Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 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

We investigated alterations of serum levels of Lp(a) and lipid profiles in type 2 diabetic patients and their normoglycemic first-degree relatives to evaluate the potential genetic association among these subjects. Serum Lp(a), triglycerride (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), and low density lipoprotein (LDL-C) levels were analyzed in 62 type 2 diabetic patients and 67 normoglycemic first-degree relatives from 29 type 2 diabetic pedigrees, and 45 healthy controls without family histories of diabetes. Dyslipidemia was observed in diabetics and their normoglycemic first-degree relatives. While higher serum TG levels were observed in both type 2 diabetics and their first-degree relatives than those in controls, higher TG levels in diabetics were found when compared with those in first-degree relatives. Meanwhile, lower serum HDL-C levels were observed in both type 2 diabetic patients and their first-degree relatives than those in controls. No significant difference of serum TC and LDL-C levels was found among the three groups. On the other hand, we did not observe significant differences of serum Lp(a) levels between type 2 diabetic patients and normoglycemic first-degree relatives, nor were any significant differences observed between diabetic patients and healthy controls (24.6+/-19.9 vs. 25.8+/-21.2, and 21.3+/-20.5 mg/dl). Although the average serum Lp(a) levels were similar in all subgroups, we did observe a positive correlation of Lp(a) between type 2 diabetic patients and their offspring (r=0.448, P<0.01), suggesting a potential genetic control for Lp(a) levels in type 2 diabetics families.
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PMID:Lipoprotein(a) level and lipids in type 2 diabetic patients and their normoglycemic first-degree relatives in type 2 diabetic pedigrees. 1248 43

Elevated concentrations of circulating apolipoprotein B (apoB)-containing lipoproteins, other than low-density lipoprotein (LDL), have been implicated as causative agents for the development of atherosclerosis. A form of dyslipidemia, the atherogenic lipoprotein profile, that consists of elevated intermediate-density lipoprotein (IDL), triglycerides (TGs), dense LDL and dense very low density lipoprotein (VLDL), and low high density lipoprotein-2, occurs in 40% to 50% of patients with coronary artery disease (CAD). The recently released Adult Treatment Panel III guidelines suggest that because elevated TGs are an independent CAD risk factor, some TG-rich lipoproteins, commonly called remnant lipoproteins, must be atherogenic. Relevant to this series on diabetes, a number of studies have shown that in type 2 diabetes, the severity of CAD is positively related to the numbers of TG-rich particles in the plasma. Although less clear, other studies in type 2 diabetes suggest that elevated levels of lipoprotein (a) [Lp(a)] may also be independently associated with CAD. In this article, we summarize evidence for the role of apoB-containing lipoprotein particles other than LDL in the development of atherosclerosis and discuss methods of quantification and possible pharmacologic interventions for lowering their plasma concentrations. The particles reviewed include the TG-rich lipoproteins: VLDL and its remnants, chylomicron remnants and IDL, and the C-rich lipoprotein: Lp(a).
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PMID:The role of non-LDL:non-HDL particles in atherosclerosis. 1264 86

The efficacy and safety profiles of various forms of niacin for treating dyslipidemia are described. Niacin is well recognized for treating dyslipidemia in adults and has been shown to be effective in reducing coronary events. It has a broad range of effects on serum lipids and lipoproteins, including lowering total cholesterol, low-density-lipoprotein (LDL) cholesterol, and triglycerides. Niacin is the most effective lipid-modifying drug for raising high-density-lipoprotein (HDL) cholesterol levels and has been shown to lower Lp(a) lipoprotein. Niacin reduces triglycerides and very-low-density-lipoprotein and LDL cholesterol synthesis, primarily by decreasing fatty acid mobilization from adipose tissue. Niacin appears to raise HDL cholesterol by reducing hepatic apolipoprotein A-l clearance and enhancing reverse cholesterol transport. Niacin is metabolized through a conjugation or nicotinamide pathway. Standard immediate-release niacin is metabolized primarily through the conjugation pathway, which results in a high frequency of flushing. Long-acting niacin is metabolized through the nicotinamide pathway, which results in less flushing but increases the risk of hepatotoxicity. Extended-release niacin has a more balanced metabolism and causes fewer of both types of adverse effects. Improved serum lipid levels during niacin therapy have been associated with clinical and angiographic evidence of reduced coronary artery disease, especially when combined with statins. Niacin is particularly useful for managing high triglyceride and low HDL cholesterol levels as well as the lipid abnormalities associated with metabolic syndrome, including those commonly encountered in patients with diabetes. Several niacin products are available with significant differences in their safety and efficacy profiles. Health care providers must consider the differences between agents when recommending niacin for dyslipidemia treatment.
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PMID:Niacin for dyslipidemia: considerations in product selection. 1278 70

The increased risk for ischemic heart disease (IHD) associated with subclinical hypothyroidism (SH) has been partly attributed to dyslipidemia. There is limited information on the effect of SH on lipoprotein (a) [Lp(a)], which is considered a significant predictor of IHD. Serum Lp(a) levels are predominantly regulated by apolipoprotein [apo(a)] gene polymorphisms. The aim of our study was to evaluate the Lp(a) levels and apo(a) phenotypes in patients with SH compared to healthy controls as well as the influence of levothyroxine substitution therapy on Lp(a) values in relation to the apo(a) isoform size. Lp(a) levels were measured in 69 patients with SH before and after restoration of a euthyroid state and in 83 age- and gender-matched healthy controls. Apo(a) isoform size was determined by sodium dodecyl sulfate (SDS) agarose gel electrophoresis followed by immunoblotting and development via chemiluminescence. Patients with SH exhibited increased Lp(a) levels compared to controls (median value 10.6 mg/dL vs. 6.0 mg/dL, p = 0.003]), but this was not because of differences in the frequencies of apo(a) phenotypes. There was no association between thyrotropin (TSH) and Lp(a) levels in patients with SH. In subjects with either low (LMW; 25 patients and 28 controls) or high (HMW; 44 patients and 55 controls) molecular weight apo(a) isoforms, Lp(a) concentrations were higher in patients than in the control group (median values 26.9 mg/dL vs. 21.8 mg/dL, p = 0.02 for LMW, and 6.0 mg/dL versus 3.3 mg/dL, p < 0.001 for HMW). Levothyroxine treatment resulted in an overall reduction of Lp(a) levels (10.6 mg/dL baseline vs. 8.9 mg/dL posttreatment, p = 0.008]). This effect was mainly evident in patients with LMW apo(a) isoforms associated with high baseline Lp(a) concentrations (median values 26.9 mg/dL vs. 23.2 mg/dL pretreatment and posttreatment, respectively; p = 0.03). In conclusion, even though a causal effect of thyroid dysfunction on Lp(a) was not clearly demonstrated in patients with SH, levothyroxine treatment is beneficial, especially in patients with increased baseline Lp(a) levels and LMW apo(a) isoforms.
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PMID:Lipoprotein (a) levels and apolipoprotein (a) isoform size in patients with subclinical hypothyroidism: effect of treatment with levothyroxine. 1281 13

Thrombogenesis depends on the balance between coagulation and fibrinolysis in vasculature. Vascular endothelial cells (EC) synthesize activators and inhibitors for fibrinolysis, tissue and urokinase plasminogen activators (tPA and uPA) and plasminogen activator inhibitor-1 (PAI-1). Increased levels of PAI-1 with various levels of tPA have been frequently found in plasma of patients with coronary heart disease (CHD) or diabetes mellitus (DM). Dyslipidemia is common feature in patients with CHD or DM, which is characterized by elevated levels of total cholesterol, triglycerides, low or very low density lipoproteins (LDL or VLDL) and decreased levels of high density lipoprotein (HDL). LDL and VLDL stimulated the generation of PAI-1 from cultured EC. LDL and lipoprotein(a) [Lp(a)], another lipoprotein risk factor for CHD, reduced the generation of tPA from EC. HDL did not greatly alter the release of PAI-1 from EC. Oxidative modification by copper, ultraviolet or long exposure to EC enhanced the effect of LDL on the generation of PAI-1 and tPA from EC. Glycation amplified the effect of LDL and Lp(a) on the changes in the generation of the fibrinolytic regulators from EC. Treatment with antioxidants or HDL normalized glycated LDL-induced changes in the generation of fibrinolytic regulators from EC. Activation of protein kinase C is required for oxidized LDL or Lp(a)-induced PAI-1 production in EC. VLDL, but not LDL or its oxidized form, stimulated PAI-1 production through the activation of the VLDL-responsive element in the PAI-1 promoter. Plasma levels of fibrinolytic regulators in CHD or DM patients may be normalized by HMG-CoA reductase inhibitors and angiotensin II converting enzyme inhibitors. This review summarizes the up-to-date information on effects, mechanism and management for disorders in EC-derived fibrinolytic regulators induced by modified lipoproteins.
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PMID:Impact and mechanism for oxidized and glycated lipoproteins on generation of fibrinolytic regulators from vascular endothelial cells. 1284 45

Atherosclerosis is the major cause of cardiovascular disease (CVD) and in addition to established risk factors as smoking, hypertension, diabetes and dyslipidemia, inflammation and autoimmune reactions have been much discussed recently. Several lines of evidence indicate that also inflammation and autoimmune reactions are highly relevant in atherosclerosis and CVD. Inflammatory cells and cytokines are present in lesions, already at an early stage; animal experiments suggest that immune reactions, though not necessary for development of atherosclerosis, can modulate disease development and systemic inflammation is associated with an enhanced risk of CVD. The enhanced risk of CVD in a major autoimmune disease, systemic lupus erythematosus (SLE), is therefore highly relevant, and in addition to being an important clinical problem, SLE-related CVD could give insights into the nature of autoimmunity in atherosclerosis and CVD in general. We recently defined traditional and non-traditional risk factors for CVD in SLE. These include increased atherosclerosis (as determined by intima-media thickness of carotid artery); raised oxidized low density lipoprotein (OxLDL) and autoantibodies to OxLDL; dyslipidemia with raised triglycerides and Lp(a) and decreased HDL-cholesterol concentrations; raised systemic inflammation; presence of anti-phospholipid antibodies including lupus anticoagulant, homocysteine-levels and more frequent osteoporosis. Disease duration, smoking, blood pressure or diabetes mellitus did not differ significantly between the groups. Taken together, immune reactions are highly relevant in atherosclerosis, and patients with autoimmune disease like SLE are at high-risk of CVD. If confirmed prospectively, non-traditional risk factors like OxLDL in the circulation, autoantibodies against OxLDL and phospholipids and inflammation could lead to new therapeutic strategies and insight into disease mechanisms.
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PMID:Autoimmunity, oxidized LDL and cardiovascular disease. 1284 1

Disorder of blood lipids plays an important role in atherosclerosis progress in patients ongoing chronic haemodialysis (PCHD). These patients have specific features of blood lipids with increment of triglycerides and decrement of HDL-cholesterol. Phenotype of lipid disorder in PCHD is mostly type IV according to Fredrickson (30%), and IIA and IIB fenotypes are less frequent. About 9% of lipid disorders in PCHD are isolated increase of Lp(a). Main reason of hypertriglyceridemia in PCHD is attenuated metabolism of VLDL-cholesterol because of lipoprotein lipasis inhibition. There are changes in lipoproteins quality, specially changes in LDL particle have atherogenic potential. Renal dyslipidemia treatment must be vigorous in the early stages of renal insufficiency. Treatment can be dietary measures (specially omega-3-fatty acids), statins, gemfibrozil, intravenous L-carnitin and bicarbonate given per os. Haemodialysis modifications such as highflux haemodialysis, low molecular weight heparin, vitamin E coated dialyzers and LDL-apheresis in extreme cases have important role in renal dyslipidemia treatment.
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PMID:[Renal dyslipidemia in patients on chronic hemodialysis]. 1289 98

Dyslipidemia is a cardiovascular risk factor which commonly develops during forty. In Europe, progestins are frequently prescribed for treatment of perimenopausal symptoms in women in this age group, as well as in combination with estrogen replacement therapy in non hysterectomised postmenopausal women. Their complete metabolic tolerance is an important, even if non exclusive, factor to take in consideration for cardiovascular protection. Our aim was to review available data on the effects of a 19-norprogesterone derivative, nomegestrol acetate, on lipid tolerability. In healthy or at risk premenopausal women, clinical studies found no significant changes in lipid parameters (total, HDL and LDL cholesterol, triglycerides, apoprotein B, Lp(a) and LpA-I) with nomegestrol acetate administered in antigonadotropic sequence, alone or combined with estrogen in inverse sequence, during 6 to 9 cycles; there was only a small statistically significant decrease in apoprotein A1, probably due to the induced hypoestrogeny. In clinical studies carried out in postmenopausal women, nomegestrol acetate combined with estrogen replacement therapy in a sequential or continuous combined regimen, did not alter the beneficial estrogen-induced lipid profile: reductions in total and LDL cholesterol, apoprotein B and Lp(a); HDL cholesterol was unchanged and an increase in triglycerides occurred only with oral estrogens. A decrease in apoprotein A1 was found after six months of a cyclic sequential hormone replacement therapy but was associated with a beneficial increase in LpA-I. Nomegestrol acetate has proven its neutral effects on lipid metabolism and does not alter the beneficial estrogen-induced lipid effects.
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PMID:[Effects of a 19-norprogesterone derivative, the fourth decade nomegestrol acetate, on lipids]. 1291 65

Heart disease is a major cause of morbidity and mortality among patients with renal failure. Premature atherosclerotic coronary heart disease is driven by multiple risk factors, including dyslipidemia and oxidative stress. In the nondialysis population, there is overwhelming evidence that treatment of dyslipidemia can significantly improve cardiovascular outcomes. Accumulating data indicate that dialysis patients have atherogenic lipid abnormalities. Although LDL cholesterol (LDL-C) levels in patients who undergo hemodialysis are normal or near normal, increased oxidized LDL-C, triglycerides, and lipoprotein (a) [Lp(a)]; decreased HDL cholesterol (HDL-C); and triglyceride-rich VLDL have been noted. Patients who receive peritoneal dialysis have a more atherogenic lipid profile with increased LDL-C, apolipoprotein B, oxidized LDL-C, triglycerides, and Lp(a) and decreased HDL-C. Furthermore, the LDL particles of peritoneal dialysis patients are small and dense. However, there is a dearth of information regarding the goals, efficacy, and safety of dyslipidemia treatment among dialysis patients. Given the strong evidence of risk reduction and the benefits of lipid-lowering treatment in the nondialysis population, the emerging consensus is that dialysis patients should be treated aggressively for dyslipidemia to an LDL-C goal below 100 mg/dl. Although physicians and patients may be reluctant to add medications because of concerns about polypharmacy, potential decreased compliance, and increased cost, the use of agents such as sevelamer that can serve multiple functions, including phosphate control, lipid lowering (decreased LDL-C and total cholesterol), and anti-inflammatory effects (decreased high-sensitivity C-reactive protein), should be explored and considered for patients who would benefit from such treatment.
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PMID:Impact of dyslipidemia in end-stage renal disease. 1293 88


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