Comparative risk assessment of cardiovascular and kidney outcomes in patients with type 2 diabetes using cystatin C and creatinine in DECLARE-TIMI 58
9 affiliations
- 1Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- 2TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- 3The Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Jerusalem, Israel
- 4Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- 5Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai Health System, New York, NY, USA
- 6University of South Carolina Floyd School of Medicine, Columbia, SC, USA
- 7Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
- 8Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, United Kingdom
- 9BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
Abstract
Background: The relationship between cystatin C and cardiovascular and kidney outcomes is not well explored in individuals with type 2 diabetes (T2D) and normal or mild kidney dysfunction.
Methods: This nested prospective biomarker study included patients enrolled in DECLARE-TIMI 58. Participants were categorized into quartiles of CysC/creatinine and eGFRCysC/eGFRCr and classified according to Kidney Disease Improving Global Outcomes (KDIGO) risk categories. Hazard ratios were estimated for a composite of cardiovascular death and hospitalization for heart failure (CVD/HHF), major adverse cardiovascular events (MACE), and a kidney-specific composite outcome (persistent ≥40% decrease in eGFR, end-stage renal disease, or renal death).
Results: Among 1899 placebo-treated patients, higher baseline CysC was associated with higher risk for CVD/HHF, MACE, and the kidney-specific composite outcome. A gradient of risk across quartiles was observed for CVD/HHF [Q4 v Q1: 1.33 (0.98–1.80), p-trend = 0.016]; MACE [1.34 (1.06–1.69), p-trend = 0.013]; and kidney-specific composite outcome [1.95 (0.95–3.99), p-trend = 0.036]. When compared with creatinine, CysC showed more pronounced and statistically significant risk gradients (CVD/HHF: KDIGO-CysC p-trend < 0.001 vs. p-trend Cr 0.34; MACE: CysC p-trend < 0.001 vs. Cr p-trend 0.52). No heterogeneity was observed in the effect of dapagliflozin across CysC concentrations (p-interactions >0.05).
Conclusion: In patients with T2D and predominantly preserved Cr-based eGFR, CysC was associated with increased cardiovascular and kidney risk. Although discrimination assessed by c-statistic was similar for CysC and Cr, risk gradients seen with CysC became attenuated and no longer statistically significant when using Cr-based analogs. The effect of dapagliflozin was consistent irrespective of baseline CysC.
Trial registration: ClinicalTrials.gov Identifier: NCT01730534
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BibTeX
@article{small2026comparative,
title = {{Comparative risk assessment of cardiovascular and kidney outcomes in patients with type 2 diabetes using cystatin C and creatinine in DECLARE-TIMI 58}},
author = {Andre M. Small and David D. Berg and Itamar Raz and Petr Jarolim and Erica L. Goodrich and Filipe A. Moura and Ofri Mosenzon and Avivit Cahn and Deepak L. Bhatt and Jamie P. Dwyer and Lawrence A. Leiter and John P.H. Wilding and Ingrid Gause-Nilsson and Marc S. Sabatine and David A. Morrow and Stephen D. Wiviott},
journal = {American Heart Journal Plus: Cardiology Research and Practice},
year = {2026},
month = oct,
doi = {10.1016/j.ahjo.2026.100929},
url = {https://doi.org/10.1016/j.ahjo.2026.100929},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Comparative risk assessment of cardiovascular and kidney outcomes in patients with type 2 diabetes using cystatin C and creatinine in DECLARE-TIMI 58
AU - Andre M. Small
AU - David D. Berg
AU - Itamar Raz
AU - Petr Jarolim
AU - Erica L. Goodrich
AU - Filipe A. Moura
AU - Ofri Mosenzon
AU - Avivit Cahn
AU - Deepak L. Bhatt
AU - Jamie P. Dwyer
AU - Lawrence A. Leiter
AU - John P.H. Wilding
AU - Ingrid Gause-Nilsson
AU - Marc S. Sabatine
AU - David A. Morrow
AU - Stephen D. Wiviott
PY - 2026
DA - 2026/10/05
JO - American Heart Journal Plus: Cardiology Research and Practice
DO - 10.1016/j.ahjo.2026.100929
UR - https://doi.org/10.1016/j.ahjo.2026.100929
AB - Background: The relationship between cystatin C and cardiovascular and kidney outcomes is not well explored in individuals with type 2 diabetes (T2D) and normal or mild kidney dysfunction. Methods: This nested prospective biomarker study included patients enrolled in DECLARE-TIMI 58. Participants were categorized into quartiles of CysC/creatinine and eGFRCysC/eGFRCr and classified according to Kidney Disease Improving Global Outcomes (KDIGO) risk categories. Hazard ratios were estimated for a composite of cardiovascular death and hospitalization for heart failure (CVD/HHF), major adverse cardiovascular events (MACE), and a kidney-specific composite outcome (persistent ≥40% decrease in eGFR, end-stage renal disease, or renal death). Results: Among 1899 placebo-treated patients, higher baseline CysC was associated with higher risk for CVD/HHF, MACE, and the kidney-specific composite outcome. A gradient of risk across quartiles was observed for CVD/HHF [Q4 v Q1: 1.33 (0.98–1.80), p-trend = 0.016]; MACE [1.34 (1.06–1.69), p-trend = 0.013]; and kidney-specific composite outcome [1.95 (0.95–3.99), p-trend = 0.036]. When compared with creatinine, CysC showed more pronounced and statistically significant risk gradients (CVD/HHF: KDIGO-CysC p-trend < 0.001 vs. p-trend Cr 0.34; MACE: CysC p-trend < 0.001 vs. Cr p-trend 0.52). No heterogeneity was observed in the effect of dapagliflozin across CysC concentrations (p-interactions >0.05). Conclusion: In patients with T2D and predominantly preserved Cr-based eGFR, CysC was associated with increased cardiovascular and kidney risk. Although discrimination assessed by c-statistic was similar for CysC and Cr, risk gradients seen with CysC became attenuated and no longer statistically significant when using Cr-based analogs. The effect of dapagliflozin was consistent irrespective of baseline CysC. Trial registration: ClinicalTrials.gov Identifier: NCT01730534
SN - 2666-6022
ER -