Among adults with a normal thyroid function, higher free thyroxine (FT4) levels were associated with a 2.5-fold increased risk of sudden cardiac death, according to a prospective, population-based cohort study. The association was independent of cardiovascular risk factors such as high cholesterol and high blood pressure.

Lead researcher Layal Chaker, MD, MSc, of the Rotterdam Thyroid Center in the Netherlands, and colleagues published their results online Sept. 6 in Circulation.

“Currently, we do not have a good way to predict sudden cardiac death in the general population,” Chaker said in a news 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.”

The researchers defined sudden cardiac death as an unexpected natural death from a cardiac cause within an hour from the onset of symptoms in people who had no previous condition that would appear to be fatal. They mentioned that sudden cardiac death accounted for more than half of cardiovascular deaths and 15 percent to 20 percent of total mortality. Risk factors for sudden cardiac death include older age, male sex, hypertension, heart failure, smoking and dyslipidemia.

This analysis included 10,318 participants from the Rotterdam Study who were at least 45 years old and had thyroid-stimulating hormone (TSH) or FT4 measurements made at baseline. The participants were followed up until the date of sudden cardiac death, death from other causes or to Dec. 12, 2010, whichever came first.

At baseline, the mean age was 64.7 years old, and 57.0 percent of participants were women.

After a median follow-up period of 9.2 years, there were 261 incident sudden cardiac death events. Higher levels of FT4 were associated with an increased risk of sudden cardiac death (hazard ratio [HR], 1.87). Among participants with normal thyroid function, there was still a significant increased risk of sudden cardiac death if participants had higher levels of FT4 (HR, 2.26).

The 10-year risk of sudden cardiac death was 4 percent among participants with higher FT4 levels and 1 percent among participants with lower FT4 levels.

“The relative risk estimates were similar in the analyses with only witnessed [sudden cardiac deaths] as outcome or when excluding prevalent cases of cardiac diseases and patients using thyroid function–altering medication,” the researchers wrote.

The researchers cited a few limitations of the study, including possible residual confounding. They also only measured thyroid function at baseline and could not assess the temporal changes of TSH and FT4. In addition, only a small percentage of participants had FT4 values outside the reference range and most participants were white, which limited the generalizability to other groups.

“We know that a considerable proportion of patients on thyroid hormone replacement therapy are over-treated and so have high blood levels of thyroid hormone,” Chaker said. “Our study suggests more caution is warranted in the treatment of thyroid hormone replacement. Replacement therapy is often aimed at the high normal range which carries a risk of overtreatment.”