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Query: UMLS:C0004153 (atherosclerosis)
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Subclinical hypothyroidism (SH) is common, especially among elderly women. There is no clear evidence to date that SH causes clinical heart disease. However, mild thyroid gland failure, evidenced solely by elevation of the serum thyrotropin (TSH) concentration, may be associated with increased morbidity, particularly for cardiovascular disease, and subtly decreased myocardial contractility. In SH, both cardiac structures and function remain normal at rest, but impaired ventricular function as well as cardiovascular and respiratory adaptation to effort may become unmasked during exercise. These changes are reversible when euthyroidism is restored. Flow-mediated vasodilatation, a marker of endothelial function, is significantly impaired in SH, and decreased heart rate variability, a marker of autonomic activity, suggests hypofunctional abnormalities in the parasympathetic nervous system. SH does result in a small increase in low-density lipoprotein (LDL) cholesterol (C) and a decrease in high-density lipoprotein (HDL)-C, changes that enhance the risk for development of atherosclerosis and coronary artery disease (CAD). After coronary revascularization, a trend toward higher rates of chest pain, dissection, and reocclusion has been noted in SH subjects. Smoking may contribute to the high incidence of SH and may aggravate its metabolic effects. Subjects with SH with marked TSH elevation and high titers of thyroid autoantibodies are at higher risk of unnoticed progression to overt hypothyroidism. Especially women over 50 years with TSH levels greater than 10 mU/L and smoking habits have the highest risk for cardiovascular complications. The magnitude of the lipid changes and the subtle impairment of left ventricular function and cardiopulmonary exercise capacity in SH may justify use of hormone replacement. Early levothyroxine (LT4) treatment in SH may reduce the C level by an average of 8% and normalize all metabolic effects in smokers, nevertheless, in some patients, LT4 therapy may exacerbate angina pectoris or an underlying cardiac arrhythmia. Longitudinal follow-up to define the actual cardiovascular disease risk associated with SH is warranted.
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PMID:Cardiovascular and atherogenic aspects of subclinical hypothyroidism. 1101 11

The composition and the transport of lipoproteins are seriously disturbed in thyroid diseases. Overt hypothyroidism is characterized by hypercholesterolaemia and a marked increase in low-density lipoproteins (LDL) and apolipoprotein B (apo A) because of a decreased fractional clearance of LDL by a reduced number of LDL receptors in the liver. The high-density lipoprotein (HDL) levels are normal or even elevated in severe hypothyroidism because of decreased activity of cholesteryl-ester transfer protein (CETP) and hepatic lipase (HL), which are enzymes regulated by thyroid hormones. The low activity of CETP, and more specifically of HL, results in reduced transport of cholesteryl esters from HDL(2) to very low-density lipoproteins (VLDL) and intermediate low-density lipoprotein (IDL), and reduced transport of HDL(2) to HDL(3). Moreover, hypothyroidism increases the oxidation of plasma cholesterol mainly because of an altered pattern of binding and to the increased levels of cholesterol, which presents a substrate for the oxidative stress. Cardiac oxygen consumption is reduced in hypothyroidism. This reduction is associated with increased peripheral resistance and reduced contractility. Hypothyroidism is often accompanied by diastolic hypertension that, in conjunction with the dyslipidemia, may promote atherosclerosis. However, thyroxine therapy, in a thyrotropin (TSH)-suppressive dose, usually leads to a considerable improvement of the lipid profile. The changes in lipoproteins are correlated with changes in free thyroxine (FT(4)) levels. Hyperthyroidism exhibits an enhanced excretion of cholesterol and an increased turnover of LDL resulting in a decrease of total and LDL cholesterol, whereas HDL are decreased or not affected. The action of thyroid hormone on Lp(a) lipoprotein is still debated, because both decrease or no changes have been reported. The discrepancies are mostly because of genetic polymorphism of apo(a) and to the differences between the various study groups. Subclinical hypothyroidism (SH) is associated with lipid disorders that are characterized by normal or slightly elevated total cholesterol levels, increased LDL, and lower HDL. Moreover, SH has been associated with endothelium dysfunction, aortic atherosclerosis, and myocardial infarction. Lipid disorders exhibit great individual variability. Nevertheless, they might be a link, although it has not been proved, between SH and atherosclerosis.
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PMID:Thyroid disease and lipids. 1203 52

Advances in thyroid disorder diagnosis have created new thyroid disorder categories such as subclinical hyperthyroidism and subclinical hypothyroidism. In the 1980s, immunometric assaying for thyroid stimulating hormone (TSH) emerged and became defined as the most cost-effective test in thyroid disorder screening. The second step in the screening of thyroid disorders is to determine free thyroxine (FT4), and cost-effective methods for its detection are now available. Using TSH and FT4, it is possible to determine four situations: clinical hyperthyroidism, clinical hypothyroidism, subclinical hyperthyroidism and subclinical hypothyroidism. Subclinical hypothyroidism can be a strong indicator of risk for atherosclerosis and myocardial infarction in elderly women. Cardiovascular mortality among Brazilian women is one of the highest in the Western world. The best-known risk factors for cardiovascular diseases are high blood pressure, smoking, diabetes, and hypercholesterolemia. Although these are recognized as primary risk factors, there are other risk factors that could be identified as primordial risk factors. This may be the case for subclinical hypothyroidism. Early detection of thyroid disorders in women over fifty could be a highly cost-effective option in the prevention of cardiovascular disorders among Brazilian women.
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PMID:Screening for thyroid disorders in asymptomatic adults from Brazilian populations. 1243 51

Subclinical hypothyroidism is comparatively frequent disorder with incidence between 3 to 7% in the general population; in females over 60 it can exceed 10%. There is no unequivocal view on the clinical significance of the syndrome; however, it may correspond with increased risk of atherosclerosis and its complications. Especially in elderly women, screening for subclinical hypothyroidism is recommended with possible hormone replacement according to given criteria. Decision about the therapy of subclinical hypothyroidism should be done together with cardiologist, psychiatrist or neurologist in order to correct possible clinical impacts and prevent further manifestations.
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PMID:[Subclinical hypothyroidism with emphasis on the cardiovascular system]. 1468 21

Subclinical hypothyroidism is defined as elevated TSH in the presence of normal free T4 and T3 levels. This review discusses the following questions concerning subclinical hypothyroidism that have not been solved yet: 1) does elevated TSH always mean failure of the thyroid gland? 2) Do patients with subclinical hypothyroidism always develop overt hypothyroidism? 3) Are they symptomatic? 4) Does treatment with L-Thyroxine cure these symptoms,--if they exist? Summarizing the results of the literature one can give the following answers: 1) Elevated TSH with normal free T4 can but does not necessarily mean thyroid failure. 2) Patients with positive thyroid antibodies and especially with TSH levels above 10 mU/l are at high risk to develop overt hypothyroidism. 3) Typical symptoms (thyroid-specific, cardiovascular, neurological and psychiatric and finally alterations of risk factors for atherosclerosis) seem to occur in a greatly varying percentage of patients--some of the described symptoms are of questionable clinical importance. 4) Some of the symptoms, especially the cardiovascular, seem to be treatable by L-T4, whereas others like most of the changes in lipid metabolism can not be influenced by normalization of the TSH levels. In conclusion, screening for TSH and free T4 seems to be justified in elderly women, where the prevalence of the disease is approximately 20%. However, treatment of "symptoms" of subclinical hypothyroidism like elevated cholesterol levels or depression should be done only in patients with a TSH > 10 mU/l and there only with great caution in order to avoid unnecessary overdosage with the danger of eliciting atrial fibrillation.
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PMID:[Possible consequences of subclinical hypothyroidism]. 1471 Apr 77

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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PMID:Effects of thyroid hormone on the cardiovascular system. 1474 96

Cardiovascular consequences of thyroid diseases, their prevalence and treatment, particularly in cases with subclinical hyper- and hypothyroidism. The aim of the study was to draw attention to an association between the thyroid and cardiovascular diseases. The main topic was to lay emphasis on the importance of cardiovascular diseases caused by subclinical hyper- and hypothyroidism in the relation to the practice. The subclinical states precede the overt hyper- and hypothyroidism, and they are often present during their treatments. The changes in the levels of thyrotropin demonstrating subclinical thyroid diseases, could be detected in different non-thyroid diseases and resulted from the effect of some drugs. Particularly, the subclinical thyroid diseases become more frequent in older age. In the background of the high prevalences of atrial fibrillation, hypertension and psychosomatic events subclinical hyperthyroidism could be revealed. Subclinical hypothyroidism is characterized by an increased prevalence of elevated serum lipid levels, atherosclerosis, ischemic heart disease and hypertension often associating with the presence of anti-thyroid antibodies. It is important to reveal subclinical thyroid diseases in time for the effective treatment and for stopping of the cardiovascular damages before manifestations of cardiovascular diseases. The paper gives advice for the practice and the rational management. At the end, a survey of the association between thyroid and heart diseases in own department of internal medicine at the last three years is given.
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PMID:[Cardiovascular consequences of thyroid diseases, their prevalence and treatment, particularly in cases with subclinical hyper- and hypothyroidism]. 1625 35

By affecting the metabolism of lipids, hypothyroidism accelerates the process of atherogenesis and increases cardiovascular risk. In manifest hypothyroidism the number of LDL receptors in the liver decreases and there is an increase in levels of overall cholesterol, LDL-cholesterol and apolipoprotein B in the blood. Levels of HDL particles remain normal or even rise slightly as a result of reduced activity of the Cholesterol ester transfer protein (CETP) and hepatic lipase. This leads to a reduction in the transport of cholesterol esters from HDL-(2) to VLDL and IDL. Subclinical hypothyroidism also has a negative effect on the lipid profile, but is more likely to lead to pro-atherogenic changes in the proportion of lipid particles than to a reduction in overall cholesterol. Subclinical hypothyroidism leads to the manifestation of certain risk factors of atherosclerosis. Although studies of overall mortality and cardiovascular morbidity have not been completely unanimous in their conclusions, increased cardiovascular risk can be considered likely in subclinical hypothyroidism. It remains an open question whether the treatment of subclinical hypothyroidism with levothyroxine. At present we have only indirect proof from studies that assessed the effect of levothyroxine treatment on risk factors of atherosclerosis. Starting treatment with lipid lowering agents (especially statins) for (sub)clinical hypothyroidism is extremely risky though due to the risk of the development or worsening of myopathy, which is a further cogent argument for the active screening and treatment of(sub)clinical hypothyroidism for all patients with dyslipidemia.
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PMID:[Thyroid diseases, dyslipidemia and cardiovascular risk]. 1757 70

Previous studies have suggested that subclinical thyroid dysfunction, as manifested by abnormalities in thyroid-stimulating hormone (TSH) levels, are associated with detrimental effects on the cardiovascular system. Subclinical hypothyroidism is characterized by abnormal lipid metabolism, cardiac dysfunction, diastolic hypertension conferring an elevated risk of atherosclerosis, and ischemic heart disease. Similarly, patients with subclinical hyperthyroidism have nearly 3 times the likelihood of atrial fibrillation over a 10-year follow-up interval, raising the question of whether patients with subclinical hyperthyroidism should be treated to prevent atrial fibrillation. A single measurement of low serum TSH in individuals aged 60 years or older has been reported to be associated with increased mortality from all causes and in particular from circulatory and cardiovascular disease in a 10-year follow-up study. Subclinical thyroid dysfunction is currently the subject of numerous studies and remains controversial, particularly as it relates to cardiovascular morbidity and mortality and clinical applications.
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PMID:Cardiovascular risk with subclinical hyperthyroidism and hypothyroidism: pathophysiology and management. 1778 84

Subclinical thyroids disease (STD) is recently defined term in clinical thyroidology, which includes mainly functional disorders. Basic diagnostic signs are: normal values of thyroid hormones (fT4, fT3) and elevated TSH level (subclinical hypothyroidism) or suppresed TSH level (subclinical hyperthyroidism). In a category of STD may be included subclinical autoimunne thyroiditis (elevated level of thyroid antigens antibodies and/or hypoechogenity in sonographic screen, increased volume of the thyroid without clinical symptoms and/or autoimminity) and microscopic lesions of papillary thyroid carcinoma. Subclinical hypothyroidism may be dangerous for tendency to development of manifest hypothyroidism and for risk of disorders of lipid profile and development of atherosclerosis and its organ complication (esp. myocardial infarction). Subclinical hyperthyroidism is a risk factor of cardiac arythmias and probably can increase a risk of cardiovascular mortality) as well for osteoporosis (esp. in peri- and post-climacteric women), and last but not least for degenerative diseases of brain (?). Indication of treatment of STD is a matter of controversies. Recomendations of experts, varied from "no therapy, monitoring only" to "treat always". Treatment of risk groups (esp. pregnant women) is probably nowadays a most rationale recommendations since results of sofisticated prospective studies will be available.
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PMID:[Subclinical thyroid diseases]. 1791 20


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