Coronary risk doesn't appear elevated with thyrotropin levels on the upper end of normal, a patient-level meta-analysis of 14 cohorts showed.
In it, people on the highest end of the normal range, at 3.50 to 4.49 mIU/L, had a similar risk of a first coronary heart disease event (hazard ratio 0.97, 95% confidence interval 0.83-1.13) and of death from coronary disease (HR 0.94, 95% CI 0.74-1.20) as people on the lowest end of normal, with 0.45 to 1.49 mIU/L thyrotropin levels. Each 1-mIU/L higher thyrotropin level had no significant association with either endpoint, Bjorn O. Asvold, MD, PhD, of the Norwegian University of Science and Technology in Trondheim, Norway, and colleagues found. Subgroup analyses yielded similar results across sexes and age groups, they reported online in JAMA Internal Medicine.
"Some experts suggest that serum thyrotropin levels in the upper part of the current reference range should be considered abnormal, an approach that would reclassify many individuals as having mild hypothyroidism," they noted. The rationale for such a shift was some evidence of increased coronary heart disease, albeit from conflicting studies and with poorly documented health hazards, Asvold's group pointed out.
With the larger and better-powered meta-analysis findings suggesting no influence on that risk, "increased coronary heart disease risk does not appear to be a reason for lowering the upper thyrotropin reference limit," they argued. Their analysis included individual participant data on 55,412 individuals from 14 cohorts with thyrotropin levels in the upper part of the reference range (0.45 to 4.49 mIU/L) and no known pre-existing thyroid or cardiovascular disease at baseline. There was a possible U-shaped relationship of FT4, another thyroid marker considered less sensitive, with coronary heart disease in the analysis, but the researchers argued this was likely not causal.
"First, FT4 measurements may be affected by low albumin levels, which have been associated with increased coronary heart disease risk and use of specific cardiovascular medications, such as aspirin, heparin, and furosemide," they wrote.
"Second, the lack of robust statistical evidence, as expressed by P values for the squared value of FT4 levels, suggests that the U-shaped association of FT4 levels with coronary heart disease risk may be a chance finding," they concluded, calling for further study of that possible link.
Limitations of the analysis included availability of only one thyroid function test at baseline and no thyroid peroxidase antibody data.
by Crystal Phend
Senior Staff Writer, MedPage Today
The Thyroid Studies Collaboration was supported by grants from the Swiss National Science Foundation and partially supported by a grant from the Swiss Heart Foundation.
Asvold reported support by the Research Council of Norway but no relevant relationships with industry.