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Progression of retinopathy and incidence of cardiovascular disease: findings from the Chronic Renal Insufficiency Cohort Study
  1. Juan E Grunwald1,
  2. Maxwell Pistilli1,
  3. Gui-Shuang Ying1,
  4. Maureen G Maguire1,
  5. Ebenezer Daniel1,
  6. Revell Whittock-Martin1,
  7. Candace Parker-Ostroff1,
  8. Douglas Jacoby1,
  9. Alan S Go2,
  10. Raymond R Townsend1,
  11. Crystal Ann Gadegbeku3,
  12. James P Lash4,
  13. Jeffrey Craig Fink5,
  14. Mahboob Rahman6,
  15. Harold Feldman1,
  16. John W Kusek1,
  17. Dawei Xie1
  18. The CRIC Study investigators
    1. 1Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    2. 2Department of Research, Kaiser Permanente, Oakland, California, USA
    3. 3Medicine, Temple University Hospital, Philadelphia, Pennsylvania, USA
    4. 4Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
    5. 5Department of Medicine, University of Maryland Baltimore County, Baltimore, Maryland, USA
    6. 6Medicine, Case Western Reserve University, Cleveland, Ohio, USA
    1. Correspondence to Dr Juan E Grunwald, Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, USA PA 19104; juan.grunwald{at}uphs.upenn.edu

    Abstract

    Purpose Chronic kidney disease (CKD) patients often develop cardiovascular disease (CVD) and retinopathy. The purpose of this study was to assess the association between progression of retinopathy and concurrent incidence of CVD events in participants with CKD.

    Design We assessed 1051 out of 1936 participants in the Chronic Renal Insufficiency Cohort Study that were invited to have fundus photographs obtained at two timepoints separated by 3.5 years, on average.

    Methods Using standard protocols, presence and severity of retinopathy (diabetic, hypertensive or other) and vessel diameter calibre were assessed at a retinal image reading centre by trained graders masked to study participants’ information. Participants with a self-reported history of CVD were excluded. Incident CVD events were physician adjudicated using medical records and standardised criteria. Kidney function and proteinuria measurements along with CVD risk factors were obtained at study visits.

    Results Worsening of retinopathy by two or more steps in the EDTRS retinopathy grading scale was observed in 9.8% of participants, and was associated with increased risk of incidence of any CVD in analysis adjusting for other CVD and CKD risk factors (OR 2.56, 95% CI 1.25 to 5.22, p<0.01). After imputation of missing data, these values were OR=1.66 (0.87 to 3.16), p=0.12.

    Conclusion Progression of retinopathy is associated with higher incidence of CVD events, and retinal-vascular pathology may be indicative of macrovascular disease even after adjustment for kidney diseases and CVD risk factors. Assessment of retinal morphology may provide important information when assessing CVD in patients with CKD.

    • retina
    • epidemiology
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    Footnotes

    • Collaborators The CRIC Study investigators: Jiang He, MD PhD and Akinlolu Ojo, MD, PhD.

    • Contributors All authors have provided substantial contributions to the conception or design of the work. All authors have provided input into the drafting of the manuscript. All authors have approved the final version of the manuscript. All authors have agreed to be accountable for the accuracy and integrity of the manuscript.

    • Funding This study was supported by NIH grant RO1 DK 74151. CRIC was funded by NIDDK cooperative agreements (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and U01DK060902), University of Pennsylvania Clinical and Translational Science Award NIH/NCATS UL1TR000003, Johns Hopkins University UL1 TR-000424, University of Maryland GCRC M01 RR-16500, Clinical and Translational Science Collaborative of Cleveland, UL1TR000439, Michigan Institute for Clinical and Health Research (MICHR) UL1TR000433, University of Illinois at Chicago CTSA UL1RR029879, Tulane COBRE for Clinical and Translational Research in Cardiometabolic Diseases P20 GM109036, Kaiser Permanente NIH/NCRR UCSF-CTSI UL1 RR-024131, Vivian S. Lasko Research Fund, Nina C. Mackall Trust, and Research to Prevent Blindness.

    • Disclaimer None of the funding sources had any role in study design, writing of the report and decision to submit this article for publication.

    • Competing interests RRT is a consultant for Medtronic, ROX Medical, and receives royalties from UpToDate. ASG has received research funding from Novartis, GlaxoSmithKline and Sanofi. All other coauthors have no financial conflict of interest regarding the contents of this manuscript.

    • Patient consent for publication Not required.

    • Ethics approval This protocol adhered to Helsinki declaration principles and HIPPA, and was approved by an Institutional Review Board.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data are available in a public, open access repository. Most of the data of this article will be available in the repository of the CRIC study https://repository.niddk.nih.gov/home/.

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