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: the BiomarCaRE project
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
AU - BiomarCaRE consortium
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 populationbased 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 populationbased 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.
U2 - 10.1186/s12916-020-01776-7
DO - 10.1186/s12916-020-01776-7
M3 - Article
C2 - 33161898
VL - 18
JO - BMC Medicine
JF - BMC Medicine
SN - 1741-7015
IS - 1
M1 - 300
ER -