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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
Thyroid 2002 Apr
PMID:Thyroid disease and lipids. 1203 52

Overt hypothyroidism may result in accelerated atherosclerosis and coronary heart disease (CHD) presumably because of the associated hypertension, hypercholesterolemia, and hyperhomocysteinemia. As many as 10%-15% of older women have subclinical hypothyroidism (SH) and thyroid autoimmunity. Whether SH is associated with risk for CHD is controversial. We examined 57 women with SH and 34 healthy controls. SH was defined as an elevated thyrotropin (TSH) (>4.5 mU/L) and normal free thyroxine (FT(4)) level (8.7-22.6 nmol/L). None of the patients had been previously treated with thyroxine. In all participants we determined blood pressure, body mass index (BMI), and fasting TSH, FT(4), antibodies to thyroid peroxidase and thyroglobulin, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, folic acid, vitamin B(12), creatinine, and total plasma homocysteine levels. The SH and control groups did not differ in their total homocysteine values. Mean diastolic blood pressure was increased in SH patients versus controls (82 vs. 75 mm Hg; p < 0.01). Mean values of TC, HDL-C, LDL-C, triglycerides, TC/HDL-C, and LDL-C/HDL-C were not different in patients with SH compared with controls. Individual analysis revealed that the percentage of patients with SH having hypertension (20%), hypertriglyceridemia (26.9%), elevated TC/HDL-C (11.5%), and LDL-C/HDL-C (4%) ratios were higher than the percentages in controls. Hyperhomocysteinemia (> or = 10.98 micromol/L) was observed in 29.4% of SH and was not significantly different from the percentage in controls (21.4%). No significant correlation between TSH and biochemical parameters was detected. We conclude that subclinical hypothyroidism in middle-aged women is associated with hypertension, hypertriglyceridemia, and elevated TC/HDL-C ratio. This may increase the risk of accelerated atherosclerosis and premature coronary artery disease in some patients.
Thyroid 2002 May
PMID:Risk factors for cardiovascular disease in women with subclinical hypothyroidism. 1209 4

The role of homocysteine as a causal risk factor for cardiovascular disease remains controversial. Moderately elevated total plasma homocysteine levels have been reported in patients with overt hypothyroidism, a condition that is associated with an increased risk for cardiovascular disease. Recently, subclinical hypothyroidism has been identified as an independent risk factor for atherosclerosis and myocardial infarction in elderly women. Therefore, we measured prospectively total fasting plasma homocysteine levels in 37 consecutive subjects (6 males, 31 females, mean age 50 +/- 18 standard deviation [SD] years) with newly diagnosed subclinical hypothyroidism at baseline and after 3-4 months of levothyroxine supplementation. During levothyroxine treatment concentrations of thyrotropin (TSH) decreased from 10.1 +/- 5.8 (SD) to 1.5 +/- 1.8 mU/L. Fasting total plasma homocysteine levels were not elevated at baseline (9.9 +/- 2.9 micromol/L) and remained unchanged (9.6 +/- 3.5 micromol/L) after levothyroxine treatment. Serum folate or vitamin B(12) levels also remained unchanged. We conclude that subclinical hypothyroidism is not associated with hyperhomocysteinemia. Levothyroxine supplementation has no influence on total plasma homocysteine levels in subclinical hypothyroidism. Hence, total plasma homocysteine does not appear to contribute to the increased risk for atherosclerotic disease and myocardial infarction in patients with subclinical hypothyroidism.
Thyroid 2002 Aug
PMID:Homocysteine: a risk factor for cardiovascular disease in subclinical hypothyroidism? 1222 43

Oxidized low density lipoproteins (LDL) are highly suspected of initiating the atherosclerosis process. Thyroid hormones and structural analogues have been reported to protect LDL from lipid peroxidation induced by Cu2+ or the free radical generator 2,2'-azobis-'2-amidinopropane' dihydrochloride in vitro. We have examined the effects of thyroid compounds on macrophage-induced LDL oxidation. Human monocyte-derived macrophages (differentiated U937 cells) were incubated for 24 h with LDL and different concentrations (0-20 microM) of 3,5,3'-triiodo-l -thyronine (T3), 3,5,3',5'-tetraiodo-L-thyronine (T4), 3,3',5'-tri-iodo-l -thyronine (rT3), the T3 acetic derivative (3,5,3'-tri-iodothyroacetic acid; TA3) or L-thyronine (T0) (experiment 1). Cells were also preincubated for 24 h with 1 or 10 microM of the compounds, washed twice, then incubated again for 24 h with LDL (experiment 2). Oxidation was evaluated by measurement of thiobarbituric acid-reactive substances (TBARS) and cell viability by lactate deshydrogenase release. In experiment 1, T0 had no effect, whereas the other compounds decreased LDL TBARS production, but T3 and TA3 were less active than T4 and rT3 (IC50: 11.0 +/- 2.6 and 8.1 +/- 0.8 vs 1.4 +/- 0.5 and 0.9 +/- 0.3 microM respectively). In experiment 2, the compounds at 1 microM had no effect; at 10 microM, T3 and rT3 slightly reduced LDL TBARS production, whereas TA3 and T4 inhibited it by about 50% and 70% respectively. TBARS released by the cells were also highly decreased by T3, T4, rT3 and TA3 in experiment 1, but only by T3 (30%) and T4 (70%) in experiment 2. Cell viability was not affected by the compounds except slightly by TA3 at 10 microM. The data suggested that the physico-chemical antioxidant capacity of thyroid compounds was modulated by their action on the intracellular redox systems of macrophage. Overall cellular effects of T3 led to a reduction of its antioxidant capacity whereas those of T4 increased it. Thus T4 might protect LDL against cellular oxidation in vivo more than T3.
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PMID:Inhibition of in vitro macrophage-induced low density lipoprotein oxidation by thyroid compounds. 1269 45

Hypothyroidism has been associated with atherosclerosis. The mechanisms of atherosclerosis in patients with thyroid failure remain controversial. Hypofibrinolysis might be a risk factor for thromboembolic disease in subclinical hypothyroidism (SH). We measured fibrinolytic activity in patients with SH before and after levothyroxine (LT(4)) treatment and compared it to those of controls. We prospectively included 35 patients with SH and 30 healthy controls. We treated patients with LT(4) until almost 6 months after the euthyroid state has been achieved. We measured fibrinogen, D-dimer, antithrombin III (ATIII), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) activity, and factor VII. Clinical and anthropometric variables were recorded for both groups. We found increased levels of fibrinogen, PAI-1, and factor VII and decreased levels of ATIII activity in patients compared to control (p < 0.001 and p < 0.05). Decrease of tPA was not significant (p > 0.05). At the end of the LT(4) treatment, significant decreases were determined in PAI-1 and factor VII (p < 0.05). In conclusion, our data suggest an important role of hypofibrinolytic and hypercoagulable state on the development of atherosclerosis in patients with SH and beneficial effects of LT(4 )treatment for decreasing the risk of atherosclerosis.
Thyroid 2003 Oct
PMID:Hemostatic system as a risk factor for cardiovascular disease in women with subclinical hypothyroidism. 1558 88

Hypothyroidism patients have increased cardiovascular risk, although the mechanism is not defined. Endothelial dysfunction may initiate atherosclerosis, is present in patients with hypothyroidism, and therefore may link hypothyroidism and vascular disease. We are unaware of studies examining the effect of thyroid replacement therapy on endothelial function in hypothyroid patients. The present study examined the effect of treatment of hypothyroidism on brachial artery reactivity. Consequently, we measured endothelium-dependent (EDV) and endothelium-independent (EIV) vasodilation using brachial artery ultrasonography in 8 hypothyroid patients (5 men, mean age 48.9 +/- 5.5 years; mean thyrotropin [TSH] 49.0 +/- 37.0 mIU/L) before and after thyroxine treatment. Thyroxine treatment reduced average TSH to 2.9 +/- 0.5 mIU/L and improved EDV (8.0% +/- 4.4% v 3.4% +/- 2.5%, P <.05), whereas EIV was unchanged (20.3% +/- 6.1% v 19.2% +/- 9.4%, P = not significant [NS]). Thyroxine treatment did not alter serum lipids. Thyroid replacement therapy improves endothelium-dependent vascular reactivity in patients with hypothyroidism irrespective of lipid changes.
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PMID:Treating hypothyroidism improves endothelial function. 1501 36

The study concerned changes in the levels of thyroid hormones (T3, T4) and their proportional relations in the serum of peripheral venous blood of patients with ischemic heart disease (IHD) with reference to severity of coronary and myocardial insufficiency and clinical symptoms. Thyroid hormones (TH) were examined in patients with stenosing atherosclerosis of the coronary arteries with incipient angina pectoris (IAP), acute myocardial infarction (AMI), chronic IHD before and after MI and postinfarction myocardial dysfunction (PIMD) depending on severity of coronary atherosclerosis. The findings were compared to hemodynamic and metabolic myocardial parameters, severity of coronary atherosclerosis assessed at coronaroangiography. It is shown that TH concentrations depend on efficiency of coronary circulation and characteristics of myocardial metabolism. IHD patients have isometric TH levels before MI, conversion of T4 into T3 being inhibited. After MI and development of PIMD at the compensation stage T4 and T3 levels lowered under control levels. This reflects intensity and pattern of metabolic processes in the myocardium. In intact myocardial function T4/T3 in the above patients was above the control levels because of high concentration of serum T4. In development of acute coronary syndrome the level of T3 fell while that of T4 went up due to suppression of its deiodination.
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PMID:[Changes of thyroid hormone levels in the progression of coronary arteriosclerosis]. 1516 4

Thyroid hormones have been reported to have significant effects on the peripheral vascular system, including relaxation of vascular smooth muscle cells and prevention of atherosclerosis. To exert its biological activity, thyroxine (T4) needs to be converted to 3,5,3'-triiodothyronine (T3) by type 1 and type 2 iodothyronine deiodinases. We have previously identified type 2 iodothyronine deiodinase (D2) expression in cultured human coronary artery smooth muscle cells (hCASMCs). In the present study, we have characterized the regulation of D2 expression in hCASMCs by stable prostacyclin analogue beraprost sodium (BPS) and platelet derived growth factor (PDGF), and the roles of thyroid hormones in the functions of hCASMCs. BPS increased D2 expression, whereas PDGF suppressed BPS stimulated D2 expression without affecting cAMP production in hCASMCs. PDGF increased DNA synthesis, while BPS, T3 or T4 suppressed PDGF stimulated DNA synthesis in hCASMCs. Inhibition of D2 activity by 3,3',5'-triiodothyronine (rT3) partially restored T4 suppression of PDGF stimulated DNA synthesis in hCASMCs. PDGF increased migration activity, whereas BPS, T3 or T4 suppressed PDGF stimulated migration activity of hCASMCs. These results suggest that D2 expression is increased by BPS and suppressed by PDGF in hCASMCs, and that intracellular thyroid hormone activation may be involved in the suppression of DNA synthesis and migration activity of hCASMCs.
Atherosclerosis 2006 May
PMID:Regulation of iodothyronine deiodinase and roles of thyroid hormones in human coronary artery smooth muscle cells. 1614 Mar 5

Several reports have appeared in the literature proving that hypothyroidism is associated with increased risk for cardiovascular disease, especially coronary heart disease. This increased risk for premature atherosclerosis is supported by autopsy and epidemiological studies in patients with thyroid hormone deficiency. Hypothyroid patients have increased diastolic blood pressure (as a result of increased systemic vascular resistance), altered lipid profile (elevated levels of total cholesterol, LDL-cholesterol and apolipoprotein B). More recently homocysteine, C-reactive protein, increased arterial stiffness, endothelial dysfunction and altered coagulation parameters have been recognized as a "new" risk factors for atherosclerosis in patients with thyroid hormone deficiency. The plasma total homocysteine concentration, an independent risk factor for atherosclerosis, is moderately elevated in overtly hypothyroid patients and it decreases with thyroid replacement therapy. Several experimental study have shown that hypothyroidism affects folate metabolism and the enzymes involved in the remetylation pathway of homocysteine (particularly 5,10-methylenotetrahydrofolate reductase - MTHFR). In hypothyroid condition the hepatic activity of flavoenzyme - MTHFR, is decreased. Thyroid hormone may affect the availability of FMN and FAD - necessary for stabilizing MTHFR. An impairment of enzyme involved in transsulfuration pathway is suggested. The increased serum creatinine level in hypothyroidism probably reflects a reduced glomerular filtration rate, which is linked to impaired renal homocysteine clearance and hyperhomocysteinemia.
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PMID:[The influence of thyroid hormones on homocysteine and atherosclerotic vascular disease]. 1633 88

Thyroid hormone has been studied in cardiovascular disease but rarely in cerebrovascular disease (CVD). Recently, hypothyroidism has been suggested to be related to risk factors such as atherosclerosis but not directly to CVD. We reported a 52-year-old woman with acute ischemic stroke, and greatly improved general conditions after thyroid hormone replacement. Hypothyroidism is reported to be one of the causes of hypertension or elevated cholesterol levels, the established risk factors of CVD. Further studies of the possible association of thyroid hormone and CVD are warranted. Thyroid hormone might need to be surveyed in CVD patients especially if there are symptoms and signs of thyroid disorders.
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PMID:Hypothyroidism and cerebral infarction: a case report and literature review. 1699


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