Thyroid Hormone Treatment Intensity May Be Modifiable Risk Factor for CV Mortality

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Both exogenous hyperthyroidism and exogenous hypothyroidism were associated with increased risk of cardiovascular mortality.

The intensity level of thyroid hormone treatment may be a modifiable risk factor for cardiovascular (CV) mortality, according to new findings.

Both exogenous hyperthyroidism and exogenous hypothyroidism were found to have associations with increased risk of cardiovascular mortality after adjustments for a comprehensive set of demographic and traditional CV risk factors, said investigators.

“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,” wrote study author Maria Papaleontiou, MD, Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan.

There has been a lack of data specifically regarding the association between the intensity of thyroid hormone treatment and CV mortality, said the study authors. Thus, they hypothesized that both exogenous hyperthyroidism and hypothyroidism would be associated with increased CV mortality, even after adjusting for risk factors.

A nationwide population was collected between January 2004 and December 2017 using data from 705,307 adults who received thyroid hormone treatment from the Veterans Health Administration. Investigators studied two cohorts:

  • 701,929 adults ≥18 years who initiated thyroid hormone treatment with ≥2 thyrotropin measurements between treatment initiation and death or end of the study period
  • 373,981 patients with ≥2 free thyroxine (FT4) measurements

Investigators then defined exogenous hyperthyroidism by thyrotropin levels lower than 0.5 mIU/L or by FT4 levels higher than 1.9 ng/dL and euthyroidism defined by thyrotropin levels from 0.5 to 5.5 mIU/L and FT4 levels from 0.7 to 1.9 ng/dL. Additionally, exogenous hypothyroidism was defined by thyrotropin levels higher than 5.5 mIU/L or by FT4 levels lower than 0.7 ng/dL.

Study outcomes were identified as cardiovascular mortality (myocardial infarction, heart failure, or stroke) and survival analyses were conducted using Cox proportional hazards regression models using serum thyrotropin and FT4 levels as time-varying covariates.

Of the study population, 625,444 (88.7%) were male, 559,173 (79.3%) patients were White, and the median age was 67 years. During the study period, 75,963 patients (10.8%) died of cardiovascular causes.

Following adjustment for age, sex, and traditional cardiovascular risk factors, investigators found patients with exogenous hyperthyroidism (thyrotropin levels, <0.1 mIU/L; adjusted hazard ratio [AHR], 1.39; 95% CI, 1.32 - 1.47; FT4 >1.9 ng/dL: AHR, 1.29; 95% CI, 1.20 - 1.40) and with exogenous hypothyroidism (thyrotropin levels, >20 mIU/L: AHR, 2.67; 95% CI, 2.55 - 2.80; FT4 levels, <0.7 ng/dL: AHR, 1.56; 95% CI, 1.50 - 1.63) had an increased risk of CV mortality compared to those with euthyoridism.

The study authors noted the risk of CV mortality seems to be directly associated with the degree of thyrotropin abnormality outside the euthyroid range, while thyrotropin level may be more associated with CV risk than the FT4 level in older adults.

“Our study findings have the potential to affect how we think about the risks and benefits associated with thyroid hormone treatment, particularly for vulnerable populations, such as older adults or those with underlying cardiovascular disease,” Papaleontiou concluded.

The study, “Association of Thyroid Hormone Treatment Intensity With Cardiovascular Mortality Among US Veterans,” was published in JAMA Network Open.