Systematic review of 32 studies with 1.3 million participants uncovers new connections between the thyroid and the heart.
It has been known for more than 200 years that severe thyrotoxicosis can lead to cardiac arrhythmia (irregular heartbeat), a leading cause of sudden cardiac death. However, the risk associated with mild hyperthyroidism or hypothyroidism has not been understood until now. A systematic evaluation of 32 studies with 1.3 million participants shows: even slight deviations in thyroid function can increase the risk of serious cardiovascular diseases.
This puts our understanding of the interaction between the thyroid gland and the heart on a new footing and could pave the way toward personalized preventive care.”
Dr. Johannes Dietrich, Associate Professor, Department of Medicine, St Josef Hospital, Ruhr University Clinic Bochum, Germany (RUB)
The researchers published their work in the journal Frontiers in Cardiovascular Medicine on August 15, 2022.
For the study, RUB heart and hormone researchers collaborated with a clinical scientist/hormone specialist affiliated with Tan Tock Seng Hospital, Nanyang Technological University Lee Kong Chian School of Medicine, and Duke-NUS School of Medicine. in Singapore.
How should mild thyroid dysfunction be treated?
Today, overt thyroid dysfunction is recognized as an established risk factor for major adverse cardiovascular events (MACE). However, the situation remained equivocal in mild thyroid dysfunction. “While in some studies, minimal elevations of thyroid hormones and even high normal concentrations within the reference range for healthy people predicted an increased risk of sudden cardiac death, other studies had shown no such correlation,” explains Johannes Dietrich. Until very recently, the jury was still out on whether to treat people with subclinical forms of hyperthyroidism and hypothyroidism.
To gain a better understanding, a new systematic review by the international team analyzed the results of 32 studies on this topic. In a statistical evaluation combined with consecutive meta-analyses, the researchers found both subclinical hypothyroidism and subclinical hyperthyroidism to predict cardiovascular mortality risk. In particular, serum concentrations of free thyroid hormone T4 (FT4) were directly correlated with the probability of cardiac death and other adverse cardiovascular events.
two different patterns
“The results suggest that cardiovascular risk increases continuously with FT4 concentration, whereas there is a complex U-shaped risk relationship with the concentration of the controlling hormone thyrotropin, ie TSH,” explains Johannes Dietrich. This dualism can be explained by two different patterns of thyroid-mediated arrhythmia.
In one form (“dyshomeostatic type”), primary thyroid disease directly elevates thyroid hormone levels and thus increases cardiovascular risk. In the other form (“allostatic type”), genetic factors, chronic stress, and psychological strain increase the set point of the regulatory circuit between the pituitary gland and the thyroid gland, so that the indirectly increased FT4 concentration also promotes the arrhythmia.
Prevention and individual treatment
“The results of this study could pave the way toward a personalized preventive strategy for cardiac outcomes,” the authors conclude. “Furthermore, thyroid function could serve as a biomarker for the respective mechanism of origin in patients harboring cardiac arrhythmia, helping to tailor the optimized medication regimen individually.”
Muller, P. et al. (2022). Minor perturbations of thyroid homeostasis and major cardiovascular endpoints: physiological mechanisms and clinical evidence. Frontiers in Cardiovascular Medicine. doi.org/10.3389/fcvm.2022.942971.