Thyroid Hormone Levels Within Reference Range Are Associated with Heart Rate, Cardiac Structure, and Function in Middle-Aged Men and Women

Roef, Greet; Taes, Youri; Kaufman, Jean‐Marc; daele, Caroline M. Van; Buyzere, Marc L. De; Gillebert, Thierry C.; Rietzschel, Ernst

doi:10.1089/thy.2012.0471

Cited by 39 publications

(38 citation statements)

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“…This suggests an individual set point for pituitary-thyroid axis function (1). We and others have shown that this between-subject variation in TH levels, although within the normal range, is nevertheless associated with a number of clinical parameters such as bone mass, BMI, metabolic indices, and heart rate (2,3,4,5). The physiological basis of the set point of this axis is poorly understood (6).…”

Section: Introductionmentioning

confidence: 97%

Heredity and lifestyle in the determination of between-subject variation in thyroid hormone levels in euthyroid men

Roef¹,

Taes

Toye

et al. 2013

European Journal of Endocrinology

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Objective: Variation in thyroid hormone (TH) concentrations between subjects is greater than in a single subject over a prolonged period of time, suggesting an individual set point for thyroid function. We have previously shown that TH levels within normal range are associated with clinical indices such as bone mass, BMI, and heart rate. The aim of this study on young men was therefore to gain insight into the determinants of variation in TH levels among healthy subjects. Methods: Healthy male siblings (nZ941, 25-45 years) were recruited in a cross-sectional, populationbased study; a history or treatment of thyroid disease and thyroid auto-immunity were exclusion criteria. A complete assessment of TH status was performed (TSH, free thyroxine (FT 4 ), free triiodothyronine (FT 3 ), thyroperoxidase, and thyroglobulin antibodies, reverse T 3 (rT 3 ), thyroidbinding globulin (TBG), and urinary iodine levels). Genotyping was performed by TaqMan and KASP (KBiosciences) genotyping assays. Results: (F)T 4 , rT 3 , and TBG had heritability estimates between 80 and 90%. Estimates were lower for (F)T 3 (60%) and lowest for TSH (49%). Significant associations were observed between different single-nucleotide polymorphisms (SNPs) in the thyroid pathway and TSH, FT 4 , ratio FT 3 :FT 4 , and rT 3 . Nevertheless, these SNPs only explain a limited part of the heredity. As to age and lifestyle-related factors, (F)T 3 was negatively related to age and education level, positively to smoking and BMI (all P!0.0001) but not substantially to urinary iodine concentrations. Smoking was also negatively related to TSH and positively to FT 4 . Conclusion: Both genetic and lifestyle-related factors play a role in determining between-subject variation in TH levels in euthyroid young men, although genetic factors seem most important.

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Section: Introductionmentioning

confidence: 97%

Heredity and lifestyle in the determination of between-subject variation in thyroid hormone levels in euthyroid men

Roef¹,

Taes

Toye

et al. 2013

European Journal of Endocrinology

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“…4-t-OP and other endocrine-disrupting compounds have been linked to endocrine disruption mediated via interference with the estrogen and thyroid hormone systems [27]. A strong positive correlation between levels of thyroid hormone and heart rate has been demonstrated [28]. Thus, based on those studies, we assume that 4-t-OP may reduce heart rate through its effects on reducing thyroid hormone.…”

Section: Discussionmentioning

confidence: 92%

Toxicity Effects of the Environmental Hormone 4-Tert-Octylphenol in Zebrafish (Danio Rerio)

Saputra¹,

Yen²

2015

J Marine Sci Res Dev

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Abstract4-tert-octylphenol (4-t-OP), an environmental exogenous estrogen is produced by microbial degradation of alkylphenol polyethoxylates (APEOs). Although it is well known that 4-t-OP can cause the feminization of male, sterility and deficiency of gonad development of aquatic animals by disrupting the endocrine reproductive signaling, less is known about the effects of 4-t-OP on embryonic development. Moreover, the presence of 4-t-OP were detected in umbilical cord blood samples of newborns suggesting infants during development may expose to the risk of 4-t-OP contaminant, hence to investigate the effect of 4-t-OP on physiological function during embryonic development is necessary. In the present study, zebrafish embryos exposed to 4-t-OP were used to evaluate the toxicity of 4-t-OP. The 50% lethal dose (LD50) for wild type zebrafish embryos exposure to 4-t-OP for 3 days is approximately 1.0 µM, and a high ratio of cardiovascular defects were showed in survival embryos. To observe the cardiovascular defects more efficiently, Tg (fil-1: EGFP) zebrafish embryos was used in 4-t-OP exposure treatment. Following exposure Tg (fil-1: EGFP) zebrafish embryos to 4-t-OP at 1.0 µM for 4 days, a highly proportion of defects revealed in cardiovascular system, including pericardical edema, irregular shape or incomplete looping of ventricle and atrium, the absence of intersegmental vessel in the tail of notochord, unformed parachordal vessel and kinks in the caudal vein. The phenotype of cardiovascular defects was accompanied by reduced heart rate and impaired blood circulation. The mRNA expression levels of transcription factors, which are critical for zebrafish heart chamber formation and blood vessel development, were analyzed by RT-PCR. The results showed that the presence of 4-t-OP significantly induce expression level of ERα and ERβ2, and caused cardiovascular defects by suppressing transcription factor Nkx2. 7, Hand2, Tbx2a, Tbx2b, Tbx5a, FGF1a, in zebrafish. The present study suggests that 4-t-OP affects the cardiovascular development in zebrafish and elucidated that early life exposure to 4-t-OP potentially may take a risk of impaired cardiovascular function.

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“…Roef et al found that fT3 level was positively associated with the peak velocity of systolic mitral annulus and late ventricular filling, whereas negatively with left ventricular end-diastolic diameter. 8) It suggested that euthyroid subjects with low-normal fT3 levels had an increased risk to suffer relatively reduced heart function, decreased fT3 level within the low-normal range might be associated with the severity of cardiac insufficiency. On the other hand, CRT can improve fT3 levels after a reverse of cardiac remodeling.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7] Recently, fT3 level was shown to be associated with cardiac function and heart structure in euthyroid subjects without HF. 8) In addition, another research reported hypothyroidism was associated with a worse prognosis after CRT implantation, but it did not supply values for complete thyroid panel (fT3 and fT4). 9) Is the prognosis of patients with HF after CRT implantation is correlated with lower fT3 levels within a normal reference range?…”

mentioning

confidence: 99%

A Low-Normal Free Triiodothyronine Level Is Associated with Adverse Prognosis in Euthyroid Patients with Heart Failure Receiving Cardiac Resynchronization Therapy

Chen

Shu

et al. 2017

Int. Heart J.

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SummaryThyroid dysfunction is prevalent in patients with heart failure (HF) and hypothyroidism is related to the adverse prognosis of HF subjects receiving cardiac resynchronization therapy (CRT). We aim to investigate whether low-normal free triiodothyronine (fT3) level is related to CRT response and the prognosis of euthyroid patients with HF after CRT implantation.One hundred and thirteen euthyroid patients who received CRT therapy without previous thyroid disease and any treatment affecting thyroid hormones were enrolled. All of patients were evaluated for cardiac function and thyroid hormones (serum levels of fT3, free thyroxine [fT4] and thyroid-stimulating hormone [TSH]). The end points were overall mortality and hospitalization for HF worsening. During a follow-up period of 39 ± 3 weeks, 36 patients (31.9%) died and 45 patients (39.8%) had hospitalization for HF exacerbation. A higher rate of NYHA III/IV class and a lower fT3 level were both observed in death group and HF event group. Multivariate Cox regression analyses disclosed that a lower-normal fT3 level (HR = 0.648, P = 0.009) and CRT response (HR = 0.441, P = 0.001) were both independent predictors of overall mortality. In addition, they were also both related to HF re-hospitalization event (P < 0.01 for both). Patients with fT3 < 3.00 pmol/L had a significantly higher overall mortality than those with fT3 !3.00 pmol/L (P = 0.027). Meanwhile, a higher HF hospitalization event rate was also found in patients with fT3 < 3.00 pmol/L (P < 0.001).A lower-normal fT3 level is correlated with a worse cardiac function an adverse prognosis in euthyroid patients with HF after CRT implantation.(Int Heart J 2017; 58: 908-914) Key words: Thyroid hormones, Cardiac dysfunction, Left ventricular dyssynchrony, CRT response, Mortality, Hospitalization C ardiac resynchronization therapy (CRT) is a considerable treatment for patients with drugrefractory heart failure (HF) and electromechanical dyssynchronoy.1,2) Though CRT improves heart failure symptoms and quality of life, and reduces both HF-related morbidity and mortality, non-response to CRT has been reported in nearly one third of patients.3) The reason of non-response to CRT is complicated and remains a question of different opinions.Thyroid hormones (THs) have cardiac and vascular effects, and they also regulate biochemical reactions in most tissues.4) TH consists of thyroxine (T4) and triiodothyronine (T3), and the cardiac myocyte does not convert T4 to T3. In other word, T3 is the bioactive form of thyroid hormone for cardiomyocytes and plays an important role in cardiovascular regulation. Many studies have confirmed that T3 is a prognostic predictor or risk stratification of HF.5-7) Recently, fT3 level was shown to be associated with cardiac function and heart structure in euthyroid subjects without HF.8) In addition, another research reported hypothyroidism was associated with a worse prognosis after CRT implantation, but it did not supply values for complete thyroid panel (fT3 and fT4). 9) Is the prognos...

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Thyroid Hormone Levels Within Reference Range Are Associated with Heart Rate, Cardiac Structure, and Function in Middle-Aged Men and Women

Cited by 39 publications

References 50 publications

Heredity and lifestyle in the determination of between-subject variation in thyroid hormone levels in euthyroid men

Heredity and lifestyle in the determination of between-subject variation in thyroid hormone levels in euthyroid men

Toxicity Effects of the Environmental Hormone 4-Tert-Octylphenol in Zebrafish (Danio Rerio)

A Low-Normal Free Triiodothyronine Level Is Associated with Adverse Prognosis in Euthyroid Patients with Heart Failure Receiving Cardiac Resynchronization Therapy

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