American Journal of Kidney Diseases
Volume 53, Issue 3 , Pages 389-398, March 2009

Cystatin C and Carotid Intima-Media Thickness in Asymptomatic Adults: The Multi-Ethnic Study of Atherosclerosis (MESA)

  • Anh L. Bui, MD

      Affiliations

    • Department of Medicine, University of California, San Francisco, CA
    • ,
  • Ronit Katz, PhD

      Affiliations

    • Collaborative Health Studies Coordinating Center, Department of Biostatistics, University of Washington, Seattle, WA
    • ,
  • Bryan Kestenbaum, MD, MS

      Affiliations

    • Division of Nephrology, University of Washington, Seattle, WA
    • ,
  • Ian H. de Boer, MD, MS

      Affiliations

    • Division of Nephrology, University of Washington, Seattle, WA
    • ,
  • Linda F. Fried, MD, MPH

      Affiliations

    • Veterans Affairs Pittsburgh Healthcare System and Renal-Electrolyte Division, University of Pittsburgh, Pittsburgh, PA
    • ,
  • Joseph F. Polak, MD, MPH

      Affiliations

    • Department of Radiology, Tufts Medical Center, Boston, MA
    • ,
  • Bruce A. Wasserman, MD

      Affiliations

    • Department of Radiology, The Johns Hopkins Hospital, Baltimore, MD
    • ,
  • Mark J. Sarnak, MD, MS

      Affiliations

    • Department of Medicine, Tufts Medical Center, Boston, MA
    • ,
  • David Siscovick, MD, MPH

      Affiliations

    • Department of Medicine, University of Washington, Seattle, WA
    • ,
  • Michael G. Shlipak, MD, MPH

      Affiliations

    • Department of Medicine, University of California, San Francisco, CA
    • General Internal Medicine Section, San Francisco Veterans Affairs Medical Center, San Francisco, CA
    • Corresponding Author InformationAddress correspondence to Michael G. Shlipak, MD, MPH, General Internal Medicine Section (111A-1), Veterans Affairs Medical Center, 4150 Clement St, San Francisco, CA 94121

Received 17 March 2007; accepted 24 June 2008. published online 29 September 2008.

Background

Persons with early kidney disease have an increased risk of cardiovascular events and mortality, but the importance of accelerated atherosclerosis in promoting these outcomes is unclear. We therefore explored whether serum cystatin C level is associated with carotid intima-media thickness (IMT) in ambulatory adults without clinical heart disease.

Study Design

Cross-sectional study.

Setting & Participants

We evaluated 6,557 ethnically diverse persons free of clinical cardiovascular disease aged 45 to 84 years at the baseline visit of the Multi-Ethnic Study of Atherosclerosis.

Predictors

Kidney function was estimated by using 2 methods: serum cystatin C level and estimated glomerular filtration rate, based on creatinine and cystatin C levels.

Outcomes & Measurements

Study outcomes were internal and common carotid IMT, measured by using high-resolution B-mode ultrasound. Multivariate linear and logistic regressions were used to evaluate the independent association of kidney function with carotid IMT.

Results

In unadjusted linear analysis, each SD (0.23 mg/L) greater cystatin C level was associated with 0.091-mm greater internal carotid IMT (P < 0.001), but this association was diminished by 70% after adjustment for age, sex, and race/ethnicity (0.027 mm; P < 0.001) and was no longer significant after adjustment for cardiovascular risk factors (0.005 mm; P = 0.5). Similarly, the strong unadjusted associations of cystatin C level with common carotid IMT disappeared after adjustment. Chronic kidney disease, defined by using either creatinine level or cystatin C–based estimated glomerular filtration rate less than 60 mL/min/1.73 m2, had no independent association with internal and common carotid IMT.

Limitations

There were few participants with severe kidney disease.

Conclusions

Cystatin C level had no independent association with carotid IMT in a population free of clinical heart disease. This observation suggests that accelerated atherosclerosis is unlikely to be the primary mechanism explaining the independent association of cystatin C level with cardiovascular risk.

Index Words: Cystatin C, intima-media thickness (IMT), atherosclerosis, cardiovascular diseases, kidney

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 Originally published online as doi:10.1053/j.ajkd.2008.06.025 on September 29, 2008.

 Because the Editor-in-Chief recused himself from consideration of this manuscript, the peer-review and decision-making processes were handled entirely by a Co-Editor (Wolfgang C. Winkelmayer, MD, ScD, Harvard Medical School) who served as Acting Editor-in-Chief. Details of the journal's procedures for potential editor conflicts are given in the Editorial Policies section of the AJKD website.

PII: S0272-6386(08)01175-X

doi:10.1053/j.ajkd.2008.06.025

American Journal of Kidney Diseases
Volume 53, Issue 3 , Pages 389-398, March 2009

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