Nontraditional Risk Factors for Coronary Heart Disease Incidence among Persons with Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study

  1. Isao Saito, MD, PhD;
  2. Aaron R. Folsom, MD;
  3. Frederick L. Brancati, MD;
  4. Bruce B. Duncan, MD, PhD;
  5. Lloyd E. Chambless, PhD; and
  6. Paul G. McGovern, PhD
  1. From Oita Medical University, Oita, Japan; School of Public Health, University of Minnesota, Minneapolis, Minnesota; Welch Center for Prevention, Epidemiology, and Clinical Research, The Johns Hopkins Medical Institutions, Baltimore, Maryland; School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Brazil; and University of North Carolina, Chapel Hill, North Carolina.

    Abstract

    Background: Major risk factors explain much of the excess risk for coronary heart disease produced by diabetes, but nontraditional factors may also relate to incident coronary heart disease.

    Objective: To examine the association of traditional and nontraditional risk factors with incidence of coronary heart disease in adults with diabetes.

    Design: Prospective cohort study.

    Setting: The Atherosclerosis Risk in Communities (ARIC) Study.

    Participants: 1676 middle-aged persons who had diabetes but no history of prevalent coronary heart disease.

    Measurements: Multiple risk factors were recorded at baseline. Follow-up was from 1987 through 1995.

    Results: 186 participants developed incident coronary heart disease events during follow-up. As expected, the incidence of coronary heart disease in participants with diabetes was associated positively with traditional risk factors (hypertension, smoking, total cholesterol level, and low high-density lipoprotein [HDL] cholesterol level). After adjustment for sex, age, ethnicity, and ARIC field center, incident coronary heart disease was also significantly associated with waist-to-hip ratio; levels of HDL3 cholesterol, apolipoproteins A-I and B, albumin, fibrinogen, and von Willebrand factor; factor VIII activity; and leukocyte count. However, after adjustment for traditional risk factors for coronary heart disease, only levels of albumin, fibrinogen, and von Willebrand factor; factor VIII activity; and leukocyte count remained independently associated with coronary heart disease (P < 0.03). The relative risks associated with the highest compared with lowest groupings of albumin, fibrinogen, factor VIII, and von Willebrand factor values and leukocyte count were 0.64 (95% CI, 0.44 to 0.92), 1.75 (CI, 1.12 to 2.73), 1.58 (CI, 1.02 to 2.42), 1.71 (CI, 1.11 to 2.63), and 1.90 (CI, 1.16 to 3.13), respectively. Adjustment for diabetes treatment status attenuated these associations somewhat.

    Conclusions: Levels of albumin, fibrinogen, and von Willebrand factor; factor VIII activity; and leukocyte count were predictors of coronary heart disease among persons with diabetes. These associations may reflect 1) the underlying inflammatory reaction or microvascular injury related to atherosclerosis and a tendency toward thrombosis or 2) common antecedents for both diabetes and coronary heart disease.

    Article and Author Information

    • Acknowledgments: The authors thank Ms. Lori Boland and Ms. Laura Kemmis for technical assistance and all ARIC staff and participants for their valuable contributions.

    • Grant Support: The ARIC study is supported by contracts N01-HC-55015, N01-HC-55016, N01-HC 55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022 from the National Heart, Lung and Blood Institute. Dr. Brancati was supported by an Established Investigator Grant from the American Heart Association, Dallas, Texas.

    • Requests for Single Reprints: Aaron R. Folsom, MD, Division of Epidemiology, School of Public Health, University of Minnesota, Suite 300, 1300 South Second Street, Minneapolis, MN 55454-1015; e-mail, folsom{at}epi.umn.edu.

    • Requests To Purchase Bulk Reprints (minimum, 100 copies): the Reprints Coordinator; phone, 215-351-2657; e-mail, reprints{at}mail.acponline.org.

    • Current Author Addresses: Dr. Saito: Department of Public Health and Hygiene, Oita Medical University, 1-1 Idaigaoka, Hasama-machi, Oita 879-5593, Japan.

    • Drs. Folsom and McGovern: Division of Epidemiology, School of Public Health, University of Minnesota, Suite 300, 1300 South Second Street, Minneapolis, MN 55454-1015.

    • Dr. Brancati: Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, 2024 East Monument Street, Suite 2-619, Baltimore, MD 21205.

    • Dr. Duncan: Department of Social Medicine, School of Medicine, Universidade Federal de Rio Grande, R. Ramiro Barcelos 2600/414, Porto Alegre, RS, Brazil.

    • Dr. Chambless: Department of Biostatistics, University of North Carolina, 137 East Franklin Street, Suite 203, Chapel Hill, NC 27514.

    • Author Contributions: Conception and design: I. Saito, A.R. Folsom, B.B. Duncan.

    • Critical revision of the article for important intellectual content: I. Saito, A.R. Folsom, F.L. Brancati, B.B. Duncan, L.E. Chambless, P.G. McGovern.

    • Final approval of the article: I. Saito, A.R. Folsom, F.L. Brancati, B.B. Duncan, L.E. Chambless, P.G. McGovern.

    • Provision of study materials or patients: I. Saito, A.R. Folsom, L.E. Chambless.

    • Statistical expertise: L.E. Chambless, P.G. McGovern.

    • Obtaining of funding: I. Saito, A.R. Folsom.

    • Collection and assembly of data: I. Saito, A.R. Folsom.

    Summary for Patients

    • Summaries for Patients:Nontraditional Risk Factors for Coronary Heart Disease among Persons with Diabetes Ann Intern Med July 18, 2000 133:81
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    1. Ann Intern Med July 18, 2000 vol. 133 no. 2 81-91
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