2016.11.08 21:01
09/06/16
Higher levels of free thyroxine are associated with an increased risk of sudden cardiac death, even in euthyroid adults, according to a report published online Sept. 6 in Circulation.
Thyroid dysfunction, even in the subclinical range, is known to correlate with increased cardiovascular disease, but until now a possible link between free thyroxine levels and sudden cardiac death (SCD) has never been explored in the general population. Any factors that could improve prediction of SCD in the general population would be helpful because almost half of these cases are the first indication that the patient had heart disease, said Layal Chaker, MD, of the Rotterdam Thyroid Center and the departments of internal medicine and epidemiology, Erasmus University, Rotterdam, and her associates.
They assessed SCD among 10,318 participants in the Rotterdam Study, a prospective population-based cohort study examining endocrine, cardiovascular, neurologic, ophthalmologic, and psychiatric diseases in middle-aged and older adults in the Netherlands. Men and women aged 45-106 years who had thyroid testing at baseline were followed for a median of 9.2 years (range, 4-21 years) for the development of SCD. There were 261 cases of SCD, and 231 of these occurred in euthyroid participants.
Higher levels of free thyroxine (T4) were associated with an increased risk of SCD, with a hazard ratio of 1.87 for every 1 ng/dL increase in free T4. When the analysis was confined to the 231 euthyroid participants, this association was even stronger, with an HR of 2.26, the investigators said (Circulation 2016 Sept 6. doi: 10.1161/CirculationAHA.115.020789).
The findings were similar in several sensitivity analyses, including one that excluded participants who had an unwitnessed SCD. In addition, adjustment of the data to account for the presence or absence of diabetes, as well as exclusion of patients who had heart failure, did not alter the risk estimates significantly. The results also were consistent across all age groups and both sexes, Dr. Chaker and her associates said.
The exact mechanism for the association between free thyroxine and SCD is not yet known but appears to be independent of traditional cardiovascular risk factors. “Bigger sample size and more detailed data are needed to determine whether these associations share the same or have distinct pathways,” they added.
The Netherlands Organisation for Health Research and Development and Erasmus Medical Center supported the study. Dr. Chaker and her associates reported having no relevant financial disclosures.
2016.11.08 21:11
2016.11.08 21:29
This is an interesting new information, the mechanism of which is unknown,
although clinicians have been aware of for a long time the association between
hyperthyroidism (and hypothyroidism as well) and heart attack.
This study indicates the level of free T4 in the presence of normal TSH is associated
with sudden cardiac death.
Most practicing general internists have been checking TSH only without T4 in their
usual screening for their patients for many years.
Circulation
ORIGINAL RESEARCH ARTICLE
Thyroid Function and Sudden Cardiac Death
A Prospective Population-Based Cohort Study
Layal Chaker, Marten E. van den Berg, Maartje N. Niemeijer, Oscar H. Franco, Abbas Dehghan, Albert Hofman, Peter R. Rijnbeek, Jaap W. Deckers, Mark Eijgelsheim, Bruno H.C. Stricker and Robin P. Peeters
http://dx.doi.org/10.1161/CIRCULATIONAHA.115.020789
Circulation. 2016;134:713-722
Originally published September 6, 2016
Abstract
BACKGROUND: The association between thyroid function and cardiovascular disease is well established, but no study to date has assessed whether it is a risk factor for sudden cardiac death (SCD). Therefore, we studied the association of thyroid function with SCD in a prospective population-based cohort.
METHODS: Participants from the Rotterdam Study ≥45 years with thyroid-stimulating hormone or free thyroxine (FT4) measurements and clinical follow-up were eligible. We assessed the association of thyroid-stimulating hormone and FT4 with the risk of SCD by using an age- and sex-adjusted Cox proportional-hazards model, in all participants and also after restricting the analysis to euthyroid participants (defined by thyroid-stimulating hormone 0.4–4.0 mIU/L). Additional adjustment included cardiovascular risk factors, notably hypertension, serum cholesterol, and smoking. We stratified by age and sex and performed sensitivity analyses by excluding participants with abnormal FT4 values (reference range of 0.85–1.95 ng/dL) and including only witnessed SCDs as outcome. Absolute risks were calculated in a competing risk model by taking death by other causes into account.
RESULTS: We included 10 318 participants with 261 incident SCDs (median follow-up, 9.1 years). Higher levels of FT4 were associated with an increased SCD risk, even in the normal range of thyroid function (hazard ratio, 2.28 per 1 ng/dL FT4; 95% confidence interval, 1.31–3.97). Stratification by age or sex and sensitivity analyses did not change the risk estimates substantially. The absolute 10-year risk of SCD increased in euthyroid participants from 1% to 4% with increasing FT4 levels.
Conclusions: Higher FT4 levels are associated with an increased risk of SCD, even in euthyroid participants.