The Association Between Cardiovascular Autonomic Neuropathy and Mortality in Individuals With Diabetes

A meta-analysis

  1. Raelene E. Maser, PHD1,
  2. Braxton D. Mitchell, PHD2,
  3. Aaron I. Vinik, MD, PHD3 and
  4. Roy Freeman, MD4
  1. 1Department of Medical Technology, University of Delaware, Newark, Delaware
  2. 2Department of Medicine, Division of Endocrinology, Diabetes & Nutrition, University of Maryland School of Medicine, Baltimore, Maryland
  3. 3Department of Medicine and Pathology/Anatomy/Neurobiology, the Strelitz Diabetes Institutes, Eastern Virginia Medical School, Norfolk, Virginia
  4. 4Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts


    OBJECTIVE—To examine by meta-analysis the relationship between cardiovascular autonomic neuropathy (CAN) and risk of mortality in individuals with diabetes.

    RESEARCH DESIGN AND METHODS—We searched Medline for English-language articles published from 1966 to 2001. Fifteen studies having a baseline assessment of cardiovascular autonomic function and mortality follow-up were identified. The analyses were stratified according to whether a single abnormality or two or more measures of cardiovascular autonomic function were used to define CAN. A global measure of association (i.e., relative risk) was generated for each group by pooling estimates across the studies using the Mantel-Haenszel procedure.

    RESULTS—CAN was significantly associated with subsequent mortality in both groups, although the magnitude of the association was stronger for those studies for which two or more measures were used to define CAN. The pooled relative risk for studies that defined CAN with the presence of two or more abnormalities was 3.45 (95% CI 2.66–4.47; P < 0.001) compared with 1.20 (1.02–1.41; P = 0.03) for studies that used one measure.

    CONCLUSIONS—These results support an association between CAN and increased risk of mortality. The stronger association observed in studies defining CAN by the presence of two or more abnormalities may be due to more severe autonomic dysfunction in these subjects or a higher frequency of other comorbid complications that contributed to their higher mortality risk. Future studies should evaluate whether early identification of subjects with CAN can lead to a reduction in mortality.


    • Address correspondence and reprint requests to Raelene E. Maser, PhD, Department of Medical Technology, 305F Willard Hall Education Building, University of Delaware, Newark, DE 19716. E-mail: rmaser{at}

      Received for publication 30 August 2002 and accepted in revised form 10 March 2003.

      R.E.M., B.D.M., A.I.V., and R.F. have received consulting fees from Boston Medical Technology.

      A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

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