The DOI matches its Crossref record; 40 of the 41 references it cites were found in a registry or an index; 7 of the 57 sources its claims cite were checked for support.
Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality
Open accessAbstract
Importance: Subclinical hypothyroidism is a common clinical entity among US adults associated in some studies with an increase in the risk of cardiovascular disease (CVD) and mortality. However, the extent to which CVD mediates the association between elevated serum thyrotropin (TSH) and mortality has not yet been well established or sufficiently quantified. Objective: To elucidate the extent to which subclinical hypothyroidism, elevated serum TSH and normal serum free thyroxine, or high-normal TSH concentrations (ie, upper normative-range TSH concentrations) are associated with mortality through CVD among US adults. Design, Setting, and Participants: This cohort study relied on representative samples of US adults enrolled in the National Health and Nutrition Examination Survey in 2001 to 2002, 2007 to 2008, 2009 to 2010, and 2011 to 2012 and their mortality data through 2015. Data were analyzed from January to August 2019. Main Outcomes and Measures: Cox proportional hazards regression models were used to investigate associations between the TSH concentration category (subclinical hypothyroidism or tertiles of serum TSH concentrations within the reference range; low-normal TSH, 0.34-1.19 mIU/L; middle-normal TSH, 1.20-1.95 mIU/L; and high-normal TSH, 1.96-5.60 mIU/L) and all-cause mortality. Mediation analysis was used within the counterfactual framework to estimate natural direct associations (not through CVD) and indirect associations (through CVD). Results: Of 9020 participants, 4658 (51.6%) were men; the mean (SD) age was 49.4 (17.8) years. Throughout follow-up (median [interquartile range], 7.3 [5.4-8.3] years), serum thyroid function test results consistent with subclinical hypothyroidism and high-normal TSH concentrations were both associated with increased all-cause mortality (subclinical hypothyroidism: hazard ratio, 1.90; 95% CI, 1.14-3.19; high-normal TSH: hazard ratio, 1.36; 95% CI, 1.07-1.73) compared with the middle-normal TSH group. Cardiovascular disease mediated 14.3% and 5.9% of the associations of subclinical hypothyroidism and high-normal TSH with all-cause mortality, respectively, with the CVD mediation being most pronounced in women (7.5%-13.7% of the association) and participants aged 60 years and older (6.0%-14.8% of the association). Conclusions and Relevance: In this study, CVD mediated the associations of subclinical hypothyroidism and high-normal TSH concentrations with all-cause mortality in the US general population. Further studies are needed to examine the clinical benefit of thyroid hormone replacement therapy targeted to a middle-normal TSH concentration or active CVD screening for people with elevated TSH concentrations.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
In a nationally representative NHANES cohort of 9020 US adults, higher thyrotropin (TSH) concentrations—including subclinical hypothyroidism and high-normal TSH—were associated with increased all-cause mortality. Cardiovascular disease mediated 14.3% of the subclinical hypothyroidism association and 5.9% of the high-normal TSH association with all-cause mortality.
Key findings
- During a median follow-up of 7.3 years, 435 deaths occurred. Compared with middle-normal TSH, adjusted hazard ratios for all-cause mortality were 1.36 (95% CI, 1.01-1.83) for low-normal TSH, 1.36 (95% CI, 1.07-1.73) for high-normal TSH, and 1.90 (95% CI, 1.14-3.19) for subclinical hypothyroidism; restricted cubic splines showed a U-shaped association between TSH and mortality.
- CVD mediated 14.3% of the association of subclinical hypothyroidism with all-cause mortality and 5.9% of the association of high-normal TSH with all-cause mortality; no evidence of CVD mediation was found for low-normal TSH.
- In sex-stratified analyses, CVD mediated 7.5% to 13.7% of the associations of high-normal TSH or subclinical hypothyroidism with mortality in women, with no or only slight mediation in men. In participants aged 60 years or older, CVD mediated 6.0% of the high-normal TSH association and 14.8% of the subclinical hypothyroidism association, but the indirect effect confidence interval for subclinical hypothyroidism included the null.
Methods
- Secondary analysis of the US National Health and Nutrition Examination Survey (NHANES), including four cycles (2001-2002, 2007-2008, 2009-2010, 2011-2012), among adults aged 20 years or older with serum TSH and free thyroxine data; after exclusions, the final analytical cohort was 9020 participants, followed for mortality through December 2015.
- TSH categories were low-normal (0.34-1.19 mIU/L), middle-normal (1.20-1.95 mIU/L), high-normal (1.96-5.60 mIU/L), and subclinical hypothyroidism (TSH >5.60 mIU/L with normal free thyroxine); CVD was ascertained by self-report at baseline.
- Multivariable Cox proportional hazards models and restricted cubic splines estimated mortality associations; mediation analysis used a marginal structural counterfactual approach, with 1000 bootstrap samples for bias-corrected 95% confidence intervals.
Limitations
- The paper states that it could not account for trends or changes in thyroid function over follow-up; exposure-mediator timing was not well defined, so reverse causation is possible; CVD and other medical histories were self-reported and may be misclassified; mediation analysis assumed no unmeasured confounders and no mediator-outcome confounding affected by exposure; and not all CVD events during follow-up were captured, so CVD mediation may be underestimated.
- Evident from the design: this is an observational cohort, so causal inferences are limited, and thyroid exposure was based on baseline TSH/free thyroxine measurements rather than longitudinal thyroid function.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
24 Own result · 23 Not checked yet · 11 Own method · 4 Own interpretation · 2 Partly supported · 2 No basis given · 1 Supported · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“Inadequate serum thyroid hormone produces impairment of cardiac function and may result in bradycardia, endothelial dysfunction, increased intima-media thickness, diastolic dysfunction, increased vascular resistance, and pericardial effusion.3”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Introduction
What the sources say
- Supportedcites [3] Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet. 2017; 390(10101): 1550- 1562. doi: 10.1016/S0140-6736(17)30703-1 28336049 PMC6619426 source
The Signs and symptoms section states that hypothyroidism decreases cardiac output and left ventricular function, supporting the attributed claim of impaired cardiac function. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Recent individual patient meta-analysis by the Thyroid Studies Collaboration8,9,10,11 did not find higher risk of CVD and all-cause mortality among adults with subclinical hypothyroidism compared with those with euthyroidism”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Introduction
What the sources say
- Partly supportedcites [8] Rodondi N, den Elzen WPJ, Bauer DC,; Thyroid Studies Collaboration. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA. 2010; 304(12): 1365- 1374. doi: 10.1001/jama.2010.1361 20858880 PMC3923470 sourceExperimental — accuracy not yet measured
The Results (page not provided) show no statistically significant increase in overall CHD events, CHD mortality, or total mortality among adults with subclinical hypothyroidism compared with those with euthyroidism. But CHD events and CHD mortality were significantly higher at TSH levels of 10 mIU/L or greater. The claim omits that qualification and says CVD broadly, while this paper assesses CHD outcomes. (LLM, conf=0.88)
- Partly supportedcites [9] Gencer B, Collet T-H, Virgini V,; Thyroid Studies Collaboration. Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts. Circulation. 2012; 126(9): 1040- 1049. doi: 10.1161/CIRCULATIONAHA.112.096024 22821943 PMC3884576 sourceExperimental — accuracy not yet measured
The Results (page unavailable) report no statistically significant increase in heart-failure events for subclinical hypothyroidism overall versus euthyroidism, but a significant increase at TSH 10.0–19.9 mIU/L. This paper examines heart-failure events, not cardiovascular disease broadly or all-cause mortality, so it does not support the full claim. (LLM, conf=0.86)
- Could not verifycites [10] Collet T-H, Gussekloo J, Bauer DC,; Thyroid Studies Collaboration. Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Arch Intern Med. 2012; 172(10): 799- 809. doi: 10.1001/archinternmed.2012.402 22529182 PMC3872478 sourceExperimental — accuracy not yet measured
The Results report increased total and coronary heart disease mortality for participants with subclinical hyperthyroidism compared with euthyroidism. The copy does not report the claimed finding for subclinical hypothyroidism; a search for that term found only a passing comparison and references, not an analysis of its cardiovascular disease or all-cause mortality risks. (LLM, conf=0.78)
- Partly supportedcites [11] Hyland KA, Arnold AM, Lee JS, Cappola AR. Persistent subclinical hypothyroidism and cardiovascular risk in the elderly: the cardiovascular health study. J Clin Endocrinol Metab. 2013; 98(2): 533- 540. doi: 10.1210/jc.2012-2180 23162099 PMC3565111 sourceExperimental — accuracy not yet measured
The Results report no association between subclinical hypothyroidism and CHD, heart failure, or cardiovascular mortality in this study of adults aged 65 or older. But this paper is a cohort study, not the attributed individual-participant meta-analysis, and it does not report all-cause mortality as an outcome. Its Discussion says the meta-analysis found increased CHD risk at higher TSH levels, so it does not support the unqualified statement about the meta-analysis. (LLM, conf=0.85)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We estimated that CVD mediated 14.3% and 5.9% of the association of subclinical hypothyroidism and high-normal TSH with all-cause mortality, respectively (Table 3).”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Results > Mediation of TSH and Mortality Associations Through CVD
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Self-reported coronary artery disease and nonfatal cardiovascular disease events accurately classify prevalent cardiovascular disease.
- Rests on an assumption: Mortality data from death certificates provided by the National Death Index accurately ascertain all-cause mortality.
- Rests on an assumption: The mediation analysis assumes no unmeasured confounding of the exposure-mediator, exposure-outcome, and mediator-outcome relationships.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We did not find any evidence for mediation through CVD for low-normal TSH levels and all-cause mortality.”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Results > Mediation of TSH and Mortality Associations Through CVD
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Self-reported coronary artery disease and nonfatal cardiovascular disease events accurately classify prevalent cardiovascular disease.
- Rests on an assumption: Mortality data from death certificates provided by the National Death Index accurately ascertain all-cause mortality.
- Rests on an assumption: The mediation analysis assumes no unmeasured confounding of the exposure-mediator, exposure-outcome, and mediator-outcome relationships.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“high-normal TSH group (hazard ratio, 1.36; 95% CI, 1.07-1.73)”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Results > TSH and Mortality
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Mortality data from death certificates provided by the National Death Index accurately ascertain all-cause mortality.
- Rests on an assumption: A single baseline serum TSH measurement adequately represents long-term thyroid function.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We did not find evidence for CVD mediation between low-normal TSH and all-cause mortality overall or stratified by sex and age.”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Results > Mediation of TSH and Mortality Associations Through CVD
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Self-reported coronary artery disease and nonfatal cardiovascular disease events accurately classify prevalent cardiovascular disease.
- Rests on an assumption: Mortality data from death certificates provided by the National Death Index accurately ascertain all-cause mortality.
- Rests on an assumption: The mediation analysis assumes no unmeasured confounding of the exposure-mediator, exposure-outcome, and mediator-outcome relationships.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“while we found no mediation or only a slight mediation through CVD in men (Table 4).”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Results > Mediation of TSH and Mortality Associations Through CVD
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Self-reported coronary artery disease and nonfatal cardiovascular disease events accurately classify prevalent cardiovascular disease.
- Rests on an assumption: Mortality data from death certificates provided by the National Death Index accurately ascertain all-cause mortality.
- Rests on an assumption: The mediation analysis assumes no unmeasured confounding of the exposure-mediator, exposure-outcome, and mediator-outcome relationships.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We also estimated that CVD mediated 6.0% of the associations of high-normal TSH with all-cause mortality for participants aged 60 years or older (eTable 4 in the Supplement).”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Results > Mediation of TSH and Mortality Associations Through CVD
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Self-reported coronary artery disease and nonfatal cardiovascular disease events accurately classify prevalent cardiovascular disease.
- Rests on an assumption: Mortality data from death certificates provided by the National Death Index accurately ascertain all-cause mortality.
- Rests on an assumption: The mediation analysis assumes no unmeasured confounding of the exposure-mediator, exposure-outcome, and mediator-outcome relationships.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“subclinical hypothyroidism group (hazard ratio, 1.90; 95% CI, 1.14-3.19)”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Results > TSH and Mortality
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Mortality data from death certificates provided by the National Death Index accurately ascertain all-cause mortality.
- Rests on an assumption: A single baseline serum TSH measurement adequately represents long-term thyroid function.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In stratified analyses, we estimated that CVD mediated 7.5% to 13.7% of the associations of high-normal TSH or subclinical hypothyroidism with all-cause mortality in women”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Results > Mediation of TSH and Mortality Associations Through CVD
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Self-reported coronary artery disease and nonfatal cardiovascular disease events accurately classify prevalent cardiovascular disease.
- Rests on an assumption: Mortality data from death certificates provided by the National Death Index accurately ascertain all-cause mortality.
- Rests on an assumption: The mediation analysis assumes no unmeasured confounding of the exposure-mediator, exposure-outcome, and mediator-outcome relationships.
- Probably not a substantial claim. 23
- It may state two separate claims as one. 13
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Current clinical guidelines from the American Thyroid Association14 and European Thyroid Association13 do not recommend treating subclinical hypothyroidism when TSH is 10 mIU/L or less (and without symptoms in younger individuals).”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion
What the sources say
- Could not verifycites [14] Jonklaas J, Bianco AC, Bauer AJ,; American Thyroid Association Task Force on Thyroid Hormone Replacement. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid. 2014; 24(12): 1670- 1751. doi: 10.1089/thy.2014.0028 25266247 PMC4267409 sourceExperimental — accuracy not yet measured
The Discussion of the clinical literature reports that cardiovascular risk was primarily increased at TSH levels above 10 mIU/L, but it does not recommend withholding treatment at or below 10 mIU/L. The Background, Objectives, and Rationale says this guideline focuses on thyroid hormone therapy rather than broader management. Searches for a treatment-initiation recommendation for asymptomatic younger people with subclinical hypothyroidism found no such passage in our copy; page numbers were unavailable. (LLM, conf=0.71)
- Partly supportedcites [13] Pearce SHS, Brabant G, Duntas LH,. 2013 ETA guideline: management of subclinical hypothyroidism. Eur Thyroid J. 2013; 2(4): 215- 228. doi: 10.1159/000356507 24783053 PMC3923601 sourceExperimental — accuracy not yet measured
The Recommendations (p. 7) advise considering a treatment trial for symptomatic younger patients with TSH <10 mU/l, while recommending treatment without symptoms when TSH is >10 mU/l. But the guideline also recommends treatment for persistent subclinical hypothyroidism with goitre or following hemithyroidectomy, so the claim's blanket statement that treatment is not recommended at TSH ≤10 mU/l is too broad. This verdict addresses the European Thyroid Association guideline, not the separately cited American guideline. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Could not verify
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A mediation through CVD was also estimated at 14.8% for subclinical hypothyroidism, but the 95% confidence interval of the estimated indirect effect size included the null, reflecting the smaller sample size.”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Results > Mediation of TSH and Mortality Associations Through CVD
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Self-reported coronary artery disease and nonfatal cardiovascular disease events accurately classify prevalent cardiovascular disease.
- Rests on an assumption: Mortality data from death certificates provided by the National Death Index accurately ascertain all-cause mortality.
- Rests on an assumption: The mediation analysis assumes no unmeasured confounding of the exposure-mediator, exposure-outcome, and mediator-outcome relationships.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“While the observed estimated indirect effect sizes were small for high-normal TSH, the impact of these associations should be considered, given that participants with high-normal TSH compose almost one-third of the total population (by definition) in the present study.”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We also observed an association between low-normal TSH concentrations (ie, high-normal thyroid function) and all-cause mortality, especially in men and in the younger population.”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We also found that high-normal TSH was associated with increased risk of all-cause mortality both in participants younger than 60 years and in those 60 years or older; however, we had insufficient power to estimate statistically significant effect sizes in younger participants, which will require larger studies with longer follow-up periods.”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Other epidemiological studies4,5,6,7 have also found an association between subclinical hypothyroidism or high-normal TSH concentrations (ie, serum TSH concentrations at the upper end of the normal range) and dyslipidemia, increased insulin resistance, and hypertension—components of metabolic syndrome.”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Introduction
What the sources say
- Not checked yetcites [4] Cooper DS, Biondi B. Subclinical thyroid disease. Lancet. 2012; 379(9821): 1142- 1154. doi: 10.1016/S0140-6736(11)60276-6 22273398 source
- Not checked yetcites [5] Inoue K, Tsujimoto T, Saito J, Sugiyama T. Association between serum thyrotropin levels and mortality among euthyroid adults in the United States. Thyroid. 2016; 26(10): 1457- 1465. doi: 10.1089/thy.2016.0156 27539006 source
- Not checked yetcites [6] Garduño-Garcia J de J, Alvirde-Garcia U, López-Carrasco G,. TSH and free thyroxine concentrations are associated with differing metabolic markers in euthyroid subjects. Eur J Endocrinol. 2010; 163(2): 273- 278. doi: 10.1530/EJE-10-0312 20516204
- Not checked yetcites [7] Le TN, Celi FS, Wickham EP III. Thyrotropin levels are associated with cardiometabolic risk factors in euthyroid adolescents. Thyroid. 2016; 26(10): 1441- 1449. doi: 10.1089/thy.2016.0055 27599541 PMC5067795
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Additional adjustment for metabolic disorder indicators (ie, diabetes, hypertension, statin prescriptions, and BMI) or using a different definition of the normal range for TSH did not qualitatively alter these results (eTable 2 and eTable 3 in the Supplement).”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Results > Mediation of TSH and Mortality Associations Through CVD
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Self-reported coronary artery disease and nonfatal cardiovascular disease events accurately classify prevalent cardiovascular disease.
- Rests on an assumption: Mortality data from death certificates provided by the National Death Index accurately ascertain all-cause mortality.
- Rests on an assumption: The mediation analysis assumes no unmeasured confounding of the exposure-mediator, exposure-outcome, and mediator-outcome relationships.
In the paper
“A previous review2 has reported cardiovascular abnormalities such as left ventricular dysfunction and impaired vascular relaxation among people with not only overt hypothyroidism but also subclinical hypothyroidism.”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Introduction
What the sources say
- Not checked yetcites [2] Biondi B, Palmieri EA, Lombardi G, Fazio S. Effects of subclinical thyroid dysfunction on the heart. Ann Intern Med. 2002; 137(11): 904- 914. doi: 10.7326/0003-4819-137-11-200212030-00011 12458990
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Despite these mechanisms and evidence about the potential burden of elevated TSH on cardiac metabolism, the potentially causal link between subclinical hypothyroidism, cardiovascular disease (CVD), and death remains unclear.”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Introduction
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“The thyroid hormone is one of the key regulators of cardiac function and cardiovascular hemodynamics; therefore, inadequate thyroid hormone levels impair the relaxation of vascular smooth muscle cells and decrease cardiac contractility by regulating calcium uptake and the expression of several contractile proteins in cardiomyocytes.37,38”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion
What the sources say
- Not checked yetcites [37] Klein I, Danzi S. Thyroid disease and the heart. Circulation. 2007; 116(15): 1725- 1735. doi: 10.1161/CIRCULATIONAHA.106.678326 17923583
- Not checked yetcites [38] Owen PJD, Sabit R, Lazarus JH. Thyroid disease and vascular function. Thyroid. 2007; 17(6): 519- 524. doi: 10.1089/thy.2007.0051 17614771
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“which is supported by current clinical guidelines proposing that thyroid hormone replacement therapy should not be routinely offered for adults with subclinical hypothyroidism.12,13,14”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Introduction
What the sources say
- Not checked yetcites [12] Bekkering GE, Agoritsas T, Lytvyn L,. Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline. BMJ. 2019; 365: l2006. doi: 10.1136/bmj.l2006 31088853 source
- Not checked yetcites [13] Pearce SHS, Brabant G, Duntas LH,. 2013 ETA guideline: management of subclinical hypothyroidism. Eur Thyroid J. 2013; 2(4): 215- 228. doi: 10.1159/000356507 24783053 PMC3923601 source
- Not checked yetcites [14] Jonklaas J, Bianco AC, Bauer AJ,; American Thyroid Association Task Force on Thyroid Hormone Replacement. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid. 2014; 24(12): 1670- 1751. doi: 10.1089/thy.2014.0028 25266247 PMC4267409 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Results from previous studies5,33,34,35,36 that examined associations of serum thyroid function within the normal range and various long-term adverse outcomes have been inconsistent across different populations.”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion
What the sources say
- Not checked yetcites [5] Inoue K, Tsujimoto T, Saito J, Sugiyama T. Association between serum thyrotropin levels and mortality among euthyroid adults in the United States. Thyroid. 2016; 26(10): 1457- 1465. doi: 10.1089/thy.2016.0156 27539006 source
- Not checked yetcites [33] Åsvold BO, Vatten LJ, Bjøro T,; Thyroid Studies Collaboration. Thyroid function within the normal range and risk of coronary heart disease: an individual participant data analysis of 14 cohorts. JAMA Intern Med. 2015; 175(6): 1037- 1047. doi: 10.1001/jamainternmed.2015.0930 25893284 PMC4732559
- Not checked yetcites [34] Cappola AR, Arnold AM, Wulczyn K, Carlson M, Robbins J, Psaty BM. Thyroid function in the euthyroid range and adverse outcomes in older adults. J Clin Endocrinol Metab. 2015; 100(3): 1088- 1096. doi: 10.1210/jc.2014-3586 25514105 PMC4333030
- Not checked yetcites [35] Chaker L, van den Berg ME, Niemeijer MN,. Thyroid function and sudden cardiac death: a prospective population-based cohort study. Circulation. 2016; 134(10): 713- 722. doi: 10.1161/CIRCULATIONAHA.115.020789 27601558
- Not checked yetcites [36] Bano A, Dhana K, Chaker L,. Association of thyroid function with life expectancy with and without cardiovascular disease: the Rotterdam Study. JAMA Intern Med. 2017; 177(11): 1650- 1657. doi: 10.1001/jamainternmed.2017.4836 28975207 PMC5710266
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Meanwhile, some recent studies5,15,16 have suggested that even high-normal TSH concentrations are associated with increased risk of CVD and mortality among the US general population or adults with chronic kidney disease”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Introduction
What the sources say
- Not checked yetcites [5] Inoue K, Tsujimoto T, Saito J, Sugiyama T. Association between serum thyrotropin levels and mortality among euthyroid adults in the United States. Thyroid. 2016; 26(10): 1457- 1465. doi: 10.1089/thy.2016.0156 27539006 source
- Not checked yetcites [15] Rhee CM, Ravel VA, Streja E,. Thyroid functional disease and mortality in a national peritoneal dialysis cohort. J Clin Endocrinol Metab. 2016; 101(11): 4054- 4061. doi: 10.1210/jc.2016-1691 27525529 PMC5095247
- Not checked yetcites [16] Rhee CM, Kim S, Gillen DL,. Association of thyroid functional disease with mortality in a national cohort of incident hemodialysis patients. J Clin Endocrinol Metab. 2015; 100(4): 1386- 1395. doi: 10.1210/jc.2014-4311 25632971 PMC4399303
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“We included cross-product terms of exposure and mediator in the model given the previous findings that underlying cardiovascular status can be a modifier of the association between hypothyroidism and the long-term adverse health outcomes.28,29”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Methods > Statistical Analysis
What the sources say
- Not checked yetcites [28] Ro K, Yuen AD, Du L,. Impact of hypothyroidism and heart failure on hospitalization risk. Thyroid. 2018; 28(9): 1094- 1100. doi: 10.1089/thy.2017.0362 29897016 PMC6154446 source
- Not checked yetcites [29] Rhee CM, Curhan GC, Alexander EK, Bhan I, Brunelli SM. Subclinical hypothyroidism and survival: the effects of heart failure and race. J Clin Endocrinol Metab. 2013; 98(6): 2326- 2336. doi: 10.1210/jc.2013-1039 23720788 PMC3667266 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our findings provide additional support for the importance of considering variations in the normative range of thyroid hormone levels (statistically defined as between percentiles 2.5 and 97.5 in a healthy population) when assessing long-term mortality risks in the general US population.”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our findings of increased risk of all-cause mortality among participants with subclinical hypothyroidism (defined by TSH >5.6 mIU/L) mediated by CVD, compared with those with middle-normal TSH concentrations, suggest that higher TSH level may be a risk factor for CVD and also mortality, even when TSH levels are only modestly elevated.”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Moreover, Collet et al10 reported that the mortality risk at lower TSH concentrations was slightly greater in men than in women.”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion
What the sources say
- Not checked yetcites [10] Collet T-H, Gussekloo J, Bauer DC,; Thyroid Studies Collaboration. Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Arch Intern Med. 2012; 172(10): 799- 809. doi: 10.1001/archinternmed.2012.402 22529182 PMC3872478 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In general, it is well established that women are at an increased risk of progression from subclinical to overt hypothyroidism.4”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion
What the sources say
- Not checked yetcites [4] Cooper DS, Biondi B. Subclinical thyroid disease. Lancet. 2012; 379(9821): 1142- 1154. doi: 10.1016/S0140-6736(11)60276-6 22273398 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although thyroid hormone therapy should not be routinely offered to patients with subclinical hypothyroidism, our findings indicate the importance of further investigations regarding clinical effectiveness of medical interventions (such as a CVD prevention program) for specific populations with subclinical hypothyroidism or even low-normal thyroid function.”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
None of the sources cited for this claim have been checked yet.
In the paper
“Previous studies10,34,36,43 have found an increased risk of CVD and mortality among people with high-normal thyroid function partially mediated by anticoagulant factors.”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion
What the sources say
- Not checked yetcites [10] Collet T-H, Gussekloo J, Bauer DC,; Thyroid Studies Collaboration. Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Arch Intern Med. 2012; 172(10): 799- 809. doi: 10.1001/archinternmed.2012.402 22529182 PMC3872478 source
- Not checked yetcites [34] Cappola AR, Arnold AM, Wulczyn K, Carlson M, Robbins J, Psaty BM. Thyroid function in the euthyroid range and adverse outcomes in older adults. J Clin Endocrinol Metab. 2015; 100(3): 1088- 1096. doi: 10.1210/jc.2014-3586 25514105 PMC4333030
- Not checked yetcites [36] Bano A, Dhana K, Chaker L,. Association of thyroid function with life expectancy with and without cardiovascular disease: the Rotterdam Study. JAMA Intern Med. 2017; 177(11): 1650- 1657. doi: 10.1001/jamainternmed.2017.4836 28975207 PMC5710266
- Not checked yetcites [43] Bano A, Chaker L, de Maat MPM,. Thyroid function and cardiovascular disease: the mediating role of coagulation factors. J Clin Endocrinol Metab. 2019; 104(8): 3203- 3212. doi: 10.1210/jc.2019-00072 30938758
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Low thyroid hormone levels also increase systemic vascular resistance and induce endothelial dysfunction by reducing nitric oxide availability.37,38,39”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion
What the sources say
- Not checked yetcites [37] Klein I, Danzi S. Thyroid disease and the heart. Circulation. 2007; 116(15): 1725- 1735. doi: 10.1161/CIRCULATIONAHA.106.678326 17923583 source
- Not checked yetcites [38] Owen PJD, Sabit R, Lazarus JH. Thyroid disease and vascular function. Thyroid. 2007; 17(6): 519- 524. doi: 10.1089/thy.2007.0051 17614771 source
- Not checked yetcites [39] Galli E, Pingitore A, Iervasi G. The role of thyroid hormone in the pathophysiology of heart failure: clinical evidence. Heart Fail Rev. 2010; 15(2): 155- 169. doi: 10.1007/s10741-008-9126-6 19110971 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A previous study from Norway42 also found an association between high-normal TSH concentrations and CVD in women but not in men, consistent with our results.”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion
What the sources say
- Not checked yetcites [42] Asvold BO, Bjøro T, Platou C, Vatten LJ. Thyroid function and the risk of coronary heart disease: 12-year follow-up of the HUNT study in Norway. Clin Endocrinol (Oxf). 2012; 77(6): 911- 917. doi: 10.1111/j.1365-2265.2012.04477.x 22724581
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Previous studies,5,6,7,40 including those using NHANES data,5,7 reported that low thyroid function even within the normal range is associated with metabolic syndrome owing to an increase in insulin resistance and might contribute to the progression of atherosclerosis and CVD risk.41”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion
What the sources say
- Not checked yetcites [5] Inoue K, Tsujimoto T, Saito J, Sugiyama T. Association between serum thyrotropin levels and mortality among euthyroid adults in the United States. Thyroid. 2016; 26(10): 1457- 1465. doi: 10.1089/thy.2016.0156 27539006 source
- Not checked yetcites [6] Garduño-Garcia J de J, Alvirde-Garcia U, López-Carrasco G,. TSH and free thyroxine concentrations are associated with differing metabolic markers in euthyroid subjects. Eur J Endocrinol. 2010; 163(2): 273- 278. doi: 10.1530/EJE-10-0312 20516204 source
- Not checked yetcites [7] Le TN, Celi FS, Wickham EP III. Thyrotropin levels are associated with cardiometabolic risk factors in euthyroid adolescents. Thyroid. 2016; 26(10): 1441- 1449. doi: 10.1089/thy.2016.0055 27599541 PMC5067795 source
- Not checked yetcites [40] Roos A, Bakker SJL, Links TP, Gans ROB, Wolffenbuttel BHR. Thyroid function is associated with components of the metabolic syndrome in euthyroid subjects. J Clin Endocrinol Metab. 2007; 92(2): 491- 496. doi: 10.1210/jc.2006-1718 17090642 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the present study does not provide any information regarding the importance of treatment with thyroid hormone replacement if high TSH levels subsequently triggered medication use in NHANES participants.”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion > Strengths and Limitations
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Elevated thyroid hormone levels have been reported to negatively affect quality of life and cognitive function as well as the cardiovascular system in young and middle-aged populations.4”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion
What the sources say
- Not checked yetcites [4] Cooper DS, Biondi B. Subclinical thyroid disease. Lancet. 2012; 379(9821): 1142- 1154. doi: 10.1016/S0140-6736(11)60276-6 22273398 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A major strength of our study includes estimation of a potential pathway from serum TSH concentrations to mortality through CVD in a large, nationally representative sample of the US general population with individualized linkage to the national mortality database with rigorous capture of death events.”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion > Strengths and Limitations
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Even though these are all likely causing nondifferential misclassifications, the bias this may generate is not always toward the null in mediation analysis.45”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion > Strengths and Limitations
What the sources say
- Not checked yetcites [45] VanderWeele TJ. Mediation analysis: a practitioner’s guide. Annu Rev Public Health. 2016; 37: 17- 32. doi: 10.1146/annurev-publhealth-032315-021402 26653405
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Second, while it is unlikely that CVD affected serum TSH concentrations, the exposure-mediator association is not well defined temporarily, and we need to consider the possibility of reverse causation (ie, that the participants’ thyroid status prior to CVD was different from their thyroid status at the time of study entry).”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion > Strengths and Limitations
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, our data did not capture all of the CVD events during the follow-up period; therefore, effect size of the CVD mediation might be underestimated.”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion > Strengths and Limitations
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“A previous meta-analysis8 reported that subclinical hypothyroidism is associated with higher CVD risk, and thus treatment with levothyroxine is recommended when serum TSH concentrations reach 10 mIU/L or greater.4,31”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion
What the sources say
- Not checked yetcites [4] Cooper DS, Biondi B. Subclinical thyroid disease. Lancet. 2012; 379(9821): 1142- 1154. doi: 10.1016/S0140-6736(11)60276-6 22273398 source
- Not checked yetcites [31] Peeters RP. Subclinical hypothyroidism. N Engl J Med. 2017; 376(26): 2556- 2565. doi: 10.1056/NEJMcp1611144 28657873
plain- Asserted: fails — The authors may not put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The authors may not put it forward as true. The paper’s conclusions may not depend on it.
In the paper
“However, it remains unclear whether thyroid hormone replacement therapy is effective in mitigating several long-term adverse outcomes, such as CVD and death, in the general population with subclinical hypothyroidism.12”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion
What the sources say
- Not checked yetcites [12] Bekkering GE, Agoritsas T, Lytvyn L,. Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline. BMJ. 2019; 365: l2006. doi: 10.1136/bmj.l2006 31088853 source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“This recommendation has been followed by 2 recent comprehensive reviews1,12 that summarized the evidence arguing against clinical benefits of thyroid hormone replacement therapy toward quality of life or hypothyroid symptoms among adults, especially elderly individuals, with subclinical hypothyroidism.”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion
What the sources say
- Not checked yetcites [1] Biondi B, Cappola AR, Cooper DS. Subclinical hypothyroidism: a review. JAMA. 2019; 322(2): 153- 160. doi: 10.1001/jama.2019.9052 31287527 source
- Not checked yetcites [12] Bekkering GE, Agoritsas T, Lytvyn L,. Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline. BMJ. 2019; 365: l2006. doi: 10.1136/bmj.l2006 31088853 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“A previous meta-analysis8 reported that subclinical hypothyroidism is associated with higher CVD risk, and thus treatment with levothyroxine is recommended when serum TSH concentrations reach 10 mIU/L or greater.4,31”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Discussion
What the sources say
- Not checked yetcites [8] Rodondi N, den Elzen WPJ, Bauer DC,; Thyroid Studies Collaboration. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA. 2010; 304(12): 1365- 1374. doi: 10.1001/jama.2010.1361 20858880 PMC3923470 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
Self-reported coronary artery disease and nonfatal cardiovascular disease events accurately classify prevalent cardiovascular disease.
“Coronary artery diseases and nonfatal CVD events (congestive heart failure, angina, myocardial infarction, or stroke) were ascertained by self-report at baseline.”
The paper relies on this without support.
Mortality data from death certificates provided by the National Death Index accurately ascertain all-cause mortality.
“Mortality data were ascertained by the National Center for Health Statistics from death certificate information provided by the National Death Index after record matching by Social Security number, name, date of birth, race/ethnicity, sex, state of birth, and state of residence.”
The paper relies on this without support.
The mediation analysis assumes no unmeasured confounding of the exposure-mediator, exposure-outcome, and mediator-outcome relationships.
“We used a marginal structural approach within the counterfactual framework.18,26,27”
The paper relies on this without support.
A single baseline serum TSH measurement adequately represents long-term thyroid function.
“Time to event was calculated from the day of TSH measurement to the end of follow-up or the death date.”
The authors state this as an assumption.
There are no other unmeasured confounders and no confounding between the mediator and outcome as affected by exposure.
“our mediation analysis was based on the assumption that there were no other unmeasured confounders and no confounding between the mediator and outcome as affected by exposure.45”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“with CVD mediating 14.3 and 5.9% of the association, respectively (104).”
From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [104]
In the citing paper
“SCH (TSH >5.60 mIU/L) and high-normal TSH (1.96–5.60 mIU/L) were associated with increased all-cause mortality (HR = 1.90 and 1.36) vs. the middle-normal TSH group (1.20–1.95 mIU/L) (104)”
From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [104]
In the citing paper
“High-normal TSH levels impact unfavorably on mortality.”
From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [104]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
“Missing or unknown | 20 (0.7) | 10 (0.3) | 20 (0.7) | 3 (0.2)”
§ Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality > Results
Reported 0.2 · recomputed 1.818182
Citations
Cites
Hollowell, J. G., Staehling, N. W., Flanders, W. D., Hannon, W. H., Gunter, E. W., Spencer, C. A., & Braverman, L. E. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.87.2.489 · Cited by 4,279
Mediation Analysis: A Practitioner's Guide
VanderWeele, T. J. (2016) · Annual Review of Public Health · doi:10.1146/annurev-publhealth-032315-021402 · Cited by 1,985
Jonklaas, J., Bianco, A. C., Bauer, A. J., Burman, K. D., Cappola, A. R., Celi, F. S., Cooper, D. S., Kim, B. W., Peeters, R. P., Rosenthal, M. S., et al. (2014) · Thyroid® · doi:10.1089/thy.2014.0028 · Cited by 1,928
Klein, I., & Danzi, S. (2007) · Circulation · doi:10.1161/circulationaha.106.678326 · Cited by 1,324
Subclinical Hypothyroidism and the Risk of Coronary Heart Disease and Mortality
Rodondi, N., den Elzen, W. P. J., Bauer, D. C., Cappola, A. R., Razvi, S., Walsh, J. P., Åsvold, B. O., Iervasi, G., Imaizumi, M., Collet, T.-H., et al. (2010) · JAMA · doi:10.1001/jama.2010.1361 · Cited by 1,216
National health and nutrition examination survey: plan and operations, 1999-2010.
Zipf, G., Chiappa, M. M., Porter, K. S., Ostchega, Y., Lewis, B. G., & Dostal, J. (2013) · PubMed · Cited by 1,182
Chaker, L., Bianco, A. C., Jonklaas, J., & Peeters, R. P. (2017) · The Lancet · doi:10.1016/s0140-6736(17)30703-1 · Cited by 1,159
Cooper, D. S., & Biondi, B. (2012) · The Lancet · doi:10.1016/s0140-6736(11)60276-6 · Cited by 1,039
2013 ETA Guideline: Management of Subclinical Hypothyroidism
Pearce, S. H. S., Brabant, G., Duntas, L. H., Monzani, F., Peeters, R. P., Razvi, S., & Wemeau, J.-L. (2013) · European Thyroid Journal · doi:10.1159/000356507 · Cited by 877
Subclinical Hypothyroidism: A Review
Biondi, B., Cappola, A. R., & Cooper, D. S. (2019) · JAMA · doi:10.1001/jama.2019.9052 · Cited by 604
Cited by
Sorted by citations
Thyroid disorders and cardiovascular manifestations: an update
Paschou, S. Α., Bletsa, E., Stampouloglou, P. K., Tsigkou, V., Valatsou, A., Stefanaki, K., Kazakou, P., Spartalis, Μ., Spartalis, E. D., Oikonomou, E. K., et al. (2022) · Endocrine · doi:10.1007/s12020-022-02982-4 · Cited by 132
“graphy, and especially male patients have higher total plaque burden when compared to females [90].”
BackgroundRatziu, V., Scanlan, T. S., & Bruinstroop, E. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.10.018 · Cited by 118
Levothyroxine for the Treatment of Subclinical Hypothyroidism and Cardiovascular Disease
Sue, L. Y., & Leung, A. M. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.591588 · Cited by 76
“11:591588. doi: 10.3389/fendo.2020.591588 MINI REVIEW published: 21 October 2020 doi: 10.3389/fendo.2020.591588 Levothyroxine for the Treatment of Subclinical Hypothyroidism and Cardiovascular Disease Laura Y. Sue1 and Angela M. Leung1,2* 1 Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, U…”
InfluentialSelf-citationInoue, K., Streja, E., Tsujimoto, T., & Kobayashi, H. H. (2020) · Annals of Epidemiology · doi:10.1016/j.annepidem.2020.12.004 · Cited by 62
“, measurement of UACR) to the death record as the previous study did [21,22].”
Self-citationXu, Y., Derakhshan, A., Hysaj, O., Wildisen, L., Ittermann, T., Pingitore, A., Abolhassani, N., Medici, M., Kiemeney, L. A. L. M., Riksen, N. P., et al. (2023) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(23)00227-9 · Cited by 61
Self-citationWang, Y., Tan, H., Zheng, H., Ma, Z., Zhan, Y., Hu, K., Yang, Z., Yao, Y., & Zhang, Y. (2023) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2023.161895 · Cited by 53
Wu, Z., Yue, J., Li, P., Wang, Y., Zhang, H., Li, Z., Li, X., Tao, L., Gao, B., & Guo, X. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04276-3 · Cited by 51
“This method has been widely used in previous studies to quantify the mediating effect [42, 43].”
MethodLow awareness and under-diagnosis of hypothyroidism
Gottwald‐Hostalek, U., & Schulte, B. (2021) · Current Medical Research and Opinion · doi:10.1080/03007995.2021.1997258 · Cited by 43
Hypothyroidism and metabolic cardiovascular disease
Patrizio, A., Ferrari, S. M., Elia, G., Ragusa, F., Balestri, E., Botrini, C., Rugani, L., Mazzi, V., Antonelli, A., Fallahi, P., et al. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1408684 · Cited by 57
“These results have also been con fi rmed in different populations all around the world such as USA (21) and Asia (22, 23).”
BackgroundUpdate on subclinical thyroid dysfunction
Hashimoto, K. (2022) · Endocrine Journal · doi:10.1507/endocrj.ej22-0182 · Cited by 44
“Other cross-sectional and longitudinal studies reported that SCH may be an independent risk factor for CHD and may increase the risk of cardiovascular outcomes [26-34].”
BackgroundMüller, P., Leow, M. K., & Dietrich, J. W. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.942971 · Cited by 39
“Similar observations were made in another populationbased study that found low-normal, high-normal and elevated TSH to be associated with higher all-cause mortality than middle-normal TSH (135).”
ResultChen, Y., Tian, S., Wu, J., Li, H., Li, S., Xu, Z., Liang, X., Adhikari, V. P., Xiao, J., Song, J.-Y., et al. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad016 · Cited by 33
Zhang, X., Wang, Y., Wang, H., & Zhang, X. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad558 · Cited by 29
Inoue, K., Nianogo, R. A., Telesca, D., Goto, A., Khachadourian, V., Tsugawa, Y., Sugiyama, T., Mayeda, E. R., & Ritz, B. R. (2020) · International Journal of Epidemiology · doi:10.1093/ije/dyaa263 · Cited by 29
“Cardiovascular disease was classified using ICD–10 codes I00–09, I11, I13, I20–51 and I60–69.27 Covariates Demographic variables included age, sex (male, female), race/ethnicity (non-Hispanic White, non-Hispanic Black, Mexican-American or others), citizenship status (US or other), educational status (less than high sc…”
MethodInfluentialSelf-citationWu, Z., Yue, J., Zhou, D., Chen, S., Zhao, Y., Zhang, H., Liu, Y., Li, X., Wang, W., Zhang, J., et al. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac110 · Cited by 24
Effect of coffee consumption on thyroid function: NHANES 2007-2012 and Mendelian randomization
Zhao, G., Wang, Z., Ji, J., & Cui, R. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1188547 · Cited by 26
“Additionally, subclinical hypothyroidism is associated with a variety of cardiovascular diseases and all-cause mortality (37, 38).”
BackgroundSubclinical Thyroid Dysfunction and the Risk of Cardiovascular Disease
Stojković, M., & Žarković, M. (2020) · Current Pharmaceutical Design · doi:10.2174/1381612826666201118094747 · Cited by 23
Wan, H., Yu, G., He, Y., Liu, S., Chen, X., Jiang, Y., Duan, H., Xu, L., Liu, L., & Shen, J. (2024) · Annals of Medicine · doi:10.1080/07853890.2024.2318418 · Cited by 23
“…tsh was measured by microparticle enzyme immunoassay, serum Ft4 by two-step enzyme immunoassay and serum Ft3 by competitive binding immunoassay [25,26]. in the sPeeD-shunde study, blood samples were collected between 7:00 am and 10:00 am from participants who had fasted for 10 h. the levels of…”
MethodInfluentialAlomair, B. M., Al-Kuraishy, H. M., Al-Gareeb, A. I., Alshammari, M. A., Alexiou, A. T., Papadakis, M., Saad, . M., & Batiha, G. E. (2024) · Thyroid Research · doi:10.1186/s13044-024-00199-3 · Cited by 25
Wang, X., Wang, H., Li, Q., Wang, P., Xing, Y., Zhang, F., Li, J., & Shan, Z. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac417 · Cited by 20
Inoue, K., Guo, R., Lee, M. L., Ebrahimi, R., Neverova, N. V., Currier, J. W., Bashir, M. T., & Leung, A. M. (2022) · Thyroid · doi:10.1089/thy.2022.0393 · Cited by 20
Self-citationHu, M., Wei, J., Hu, Y., et al. (2022) · Environmental Research · doi:10.1016/j.envres.2022.114860 · Cited by 20
Decision Making in Subclinical Thyroid Disease
Evron, J. M., & Papaleontiou, M. (2021) · Medical Clinics of North America · doi:10.1016/j.mcna.2021.05.014 · Cited by 25
Relationship Between Subclinical Hypothyroidism and the Risk of Cardiovascular Complications
Kaushik, A., & Agrawal, M. (2023) · Cureus · doi:10.7759/cureus.33708 · Cited by 21
“T4 is one of the most significant regulators for monitoring cardiac activity and cardiovascular hemodynamics [16].”
BackgroundEffect of physical exercise in people with hypothyroidism: systematic review and meta-analysis
Duñabeitia, I., González-Devesa, D., Varela, S., Diz, J. C., & Ayán, C. (2023) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365513.2023.2286651 · Cited by 19
“It should also be noted that an increase in the risk of cardiovascular disease and mortality has been observed in people with SCH [8].”
BackgroundDuan, Q., Huang, H. F., Zhang, S., Wang, Y., Lu, D., Wan, L., Sun, Y., & Wu, Y. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1389714 · Cited by 18
“The potential nonlinear association was assessed using a restricted cubic spline (RCS) model with three knots placed at the 10th, 50th, and 90th percentiles of CDAI (32, 33).”
MethodThe Two Faces of Janus: Why Thyrotropin as a Cardiovascular Risk Factor May Be an Ambiguous Target
Dietrich, J. W., Hoermann, R., Midgley, J. E. M., Bergen, F., & Müller, P. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.542710 · Cited by 19
“Our analysis suggests a possible mechanism linking TSH to cardiovascular complications, which is a sensible alternative to the thyroid failure hypothesis by other authors (16).”
BackgroundResultMachine Learning Coronary Artery Disease Prediction Based on Imaging and Non-Imaging Data
Kigka, V. I., Georga, E. I., Tsakanikas, V., Kyriakidis, S., Tsompou, P. I., Siogkas, P. K., Michalis, L. K., Naka, K. Κ., Neglia, D., Rocchiccioli, S., et al. (2022) · Diagnostics · doi:10.3390/diagnostics12061466 · Cited by 18
“In the presented model, we observe that the most significant predictor for the prognosis of CAD is thyroid stimulating hormone, which confirms the effect of the thyroid hormones on the cardiovascular system [29,30].”
BackgroundLi, J., Ren, Y., Wang, L., Zou, X., Ding, X., Hou, T., Zhang, Q., Tang, S., Han, X., Song, L., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.14491 · Cited by 16
Wang, S., Gu, L., Chen, J. C., Jiang, Q., Sun, J., Wang, H., & Wang, L. (2022) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2022.109990 · Cited by 15
Thyrotropin inhibits osteogenic differentiation of human periodontal ligament stem cells
Zeng, Y., Deng, J., Jiang, Q.-L., Wang, C., Zhang, L., Li, T., & Jiang, J. (2023) · Journal of Periodontal Research · doi:10.1111/jre.13109 · Cited by 18
Luo, Y., Wu, F., Huang, Z., Gong, Y., & Zheng, Y. (2022) · Lipids in Health and Disease · doi:10.1186/s12944-022-01749-0 · Cited by 24
Holley, M., Razvi, S., Farooq, M. S., Dew, R., Maxwell, I., & Wilkes, S. (2024) · Systematic Reviews · doi:10.1186/s13643-024-02548-7 · Cited by 17
Iacoviello, M., Santamato, V., Pagano, A., & Marengo, A. (2025) · Frontiers in Digital Health · doi:10.3389/fdgth.2025.1583399 · Cited by 16
“Further investigations into the connection between subclinical hypothyroidism and cardiovascular diseases have also examined the potential for accurately predicting mortality and hospitalization in patients with HF (19, 20).”
Fang, H., Zhao, R., Cui, S., & Wan, W. (2022) · Aging · doi:10.18632/aging.204352 · Cited by 15
Campi, I., Dell’Acqua, M., Stellaria Grassi, E., Cristina Vigone, M., & Persani, L. (2023) · European Thyroid Journal · doi:10.1530/etj-23-0012 · Cited by 13
L-T4 therapy in the presence of pharmacological interferents
Benvenga, S. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.607446 · Cited by 13
“9% of the association, respectively (104).”
Iodine‐Induced Hypothyroidism and Long‐Term Risks of Incident Heart Failure
Inoue, K., Guo, R., Lee, M. L., Neverova, N. V., Ebrahimi, R., Currier, J. W., Bashir, M. T., & Leung, A. M. (2023) · Journal of the American Heart Association · doi:10.1161/jaha.123.030511 · Cited by 13
Self-citationA Clinical Debate: Subclinical Hypothyroidism
Jasim, S., Abdi, H., Gharib, H., & Biondi, B. (2021) · Intern J Endocrinol Metab · doi:10.5812/ijem.115948 · Cited by 15
“An association of SCH with ischemic heart disease and mortality was also suggested (28, 29).”
BackgroundLu, Y., Chen, S., Jin, H., Tang, L., & Xia, M. X. (2022) · Journal of Applied Toxicology · doi:10.1002/jat.4401 · Cited by 15
“X04), which referred to previous studies (Cai et al., 2020; Inoue et al., 2020).”
Wang, S., Sun, J., Gu, L., Wang, Y., Du, C., Wang, H., Ma, Y., & Wang, L. (2022) · Biological Trace Element Research · doi:10.1007/s12011-022-03451-9 · Cited by 12
Cardiovascular outcomes in subclinical thyroid disease: an update
Ettleson, M. D. (2023) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000818 · Cited by 15
Souza, D. S., Marques, L. P., Costa, A., Cruz, J. S., Rhana, P., Santos‐Miranda, A., Joviano‐Santos, J. V., Durço, A. O., de Vasconcelos, C. M. L., & Roman‐Campos, D. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120945 · Cited by 14
Wang, S., Gu, L., Zhu, J. W., Shan, T., Sun, J., Jiang, Q., Wang, H., Zhao, D., Wang, Q., & Wang, L. (2022) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2022.110116 · Cited by 13
Yu, G., Liu, S. M., Song, C., Ma, Q., Chen, X., Jiang, Y., Duan, H., He, Y., Wang, D., Wan, H., et al. (2024) · European Thyroid Journal · doi:10.1530/etj-23-0130 · Cited by 13
“In the NHANES datasets, serum TSH levels were measured using a microparticle enzyme immunoassay, serum FT4 levels were measured using a two-step enzyme immunoassay, and serum FT3 levels were measured using a competitive binding immunoenzymatic assay (27, 28).”
Isailă, O.-M., Stoian, V. E., Fulga, I., Piraianu, A. I., & Hostiuc, S. (2024) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd11040098 · Cited by 13
“A recently conducted joint study of 9020 U.S. adults, by Inoue et al., found that cardiovascular disease mediated the association between subclinical hypothyroidism and all-cause mortality, especially among women and the elderly [65].”
BackgroundUyar, G. C., & Kılıç, M. K. (2024) · BMC Geriatrics · doi:10.1186/s12877-024-05643-5 · Cited by 11
Association Between Carotid Atherosclerosis and Atrial Fibrillation, Cardiac, and Renal Function
Rimmele, D. L., Borof, K., Jensen, M., Behrendt, C., Cheng, B., Debus, E. S., Gerloff, C. P., & Thomalla, G. (2022) · European Journal of Vascular and Endovascular Surgery · doi:10.1016/j.ejvs.2022.01.010 · Cited by 11
Wang, S., Zhao, D., Yang, T., Deng, B., Sun, J., Gu, L., Wang, H., & Wang, L. (2023) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2023.01.007 · Cited by 10
Wang, L., Xu, H., Yang, Y., Guan, H., He, X., Wu, R., Wu, J., Yuan, N., Guo, T., Zhang, Y., et al. (2023) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2023.133094 · Cited by 10
Chen, J., Zhang, L., & Zhang, X. (2024) · Frontiers in Public Health · doi:10.3389/fpubh.2024.1366485 · Cited by 13
Zhang, Z., Wang, C., Lin, C., Wu, Y., Wei, J., Lu, J., Chen, B., Wu, C., Zhang, X., Yang, Y., et al. (2024) · The Lancet Regional Health - Western Pacific · doi:10.1016/j.lanwpc.2024.101222 · Cited by 13
“38,39 If the relationship was found to be nonlinear, a recursive algorithm was employed to determine the in fl ection point between O 3 exposure and CVD mortality.”
MethodT4 rather than TSH correlates with BMD among euthyroid adults
Sheng, N., Xing, F., Wang, J., Duan, X., & Xiang, Z. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1039079 · Cited by 10
Liu, G., Ren, M., Du, Y., Zhao, R., Wu, Y. F., Liu, Y., & Liang, Q. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1263861 · Cited by 10
“Inadequate serum thyroid hormone levels impair cardiac function and may result in multiple cardiovascular risk factors, such as endothelial dysfunction, increased intima-media thickness, increased vascular resistance, and pericardial effusion (3).”
BackgroundQin, Z., Muhanhali, D., & Ling, Y. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad735 · Cited by 12
Nilkantham, S., Singh, A., Majumdar, V., Harini, K. N., & Snigdha, A. (2025) · Journal of Medical Internet Research · doi:10.2196/54078 · Cited by 12
“Hence, the TSH screening test is considered essential for thyroid dysfunction, and a disproportionately high concentration of TSH may warrant thyroxine and triiodothyronine measurements as well [8-10].”
Lifestyle Interventions to Tackle Cardiovascular Risk in Thyroid Hormone Signaling Disorders
Rodolfi, S., Rurale, G., Marelli, F., Persani, L., & Campi, I. (2025) · Nutrients · doi:10.3390/nu17132053 · Cited by 12
“…between subclinical hypothyroidism, impaired endothelial function [27,28], dyslipidemia, increased insulin resistance, hypertension and left ventricular dysfunction have been reported [34,35], the significance of the impact of hypothyroidism on CVDs and CV mortality remains undefined [36].”
Dell'Aquila, M., Rossi, C. S., Caldonazo, T. M. M., Cancelli, G., Harik, L., Soletti, G. J., An, K. R., Leith, J., Kirov, H., Ibrahim, M., et al. (2024) · JTCVS Open · doi:10.1016/j.xjon.2024.02.009 · Cited by 10
Autoimmune Thyroid Disease in the United States: Population Prevalence, Diagnosis Rates, and Trends
Dillon, C. F., Weisman, M. H., Leung, A. M., Brent, G. A., & Miller, F. W. (2025) · Journal of the Endocrine Society · doi:10.1210/jendso/bvaf120 · Cited by 9
Self-citationAbdul, M. R., Rahim, S. M., & Saleh, A. (2023) · HAYATI Journal of Biosciences · doi:10.4308/hjb.30.6.1054-1060 · Cited by 10
“Numerous research have investigated the potential links between subclinical hypothyroidism and CVD (Leong et al. 2017; Inoue et al. 2020).”
BackgroundGu, L., Wang, S., Du, C., Deng, B., Ma, Y., Yang, T., Shan, T., Sun, J., Wang, H., & Wang, L. (2023) · Diabetes Obesity and Metabolism · doi:10.1111/dom.15078 · Cited by 7
“During the 200 018 person-years of follow-up (median follow-up, 16.8 years; the maximum follow-up, 20.8 years), 3528 deaths T A B L E 1 B as el in e ch ar ac te ri st ic s o f th e st ud y po pu la ti o n C en ti le s o f G G ap (% ) C ha ra ct er is ti c O ve ra ll 1 st -5 th 6 th -2 0 th 2 1 st -4 0 th 4 1 st -6 0 t…”
MethodInfluentialIs subclinical hypothyroidism associated with cardiovascular disease in the elderly?
Yamamoto, K., Nakano, Y., Soejima, Y., Suyama, A., Oguni, K., Hasegawa, K., & Otsuka, F. (2025) · Endocrine Connections · doi:10.1530/ec-24-0601 · Cited by 8
“A study using data from the National Health and Nutrition Examination Survey in the United States revealed that SCH was associated with all-cause mortality mediated by cardiovascular disease (CVD) (6).”
Kim, H., Jung, D. Y., Lee, S., Cho, J., Yim, H. W., & Kim, H. (2022) · Journal of Diabetes · doi:10.1111/1753-0407.13315 · Cited by 7
“Subclinical hypothyroidism, along with hypothyroidism, has been medically evaluated as a risk factor for cardiovascular diseases.(30) In this study, in the euthyroid state, the lower the TSH level, the higher the heart rate, and the tendency to increase significantly even after 2 years.”
BackgroundAl-Gburi, A. J. J., Al-Obaidi, S. R. Y., & Abdullah, W. H. (2023) · Ghana Medical Journal · doi:10.4314/gmj.v57i1.6 · Cited by 7
Brenta, G., Nepote, A., Barreto, A., Musso, C., Faingold, C., Fossati, P., Antonelli, A., Fallahi, P., Famà, F., & Meroño, T. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1162626 · Cited by 7
Yuan, J., Jin, Z., Qin, Y., Xing, Y., Yu, Z., Zhang, Y., Wu, H., Zheng, Q., Hui, Y., Guo, S., et al. (2024) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2024.01.032 · Cited by 7
Nanoscale organization of cardiac calcium channels is dependent on thyroid hormone status
Charest, A., Nasta, N., Siddiqui, S., Menkes, S., Thomas, A., Saad, D., Forman, J., Huang, X., Sison, C. P., Gerdes, A. M., et al. (2024) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00272.2024 · Cited by 7
Associations of thyroid hormones with chronic diarrhea and constipation in euthyroid individuals
Zeng, W., Wang, Y., & Zhang, L. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1395743 · Cited by 7
“Participants were classi fi ed as euthyroid if their serum TSH and FT4 levels were within the normal limits (16, 17).”
BackgroundInfluentialGökkaya, N., & Aydın, K. (2024) · Scientific Reports · doi:10.1038/s41598-024-78185-w · Cited by 6
“Hypothyroidism, even subclinical hypothyroidism, has been associated with various health problems such as dyslipidemia, hypertension, obesity, and diabetes 19–21 .”
Ni, W.-C., Kong, S., Lin, K., Huang, Y., Li, J., Shi, S., Lu, Y.-C., Cheng, L., Chen, C., & Zhou, H. (2023) · European journal of medical research · doi:10.1186/s40001-023-01149-9 · Cited by 7
“Patients with high normal TSH were at greater risk of all-cause death and CVD than those with mid- to normal TSH [22].”
BackgroundZhang, F., Wan, Y., Tang, H., Zhao, D., Zhu, S., Ruan, L., & Zhu, W. (2023) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2023.167093 · Cited by 6
Yao, L., Ni, J., Wei, M., Li, T., Long, Z., Shi, J., & Tian, J. (2024) · European Neurology · doi:10.1159/000540277 · Cited by 8
“We used restricted cubic spline fi tted for logistic models with three knots at the 25th, 50th, and 75th percentiles of depression scores and a p value for nonlinearity was calculated [29].”
Fang, X., Hu, R., Fei, S., Ding, Z., Zhao, J., & Shang, J. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1437386 · Cited by 6
“Kosuke et al. discovered that CVDs acted as a mediator connecting SCH and high-normal TSH levels with all-cause mortality among US adults, especially in women and the elderly, suggesting possible threats to the health of patients even with only mildly elevated TSH levels (22).”
BackgroundLu, X., Wang, A., Liu, K., Chen, Y., Chen, W., Mao, Y., & Ye, D. (2024) · Biological Trace Element Research · doi:10.1007/s12011-024-04395-y · Cited by 6
“In this study, we used restricted cubic spline models with three knots, corresponding to the 10th, 50th, and 90th percentiles [33–35].”
Sun, Q., Wang, S., Han, X., Gu, L., Wang, H., Yang, Q., & Wang, L. (2025) · BMC Public Health · doi:10.1186/s12889-025-22428-6 · Cited by 6
“Furthermore, to explore the dose-response relationship between VAI and mortality, restricted cubic spline (RCS) regression with 3 default knots at the 10th, 50th and 90th percentiles of VAI was conducted for visualization [27].”
Che, W., Wang, Y., Wang, X., & Lyu, J. (2022) · Frontiers in Public Health · doi:10.3389/fpubh.2022.1000415 · Cited by 6
Song, J., Hu, J., Li, L., Xu, Z., Li, J., Sun, S., & Chen, C. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1323994 · Cited by 6
Liu, K., Lu, X., Wang, A., Chen, W., Chen, Y., Li, J., Sun, X., Huang, L., He, Z., Wen, C., et al. (2024) · Nutrition Journal · doi:10.1186/s12937-024-00992-8 · Cited by 6
“Given the complex survey designs adopted by NHANES, all estimates accounted for sample weights, clustering, and stratification [19].”
MethodFolate deficiency may increase the risk for elevated TSH in patients with type 2 diabetes mellitus
Lin, L., Du, Y., Niu, G., Xia, S., & Liu, J. (2023) · BMC Endocrine Disorders · doi:10.1186/s12902-023-01422-2 · Cited by 5
“Subclinical hypothyroidism and elevated TSH concentration is associated with an increased risk for CVD and all-cause mortality, particularly in individuals with high CVD risk (e.g. T2DM patients) [12, 13].”
BackgroundLipid Profile Pitfalls in Subclinical Hypothyroidism Pathophysiology and Treatment
Nicolaou, M., & Toumba, M. (2024) · Lipidology · doi:10.3390/lipidology1020008 · Cited by 8
Fan, M., Song, S., Chu, T., Li, R., Yue, M., Li, X., & Yang, J. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1458039 · Cited by 5
Chen, J., Lin, S., Wang, X., et al. (2023) · Biological Trace Element Research · doi:10.1007/s12011-023-03727-8 · Cited by 5
“For example, Mg is the raw material of various enzymes and coenzymes, and regulates energy metabolism, bone development, and neuromuscular excitability [3].”
Causal inference and machine learning in endocrine epidemiology
Inoue, K. (2024) · Endocrine Journal · doi:10.1507/endocrj.ej24-0193 · Cited by 5
“Another study investigated how subclinical hypothyroidism and high-normal serum thyrotropin (TSH) levels contribute to mortality mediated through cardiovascular disease [10].”
Self-citationLi, J., Wan, S., Dai, X., Cui, Y., & Lu, Z. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1530025 · Cited by 5
Prognostic Value of Normal Thyroid Stimulating Hormone in Long-Term Mortality in Patients With STEMI
Sun, L., Xiao, K., Miao, Z., Zhang, Y., Jin, S., Shi, N., Zhang, H., Zhao, T., & Li, J. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.806997 · Cited by 5
“(32) have reported that a U-curved association between TSH and the risk of all-cause mortality in the cohort study of 9,020 US adults and higher TSH levels (>1.”
Background2023 Korean Thyroid Association Management Guidelines for Patients with Subclinical Hypothyroidism
Chung, H. K., Ku, E. J., Yoo, W. S., Kang, Y. E., Kim, K. J., Kim, B. H., Kim, T. Y., Park, Y. J., Ahn, C. H., Yoon, J. H., et al. (2023) · International Journal of Thyroidology · doi:10.11106/ijt.2023.16.1.32 · Cited by 6
Inoue, K., Noh, J. Y., Yoshihara, A., Watanabe, N., Matsumoto, M., Fukushita, M., Suzuki, N., Hoshiyama, A., Mitsumatsu, T., Suzuki, A., et al. (2021) · Journal of the Endocrine Society · doi:10.1210/jendso/bvab181 · Cited by 5
“Ample evidence has shown that, if untreated or uncontrolled, such hypothyroid status increases the risk of long-term adverse health outcomes (eg, cardiovascular disease and death) [7-11].”
BackgroundSelf-citationTsilingiris, D., Stratigou, T., Kounatidis, D., Vallianou, N. G., Karampela, Ι., & Dalamaga, Μ. (2025) · Metabolism Open · doi:10.1016/j.metop.2025.100394 · Cited by 4
“Overall, the net result is an increased incidence of cardiovascular events in SH than the general population, which also mediates the association of SH with an increased overall mortality [40], particularly in those with TSH levels ≥ 10 mIU/L [4,41].”
Janovsky, C. C. P. S., Meneghini, V., Tebar, W. R., Martins, J. R. M., Sgarbi, J. A., Teixeira, P. D. F. D. S., Santos, I. S., Jones, S. R., Blaha, M. J., Toth, P. P., et al. (2025) · Metabolites · doi:10.3390/metabo15090606 · Cited by 4
“Such deficits exacerbate cardiovascular risk by fostering frailty, reducing metabolic resilience, and weakening immune responses [5,20].”
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“To depict the C-R relationships between long-term exposure to PM 2.5 constituents and all-cause mortality, we adopted restricted cubic spline function with three knots at the 10th, 50th and 90th percentiles to smooth the exposure of interest in the multivariable-adjusted model (Inoue et al., 2020).”
InfluentialHypothyroidism predicts worsened prognosis in patients undergoing percutaneous coronary intervention
Cohen, B., Bental, T., Perl, L., Assa, H. V., Codner, P., Orvin, K., Talmor‐Barkan, Y., Levi, A., Kornowski, R., & Perl, L. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.984952 · Cited by 4
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“org CVD in the general population (53, 54).”
BackgroundHoffmann, M. A., Knoll, S. N., Baqué, P.-E., Rosar, F., Scharrer, I., Reuss, S., & Schreckenberger, M. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12185905 · Cited by 4
“analyzed data based on a nationally representative database of US adults [20].”
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Best Achievements in Clinical Thyroidology in 2020
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“To explore the concentration-response (C-R) relationship between PM 2.5 concentrations and prevalence of thyroid nodules, PM 2.5 was fitted as a smooth term in age-and sex-adjusted models using a restricted cubic spline (RCS) with three knots at the 10th, 50th, and 90th percentiles [43].”
InfluentialCentral hypothyroidism and cardiovascular disease: a Spanish cohort observational study
Guerrero‐Pérez, F., Iglesias, P., Fano, M. P., Rodríguez, M. D. M., Biagetti, B., Cordido, F., Novoa-Testa, I., García-Centeno, R., Fernández, L. G., Araujo-Castro, M., et al. (2025) · HORMONES · doi:10.1007/s42000-025-00707-6 · Cited by 4
Liu, L., Zhang, H., Chen, X., Liu, Z., Zhao, H.-Y., Ma, S., Zhao, M., Shen, P., Sun, Y., Lin, H., et al. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1640086 · Cited by 4
“Additionally, population-based studies have also illustrated that SCH increases the incidence of heart failure, coronary heart disease, and stroke and thereby increases the risk of cardiovascular mortality and all-cause mortality (9 – 12).”
Metadata
- Authors
- Inoue, K., Ritz, B., Brent, G. A., Ebrahimi, R., Rhee, C. M., & Leung, A. M.
- Affiliations
- University of California, Los Angeles (US)
- University of California, Irvine (US)
- Corresponding author
- Inoue, Kosuke
- Venue
- JAMA Network Open
- Publisher
- American Medical Association (AMA)
- Published
- 2020-02-07
- Volume
- 3
- Issue
- 2
- Pages
- e1920745
- ISSN
- 2574-3805 (ISSN-L)
- PMC
- PMC12064075
- OpenAlex
- W3005006611
- Semantic Scholar
- 3f19a13e8db57a3ff39575d0c47927ac5942739c
- Cited by
- 191
- References
- 41
- Citations by year
- 2026: 19 · 2025: 39 · 2024: 42 · 2023: 41 · 2022: 31 · 2021: 13 · 2020: 6
- FWCI
- 17.16
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- JAMA Network Open (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P2CHD041022)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- subclinical hypothyroidism, cardiovascular disease, all-cause mortality, thyroid-stimulating hormone, mediation analysis, natural direct and indirect effects, free thyroxine, thyroid function
- MeSH terms
- Adult, Aged, Cardiovascular Diseases, Cause of Death, Female, Humans, Hypothyroidism, Male, Middle Aged, Nutrition Surveys, Risk Factors, Thyrotropin, United States, Cohort Studies, Proportional Hazards Models
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
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