The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Levothyroxine Treatment of Subclinical Hypothyroidism, Fatal and Nonfatal Cardiovascular Events, and Mortality
Open accessAbstract
BACKGROUND Subclinical hypothyroidism (SCH) has been associated with ischemic heart disease (IHD); however, it is unknown whether treatment of SCH with levothyroxine sodium will reduce the risk of IHD. The aim of this study was to investigate the association between levothyroxine treatment of SCH with IHD morbidity and mortality. METHODS We used the United Kingdom General Practitioner Research Database to identify individuals with new SCH (serum thyrotropin levels of 5.01-10.0 mIU/L and normal free thyroxine levels) recorded during 2001 with outcomes analyzed until March 2009. All analyses were performed separately for younger (40-70 years) and older (>70 years) individuals. Hazard ratios (HRs) for IHD events (fatal and nonfatal) were calculated after adjustment for conventional IHD risk factors, baseline serum thyrotropin levels, and initiation of levothyroxine treatment as a time-dependent covariate. RESULTS Subclinical hypothyroidism was identified in 3093 younger and 1642 older individuals. For a median follow-up period of 7.6 years, 52.8% and 49.9% of younger and older patients with SCH were treated with levothyroxine, respectively. There were 68 incident IHD events in 1634 younger patients treated with levothyroxine (4.2%) vs 97 IHD events in 1459 untreated individuals (6.6%) (multivariate-adjusted HR, 0.61; 95% CI, 0.39-0.95). In contrast, in the older group there were 104 events in 819 treated patients (12.7%) vs 88 events in 823 untreated individuals (10.7%) (HR, 0.99; 95% CI, 0.59-1.33). CONCLUSIONS Treatment of SCH with levothyroxine was associated with fewer IHD events in younger individuals, but this was not evident in older people. An appropriately powered randomized controlled trial of levothyroxine in SCH examining vascular outcomes is now warranted.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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
“Subclinical hypothyroidism is associated with increased risk of cardiovascular mortality in younger (<65 years) populations but not in older (≥65 years) individuals.151,152”
From Hypothyroidism (2024) · cites this paper as [152]
In the citing paper
“treatment of subclinical hypothyroidism with levothyroxine in younger individuals was linked with fewer adverse cardiovascular outcomes in younger but not older individuals.151,152”
From Hypothyroidism (2024) · cites this paper as [152]
In the citing paper
“In an additional retrospective study, fewer ischemic heart disease events were associated with treatment of SCH in those under age 70 years (53).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [53]
In the citing paper
“An analysis of the United Kingdom general practitioner registry showed that LT4 therapy is associated with a lower number of coronary ischemic events in young subjects with SC-HT (40–70 years) but not in older ones [33].”
From Thyroid and heart, a clinically relevant relationship (2021) · cites this paper as [33]
In the citing paper
“Furthermore, a retrospective observational study showed that treatment of SCH with levothyroxine was associated with fewer ischemic heart disease events in younger individuals, but this was not evident in older people (102).”
From Thyroid Hormones and Cardiovascular Function and Diseases (2018) · cites this paper as [102]
In the citing paper
“findings indicating a protective effect of mild or subclinical primary hypothyroidism on cardiovascular mortality risk in the elderly (55).”
From The diagnosis and management of central hypothyroidism in 2018 (2019) · cites this paper as [55]
Citations
Cites
The Colorado Thyroid Disease Prevalence Study
Canaris, G. J., Manowitz, N. R., Mayor, G., & Ridgway, E. C. (2000) · Archives of Internal Medicine · doi:10.1001/archinte.160.4.526 · Cited by 2,824
Subclinical Thyroid Disease: Scientific Review and Guidelines for Diagnosis and Management
Surks, M. I., Ortiz, E., Daniels, G. H., Sawin, C. T., Col, N. F., Cobin, R. H., Franklyn, J. A., Hershman, J. M., Burman, K. D., Denke, M. A., et al. (2004) · JAMA · doi:10.1001/jama.291.2.228 · Cited by 1,800
The English indices of deprivation 2004
Noble, M., Wright, G., Dibben, C., Smith, G., McLennan, D., Anttila, C., Barnes, H., Mokhtar, C., Noble, S., & Gardner, J. (2004) · Cited by 1,494
The Clinical Significance of Subclinical Thyroid Dysfunction
Biondi, B., & Cooper, D. S. (2008) · Endocrine Reviews · doi:10.1210/er.2006-0043 · Cited by 1,418
Hak, A. E., Pols, H. A. P., Visser, T. J., Drexhage, H. A., Hofman, A., & Witteman, J. C. M. (2000) · Annals of Internal Medicine · doi:10.7326/0003-4819-132-4-200002150-00004 · Cited by 1,336
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
Self-citationThyroid Status, Disability and Cognitive Function, and Survival in Old Age
Gussekloo, J. (2004) · JAMA · doi:10.1001/jama.292.21.2591 · Cited by 899
Thyroid Status, Cardiovascular Risk, and Mortality in Older Adults
Cappola, A. R., Fried, L. P., Arnold, A. M., Danese, M. D., Kuller, L. H., Burke, G. L., Tracy, R. P., & Ladenson, P. W. (2006) · JAMA · doi:10.1001/jama.295.9.1033 · Cited by 862
Jick, H., Jick, S. S., & Derby, L. E. (1991) · BMJ · doi:10.1136/bmj.302.6779.766 · Cited by 839
Surks, M. I., & Hollowell, J. G. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-1499 · Cited by 750
Parle, J. V., Maisonneuve, P., Sheppard, M. C., Boyle, P., & Franklyn, J. A. (2001) · The Lancet · doi:10.1016/s0140-6736(01)06067-6 · Cited by 669
The UK General Practice Research Database
Walley, T., & Mantgani, A. (1997) · The Lancet · doi:10.1016/s0140-6736(97)04248-7 · Cited by 624
Subclinical thyroid dysfunction as a risk factor for cardiovascular disease
Walsh, J. P., Bremner, A. P., Bulsara, M. K., O’Leary, P., Leedman, P. J., Feddema, P., & Michelangeli, V. (2005) · Archives of Internal Medicine · doi:10.1001/archinte.165.21.2467 · Cited by 536
Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death
Rodondi, N., Newman, A. B., Vittinghoff, E., de Rekeneire, N., Satterfield, S., Harris, T. B., & Bauer, D. C. (2005) · Archives of Internal Medicine · doi:10.1001/archinte.165.21.2460 · Cited by 503
Meta-analysis: Subclinical Thyroid Dysfunction and the Risk for Coronary Heart Disease and Mortality
Ochs, N., Auer, R., Bauer, D. C., Nanchen, D., Gussekloo, J., Cornuz, J., & Rodondi, N. (2008) · Annals of Internal Medicine · doi:10.7326/0003-4819-148-11-200806030-00225 · Cited by 477
Taddei, S., Caraccio, N., Virdis, A., Dardano, A., Versari, D., Ghiadoni, L., Salvetti, A., Ferrannini, E., & Monzani, F. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030039 · Cited by 431 · cited 1×
“6 (1-21) Contact with health professionals per year per participant, median (range) 1.”
BackgroundDanese, M. D., Ladenson, P. W., Meinert, C. L., & Powe, N. R. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.9.2993 · Cited by 423
Acute respiratory-tract infections and risk of first-time acute myocardial infarction
Meier, C. R., Jick, S. S., Derby, L. E., Vasilakis‐Scaramozza, C., Jick, H., Meier, C. R., Jick, S. S., Derby, L. E., Vasilakis‐Scaramozza, C., & Jick, H. (1998) · The Lancet · doi:10.1016/s0140-6736(97)11084-4 · Cited by 390
Razvi, S., Ingoe, L., Keeka, G., Oates, C., McMillan, C., & Weaver, J. U. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1869 · Cited by 389
Self-citationRisk for Ischemic Heart Disease and All-Cause Mortality in Subclinical Hypothyroidism
Imaizumi, M., Akahoshi, M., Ichimaru, S., Nakashima, E., Hida, A., Soda, M., Usa, T., Ashizawa, K., Yokoyama, N., Maeda, R., et al. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031089 · Cited by 373
Left Ventricular Diastolic Dysfunction in Patients with Subclinical Hypothyroidism
Biondi, B., Fazio, S., Palmieri, E. A., Carella, C., Panza, N., Cittadini, A., Bonè, F., Lombardi, G., & Saccà, L. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.6.5733 · Cited by 334
Razvi, S., Shakoor, A., Vanderpump, M., Weaver, J. U., & Pearce, S. H. S. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0167 · Cited by 330
Self-citationThyroid hormone replacement for subclinical hypothyroidism
Villar, H. C. C. E., Saconato, H., Valente, O., & Atallah, Á. N. (2007) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003419.pub2 · Cited by 329
Danese, M. D., Ladenson, P. W., Meinert, C. L., et al. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.9.6841 · Cited by 308
Razvi, S., Weaver, J. U., Vanderpump, M. P. J., & Pearce, S. H. S. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1749 · Cited by 264
Self-citationBoekholdt, S. M., Titan, S. M., Wiersinga, W. M., Chatterjee, K., Basart, D. C. G., Luben, R., Wareham, N. J., & Khaw, K. (2010) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2009.03640.x · Cited by 167
PRECLINICAL HYPOTHYROIDISM: A RISK FACTOR FOR CORONARY HEART-DISEASE*1
Bastenie, P. A. (1971) · The Lancet · doi:10.1016/s0140-6736(71)90947-0 · Cited by 152
Hypothyroidism Might Be Related to Breast Cancer in Post-Menopausal Women
Kuijpens, J. L. P., Nyklíčtek, I., Louwman, M. W. J., Weetman, T., Pop, V. J. M., & Coebergh, J. W. W. (2005) · Thyroid · doi:10.1089/thy.2005.15.1253 · Cited by 126
Thyroid autoimmunity in patients with malignant and benign breast diseases before surgery
Giustarini, E., Pinchera, A., Fierabracci, P., Roncella, M., Fustaino, L., Mammoli, C., & Giani, C. (2006) · European Journal of Endocrinology · doi:10.1530/eje.1.02108 · Cited by 89
PREMYXŒDEMA AND CORONARY-ARTERY DISEASE
Fowler, P. B. S., & Swale, J. (1967) · The Lancet · doi:10.1016/s0140-6736(67)92650-5 · Cited by 83
Cited by
Sorted by citations
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
“In an additional retrospective study, fewer ischemic heart disease events were associated with treatment of SCH in those under age 70 years (53).”
Garber, J. R., Cobin, R. H., Gharib, H., Hennessey, J. V., Klein, I., Mechanick, J. I., Pessah-Pollack, R., Singer, P. A., & Woeber, K. A. (2012) · Endocrine Practice · doi:10.4158/ep12280.gl · Cited by 1,567
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
Self-citationThyroid hormones and cardiovascular disease
Jabbar, A., Pingitore, A., Pearce, S. H. S., Zaman, A., Iervasi, G., & Razvi, S. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2016.174 · Cited by 729
Self-citationSubclinical Hypothyroidism: A Review
Biondi, B., Cappola, A. R., & Cooper, D. S. (2019) · JAMA · doi:10.1001/jama.2019.9052 · Cited by 604
Metadata
- Authors
- Razvi, S., Weaver, J. U., Butler, T. J., & Pearce, S. H. S.
- Corresponding author
- Razvi, Salman
- Venue
- Archives of Internal Medicine
- Publisher
- American Medical Association (AMA)
- Published
- 2012-05-28
- Volume
- 172
- Issue
- 10
- Pages
- 811-7
- ISSN
- 0003-9926 (ISSN-L)
- OpenAlex
- W2127148210
- Cited by
- 266
- References
- 30
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 13 · 2023: 16 · 2022: 13 · 2021: 20 · 2020: 22 · 2019: 26 · 2018: 16 · 2017: 23 · 2016: 16 · 2015: 20 · 2014: 23 · 2013: 24 · 2012: 10
- FWCI
- 19.73
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Archives of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Medical Research Council (G0500783)
- 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, levothyroxine, ischemic heart disease, cardiovascular events, mortality, thyroid-stimulating hormone, age differences, thyroid hormone replacement, cardiovascular risk
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
