Subclinical hypothyroidism ups CHD deaths in women

April 29, 2008

Trondheim, Norway - 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 Å svold (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 heart wire . 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 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 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."

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