{
  "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.\n\nMethods: 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).\n\nResults: 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).\n\nConclusion: 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.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT01730534",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA",
    "TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA",
    "The Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Jerusalem, Israel",
    "Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA",
    "Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai Health System, New York, NY, USA",
    "University of South Carolina Floyd School of Medicine, Columbia, SC, USA",
    "Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada",
    "Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, United Kingdom",
    "BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Andre M. Small"
    },
    {
      "affs": [
        1
      ],
      "name": "David D. Berg"
    },
    {
      "affs": [
        2
      ],
      "name": "Itamar Raz"
    },
    {
      "affs": [
        3
      ],
      "name": "Petr Jarolim"
    },
    {
      "affs": [
        1
      ],
      "name": "Erica L. Goodrich"
    },
    {
      "affs": [
        1
      ],
      "name": "Filipe A. Moura"
    },
    {
      "affs": [
        2
      ],
      "name": "Ofri Mosenzon"
    },
    {
      "affs": [
        2
      ],
      "name": "Avivit Cahn"
    },
    {
      "affs": [
        4
      ],
      "name": "Deepak L. Bhatt"
    },
    {
      "affs": [
        5
      ],
      "name": "Jamie P. Dwyer"
    },
    {
      "affs": [
        6
      ],
      "name": "Lawrence A. Leiter"
    },
    {
      "affs": [
        7
      ],
      "name": "John P.H. Wilding"
    },
    {
      "affs": [
        8
      ],
      "name": "Ingrid Gause-Nilsson"
    },
    {
      "affs": [
        1
      ],
      "name": "Marc S. Sabatine"
    },
    {
      "affs": [
        1
      ],
      "name": "David A. Morrow"
    },
    {
      "affs": [
        1
      ],
      "name": "Stephen D. Wiviott"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/26cmkv1xrqgh9.bib",
  "cited_by": 0,
  "doi": "10.1016/j.ahjo.2026.100929",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696131/",
  "id": "26cmkv1xrqgh9",
  "issns": [
    "2666-6022"
  ],
  "landing_url": "https://doi.org/10.1016/j.ahjo.2026.100929",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Paper"
    ],
    [
      "openalex",
      "2727|Chronic Kidney Disease and Diabetes"
    ]
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  "openalex": "W7220409326",
  "pdf_url": "https://europepmc.org/articles/PMC13696131?pdf=render",
  "pmcid": "PMC13696131",
  "pmid": "42935495",
  "published": "2026-10-05",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/26cmkv1xrqgh9.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:32Z",
      "native_id": "PMC13696131",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.ahjo.2026.100929"
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    {
      "first_seen": "2026-10-30T12:22:24Z",
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      "url": "https://europepmc.org/article/MED/42935495"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "journal-openalex:2705|Heart Failure Treatment and Management",
      "subfield": "cardiovascular"
    }
  ],
  "title": "Comparative risk assessment of cardiovascular and kidney outcomes in patients with type 2 diabetes using cystatin C and creatinine in DECLARE-TIMI 58",
  "title_text": "Comparative risk assessment of cardiovascular and kidney outcomes in patients with type 2 diabetes using cystatin C and creatinine in DECLARE-TIMI 58",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:33:31Z",
  "url": "https://research.draconitic.com/paper/26cmkv1xrqgh9",
  "venue": "American Heart Journal Plus: Cardiology Research and Practice",
  "versions": []
}