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      Hyperthyroidism and cardiovascular complications: a narrative review on the basis of pathophysiology

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          Abstract

          Cardiovascular complications are important in hyperthyroidism because of their high frequency in clinical presentation and increased mortality and morbidity risk. The cause of hyperthyroidism, factors related to the patient, and the genetic basis for complications are associated with risk and the basic underlying mechanisms are important for treatment and management of the disease. Besides cellular effects, hyperthyroidism also causes hemodynamic changes, such as increased preload and contractility and decreased systemic vascular resistance causes increased cardiac output. Besides tachyarrythmias, impaired systolic ventricular dysfunction and diastolic dysfunction may cause thyrotoxic cardiomyopathy in a small percentage of the patients, as another high mortality complication. Although the medical literature has some conflicting data about benefits of treatment of subclinical hyperthyroidism, even high-normal thyroid function may cause cardiovascular problems and it should be treated. This review summarizes the cardiovascular consequences of hyperthyroidism with underlying mechanisms.

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          Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study.

          Low serum thyrotropin, in combination with normal concentrations of circulating thyroid hormones, is common, especially in elderly people and in individuals with a history of thyroid disease. We aimed to assess the long-term effects of subclinical hyperthyroidism on mortality. We did a population-based study of mortality in a cohort of 1191 individuals not on thyroxine or antithyroid medication. All participants were aged 60 years or older. We measured concentration of thyrotropin in serum at baseline in 1988-89. We recorded vital status on June 1, 1999, and ascertained causes of death for those who had died. We compared data for causes of death with age-specific, sex-specific, and year-specific data for England and Wales. We also compared mortality within the cohort according to initial thyrotropin measurement. During 9733 person-years of follow-up, 509 of 1191 people died, the expected number of deaths being 496 (standardised mortality ratio [SMR] 1.0, 95% CI 0.9-1.1). Mortality from all causes was significantly increased at 2 (SMR 2.1), 3 (2.1), 4 (1.7), and 5 (1.8) years after first measurement in those with low serum thyrotropin (n471). These increases were largely accounted for by significant increases in mortality due to circulatory diseases (SMR 2.1, 2.2, 1.9, 2.0, at years 2, 3, 4, and 5 respectively). Increases in mortality from all causes in years 2-5 were higher in patients with low serum thyrotropin than in the rest of the cohort (hazard ratios for years 2, 3, 4, and 5 were 2.1, 2.2, 1.8, and 1.8, respectively). This result reflects an increase in mortality from circulatory diseases (hazard ratios at years 2, 3, 4, and 5 were 2.3, 2.6, 2.3, 2.3), and specifically from cardiovascular diseases (hazard ratios at years 2, 3, 4, and 5 were 3.3, 3.0, 2.3, 2.2). A single measurement of low serum thyrotropin in individuals aged 60 years or older is associated with increased mortality from all causes, and in particular mortality due to circulatory and cardiovascular diseases.
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            Effects of thyroid hormone on the cardiovascular system.

            Increased or reduced action of thyroid hormone on certain molecular pathways in the heart and vasculature causes relevant cardiovascular derangements. It is well established that overt hyperthyroidism induces a hyperdynamic cardiovascular state (high cardiac output with low systemic vascular resistance), which is associated with a faster heart rate, enhanced left ventricular (LV) systolic and diastolic function, and increased prevalence of supraventricular tachyarrhythmias - namely, atrial fibrillation - whereas overt hypothyroidism is characterized by the opposite changes. However, whether changes in cardiac performance associated with overt thyroid dysfunction are due mainly to alterations of myocardial contractility or to loading conditions remains unclear. Extensive evidence indicates that the cardiovascular system responds to the minimal but persistent changes in circulating thyroid hormone levels, which are typical of individuals with subclinical thyroid dysfunction. Subclinical hyperthyroidism is associated with increased heart rate, atrial arrhythmias, increased LV mass, impaired ventricular relaxation, reduced exercise performance, and increased risk of cardiovascular mortality. Subclinical hypothyroidism is associated with impaired LV diastolic function and subtle systolic dysfunction and an enhanced risk for atherosclerosis and myocardial infarction. Because all cardiovascular abnormalities are reversed by restoration of euthyroidism ("subclinical hypothyroidism") or blunted by beta-blockade and L-thyroxine (L-T4) dose tailoring ("subclinical hyperthyroidism"), timely treatment is advisable in an attempt to avoid adverse cardiovascular effects. Interestingly, some data indicate that patients with acute and chronic cardiovascular disorders and those undergoing cardiac surgery may have altered peripheral thyroid hormone metabolism that, in turn, may contribute to altered cardiac function. Preliminary clinical investigations suggest that administration of thyroid hormone or its analogue 3,5-diiodothyropropionic acid greatly benefits these patients, highlighting the potential role of thyroid hormone treatment in patients with acute and chronic cardiovascular disease.
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              A critical review and meta-analysis of the association between overt hyperthyroidism and mortality.

              Overt hyperthyroidism has been associated with cardiac arrhythmias, hypercoagulopathy, stroke, and pulmonary embolism, all of which may increase mortality. Some, but not all, studies show an increased mortality in patients with hyperthyroidism. This inconsistency may be due to differences in study design, characteristics of participants, or confounders. In order to test whether hyperthyroidism influences mortality, we performed a critical review and statistical meta-analysis. Based on an electronic PubMed search, using the Medical Subject Heading words such as hyperthyroidism, thyrotoxicosis, and mortality or survival, case-control and cohort studies were selected and reviewed. Using meta-analysis, an overall relative risk (RR) of mortality was calculated. Eight studies fulfilled the inclusion criteria, six of which showed an increased all-cause mortality; seven studies, including 31,138 patients and 400,000 person years at risk, allowed calculation of mortality in a meta-analysis. Based on this, the RR of overall mortality was 1.21 (95% confidence interval: 1.05-1.38). Analyses including studies considering setting, treatment, and control for co-morbidity did not significantly alter this finding. As the measured heterogeneity (I(2)) ranges from 89.1 to 98.3%, which is much higher than the 50% generally viewed on as a threshold, the statistical heterogeneity is very pronounced in the included studies. In patients diagnosed with hyperthyroidism, mortality is increased by ∼ 20%. Future studies need to address the cause of hyperthyroidism, impact of type of therapy, time dependency, as well as the potential influence of confounding or genetic susceptibility before the question of causality can be answered.
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                Author and article information

                Journal
                Arch Med Sci
                Arch Med Sci
                AMS
                Archives of Medical Science : AMS
                Termedia Publishing House
                1734-1922
                1896-9151
                05 November 2013
                31 October 2013
                : 9
                : 5
                : 944-952
                Affiliations
                [1 ]Ufuk University Medical Faculty, Dr. R. Ege Hospital, Endocrinology and Metabolic Diseases Department, Ankara, Turkey
                [2 ]Bologna University, Department of Internal Medicine, Aging and Kidney Diseases, Bologna, Italy
                Author notes
                Corresponding author: Sibel Ertek, Turkish Ministry of Health Sanliurfa Education and Research Hospital, Department of Endocrinology and Metabolic Diseases, Esentepe 63100 Sanliurfa, Turkey. Phone: +90 414 318 60 60, Fax: +90 414 318 68 12. E-mail: sibelertek@ 123456yahoo.it
                Article
                21685
                10.5114/aoms.2013.38685
                3832836
                24273583
                41405cf2-6605-4392-8046-1d6116695b3a
                Copyright © 2013 Termedia & Banach

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 March 2012
                : 28 July 2012
                : 20 August 2012
                Categories
                State of the Art Paper

                Medicine
                hyperthyroidism,subclinical hyperthyroidism,overt hyperthyroidism,atrial fibrillation,graves’ disease,toxic nodular goitre

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