Gene/Protein Disease Symptom Drug Enzyme Compound
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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.
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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.
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PMID:Risk factors for cardiovascular disease in women with subclinical hypothyroidism. 1209 4

The influence of hypothyroidism on haemostasis is controversial; both hypocoagulable and hypercoagulable states have been reported. Hypothyroidism has been associated with atherosclerosis; a hypercoagulable state in addition might represent a risk factor for thromboembolic disease. The aim of the present study was to investigate the markers of endogenous coagulation and vascular endothelial cell function and to evaluate the relationship between serum lipid profile, thyroid hormones and haemostatic parameters in hypothyroid patients. We investigated various haemostatic parameters in 20 patients with hypothyroidism and compared them with 20 euthyroid controls. The relationship between serum thyroid hormones and the haemostatic parameters was examined. The plasma levels of fibrinogen, AT III and PAI-1 were significantly increased in hypothyroid patients compared with the control group, whereas factors VIII and X activity was decreased. We showed that free T3 levels correlated with factor IX activity. Free T4, FT3 and TSH did not correlate with fibrinogen, vWF, AT III, t-PA, or PAI-1. aPTT correlated inversely with t-PA activity and positively with protein C activity. Anti-Tg correlated inversely with FV. There was a positive correlation between triglycerides and protein C. Protein S correlated inversely with high density lipoprotein cholesterol. We found a hypofibrinolytic state in patients with hypothyroidism. Our results suggest that the risk of developing thrombosis and ultimately myocardial infarction via high PAI-1 levels may be increased in patients with hypothyroidism, a result in line with recent epidemiological data. However, thyroid hormones may play a role at different levels of the complex haemostatic system.
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PMID:Blood coagulation and fibrinolytic activity in hypothyroidism. 1266 86

Neuropeptide Y (NPY) is an important neurotransmitter in the central and peripheral nervous systems. It has a regulatory role in cardiovascular and metabolic functions and control of hormone release. The leucine 7 to proline 7 (Leu7Pro) polymorphism in the signal peptide of prepro-NPY is associated with increased blood lipid levels, accelerated atherosclerosis, and diabetic retinopathy. This study elucidated the role of this polymorphism in diurnal cardiovascular, metabolic, and hormonal functions of healthy subjects during rest. The two study groups comprised individuals with different genotype, but they were matched for age and body mass index. Subjects with the Leu7Pro polymorphism had significantly lower plasma NPY and norepinephrine concentrations, lower insulin concentrations, higher glucose concentrations, and lower insulin-glucose ratio in plasma than the controls. Heart rate was significantly higher during daytime in the subjects with Leu7Pro polymorphism. Furthermore, these subjects had significantly lower prolactin concentrations in plasma. Systolic and diastolic blood pressure, serum free fatty acid and plasma leptin, ACTH, cortisol, LH, FSH, TSH, free thyroxin, and melatonin concentrations were similar during the 24-h period, compared with controls. These results show that genetically determined changes in NPY levels lead to widespread consequences in the control of sympathoadrenal, metabolic, and hormonal balance in healthy subjects.
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PMID:Changes in diurnal sympathoadrenal balance and pituitary hormone secretion in subjects with Leu7Pro polymorphism in the prepro-neuropeptide Y. 1284 76

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

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 cardiovascular risk in patients with hypothyroidism is related to an increased risk of functional cardiovascular abnormalities and to an increased risk of atherosclerosis. The pattern of cardiovascular abnormalities is similar in subclinical and overt hypothyroidism, suggesting that a lesser degree of thyroid hormone deficiency may also affect the cardiovascular system. Hypothyroid patients, even those with subclinical hypothyroidism, have impaired endothelial function, normal/depressed systolic function, left ventricular diastolic dysfunction at rest, and systolic and diastolic dysfunction on effort, which may result in poor physical exercise capacity. There is also a tendency to increase diastolic blood pressure as a result of increased systemic vascular resistance. All these abnormalities regress with L-T4 replacement therapy. An increased risk for atherosclerosis is supported by autopsy and epidemiological studies in patients with thyroid hormone deficiency. The "traditional" risk factors are hypertension in conjunction with an atherogenic lipid profile; the latter is more often observed in patients with TSH >10 mU/L. More recently, C-reactive protein, homocysteine, increased arterial stiffness, endothelial dysfunction, and altered coagulation parameters have been recognized as risk factors for atherosclerosis in patients with thyroid hormone deficiency. This constellation of reversible cardiovascular abnormalities in patient with TSH levels <10 mU/L indicate that the benefits of treatment of mild thyroid failure with appropriate doses of L-thyroxine outweigh the risk.
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PMID:Hypothyroidism as a risk factor for cardiovascular disease. 1524 98

Previous studies showed that subclinical hypothyroidism (SH) was associated with cardiovascular disorders, such as endothelial dysfunction, atherosclerosis and myocardial dysfunction. Only one study investigated left ventricular (LV) function using pulsed tissue Doppler echocardiography (TDE) in patients with SH. However, no study has used this technique in the identification of right ventricular (RV) function in these patients. We aimed to investigate the effect of SH on RV and LV function using TDE technique. The present study included 36 newly diagnosed SH patients and 28 healthy controls. For each subjects, serum free T3 (FT3), free T4 (FT4), total T3 (TT3), total T4 (TT4), TSH, peroxidase antibody (TPOab) and thyroglobulin antibody (TGab) levels were measured, and standard echocardiography and TDE were performed. In patients with SH, TSH levels were significantly higher, and TPOab and TGab levels were significantly higher when compared to healthy controls. TDE showed that the patients had significantly lower early diastolic mitral and tricuspid annular velocity (Ea) and early/late (Ea/Aa) diastolic mitral and tricuspid annular velocity ratio (p<0.05, p<0.05 and p<0.001, p<0.001, respectively), and significantly longer isovolumetric relaxation time (IRT) of left and right ventricles (p<0.001 and p<0.001, respectively). However, Aa, Sa, and isovolumetric contraction time (ICT) and ET (ejection time) of left and right ventricle did not significantly differ (p=ns for all). In addition, a negative correlation between TSH and TD-derived tricuspid Ea velocity and Ea/Aa ratio, and a positive correlation between TSH and IRT of right ventricle were observed. Our findings demonstrated that SH is associated with impaired RV diastolic function in addition to impaired LV diastolic function.
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PMID:Evaluation of right and left ventricular function using pulsed-wave tissue Doppler echocardiography in patients with subclinical hypothyroidism. 1627 66

Postprandial lipoprotein metabolism is suggested to play a role in the pathogenesis of atherosclerosis. In this study, we investigated postprandial lipemia and its relationship to cardiovascular risk factors in patients with overt and subclinical hypothyroidism. Twenty-nine female patients with TSH levels greater than 5 microIU/mL and 12 euthyroid control female subjects were included in the study. Fifteen patients had subclinical hypothyroidism and 14 had overt hypothyroidism. All subjects underwent an oral lipid tolerance test. If triglyceride levels increased by 80% or more, subjects were considered postprandial lipemia positive. Control, overt hypothyroid, and subclinical hypothyroid groups were not statistically different with respect to anthropometric measurements, fasting blood C-reactive protein, uric acid, homocysteine, glucose, insulin, lipoprotein (a), apolipoprotein B levels, and homeostasis model assessment index. Fasting triglyceride levels correlated positively with TSH levels. Postprandial lipemia frequency was higher in overt hypothyroid subjects than in the control group. The subclinical hypothyroid group did not differ from the hypothyroid group with respect to postprandial lipemia frequency. In subjects with TSH levels higher than 5 microIU/mL, PPL risk was increased sevenfold. The results of this study show that postprandial triglyceride metabolism is affected in hypothyroidism.
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PMID:Postprandial lipemia as a risk factor for cardiovascular disease in patients with hypothyroidism. 1694 84

Serum thyroid parameters show substantial inter-individual variability, in which genetic variation is a major factor. Findings in patients with subclinical hyper- and hypothyroidism illustrate that even minor alterations in serum thyroid function tests can have important consequences for a variety of thyroid hormone-related clinical endpoints, such as atherosclerosis, bone mineral density, obesity, and heart rate. In the last few years, several studies described polymorphisms in thyroid hormone pathway genes that alter serum thyroid function tests. In this review, we discuss the genetic variation in the TSH receptor and iodothyronine deiodinases. We discuss the possible consequences of these studies for the individual patient and also the new insights in thyroid hormone action that can be obtained from these data.
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PMID:Genetic variation in thyroid hormone pathway genes; polymorphisms in the TSH receptor and the iodothyronine deiodinases. 1706 80


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