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High free thyroxine may increase risk of sudden cardiac death

LAKE BUENA VISTA, FLA. – High levels of free thyroxine (T4) can double the risk of sudden cardiac death, a large cohort study has determined.

Even people with free T4 in the upper range of normal may face an increased risk – up to 4% over 10 years, Dr. Layal Chaker said at the International Thyroid Conference.

Dr. Layal Chaker

The association remained significant, even when researchers controlled for independent cardiovascular risk factors, including hypertension and hyperlipidemia, said Dr. Chaker of Erasmus Medical Center, Rotterdam, the Netherlands.

The findings were based on a 9-year analysis of about 10,000 people included in the Rotterdam Elderly Study, conducted from 1990 to 2008. That study followed 15,000 people from middle age to old age, assessing cardiovascular and neurological diseases and their relationship to aging.

Dr. Chaker’s study comprised a subset of those who were without frank cardiovascular disease at baseline. She defined sudden cardiac death as a natural death from cardiac causes, heralded by an abrupt loss of consciousness within an hour of the onset of acute symptoms. Unwitnessed deaths were also included in the analysis. All of the death records were reviewed by two clinicians and a senior cardiologist.

The cohort comprised 10,318 subjects who had measurements of thyroid stimulating hormone (TSH) and free thyroxine (free T4); the mean age was 65 years.

Dr. Chaker stratified the group into tertiles based on the levels of these biomarkers. She conducted a multivariate analysis that controlled for age, sex, pulse, hypertension, cholesterol levels, diabetes, body mass index, smoking, and QT interval.

There were 261 sudden cardiac deaths by the end of follow-up.

There was no significant relationship between any level of TSH and sudden cardiac death. However, when she assessed the deaths by tertiles of free T4, she found a significant 40% increase in the risk among those whose levels ranged from 1.29 to 4 ng/L. The absolute 10-year risk rose from 1% at the lowest tertile to 7% in the highest.

Dr. Chaker then included only patients whose free T4 levels were in the euthyroid range of 0.85-1.95 ng/L. Among these, the risk of sudden cardiac death increased as free T4 increased (hazard ratio [HR], 2.25 for the highest level). The absolute 10-year risk rose from 1% at the lowest euthyroid level to 4% at 1.95 ng/L.

The reason for this finding isn’t completely clear, although other studies have shown a relationship between cardiac problems and thyroid function, she said.

“There may be some hemodynamic abnormalities that go along with even subclinical hyperthyroidism. High free T4 also has been associated with atrial fibrillation; both subclinical hyper- and hypothyroidism are associated with a prolongation of the QT interval.”

The meeting was held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society. Dr. Chaker had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

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LAKE BUENA VISTA, FLA. – High levels of free thyroxine (T4) can double the risk of sudden cardiac death, a large cohort study has determined.

Even people with free T4 in the upper range of normal may face an increased risk – up to 4% over 10 years, Dr. Layal Chaker said at the International Thyroid Conference.

Dr. Layal Chaker

The association remained significant, even when researchers controlled for independent cardiovascular risk factors, including hypertension and hyperlipidemia, said Dr. Chaker of Erasmus Medical Center, Rotterdam, the Netherlands.

The findings were based on a 9-year analysis of about 10,000 people included in the Rotterdam Elderly Study, conducted from 1990 to 2008. That study followed 15,000 people from middle age to old age, assessing cardiovascular and neurological diseases and their relationship to aging.

Dr. Chaker’s study comprised a subset of those who were without frank cardiovascular disease at baseline. She defined sudden cardiac death as a natural death from cardiac causes, heralded by an abrupt loss of consciousness within an hour of the onset of acute symptoms. Unwitnessed deaths were also included in the analysis. All of the death records were reviewed by two clinicians and a senior cardiologist.

The cohort comprised 10,318 subjects who had measurements of thyroid stimulating hormone (TSH) and free thyroxine (free T4); the mean age was 65 years.

Dr. Chaker stratified the group into tertiles based on the levels of these biomarkers. She conducted a multivariate analysis that controlled for age, sex, pulse, hypertension, cholesterol levels, diabetes, body mass index, smoking, and QT interval.

There were 261 sudden cardiac deaths by the end of follow-up.

There was no significant relationship between any level of TSH and sudden cardiac death. However, when she assessed the deaths by tertiles of free T4, she found a significant 40% increase in the risk among those whose levels ranged from 1.29 to 4 ng/L. The absolute 10-year risk rose from 1% at the lowest tertile to 7% in the highest.

Dr. Chaker then included only patients whose free T4 levels were in the euthyroid range of 0.85-1.95 ng/L. Among these, the risk of sudden cardiac death increased as free T4 increased (hazard ratio [HR], 2.25 for the highest level). The absolute 10-year risk rose from 1% at the lowest euthyroid level to 4% at 1.95 ng/L.

The reason for this finding isn’t completely clear, although other studies have shown a relationship between cardiac problems and thyroid function, she said.

“There may be some hemodynamic abnormalities that go along with even subclinical hyperthyroidism. High free T4 also has been associated with atrial fibrillation; both subclinical hyper- and hypothyroidism are associated with a prolongation of the QT interval.”

The meeting was held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society. Dr. Chaker had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

LAKE BUENA VISTA, FLA. – High levels of free thyroxine (T4) can double the risk of sudden cardiac death, a large cohort study has determined.

Even people with free T4 in the upper range of normal may face an increased risk – up to 4% over 10 years, Dr. Layal Chaker said at the International Thyroid Conference.

Dr. Layal Chaker

The association remained significant, even when researchers controlled for independent cardiovascular risk factors, including hypertension and hyperlipidemia, said Dr. Chaker of Erasmus Medical Center, Rotterdam, the Netherlands.

The findings were based on a 9-year analysis of about 10,000 people included in the Rotterdam Elderly Study, conducted from 1990 to 2008. That study followed 15,000 people from middle age to old age, assessing cardiovascular and neurological diseases and their relationship to aging.

Dr. Chaker’s study comprised a subset of those who were without frank cardiovascular disease at baseline. She defined sudden cardiac death as a natural death from cardiac causes, heralded by an abrupt loss of consciousness within an hour of the onset of acute symptoms. Unwitnessed deaths were also included in the analysis. All of the death records were reviewed by two clinicians and a senior cardiologist.

The cohort comprised 10,318 subjects who had measurements of thyroid stimulating hormone (TSH) and free thyroxine (free T4); the mean age was 65 years.

Dr. Chaker stratified the group into tertiles based on the levels of these biomarkers. She conducted a multivariate analysis that controlled for age, sex, pulse, hypertension, cholesterol levels, diabetes, body mass index, smoking, and QT interval.

There were 261 sudden cardiac deaths by the end of follow-up.

There was no significant relationship between any level of TSH and sudden cardiac death. However, when she assessed the deaths by tertiles of free T4, she found a significant 40% increase in the risk among those whose levels ranged from 1.29 to 4 ng/L. The absolute 10-year risk rose from 1% at the lowest tertile to 7% in the highest.

Dr. Chaker then included only patients whose free T4 levels were in the euthyroid range of 0.85-1.95 ng/L. Among these, the risk of sudden cardiac death increased as free T4 increased (hazard ratio [HR], 2.25 for the highest level). The absolute 10-year risk rose from 1% at the lowest euthyroid level to 4% at 1.95 ng/L.

The reason for this finding isn’t completely clear, although other studies have shown a relationship between cardiac problems and thyroid function, she said.

“There may be some hemodynamic abnormalities that go along with even subclinical hyperthyroidism. High free T4 also has been associated with atrial fibrillation; both subclinical hyper- and hypothyroidism are associated with a prolongation of the QT interval.”

The meeting was held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society. Dr. Chaker had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

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Key clinical point: Even subclinical hyperthyroidism may increase the risk of sudden cardiac death.

Major finding: High free thyroxine in euthyroid patients doubled the risk of sudden cardiac death.

Data source: A longitudinal cohort study comprising 10,318 subjects.

Disclosures: Dr. Chaker had no financial disclosures.