Meta-Analysis: Glycosylated Hemoglobin and Cardiovascular Disease in Diabetes Mellitus

  1. Elizabeth Selvin, MPH;
  2. Spyridon Marinopoulos, MD, MBA;
  3. Gail Berkenblit, MD, PhD;
  4. Tejal Rami, MPH;
  5. Frederick L. Brancati, MD, MHS;
  6. Neil R. Powe, MD, MPH, MBA; and
  7. Sherita Hill Golden, MD, MHS
  1. From Johns Hopkins University Bloomberg School of Public Health and Johns Hopkins University School of Medicine, Baltimore, Maryland.

    Abstract

    Background: In persons with diabetes, chronic hyperglycemia (assessed by glycosylated hemoglobin level) is related to the development of microvascular disease; however, the relation of glycosylated hemoglobin to macrovascular disease is less clear.

    Purpose: To conduct a meta-analysis of observational studies of the association between glycosylated hemoglobin and cardiovascular disease in diabetic persons.

    Data Sources: Search of the MEDLINE database by using Medical Subject Heading search terms and key words related to glycosylated hemoglobin, diabetes, and cardiovascular disease.

    Study Selection: Prospective cohort studies with data on glycosylated hemoglobin levels and incident cardiovascular disease.

    Data Extraction: Relative risk estimates were derived or abstracted from each cohort study that met the inclusion criteria.

    Data Synthesis: Adjusted relative risk estimates for glycosylated hemoglobin (total glycosylated hemoglobin, hemoglobin A1, or hemoglobin A1c levels) and cardiovascular disease events (coronary heart disease and stroke) were pooled by using random-effects models. Three studies involved persons with type 1 diabetes (n = 1688), and 10 studies involved persons with type 2 diabetes (n = 7435). The pooled relative risk for cardiovascular disease was 1.18; this represented a 1–percentage point increase in glycosylated hemoglobin level (95% CI, 1.10 to 1.26) in persons with type 2 diabetes. Results in persons with type 1 diabetes were similar but had a wider CI (pooled relative risk, 1.15 [CI, 0.92 to 1.43]).

    Limitations: This review largely reflects the limitations of the literature. Important concerns were residual confounding, the possibility of publication bias, the small number of studies, and the heterogeneity of study results.

    Conclusions: Pending confirmation from large, ongoing clinical trials, this analysis shows that observational studies are consistent with limited clinical trial data and suggests that chronic hyperglycemia is associated with an increased risk for cardiovascular disease in persons with diabetes.

    Article and Author Information

    • Grant Support: By the Agency for Healthcare Research and Quality (contract no. 290-97-0006). Ms. Selvin was supported by a grant from the National Heart, Lung, and Blood Institute (grant no. T32HL07024). Dr. Golden was supported by a grant from the Robert Wood Johnson Foundation Minority Medical Faculty Development Program. Dr. Brancati was supported by a Mid-Career Award for Patient-Oriented Research from the National Institutes of Health (contract no. K24-DK6222-O1). Dr. Powe was supported in part by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (grant no. K24DK02643).

    • Potential Financial Conflicts of Interest: None disclosed.

    • Requests for Single Reprints: Sherita Hill Golden, MD, MHS, Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, 2024 East Monument Street, Suite 2-616, Baltimore, MD 21205; e-mail, sgolden1{at}jhem.jhmi.edu.

    • Current Author Addresses: Ms. Selvin, Ms. Rami, and Drs. Brancati, Powe, and Golden: Johns Hopkins University, Welch Center for Prevention, Epidemiology and Clinical Research, 2024 East Monument Street, Suite 2-600, Baltimore, MD 21205.

    • Dr. Marinopoulos: Johns Hopkins University, 10753 Falls Road, Suite 325, Lutherville, MD 21093.

    • Dr. Berkenblit: Johns Hopkins Outpatient Center, 601 North Caroline Street, Suite 7143, Baltimore, MD 21287.

    • Author Contributions: Conception and design: E. Selvin, S. Marinopoulos, T. Rami, F.L. Brancati, N.R. Powe, S.H. Golden.

    • Analysis and interpretation of the data: E. Selvin, S. Marinopoulos, G. Berkenblit, T. Rami, F.L. Brancati, N.R. Powe, S.H. Golden.

    • Drafting of the article: E. Selvin, S.H. Golden.

    • Critical revision of the article for important intellectual content: E. Selvin, S. Marinopoulos, G. Berkenblit, F.L. Brancati, N.R. Powe, S.H. Golden.

    • Final approval of the article: E. Selvin, S. Marinopoulos, G. Berkenblit, T. Rami, F.L. Brancati, N.R. Powe, S.H. Golden.

    • Statistical expertise: E. Selvin.

    • Obtaining of funding: F.L. Brancati, N.R. Powe, S.H. Golden.

    • Administrative, technical, or logistic support: T. Rami, N.R. Powe.

    • Collection and assembly of data: E. Selvin, S. Marinopoulos, G. Berkenblit, T. Rami, S.H. Golden.

    Summary for Patients

    • Summaries for Patients:The Relationship between Blood Sugar Control and Cardiovascular Disease in Patients with Diabetes Ann Intern Med September 21, 2004 141:I-21
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    1. Ann Intern Med September 21, 2004 vol. 141 no. 6 421-431
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