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Higher thyroid hormone levels were associated with a substantially higher risk of sudden cardiac death (SCD), a population-based cohort study showed.

Each 1 ng/dL increase in the thyroid function hormone FT4 was associated with an 1.77-fold elevated risk of SCD (95% CI, 1.09-2.86) overall during an average follow-up period of about 9 years, reported , of Erasmus University Medical Center in Rotterdam, The Netherlands, and colleagues in .

A higher risk of SCD was also identified even in participants considered euthyroid, whose FT4 levels were at the high end of normal (HR 2.26 per 1 ng/dL FT4; 95% CI, 1.30-3.94). Euthyroidism was defined by a TSH level of 0.4 to 4.0 mIU/L.

Overall, participants whose FT4 levels at the top of the normal range had approximately a 2.5 times greater mortality rate due to SCD, compared to those at the low end of the normal range. Their absolute 10-year risk went from 1% to 4% with increasing FT4.

"Our study findings suggest that persons with higher thyroid hormone levels, even within what we consider the normal range of thyroid function, have a four-fold increased risk of sudden cardiac death compared to persons with lower thyroid hormone levels," said Chaker in an interview with 乌鸦传媒視頻.

"Our hypothesis was that thyroid hormone levels could increase the risk of sudden cardiac death by changing levels of cardiovascular risk factors such as blood pressure. We were surprised to see that when we control our analyses for these cardiovascular risk factors, the association remained similar, suggesting that other pathways could play a role."

The study of 10,318 individuals from the Rotterdam Study assessed serum TSH and FT4 levels against occurrences of SCD.

Previous research recognized a established link between thyroid dysfunction and cardiovascular disease. Because there is little data available on abnormal thyroid hormone levels and sudden cardiac death, the authors aimed to explore this relationship.

"Currently, we do not have a good way to predict sudden cardiac death in the general population," Chaker said in a press release. "Thus identifying additional risk factors is crucial. Our results indicate that thyroid hormone levels may be useful for assessing risk to prevent sudden cardiac death."

Eligible participants included individuals who had baseline measurements for serum thyroid-stimulating hormone (TSH) or free thyroxine (FT4). Chaker and colleagues divided the population-based cohort, average age of 65, into three independent cohorts from the Rotterdam Study, labeled as RSI, RSII, and RSIII. The RSI group was further divided into participants with baseline serum measurements (RSI-1) and participants whose levels were measured at their third visit (RSI-3). Baseline TSH and FT4 levels were measured through blood samples.

Data on sudden cardiac deaths, which were each reviewed by senior cardiologist, were gathered from death certificates and medical records of participants. The researchers officially defined SCD according to the Myerburg definition, "a natural death due to cardiac causes, heralded by abrupt loss of consciousness within one hour from onset of acute symptoms." Overall, there were 261 total SCD events during the study.

Additionally, the researchers gathered data on clinical baseline characteristics which included hypertension, pulse rate, use of antihypertensive medications at baseline, heart rate variability, total cholesterol, diabetes status, BMI, cardiac dysfunction, and smoking status.

But while FT4 levels appeared predictive of sudden cardiac death, higher TSH levels in the study were not significantly associated with increased SCD risk. Also, there were insignificant differential risks of SCD among various age groups.

It's important to consider use of thyroid hormone replacement therapy in regards to SCD risk, Chaker said, particularly for individuals with thyroid function levels at the top range for normal levels.

"We know that a substantial proportion of these patients is overtreated, where thyroid hormone levels are high-normal to high," she told 乌鸦传媒視頻 via email. "In these individuals, the thyroid hormone levels are modifiable by decreasing the dose of therapy and thereby perhaps decreasing sudden cardiac death risk."

Limits of the study included a small sample size with abnormal FT4 levels. Also, due to the demographics of the population-based cohort, there are limits to the generalizability of the results.

While the effects of thyroid medications on SCD risk were not studied in the current trial, the authors noted that future research should investigate. Furthermore, future studies are necessary to identify "which pathway could be responsible for the increased risk of sudden cardiac death with higher thyroid hormone levels," according to the researchers.

"This could lead to better risk stratification and identifying possible prevention targets," Chaker said. "Low thyroid function is also associated with several cardiovascular disease and it is therefore important to find where the optimum levels of thyroid function for cardiovascular health exactly are."

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