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June 10, 2022
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Exogenous hyper-, hypothyroidism increase risk for CV mortality

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Both exogenous hyperthyroidism and exogenous hypothyroidism were linked to an elevated risk for cardiovascular mortality, according to results published in JAMA Network Open.

Maria Papaleontiou

“These findings emphasize the importance of maintaining euthyroidism to decrease cardiovascular risk and death among patients receiving thyroid hormone treatment,” Maria Papaleontiou, MD, assistant professor in the division of metabolism, endocrinology and diabetes and research assistant professor in the Institute of Gerontology at the University of Michigan North Campus Research Complex, and fellow researchers wrote.

neck thyroid
Source: Adobe Stock

For the retrospective, population-based cohort study, Papaleontiou and colleagues aimed to assess the association between thyroid hormone treatment intensity and CV mortality. They included data from the Veterans Health Administration on 705,307 who received thyroid hormone treatment between January 2004 and December 2017. Median follow-up was 4 years.

CV mortality, a composite of death from myocardial infarction, heart failure or stroke, served as the main outcome measure.

Researchers evaluated two cohorts. The first featured 701,929 adults who initiated thyroid hormone treatment with at least two thyroid-stimulating hormone measurements between treatment initiation and either death or the end of the study period. The second cohort involved 373,981 adults with at least two free thyroxine measurements. Researchers merged data with the National Death Index to determine mortality and cause of death.

Euthyroidism was defined as a TSH level of 0.5 mIU/L to 5.5 mIU/L or a free T4 level of 0.7 ng/dL to 1.9 ng/dL; exogenous hyperthyroidism was a TSH level less than 0.5 mIU/L or a free T4 level greater than 1.9 ng/dL; and exogenous hypothyroidism was a TSH level greater than 5.5 mIU/L or a free T4 level less than 0.7 ng/dL.

In all, 88.7% of patients were men, the median age was 67 years, and 10.8% died of CV causes.

After adjustment for age, sex and traditional CV risk factors, such as hypertension and smoking, the researchers made the following observations: Compared with individuals with euthyroidism, those with exogenous hyperthyroidism had an adjusted HR for CV mortality of 1.39 (95% CI, 1.32-1.47) with TSH levels less than 0.1 mIU/L and 1.29 (95% CI, 1.2-1.4) with free T4 levels greater than 1.9 ng/dL; those with exogenous hypothyroidism had an aHR of 2.67 (95% CI, 2.55-2.8) with TSH levels greater than 20 mIU/L and 1.56 (95% CI, 1.5-1.63) with free T4 levels less than 0.7 ng/dL.

“We found that both exogenous hyperthyroidism and hypothyroidism were associated with an increased risk of cardiovascular mortality after adjusting for a comprehensive set of demographic and traditional cardiovascular risk factors,” the researchers concluded.

They noted that CVD remains the leading cause of death in the United States, and its economic impact is enormous.

“Identifying and addressing modifiable risk factors continues to be critically important to reducing the rates of cardiovascular disease and mortality,” they wrote. “The emergence of the intensity of thyroid hormone treatment as a potential associated risk factor provides a highly relevant and easily modifiable clinical parameter for patients who receive thyroid hormone treatment.”