Higher Reference-Range Thyrotropin Levels Not Associated With CHD Risk

Thyrotropin levels within the reference range do not appear to be linked to risk for CHD events and CHD mortality.

Thyrotropin levels at the upper end of the current reference range do not appear to be linked to risk for coronary heart disease (CHD) events or CHD mortality, according to data published in JAMA Internal Medicine.

Some experts have argued in favor of lowering the upper limit of the thyrotropin reference range from 4.5 mIU/L to 2.5 mIU/L or 3.0 mIU/L, but others disagree, citing a lack of good data linking higher thyrotropin levels within the reference range to adverse health consequences, according to background information in the article.

“Most research on such potential consequences has focused on CHD and its risk factors, and a recent review concluded that there was good evidence for associations between higher thyrotropin levels within the reference range and cardiovascular risk factors and events,” the researchers wrote. “However, most of this evidence comes from cross-sectional studies, which are inferior to prospective studies for causal inference.”

To investigate this association more closely, the researchers conducted a meta-analysis of individual participant data from 14 studies included in the Thyroid Studies Collaboration consortium.

Participants had baseline examinations between 1972 and 2002 and median follow-up of 3.3 to 20.0 years. A total of 55,412 participants with thyrotropin levels ranging from 0.45 mIU/L to 4.49 mIU/L and no previous thyroid dysfunction or cardiovascular disease (CVD) at baseline were included in the study.

Of all participants, 1,813 (3.3%) died from CHD during 643,183 person-years of follow-up, according to the data. In 10 cohorts, 4,666 of 48,875 participants (9.5%) experienced a first-time event during 533,408 person-years of follow-up.

Results indicated that, with each 1-mIU/L increase in thyrotropin level, HRs were 0.97 (95% CI, 0.90-1.04) for CHD mortality and 1.00 (95% CI, 0.97-1.03) for a first-time CHD event.

Additionally, when analyzed by thyrotropin categories, the HRs for CHD mortality (HR=0.94; 95% CI, 0.74-1.20) and CHD events (HR=0.97; 95% CI, 0.83-1.13) were comparable for participants with the highest levels, defined as 3.50 mIU/L to 4.49 mIU/L, vs. the lowest levels, defined as 0.45 mIU/L to 1.49 mIU/L.

Data were similar for subgroup analyses according to age and sex, the researchers noted.

“In this individual participant data analysis of 55,412 individuals from 14 cohorts, thyrotropin levels in the upper part of the reference range were not associated with an increased risk of CHD events or CHD mortality,” the researchers wrote.

“This finding suggests that differences in thyroid function within the population reference range do not influence the risk of CHD. Increased risk of CHD does not appear to be a reason for lowering the upper thyrotropin reference limit,” they concluded.


  1. Åsvold BO et al. JAMA Intern Med. 2015;doi:10.1001/jamainternmed.2015.0930.