Cystatin C Concentration as a Risk Factor for Heart Failure in Older Adults

  1. Mark J. Sarnak, MD, MS;
  2. Ronit Katz, PhD;
  3. Catherine O. Stehman-Breen, MD, MS;
  4. Linda F. Fried, MD, MPH;
  5. Nancy Swords Jenny, PhD;
  6. Bruce M. Psaty, MD, PhD;
  7. Anne B. Newman, MD, MPH;
  8. David Siscovick, MD, MPH;
  9. Michael G. Shlipak, MD, MPH; and
  10. and the Cardiovascular Health Study*
  1. From Tufts-New England Medical Center, Boston, Massachusetts; Collaborative Health Studies Coordinating Center and University of Washington, Seattle, Washington; Amgen, Inc., Thousand Oaks, and Veterans Affairs Medical Center and University of California, San Francisco, California; University of Pittsburgh School of Medicine, Veterans Affairs Pittsburgh Healthcare System, and University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania; and University of Vermont, Burlington, Vermont.

    Abstract

    Background: Previous studies that evaluated the association of kidney function with incident heart failure may be limited by the insensitivity of serum creatinine concentration for detecting abnormal kidney function.

    Objective: To compare serum concentrations of cystatin C (a novel marker of kidney function) and creatinine as predictors of incident heart failure.

    Design: Observational study based on measurement of serum cystatin C from frozen sera obtained at the 1992–1993 visit of the Cardiovascular Health Study. Follow-up occurred every 6 months.

    Setting: Adults 65 years of age or older from 4 communities in the United States.

    Participants: 4384 persons without previous heart failure who had measurements of serum cystatin C and serum creatinine.

    Measurements: Incident heart failure.

    Results: The mean (±SD) serum concentrations of cystatin C and creatinine were 82 ± 25 nmol/L (1.10 ± 0.33 mg/L) and 89 ± 34 µmol/L (1.01 ± 0.39 mg/dL), respectively. During a median follow-up of 8.3 years (maximum, 9.1 years), 763 (17%) participants developed heart failure. After adjustment for demographic factors, traditional and novel cardiovascular risk factors, cardiovascular disease status, and medication use, sequential quintiles of cystatin C concentration were associated with a stepwise increased risk for heart failure in Cox proportional hazards models (hazard ratios, 1.0 [reference], 1.30 [95% CI, 0.96 to 1.75], 1.44 [CI, 1.07 to 1.94], 1.58 [CI, 1.18 to 2.12], and 2.16 [CI, 1.61 to 2.91]). In contrast, quintiles of serum creatinine concentration were not associated with risk for heart failure in adjusted analysis (hazard ratios, 1.0 [reference], 0.77 [CI, 0.59 to 1.01], 0.85 [CI, 0.64 to 1.13], 0.97 [CI, 0.72 to 1.29], and 1.14 [CI, 0.87 to 1.49]).

    Limitations: The mechanism by which cystatin C concentration predicts risk for heart failure remains unclear.

    Conclusions: The cystatin C concentration is an independent risk factor for heart failure in older adults and appears to provide a better measure of risk assessment than the serum creatinine concentration.

    *For a full list of participating Cardiovascular Health Study investigators and institutions, see http://www.chs-nhlbi.org.

    Article and Author Information

    • Grant Support: Drs. Shlipak, Fried, and Katz are funded by grant R01 HL073208-01 (to Dr. Shlipak) from the National Heart, Lung, and Blood Institute. Dr. Shlipak is also supported by the American Federation for Aging Research and National Institute on Aging (Paul Beeson Scholars Program) and the Robert Wood Johnson Foundation (Generalist Faculty Scholars Program). Dr. Sarnak is supported by grant K23 DK67303 from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Fried is funded by an Advanced Research Career Development award from the Office of Research and Development, Medical Service, of the Department of Veterans Affairs. The Cardiovascular Health Study is supported by contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129, and N01 HC-15103 from the National Heart, Lung, and Blood Institute.

    • Potential Financial Conflicts of Interest: None disclosed.

    • Requests for Single Reprints: Michael G. Shlipak, MD, MPH, Veterans Affairs Medical Center (111A1), 4150 Clement Street, San Francisco, CA 94121; e-mail, shlip{at}itsa.ucsf.edu.

    • Current Author Addresses: Dr. Sarnak: Division of Nephrology, Tufts-New England Medical Center, 750 Washington Street, NEMC 391, Boston, MA 02111.

    • Dr. Katz: Collaborative Health Studies Coordinating Center, University of Washington, Box 354922, Building 29, Suite 310, 6200 NE 74th Street, Seattle, WA 98115.

    • Dr. Stehman-Breen: Amgen, Inc., 1 Amgen Center Drive, Mailstop 38-3-C, Thousand Oaks, CA 91320.

    • Dr. Fried: Veterans Affairs Pittsburgh Healthcare System, University Drive, 111F-U, Pittsburgh, PA 15240.

    • Dr. Swords Jenny: Department of Pathology, College of Medicine, University of Vermont, Colchester Research Facility, 208 South Park Drive, Suite 2, Colchester, VT 05446.

    • Drs. Psaty and Siscovick: Medicine and Epidemiology, University of Washington, Cardiovascular Health Research Unit, 1730 Minor Avenue, Suite 1360, Seattle, WA 98101-1448.

    • Dr. Newman: Healthy Aging Research Program, Bellefield Professional Building, 130 North Bellefield Avenue, Room 532, Pittsburgh, PA 15213.

    • Dr. Shlipak: Veterans Affairs Medical Center (111A1), 4150 Clement Street, San Francisco, CA 94121.

    • Author Contributions: Conception and design: M.J. Sarnak, R. Katz, C.O. Stehman-Breen, L.F. Fried, B.M. Psaty, D. Siscovick, M.G. Shlipak.

    • Analysis and interpretation of the data: M.J. Sarnak, R. Katz, C.O. Stehman-Breen, D. Siscovick, M.G. Shlipak.

    • Drafting of the article: M.J. Sarnak, R. Katz, C.O. Stehman-Breen, D. Siscovick, M.G. Shlipak.

    • Critical revision of the article for important intellectual content: M.J. Sarnak, R. Katz, C.O. Stehman-Breen, L.F. Fried, N.S. Jenny, B.M. Psaty, A.B. Newman, D. Siscovick, M.G. Shlipak.

    • Final approval of the article: M.J. Sarnak, R. Katz, C.O. Stehman-Breen, L.F. Fried, B.M. Psaty, A.B. Newman, D. Siscovick, M.G. Shlipak.

    • Provision of study materials or patients: B.M. Patsy, A.B. Newman, D. Siscovick.

    • Statistical expertise: R. Katz, B.M. Psaty.

    • Obtaining of funding: M.G. Shlipak, B.M. Psaty.

    • Administrative, technical, or logistic support: C.O. Stehman-Breen, N.S. Jenny, A.B. Newman.

    • Collection and assembly of data: R. Katz, B.M. Psaty, A.B. Newman.

    Responses to this article

    • The Cystatin C Paradox
      • Regina Bökenkamp and
      • Arend Bökenkamp, MD, PhD, Dpt. of Pediatric Nephrology, VUMC, Postbox 7057, 1007 MB Amsterdam, The Netherlands
      Ann Intern Med published online October 26, 2009
    • Cystatin C not a marker for kidney function
      • Arie Berghout and
      • Remi Wulkan, Jan den Hollander
      Ann Intern Med published online October 26, 2009

    Summary for Patients

    • Summaries for Patients:Can a New Blood Test Help Predict Who Is at Risk for Developing Heart Failure? Ann Intern Med April 5, 2005 142:I-53
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