44
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Thyroxine in acute myocardial infarction (ThyrAMI) - levothyroxine in subclinical hypothyroidism post-acute myocardial infarction: study protocol for a randomised controlled trial

      research-article
      , , , ,
      Trials
      BioMed Central

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Cardiac disease is the most common cause of morbidity and mortality in the United Kingdom. Even minor changes in thyroid hormone concentration may impact adversely on the cardiovascular system. Subclinical hypothyroidism (SCH) after admission for an acute cardiac problem has been associated with an increase in cardiac mortality and overall death. We have designed protocols for a prospective observational study to assess the association of thyroid function at the time of acute myocardial infarction (AMI) with cardiovascular outcomes, and a double-blinded randomised placebo-controlled trial of levothyroxine to evaluate its effect on LV function and vascular health.

          Methods/Design

          ThyrAMI 1: This will be a prospective longitudinal observational study of patients with AMI that will be followed for 24 months to study the association between thyroid status at the time of AMI (within 24 hours of diagnosis) with vascular outcomes.

          ThyrAMI 2: This will be a prospective double-blinded randomised placebo-controlled trial of levothyroxine of 12 months duration in patients with AMI and SCH.

          Setting: Patients will be recruited from five hospitals in the North East of England.

          Participants: One hundred patients with thyroid function tests within the subclinical hypothyroid range upon admission with an AMI and no previous history of thyroid disease.

          Intervention: Levothyroxine will be administered at a starting dose of 25 mcg once daily, which will be increased at intervals if needed to maintain a TSH level between 0.4 to 2.5 mU/L, versus a placebo.

          Randomisation: Participants will be randomized with a computerised randomisation algorithm, stratified by type of MI (NSTEMI versus STEMI), in a 1:1 ratio to levothyroxine therapy or placebo (as container or bottle numbers), starting within 21 (+/− 7) days of AMI.

          Blinding: Assignment to either the LT4 or placebo arm will be double-blinded.

          Outcomes: The outcome will be the effect of levothyroxine on ventricular function, endothelial function and blood coagulability and rheology.

          Discussion

          There is evidence to suggest that treatment of SCH can improve cardiovascular parameters. Therefore, ThyrAMI 1 and ThyrAMI 2 will be the first trials investigating SCH in AMI to give a better insight into whether thyroid hormone levels are a key target for improving cardiovascular outcomes.

          Trial registration

          ISRCTN number: ISRCTN52505169. Date of registration: 09/01/2015

          Related collections

          Most cited references28

          • Record: found
          • Abstract: found
          • Article: not found

          The clinical significance of subclinical thyroid dysfunction.

          Subclinical thyroid disease (SCTD) is defined as serum free T(4) and free T(3) levels within their respective reference ranges in the presence of abnormal serum TSH levels. SCTD is being diagnosed more frequently in clinical practice in young and middle-aged people as well as in the elderly. However, the clinical significance of subclinical thyroid dysfunction is much debated. Subclinical hyper- and hypothyroidism can have repercussions on the cardiovascular system and bone, as well as on other organs and systems. However, the treatment and management of SCTD and population screening are controversial despite the potential risk of progression to overt disease, and there is no consensus on the thyroid hormone and thyrotropin cutoff values at which treatment should be contemplated. Opinions differ regarding tissue effects, symptoms, signs, and cardiovascular risk. Here, we critically review the data on the prevalence and progression of SCTD, its tissue effects, and its prognostic implications. We also examine the mechanisms underlying tissue alterations in SCTD and the effects of replacement therapy on progression and tissue parameters. Lastly, we address the issue of the need to treat slight thyroid hormone deficiency or excess in relation to the patient's age.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The Colorado thyroid disease prevalence study.

            The prevalence of abnormal thyroid function in the United States and the significance of thyroid dysfunction remain controversial. Systemic effects of abnormal thyroid function have not been fully delineated, particularly in cases of mild thyroid failure. Also, the relationship between traditional hypothyroid symptoms and biochemical thyroid function is unclear. To determine the prevalence of abnormal thyroid function and the relationship between (1) abnormal thyroid function and lipid levels and (2) abnormal thyroid function and symptoms using modern and sensitive thyroid tests. Cross-sectional study. Participants in a statewide health fair in Colorado, 1995 (N = 25 862). Serum thyrotropin (thyroid-stimulating hormone [TSH]) and total thyroxine (T4) concentrations, serum lipid levels, and responses to a hypothyroid symptoms questionnaire. The prevalence of elevated TSH levels (normal range, 0.3-5.1 mIU/L) in this population was 9.5%, and the prevalence of decreased TSH levels was 2.2%. Forty percent of patients taking thyroid medications had abnormal TSH levels. Lipid levels increased in a graded fashion as thyroid function declined. Also, the mean total cholesterol and low-density lipoprotein cholesterol levels of subjects with TSH values between 5.1 and 10 mIU/L were significantly greater than the corresponding mean lipid levels in euthyroid subjects. Symptoms were reported more often in hypothyroid vs euthyroid individuals, but individual symptom sensitivities were low. The prevalence of abnormal biochemical thyroid function reported here is substantial and confirms previous reports in smaller populations. Among patients taking thyroid medication, only 60% were within the normal range of TSH. Modest elevations of TSH corresponded to changes in lipid levels that may affect cardiovascular health. Individual symptoms were not very sensitive, but patients who report multiple thyroid symptoms warrant serum thyroid testing. These results confirm that thyroid dysfunction is common, may often go undetected, and may be associated with adverse health outcomes that can be avoided by serum TSH measurement.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study.

              Overt hypothyroidism has been found to be associated with cardiovascular disease. Whether subclinical hypothyroidism and thyroid autoimmunity are also risk factors for cardiovascular disease is controversial. To investigate whether subclinical hypothyroidism and thyroid autoimmunity are associated with aortic atherosclerosis and myocardial infarction in postmenopausal women. Population-based cross-sectional study. A district of Rotterdam, The Netherlands. Random sample of 1149 women (mean age +/- SD, 69.0 +/- 7.5 years) participating in the Rotterdam Study. Data on thyroid status, aortic atherosclerosis, and history of myocardial infarction were obtained at baseline. Subclinical hypothyroidism was defined as an elevated thyroid-stimulating hormone level (>4.0 mU/L) and a normal serum free thyroxine level (11 to 25 pmol/L [0.9 to 1.9 ng/dL]). In tests for antibodies to thyroid peroxidase, a serum level greater than 10 IU/mL was considered a positive result. Subclinical hypothyroidism was present in 10.8% of participants and was associated with a greater age-adjusted prevalence of aortic atherosclerosis (odds ratio, 1.7 [95% CI, 1.1 to 2.6]) and myocardial infarction (odds ratio, 2.3 [CI, 1.3 to 4.0]). Additional adjustment for body mass index, total and high-density lipoprotein cholesterol level, blood pressure, and smoking status, as well as exclusion of women who took beta-blockers, did not affect these estimates. Associations were slightly stronger in women who had subclinical hypothyroidism and antibodies to thyroid peroxidase (odds ratio for aortic atherosclerosis, 1.9 [CI, 1.1 to 3.6]; odds ratio for myocardial infarction, 3.1 [CI, 1.5 to 6.3]). No association was found between thyroid autoimmunity itself and cardiovascular disease. The population attributable risk percentage for subclinical hypothyroidism associated with myocardial infarction was within the range of that for known major risk factors for cardiovascular disease. Subclinical hypothyroidism is a strong indicator of risk for atherosclerosis and myocardial infarction in elderly women.
                Bookmark

                Author and article information

                Contributors
                avais.jabbar@ncl.ac.uk
                lorna.ingoe@ghnt.nhs.uk
                simon.pearce@newcastle.ac.uk
                azfar.zaman@nuth.nhs.uk
                salman.razvi@ncl.ac.uk
                Journal
                Trials
                Trials
                Trials
                BioMed Central (London )
                1745-6215
                25 March 2015
                25 March 2015
                2015
                : 16
                : 115
                Affiliations
                [ ]Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ UK
                [ ]Department of Endocrinology, Gateshead Health NHS Foundation trust, Sheriff Hill, Gateshead, NE9 6SX UK
                [ ]Endocrine Unit, Newcastle upon Tyne Hospitals NHS foundation trust, Queen Victoria Road, Newcastle upon Tyne, NE1 4LP UK
                [ ]Department of Cardiology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Road, NE7 7DN Newcastle upon Tyne, UK
                [ ]Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH UK
                [ ]Newcastle University, Queen Elizabeth Hospital, Sheriff Hill, Gateshead, NE9 6SX UK
                Article
                621
                10.1186/s13063-015-0621-5
                4379597
                078d5d9d-219c-4859-9efc-8d4d8e521212
                © Jabbar et al.; licensee BioMed Central. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 18 December 2014
                : 26 February 2015
                Categories
                Study Protocol
                Custom metadata
                © The Author(s) 2015

                Medicine
                Medicine

                Comments

                Comment on this article