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Subclinical Hypothyroidism Ups CHD Deaths in Women

  • Authors: News Author: Lisa Nainggolan
    CME Author: Désirée Lie, MD, MSEd
  • CME Released: 5/1/2008
  • Valid for credit through: 5/1/2009
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Target Audience and Goal Statement

This article is intended for primary care clinicians, endocrinologists, cardiologists, and other specialists who care for patients at risk for coronary heart disease.

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.

Upon completion of this activity, participants will be able to:

  1. Describe the association between thyrotropin levels and the risk for coronary heart disease.
  2. Describe the risk for coronary heart disease associated with healthy levels of thyrotropin in women.


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  • Lisa Nainggolan

    Lisa Nainggolan is a journalist for, part of the WebMD Professional Network. She has been with since 2000. Previously, she was science editor of Scrip World Pharmaceutical News, covering news about research and development in the pharmaceutical industry, and a consultant editor of Scrip Magazine. Graduating in physiology from Sheffield University, UK, she began her career as a poisons information specialist at Guy's Hospital before becoming a medical journalist in 1995. She can be reached at [email protected]


    Disclosure: Lisa Nainggolan has disclosed no relevant financial relationships.


  • Brande Nicole Martin

    Brande Nicole Martin is the News CME editor for Medscape Medical News.


    Disclosure: Brande Nicole Martin has disclosed no relevant financial information.

CME Author(s)

  • Désirée Lie, MD, MSEd

    Clinical Professor, Family Medicine, University of California, Orange; Director, Division of Faculty Development, UCI Medical Center, Orange, California


    Disclosure: Désirée Lie, MD, MSEd, has disclosed no relevant financial relationships.

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Subclinical Hypothyroidism Ups CHD Deaths in Women

Authors: News Author: Lisa Nainggolan CME Author: Désirée Lie, MD, MSEdFaculty and Disclosures

CME Released: 5/1/2008

Valid for credit through: 5/1/2009


From Heartwire — a professional news service of WebMD

May 1, 2008 — A new study has shown that women with subclinical hypothyroidism have a higher risk of coronary heart disease (CHD) death than women with normal thyroid function [1]. The same association was not seen in men, however, say Dr Bjorn O Åsvold (Norwegian University of Science and Technology, Trondheim) and colleagues in their paper in the April 28, 2008 issue of the Archives of Internal Medicine.

"We don't know if our lack of findings among men is purely due to chance, or if there really is a biological difference. We can't say from this study," Åsvold told heartwire . This was because there were only around 400 coronary deaths in the population-based cohort study, despite there being more than 25,000 people in the trial, he noted, "and in such an analysis it's the number of cases that is crucial to the statistical power."

Åsvold also said: "I don't think this study is an argument for treating very mild hypothyroidism [with thyroxine] to prevent CHD. We cannot say that." Further research will be needed, he says, and his team is planning another study on subclinical hypothyroidism, with incidence of myocardial infarction (MI) as the primary outcome rather than CHD deaths, he noted.

Deaths increased by 40% to 60% in women with higher thyrotropin

Åsvold explained that it has long been recognized that people who have overt hypothyroidism have an increased risk of CHD. What is less clear, he says, is whether there is a relationship between subclinical hypothyroidism — characterized by elevated thyrotropin levels but a lack of symptoms — and CHD. Although some cross-sectional and prospective studies have addressed this issue, the results have been inconsistent, he notes.

In their study, Åsvold and colleagues prospectively studied the association between thyrotropin levels and fatal CHD in participants of the Norwegian Nord-Trøndelag Health Study (HUNT) study, 17,311 women and 8002 men without known thyroid, cardiovascular disease, or diabetes mellitus at baseline (1995 - 1997). The Norwegian population is generally considered to have sufficient iodine intake, they note.

During median follow-up of 8.3 years, 228 women and 182 men died of CHD. Of these, 192 women and 164 men had thyrotropin levels within the normal clinical reference range of 0.50 to 3.5 mIU/L.

Women with intermediate or high levels of thyrotropin (1.14 - 2.52 mIU/L and 2.5 - 3.5 mIU/L, respectively) had hazard ratios for CHD death of 1.41 and 1.69 compared with women who had levels of thyrotropin in the lower range of normal (0.50 - 1.4 mIU/L). This trend was statistically significant in women (p = 0.005) but not in men.

The researchers say it is not known how thyrotropin may exert an effect on CHD mortality. They saw a modest attenuation of the effect when they adjusted for blood pressure and serum lipids, suggesting that the effect of thyrotropin levels might, at least partly, be mediated via these factors.

More studies needed

"These results indicate that relatively low but clinically normal thyroid function may increase the risk of fatal CHD," the researchers say. They add that, to their knowledge, no clinical trial has tested whether thyroxine replacement could protect against CHD.

Åsvold concluded: "We know thyroid function is important for CHD, and even differences within the relatively normal range can make a difference. This is surely an argument to do more studies to address whether thyroxine treatment will be beneficial, but our study is no proof of that."

This study was supported by the Norwegian University of Science and Technology and by the Central Norway Regional Health Authority. Two of the study authors have obtained funding. The other study authors have disclosed no relevant financial relationships.


  • Åsvold BO, Bjoro T, Nilsen TIL, et al. Thyrotropin levels and risk of fatal coronary heart disease. The HUNT study. Arch Intern Med. 2008;168:855-860.

The complete contents of Heartwire , a professional news service of WebMD, can be found at, a Web site for cardiovascular healthcare professionals.

Clinical Context

Levels of thyrotropin within the normal range are positively and linearly associated with blood pressure, body mass index, and serum lipid levels with adverse effects on cardiovascular health, and relatively low thyroid function is associated with more severe CHD in patients with healthy thyroid function. Although studies indicate that patients with hypothyroidism or hyperthyroidism are at increased risk for CHD, there are limited data on the association between normal range of thyrotropin values and the risk for CHD.

This is a longitudinal, population-based study to examine the association between thyrotropin levels within the clinical reference range and CHD mortality in a Norwegian cohort with adequate iodine intake.

Study Highlights

  • Included were men and women from the HUNT cohort recruited between 1995 and 1997 who completed a self-administered questionnaire on health, lifestyle, and medical conditions including cardiovascular disease.
  • The cohort was from 1 county in Norway and was stable and homogeneous.
  • Excluded were those with diabetes, thyroid disease, or cardiovascular disease at baseline.
  • Clinical measurements included weight, height, blood pressure, and laboratory measures of lipid panel and renal and thyroid functions.
  • 17,311 men and 8002 women age 40 years and older without baseline cardiovascular disease, diabetes, or stroke were included for follow-up.
  • Thyrotropin levels were analyzed at 1 laboratory with use of noncompetitive immunofluorometric assay.
  • Lipid and creatinine levels were analyzed at a central laboratory.
  • The 11-digit national identification number was used to determine vital status and cause of death with use of the death registry and codes from the International Classification of Diseases, Ninth and 10th Revisions.
  • Thyrotropin level was categorized by 5 levels: 3 levels for the reference range, 1 for below the reference range, and 1 for above the reference range.
  • The reference range of thyrotropin level was defined as 0.50 to 3.5 mIU/L.
  • The lowest part of the reference range (0.5 - 1.4 mIU/L) was used as a comparator in hazard ratio (HR) calculations.
  • The intermediate range was 1.5 to 2.4 mIU/L, and the high-normal range was 2.5 to 3.5 mIU/L.
  • During a median follow-up of 8.3 years, 228 (1.3%) women and 182 (2.3%) men died of CHD.
  • Of these patients, 192 women and 164 men had thyrotropin levels within the reference range.
  • Thyrotropin levels in the normal range were associated with an increased risk for CHD death, with a significant trend for nonsmokers (P = .007).
  • There was a positive association of thyrotropin level within the reference range, with the risk for fatal CHD in women (P for trend = .005) vs women in the lowest part of the reference range.
  • The HRs were 1.41 and 1.69, respectively, for the women in the intermediate and high parts of the reference range.
  • The association was unchanged when applied only to nonsmokers.
  • In men, there was no clear association of thyrotropin levels in the reference range and CHD mortality rate.
  • For 1426 women and 4222 men with thyrotropin levels above the reference range, the HRs for fatal CHD were 1.38 and 1.15, respectively, vs those with levels in the lowest part of the reference range.
  • In nonsmokers, the respective HRs were 1.69 and 1.57.
  • Analysis of data after 2 years of follow-up did not change the associations.
  • Accounting for serum lipids and blood pressure showed a one-fifth influence of these factors on the association.
  • The authors concluded that high-normal thyrotropin levels in women, but not in men, were positively and linearly associated with the increased risk for fatal CHD.

Pearls for Practice

  • Elevated thyrotropin levels within the reference range are associated with an increased risk for CHD death in women.
  • The HR for CHD death associated with intermediate and high-normal thyrotropin levels in women is higher for higher levels of thyrotropin.

CME Test

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