Abstract
Aims
Thyroid dysfunction is a risk factor for cardiovascular disease. Whether thyroid function
within the normal range is a risk factor for cardiovascular disease remains uncertain.
The aim of this study is to evaluate whether plasma thyroid-stimulating hormone (TSH)
levels in the normal range are a risk factor for cardiovascular disease and mortality
in participants with type 2 diabetes mellitus with high cardiovascular risk.
Methods
We included 1265 participants with high cardiovascular risk, type 2 diabetes, and
TSH within the normal range (0.35–5.00 mIU/L) from the Second Manifestations of ARTerial
disease cohort. The primary outcome was major cardiovascular events (MACE; vascular
death, stroke and myocardial infarction). Secondary outcomes of interest were the
separate vascular outcomes and all-cause mortality. Cox proportional hazard models
were used to evaluate the risk of plasma TSH levels on all outcomes.
Results
A total of 191 MACE occurred during a total follow-up of 8183 years. Plasma TSH levels
were not associated with MACE (hazard ratio (HR) per mIU/L TSH increase 0.93; 95%
confidence interval (95%CI) 0.80–1.08). With a total of 54 strokes during the study
period, plasma TSH was associated with a lower risk of stroke (HR per mIU/L 0.64,
95% CI 0.45–0.89). There was no association between plasma TSH levels and risk of
myocardial infarction, vascular death, or all-cause mortality.
Conclusions
Higher TSH levels within the normal range are associated with a lower risk of stroke
in high-risk patients with type 2 diabetes, but not associated with the risk of other
cardiovascular events or mortality.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Diabetes Research and Clinical PracticeAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Achievement of goals in U.S. diabetes care, 1999–2010.N Engl J Med. 2013; 368: 1613-1624https://doi.org/10.1056/NEJMsa1213829
- Effect of type 2 diabetes on recurrent major cardiovascular events for patients with symptomatic vascular disease at different locations.Diabetes Care. 2015; 38: 1528-1535https://doi.org/10.2337/dc14-2900
- Incidence of cardiovascular events and vascular interventions in patients with type 2 diabetes.Int J Cardiol. 2017; 248: 301-307https://doi.org/10.1016/j.ijcard.2017.07.081
- Impact of subclinical thyroid disorders on coronary heart disease, cardiovascular and all-cause mortality: a meta-analysis.Int J Cardiol. 2008; 125: 41-48https://doi.org/10.1016/j.ijcard.2007.02.027
- Relationship between circulating thyroid-stimulating hormone, free thyroxine, and free triiodothyronine concentrations and 9-year mortality in euthyroid elderly adults.J Am Geriatr Soc. 2016; 64: 553-560https://doi.org/10.1111/jgs.14029
- Subclinical thyroid dysfunction and the risk of stroke: a systematic review and meta-analysis.Eur J Endocrinol. 2014; 29: 791-800https://doi.org/10.1007/s10654-014-9946-8
- TSH and free thyroxine concentrations are associated with differing metabolic markers in euthyroid subjects.Eur J Endocrinol. 2010; 163: 273-278https://doi.org/10.1530/EJE-10-0312
- Association between lipids profile and thyroid parameters in euthyroid diabetic subjects: a cross-sectional study.BMC Endocr Disord. 2015; 15: 12https://doi.org/10.1186/s12902-015-0008-3
- Association between blood pressure and serum thyroid-stimulating hormone concentration within the reference range: a population-based study.J Clin Endocrinol Metab. 2007; 92: 841-845https://doi.org/10.1210/jc.2006-2208
- The relation between thyroid-stimulating hormone and measures of adiposity in patients with manifest vascular disease.Eur J Clin Invest. 2011; 41: 159-166https://doi.org/10.1111/j.1365-2362.2010.02391.x
- Thyroid disease and the cardiovascular system.Endocrinol Metab Clin North Am. 2014; 43: 517-528https://doi.org/10.1016/j.ecl.2014.02.005
- Subclinical hypothyroidism and type 2 diabetes: a systematic review and meta-analysis.PLoS ONE. 2015; 10e0135233https://doi.org/10.1371/journal.pone.0135233
- Type 2 diabetes mellitus and hypothyroidism: the possible influence of metformin therapy.Diabet Med. 2014; 31: 172-175https://doi.org/10.1111/dme.12342
- Hypothyroidism is a risk factor for new-onset diabetes: a cohort study.Diabetes Care. 2015; 38: 1657-1664https://doi.org/10.2337/dc14-2515
- Morbidity before and after the diagnosis of hyperthyroidism: a nationwide register-based study.PLoS ONE. 2013; 8e66711https://doi.org/10.1371/journal.pone.0066711
- Second manifestations of ARTerial disease (SMART) study: rationale and design.Eur J Endocrinol. 1999; 15: 773-781
- Relation between thyroid-stimulating hormone and the occurrence of cardiovascular events and mortality in patients with manifest vascular diseases.Eur J Prev Cardiol. 2012; 19: 864-873https://doi.org/10.1177/1741826711416045
- Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III).J Clin Endocrinol Metab. 2002; 87: 489-499
- Relations of thyroid function to body weight: cross-sectional and longitudinal observations in a community-based sample.Arch Intern Med. 2008; 168: 587-592https://doi.org/10.1001/archinte.168.6.587
- Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association.Thyroid. 2012; 22: 1200-1235https://doi.org/10.1089/thy.2012.0205
- Thyroid function in the euthyroid range and adverse outcomes in older adults.J Clin Endocrinol Metab. 2015; 100: 1088-1096https://doi.org/10.1210/jc.2014-3586
- Thyroid function within the reference range and the risk of stroke: an individual participant data analysis.J Clin Endocrinol Metab. 2016; 101: 4270-4282https://doi.org/10.1210/jc.2016-2255
- Association of thyroid function with life expectancy with and without cardiovascular disease: the Rotterdam study.JAMA Intern Med. 2017; https://doi.org/10.1001/jamainternmed.2017.4836
- Normal thyroid function and the risk of atrial fibrillation: the Rotterdam study.J Clin Endocrinol Metab. 2015; 100: 3718-3724https://doi.org/10.1210/jc.2015-2480
- Atrial fibrillation as an independent risk factor for stroke: the Framingham Study.Stroke. 1991; 22: 983-988
- Clinical review: Thyroid dysfunction and effects on coagulation and fibrinolysis: a systematic review.J Clin Endocrinol Metab. 2007; 92: 2415-2420https://doi.org/10.1210/jc.2007-0199
- Diabetes mellitus: a hypercoagulable state.J Diabetes Complications. 2001; 15: 44-54
- Hypercoagulability Is a stronger risk factor for ischaemic stroke than for myocardial infarction: a systematic review.PLoS ONE. 2015; 10e0133523https://doi.org/10.1371/journal.pone.0133523
- Thyroid hormone and blood pressure regulation.Curr Hypertens Rep. 2003; 5: 513-520
- Arterial hypertension and ischaemic stroke.Acta Neurol Scand. 2003; 107: 241-251
- Association between serum thyrotropin levels and mortality among euthyroid adults in the United States.Thyroid. 2016; 26: 1457-1465https://doi.org/10.1089/thy.2016.0156
- Thyroid function and the risk of coronary heart disease: 12-year follow-up of the HUNT study in Norway.Clin Endocrinol (Oxf). 2012; 77: 911-917https://doi.org/10.1111/j.1365-2265.2012.04477.x
- Thyroid function and sudden cardiac death: a prospective population-based cohort study.Circulation. 2016; 134: 713-722https://doi.org/10.1161/CIRCULATIONAHA.115.020789
- Thyroid hormones and mortality risk in euthyroid individuals: the Kangbuk Samsung health study.J Clin Endocrinol Metab. 2014; 99: 2467-2476https://doi.org/10.1210/jc.2013-3832
- 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: 1037-1047https://doi.org/10.1001/jamainternmed.2015.0930
- Thyroid function and ischemic heart disease: a Mendelian randomization study.Sci Rep. 2017; 7: 8515https://doi.org/10.1038/s41598-017-07592-z
- Mendelian randomization: using genes as instruments for making causal inferences in epidemiology.Stat Med. 2008; 27: 1133-1163https://doi.org/10.1002/sim.3034
- Avoiding bias from weak instruments in Mendelian randomization studies.Int J Epidemiol. 2011; 40: 755-764https://doi.org/10.1093/ije/dyr036
Article info
Publication history
Published online: October 16, 2019
Accepted:
October 11,
2019
Received in revised form:
September 25,
2019
Received:
July 26,
2019
Identification
Copyright
© 2019 Elsevier B.V. All rights reserved.
