Subclinical Hypothyroidism and the Risk of Cardiovascular Disease and All-Cause Mortality: A Meta-Analysis of Prospective Cohort Studies

Moon, Shinje; Kim, Min Joo; Yu, Jae Myung; Yoo, Hyung Joon; Park, Young Joo

doi:10.1089/thy.2017.0414

Cited by 115 publications

(80 citation statements)

References 61 publications

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“…C ardiovascular disorders (CVD) are a leading cause of mortality worldwide (1). Whereas traditional cardiovascular risk factors, such as dyslipidemia, hypertension, type 2 diabetes (T2D), and obesity, are well-recognized, observational studies have shown that also overt and subclinical thyroid dysfunction is associated with a higher risk of CVD (2)(3)(4)(5)(6). More recently, even variation in normal range thyroid function has been associated with an increased risk of CVD, including atherosclerotic disease and stroke (7)(8)(9)(10), as well as with serum lipid levels (11), blood pressure (12), T2D risk (13), and obesity (14).…”

Section: Introductionmentioning

confidence: 99%

Variation in Normal Range Thyroid Function Affects Serum Cholesterol Levels, Blood Pressure, and Type 2 Diabetes Risk: A Mendelian Randomization Study

Kuś

Marouli

et al. 2021

Thyroid

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Background: Observational studies have demonstrated that variation in normal range thyroid function is associated with major cardiovascular risk factors, including dyslipidemia, hypertension, type 2 diabetes (T2D), and obesity. As observational studies are prone to residual confounding, reverse causality, and selection bias, we used a Mendelian randomization (MR) approach to investigate whether these associations are causal or not. Methods: Two-sample MR analysis using data from the largest available genome-wide association studies on normal range thyrotropin (TSH) and free thyroxine (fT4) levels, serum lipid levels, blood pressure measurements, T2D, and obesity traits (body mass index [BMI] and waist/hip ratio). Results: A one standard deviation (SD) increase in genetically predicted TSH levels was associated with a 0.037 SD increase in total cholesterol levels (p = 3.0 • 10-4). After excluding pleiotropic instruments, we also observed significant associations between TSH levels and low-density lipoprotein levels (b = 0.026 SD, p = 1.9 • 10-3), pulse pressure (b =-0.477 mmHg, p = 7.5 • 10-10), and T2D risk (odds ratio = 0.95, p = 2.5 • 10-3). While we found no evidence of causal associations between TSH or fT4 levels and obesity traits, we found that a one SD increase in genetically predicted BMI was associated with a 0.075 SD decrease in fT4 levels (p = 3.6 • 10-4). Conclusions: Variation in normal range thyroid function affects serum cholesterol levels, blood pressure, and T2D risk.

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Section: Introductionmentioning

confidence: 99%

Variation in Normal Range Thyroid Function Affects Serum Cholesterol Levels, Blood Pressure, and Type 2 Diabetes Risk: A Mendelian Randomization Study

Kuś

Marouli

et al. 2021

Thyroid

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“…11 Although the manifestation of subclinical hypothyroidism (SHypo) is often silent and obscure, SHypo is related to an increased risk of fracture, cardiovascular disease and all-cause mortality. 12,13 The prevalence of SHypo is much higher than that of overt hypo-or hyperthyroidism. 14 However, the relationships of thyroid hormones with GA and GA/HbA 1c in euthyroid and SHypo individuals have not been reported previously.…”

Section: Introductionmentioning

confidence: 99%

<p>Associations Between Thyroid Hormones and Glycated Albumin in Euthyroid and Subclinical Hypothyroid Individuals: Results of an Observational Study</p>

Nie¹,

Shen²,

Ma³

et al. 2020

DMSO

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Although overt thyroid dysfunction has been found to influence the level of glycated albumin (GA), the associations between thyroid hormones and GA in individuals with euthyroidism and subclinical hypothyroidism (SHypo) are still unknown. The present study aimed to investigate whether thyroid hormones were related to GA in euthyroid and SHypo individuals. Methods: We recruited 685 euthyroid and 103 SHypo subjects with normal weight from communities in Shanghai. Electrochemiluminescence immunoassay was used to detect the serum levels of free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone. GA was detected by the enzymatic method. Glycated hemoglobin (HbA 1c) was detected by high-performance liquid chromatography. Results: Among the 788 subjects (age range 31-81 years old), 307 were men and 481 were women. In the Spearman correlation analysis and multiple stepwise regression analysis, FT3 was negatively correlated with both GA and GA/HbA 1c in euthyroid subjects (all P < 0.05). The values of GA and GA/HbA 1c were reduced by approximately 0.30 and 0.05, respectively, for each 0.50 pmol/L increment in FT3. In SHypo subjects, FT4 was negatively associated with both GA and GA/HbA 1c (all P < 0.05). The values of GA and GA/HbA 1c were reduced by approximately 0.23 and 0.03, respectively, for each 1.00 pmol/L increment in FT4. Conclusion: In euthyroid and SHypo subjects, more attention should be paid to the potential effects of individual differences in thyroid hormones on GA.

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“…H ypothyroidism is a common condition (1,2) associated with an increased cardiovascular risk profile (3)(4)(5) and poor quality of life (6,7). The goal of its therapy is the relief of symptoms and restoration of normal thyroid hormone levels by administration of synthetic thyroxine (T4), levothyroxine (LT4), which is then converted in the periph-eral tissues into the hormonally active triiodothyronine (T3) (8).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of L-Triiodothyronine in Patients Undergoing Thyroid Hormone Therapy Withdrawal

Wohlford

et al. 2019

Thyroid

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Background: L-triiodothyronine (LT3) is a substitute for levothyroxine (LT4) for thyroid cancer (TC) patients during the preparation for nuclear medicine procedures, and it is used in combination with LT4 in patients who do not respond to the standard treatment for hypothyroidism. This therapy is commonly done by using fixed doses, potentially resulting in supraphysiologic levels of triiodothyronine (T3). A good understanding of the LT3 pharmacokinetics (PK) is necessary to design combination treatment schemes that are able to maintain serum T3 levels within the reference range, but data on the PK of LT3 are conflicting. Here, we present a study designed to characterize the PK of LT3 in patients devoid of endogenous thyroid hormone production, and not receiving LT4 therapy. Methods: We performed an open-label, PK study in patients undergoing thyroid hormone withdrawal in preparation for nuclear medicine procedures for the evaluation and treatment of follicular-derived TC. LT3 was substituted for LT4 at a 1:3 mcg/mcg dosage ratio thrice daily for at least 30 days. PK of the last LT3 dose while at steady state and terminal elimination was assessed over 11 days. Thereafter, a PK study was performed following the nuclear medicine procedure in patients who volunteered for a second study. Results: Fourteen patients age 48.5-16.0 years completed the last dose study and five completed the second PK study. PK analysis indicates a time to maximum serum concentration of 1.8-0.32 hours and two distinct phases of linear elimination, with a fast distribution phase and slow elimination phases with half-lives of 2.3-0.11 hours and 22.9-7.7 hours, supporting a two-compartment model. PK modeling predicts that a twicedaily administration of low-dose LT3 (0.07 mcg/kg twice daily) in combination with LT4 can predictably increase the serum T3 concentration without significant peaks above the reference range. Conclusions: The PK of LT3 is well described by a two-compartment model that assumes elimination only from the sampling compartment, with a rapid distribution phase and a slow elimination phase. This information will contribute to design therapeutic strategies for LT3/LT4 combination therapies directed to maintain stable T3 serum levels.

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Subclinical Hypothyroidism and the Risk of Cardiovascular Disease and All-Cause Mortality: A Meta-Analysis of Prospective Cohort Studies

Abstract: SCH is associated with an increased CVD risk and all-cause mortality, particularly in participants with high CVD risk.

Cited by 115 publications

References 61 publications

Variation in Normal Range Thyroid Function Affects Serum Cholesterol Levels, Blood Pressure, and Type 2 Diabetes Risk: A Mendelian Randomization Study

Variation in Normal Range Thyroid Function Affects Serum Cholesterol Levels, Blood Pressure, and Type 2 Diabetes Risk: A Mendelian Randomization Study

<p>Associations Between Thyroid Hormones and Glycated Albumin in Euthyroid and Subclinical Hypothyroid Individuals: Results of an Observational Study</p>

Pharmacokinetics of L-Triiodothyronine in Patients Undergoing Thyroid Hormone Therapy Withdrawal

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