Subclinical Hypothyroidism Is an Independent Risk Factor for Atherosclerosis and Myocardial Infarction in Elderly Women: The Rotterdam Study

  1. A. Elisabeth Hak, MD, MSc;
  2. Huibert A.P. Pols, MD, PhD;
  3. Theo J. Visser, MD, PhD;
  4. Hemmo A. Drexhage, MD, PhD;
  5. Albert Hofman, MD, PhD; and
  6. Jacqueline C.M. Witteman, PhD
  1. From Erasmus University Medical School, Rotterdam, the Netherlands.

    Abstract

    Background: Overt hypothyroidism has been found to be associated with cardiovascular disease. Whether subclinical hypothyroidism and thyroid autoimmunity are also risk factors for cardiovascular disease is controversial.

    Objective: To investigate whether subclinical hypothyroidism and thyroid autoimmunity are associated with aortic atherosclerosis and myocardial infarction in postmenopausal women.

    Design: Population-based cross-sectional study.

    Setting: A district of Rotterdam, the Netherlands.

    Participants: Random sample of 1149 women (mean age ± SD, 69.0 ± 7.5 years) participating in the Rotterdam Study.

    Measurements: Data on thyroid status, aortic atherosclerosis, and history of myocardial infarction were obtained at baseline. Subclinical hypothyroidism was defined as an elevated thyroid-stimulating hormone level (>4.0 mU/L) and a normal serum free thyroxine level (11 to 25 pmol/L [0.9 to 1.9 ng/dL]). In tests for antibodies to thyroid peroxidase, a serum level greater than 10 IU/mL was considered a positive result.

    Results: Subclinical hypothyroidism was present in 10.8% of participants and was associated with a greater age-adjusted prevalence of aortic atherosclerosis (odds ratio, 1.7 [95% CI, 1.1 to 2.6]) and myocardial infarction (odds ratio, 2.3 [CI, 1.3 to 4.0]). Additional adjustment for body mass index, total and high-density lipoprotein cholesterol level, blood pressure, and smoking status, as well as exclusion of women who took β-blockers, did not affect these estimates. Associations were slightly stronger in women who had subclinical hypothyroidism and antibodies to thyroid peroxidase (odds ratio for aortic atherosclerosis, 1.9 [CI, 1.1 to 3.6]; odds ratio for myocardial infarction, 3.1 [CI, 1.5 to 6.3]). No association was found between thyroid autoimmunity itself and cardiovascular disease. The population attributable risk percentage for subclinical hypothyroidism associated with myocardial infarction was within the range of that for known major risk factors for cardiovascular disease.

    Conclusion: Subclinical hypothyroidism is a strong indicator of risk for atherosclerosis and myocardial infarction in elderly women.

    Article and Author Information

    • Acknowledgments: The authors thank the participants of the Rotterdam Study for participation and the research physicians and assistants of the Rotterdam Study for data collection. They also thank Professor Roel Doctor for supervision of laboratory measurements and Mr. Hans van Toor for performing the laboratory measurements.

    • Grant Support: By a grant from the Health Research and Development Council, The Hague, the Netherlands (no. 28.2897) (Dr. Witteman).

    • Requests for Single Reprints: Jacqueline C.M. Witteman, PhD, Department of Epidemiology and Biostatistics, Erasmus University Medical School, PO Box 1738, 3000 DR Rotterdam, the Netherlands; e-mail, witteman{at}epib.fgg.eur.nl.

    • 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: Drs. Hak, Hofman, and Witteman: Department of Epidemiology and Biostatistics, Erasmus University Medical School, Box 1738, 3000 DR Rotterdam, the Netherlands.

    • Drs. Pols and Visser: Department of Internal Medicine III, Erasmus University Medical School, Box 1738, 3000 DR Rotterdam, the Netherlands.

    • Dr. Drexhage: Department of Immunology, Erasmus University Medical School, Box 1738, 3000 DR Rotterdam, the Netherlands.

    • Author Contributions: Conception and design: A.E. Hak, H.A.P. Pols, A. Hofman, J.C.M. Witteman.

    • Analysis and interpretation of the data: A.E. Hak, H.A.P. Pols, T.J. Visser, H.A. Drexhage, J.C.M. Witteman.

    • Drafting of the article: A.E. Hak.

    • Critical revision of the article for important intellectual content: H.A.P. Pols, T.J. Visser, H.A. Drexhage, A. Hofman, J.C.M. Witteman.

    • Final approval of the article: A.E. Hak, H.A.P. Pols, T.J. Visser, H.A. Drexhage, A. Hofman, J.C.M. Witteman.

    • Statistical expertise: A.E. Hak, J.C.M. Witteman.

    • Obtaining of funding: A. Hofman, J.C.M. Witteman.

    Summary for Patients

    • Summaries for Patients:Low Thyroid Function without Symptoms as a Risk Indicator for Heart Disease in Older Women Ann Intern Med February 15, 2000 132:270
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    1. Ann Intern Med February 15, 2000 vol. 132 no. 4 270-278
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