/9
Y1 - 2020/11/9
N2 - Background: Chronic kidney disease has emerged as a strong cardiovascular risk factor, and in many current guidelines, it is already considered as a coronary heart disease (CHD) equivalent. Routinely, creatinine has been used as the main marker of renal function, but recently, cystatin C emerged as a more promising marker. The aim of this study was to assess the comparative cardiovascular and mortality risk of chronic kidney disease (CKD) using cystatin C-based and creatinine-based equations of the estimated glomerular filtration rate (eGFR) in participants of population-based and disease cohorts.Methods: The present study has been conducted within the BiomarCaRE project, with harmonized data from 20 population-based cohorts (n = 76,954) from 6 European countries and 3 cardiovascular disease (CVD) cohorts (n = 4982) from Germany. Cox proportional hazards models were used to assess hazard ratios (HRs) for the various CKD definitions with adverse outcomes and mortality after adjustment for the Systematic COronary Risk Evaluation (SCORE) variables and study center. Main outcome measures were cardiovascular diseases, cardiovascular death, and all-cause mortality.Results: The overall prevalence of CKD stage 3–5 by creatinine- and cystatin C-based eGFR, respectively, was 3.3% and 7.4% in the population-based cohorts and 13.9% and 14.4% in the disease cohorts. CKD was an important independent risk factor for subsequent CVD events and mortality. For example, in the population-based cohorts, the HR for CVD mortality was 1.72 (95% CI 1.53 to 1.92) with creatinine-based CKD and it was 2.14 (95% CI 1.90 to 2.40) based on cystatin-based CKD compared to participants without CKD. In general, the HRs were higher for cystatin C-based CKD compared to creatinine-based CKD, for all three outcomes and risk increased clearly below the conventional threshold for CKD, also in older adults. Net reclassification indices were larger for a cystatin-C based CKD definition. Differences in HRs (between the two CKD measures) in the disease cohorts were less pronounced than in the population-based cohorts.Conclusion: CKD is an important risk factor for subsequent CVD events and total mortality. However, point estimates of creatinine- and cystatin C-based CKD differed considerably between low- and high-risk populations. Especially in low-risk settings, the use of cystatin C-based CKD may result in more accurate risk estimates and have better prognostic value.
AB - Background: Chronic kidney disease has emerged as a strong cardiovascular risk factor, and in many current guidelines, it is already considered as a coronary heart disease (CHD) equivalent. Routinely, creatinine has been used as the main marker of renal function, but recently, cystatin C emerged as a more promising marker. The aim of this study was to assess the comparative cardiovascular and mortality risk of chronic kidney disease (CKD) using cystatin C-based and creatinine-based equations of the estimated glomerular filtration rate (eGFR) in participants of population-based and disease cohorts.Methods: The present study has been conducted within the BiomarCaRE project, with harmonized data from 20 population-based cohorts (n = 76,954) from 6 European countries and 3 cardiovascular disease (CVD) cohorts (n = 4982) from Germany. Cox proportional hazards models were used to assess hazard ratios (HRs) for the various CKD definitions with adverse outcomes and mortality after adjustment for the Systematic COronary Risk Evaluation (SCORE) variables and study center. Main outcome measures were cardiovascular diseases, cardiovascular death, and all-cause mortality.Results: The overall prevalence of CKD stage 3–5 by creatinine- and cystatin C-based eGFR, respectively, was 3.3% and 7.4% in the population-based cohorts and 13.9% and 14.4% in the disease cohorts. CKD was an important independent risk factor for subsequent CVD events and mortality. For example, in the population-based cohorts, the HR for CVD mortality was 1.72 (95% CI 1.53 to 1.92) with creatinine-based CKD and it was 2.14 (95% CI 1.90 to 2.40) based on cystatin-based CKD compared to participants without CKD. In general, the HRs were higher for cystatin C-based CKD compared to creatinine-based CKD, for all three outcomes and risk increased clearly below the conventional threshold for CKD, also in older adults. Net reclassification indices were larger for a cystatin-C based CKD definition. Differences in HRs (between the two CKD measures) in the disease cohorts were less pronounced than in the population-based cohorts.Conclusion: CKD is an important risk factor for subsequent CVD events and total mortality. However, point estimates of creatinine- and cystatin C-based CKD differed considerably between low- and high-risk populations. Especially in low-risk settings, the use of cystatin C-based CKD may result in more accurate risk estimates and have better prognostic value.
KW - Adverse outcome
KW - Chronic kidney disease
KW - Cohort study
KW - Creatinine
KW - Cystatin C
KW - Estimated glomerular filtration rate
UR - http://www.scopus.com/inward/record.url?scp=85095587513&partnerID=8YFLogxK
U2 - 10.1186/s12916-020-01776-7
DO - 10.1186/s12916-020-01776-7
M3 - Article
C2 - 33161898
AN - SCOPUS:85095587513
SN - 1741-7015
VL - 18
JO - BMC Medicine
JF - BMC Medicine
M1 - 300
ER -