Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a) (Lp[a]) levels, and coronary heart disease (CHD) refractory to diet and lipid-lowering drugs is poor. For such patients, regular treatment with low-density lipoprotein (LDL) apheresis is the therapeutic option. Today, there are four different LDL-apheresis systems available: immunoadsorption, heparin-induced extracorporeal LDL/fibrinogen precipitation, dextran sulfate LDL-adsorption, and LDL-hemoperfusion. Despite substantial progress in diagnostics, drug therapy, and cardiosurgical procedures, atherosclerosis with myocardial infarction, stroke, and peripheral cellular disease still maintains its position at the top of morbidity and mortality statistics in industrialized nations. Established risk factors widely accepted are smoking, arterial hypertension, diabetes mellitus, and central obesity. Furthermore, there is a strong correlation between hyperlipidemia and atherosclerosis. Besides the elimination of other risk factors, in severe hyperlipidemia (HLP) therapeutic strategies should focus on a drastic reduction of serum lipoproteins. Despite maximum conventional therapy with a combination of different kinds of lipid-lowering drugs, however, sometimes the goal of therapy cannot be reached. Mostly, the prognosis of patients suffering from severe HLP, sometimes combined with elevated Lp(a) levels and CHD refractory to diet and lipid-lowering drugs is poor. Hence, in such patients, treatment with LDL-apheresis can be useful. Regarding the different LDL-apheresis systems used, there were no significant differences with respect to the clinical outcome or concerning total cholesterol, LDL, high-density lipoprotein, or triglyceride concentrations. With respect to elevated Lp(a) levels, however, the immunoadsorption method seems to be the most effective. The published data clearly demonstrate that treatment with LDL-apheresis in patients suffering from severe hyperlipidemia refractory to maximum conservative therapy is effective and safe in long-term application.
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PMID:Current topics on low-density lipoprotein apheresis. 1172 15

The guideline for the reference value of serum lipid(total cholesterol, LDL-cholesterol, HDL-cholesterol and triglyceride) was proposed by the Japan Atherosclerosis Society in 1997. These values are utilized for the diagnosis and treatment of hyperlipidemia to protect patients from ischemic heart disease. The upper limit of reference value was not determined by the 95 percentile range from healthy subjects, but on the basis of clinical data on serum lipid in the Japanese. This way to determine the reference value will be suitable in case of lipid, because there is a tendency to increase cholesterol level in the Japanese for these thirty years. The standardization for each lipid assay is crucial. The CDC-established Reference Methods for measuring total cholesterol(TC), HDL-C. LDL-C, and triglyceride(TG) are used to set reference values for the serum pools used for LSP(Lipid Standardization Panel) standardization. In Japan, the routine methods for cholesterol and triglyceride have been proposed by the special committee in the Japan Society of Clinical Chemistry. In contrast, homogeneous assay for HDL- and LDL-C, which are used routinely at present, have still some problems in the point of accuracy. A new ELISA for Lp(a) has been developed using antibody not reacting to kringle IV type 2. Its standardized assay, thus, will be available sooner or later. With respect to other lipid-related test such as RLP(remnant-like particles) and oxidized LDL, it is necessary to accumulate more clinical data for the determination of reference value.
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PMID:[Reference values of serum lipid]. 1176 57

Obesity is very frequently found after renal transplantation (Tx). It may represent risk factor for development of atherosclerosis and chronic allograft nephropathy. In a prospective randomized metabolic study we monitored for a period of 12 months a total of 427 patients (pts) (M 228/F 199) aged 20-70 yrs after Tx. All patients were treated with cyclosporin A and prednisone at standard doses. We compared the findings of 118 pts with a body mass index (BMI) > or = 30 (kg/m2, Group I) with data obtained from 309 pts with BMI < 30 (Group II) one year after Tx. The mean values of the analysed parameters were as follows (Gr I vs Gr II): total cholesterol (TC): 7.2 +/- 2.4 vs 6.1 +/- 2.0, triglycerides (TG) 3.8 +/- 1.6 vs 2.6 +/- 0.6; LDL-cholesterol 4.1 +/- 1.2 vs 3.0 +/- 0.7; fasting glycemia 8.0 +/- 3.2 vs 5.2 +/- 2.0 (all mmol/L, all p < 0.01); HDL-cholesterol/TG 0.28 +/- 0.07 vs 0.38 + 0.06, p < 0.025). The mean values of corrected Ccr, cyclosporine level, Lp(a) and proteinuria did not differ significantly. There were also no statistical differences in apo E isoforms. In conclusion, our data suggest hyperlipidemia-associated obesity should be treated effectively as a high-risk factor after Tx.
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PMID:Hyperlipidemia and obesity after renal transplantation. 1180 13

Impaired fibrinolysis and elevated lipoprotein(a) (Lp[a]) are possible nonclassic risk factors for myocardial infarction (MI) at young age. The fibrinolytic system in young women with MI has not been evaluated yet and the role of Lp(a) is still controversial. The authors determined fibrinolytic parameters and Lp(a) in premenopausal women (mean age 42+/-3 years, n = 22) 0.5 to 6 (mean 3.5) years after MI, who were all without severe classic risk factors and had an otherwise low risk for MI. Elevated levels of tissue type plasminogen activator (t-PA) (p< 0.05) were measured in comparison to 52 age-matched controls; no difference was found in plasminogen activator inhibitor, plasminogen, fibrinogen, euglobulin clotting time and D-dimers. Significantly more MI patients had Lp(a) levels greater than 300 mg/L compared to controls (36% vs 13.5%, p< 0.05). The combination of elevated Lp(a), mild hyperlipidemia, and nonsevere smoking was found in 62.5% of MI patients who had elevated levels of Lp(a), in 23% of all women with MI, and in none of the controls. Elevated t-PA is probably only a marker of increased risk of MI, whereas elevated Lp(a) probably has a causative role. A combination of elevated Lp(a), hyperlipidemia, and nonsevere smoking seems to be a high-risk profile, relatively common in young women with MI.
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PMID:Fibrinolytic parameters and lipoprotein(a) in young women with myocardial infarction. 1195 5

About 15% of the adult Kuwaiti population has type 2 diabetes and over 50% are hyperlipidaemic by current diagnostic criteria. Not surprisingly, coronary heart disease (CHD) is the leading cause of death in Kuwait. Reports from coronary care units in Kuwait suggest that 40-80% of the CHD patients were diabetic and 50-80% hyperlipidaemic. The pattern worldwide is similar. International guidelines have therefore consistently recognised diabetes as a major risk factor for CHD. In our Lipid Clinic population in Kuwait, about 30% are diabetic. The commonest lipid abnormalities seen in Kuwaiti diabetic patients, as elsewhere, are hypertriglyceridaemia with low HDL levels and variable LDL levels. About 75% of the subjects had either mixed hyperlipidaemia or predominant hypertriglyceridaemia. There are possibly some compositional changes in LDL in the diabetic subjects in that there were important differences in the statistical relationships between LDL and HDL and their respective apolipoproteins - apo B and apo A-1 in diabetic as compared to non-diabetic subjects. Other important observations made in diabetic subjects in Kuwait are: (i) similar serum Lp (a) levels and pattern of apo(a) polymorphism with non-diabetic subjects, with no demonstrable relationship between serum levels of Lp(a) and insulin/insulin sensitivity, although with CHD, Lp(a) levels were increased; (ii) diabetic hyperlipidaemic subjects had elevated PAI-1 levels with significant correlations between blood PAI-1 and insulin levels suggesting underlying insulin resistance (syndrome X). Various landmark trials of cholesterol-lowering therapies in the prevention of CHD have consistently demonstrated near-normalization of the increased CHD risk in diabetes. Our experience in Kuwait suggests that diabetic patients and others with mixed hyperlipidaemia benefit from tight glycaemic control, appropriate advice on diet and exercise with regular reinforcement by continuing contact with professional dietitians and regular availability of drugs where prescribed. Often, it is the regular compliance with medication that is important, rather than the specific medication used particularly where HMG CoA reductase inhibitors (statin drugs) are not always available. A useful guideline for management of dyslipidaemia in diabetes is suggested.
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PMID:Diabetic dyslipidaemia in Kuwait. 1244 10

This study was designed to investigate whether serum lipoprotein (a) is affected by pregnancy and to relate this to changes in other lipids, lipoproteins and apolipoproteins. The study involved twenty-nine healthy Caucasian pregnant women at term and 27 non-pregnant women matched for age who acted as controls. Samples of venous blood were obtained from 29 pregnant women at term (between 37 and 42 weeks) and 22 of these women provided a second sample after 12 weeks post-partum. Twenty-seven non-pregnant women acted as controls. Samples were taken for Lp(a) and also cholesterol, triglyceride, HDL-cholesterol, apolipoprotein (apo) A and B1. No significant difference was found in the serum concentrations of Lp(a). However, the pregnant women had significantly higher serum concentrations of cholesterol, triglyceride, apo A1 and B (P<0.001) than the controls. The ratio of apo A1: apo B was significantly lower than controls (P<0.001). HDL-cholesterol was not altered by pregnancy but was lower (P<0.05) than the controls after a period of 12 weeks post-partum. Despite a hyperlipidaemia in pregnancy the serum concentrations of Lp(a) are not affected suggesting different metabolic control for this lipoprotein.
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PMID:Serum lipoprotein (A) and apolipoproteins during pregnancy and postpartum in normal women. 1252 94

The relations of gene polymorphism at the apolipoprotein B locus and serum lipid profile in children was studied in 308 normal 7-11 year-old children, including 151 boys and 157 girls. Blood samples were collected for all subjects, and then the serum and blood clot were separated. Serum lipids, including TC, TG, LDL-C, HDL-C, apoB, apoA I and Lp(a) were detected. Genome DNA was extracted from blood clot, then apoB-Xba I gene polymorphism were tested by PCR-RFLP method. The results showed that the distribution of apoB-Xba I genotype in 308 children accorded with Hardy-Weiberg inheritance equilibrium law. The frequency of heterozygote(+/-) was 13.3%, allele(+) was 0.067. The frequency of allele(+) was closed to the internal and Japanese reports (0.033 and 0.04), but much less than the Caucasians (0.50). This showed a ethnic and population difference in the inheritance variation. The average LDL-C levels of the heterozygotes(+/-) were 2.17 mmol/L, no difference compared with homozygotes(-/-) (2.21 mmol/L, P > 0.05). There was also no difference for the genotype distribution between the hyperlipidemia group and control group, which may be the results of no enough sample size and the sample selection, and so on. On the other hand, in normal children, serum lipids controlled by many genes, the effect of a single gene might be small. More studies and analysis on the relationship between serum lipids and multiple genes in multisites should be the next step.
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PMID:[Gene polymorphism at apoB locus and the serum lipids profile in children]. 1256 93

The R219K polymorphism in the ATP-binding cassette transporter 1 gene ( ABCA1) has been associated with reduced severity of atherosclerosis, fewer coronary events, decreased triglycerides and a trend to increased HDL in men with coronary heart disease (CHD). This study examined the frequency and the effect on CHD and plasma lipids of the polymorphism in patients of both sexes attending a lipid out-patient clinic. The overall frequency of the K allele was 0.26. It was lower in patients with CHD (0.21) than in those without (0.27) but this was not statistically significant. Amongst patients with elevated Lp(a) the frequency of the K allele was significantly lower in those with CHD (0.16) than in those without (0.29). There were no statistically significant differences in total cholesterol, LDL, HDL, apoB or apoAI between carriers and non-carriers. When patients with probable secondary hypertriglyceridaemia (triglycerides >1000 mg/dl), type 2 diabetes and carriers of lipoprotein lipase polymorphisms associated with hypertriglyceridaemia were excluded, the K allele was significantly associated with reduced triglycerides but only in patients with apoE 3/3 genotype. In conclusion, we provide additional evidence that the R219K polymorphism in the ABCA1 gene either directly or as a result of linkage disequilibrium with additional functional variant(s), has a protective effect against CHD and is associated with lower plasma triglycerides in sub-groups of patients with hyperlipidaemia.
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PMID:The association of the R219K polymorphism in the ATP-binding cassette transporter 1 ( ABCA1) gene with coronary heart disease and hyperlipidaemia. 1270 Aug 93

Current topics and new developments in risk factors for ischemic stroke were reviewed. Hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, cigarrette smoking, and heavy alcohol drinking have been established as being common treatable risk factors for stroke. Recent studies have clarified that homocysteine, various cardiac sources of embolism such as patent foramen ovale, antiphopholipid antibodies, lipoprotein (Lp) abnormalities including Lp(a) and remnant-like particle, insulin resistance or hyperinsulinemia, infectious diseases such as Chlamydia Pneumoniae, and CRP are additional risk factors for stroke. In addition, genetic studies using single nucleotide polymorphisms have suggested that many gene polymorphisms are significant risk factors for certain subpopulations of stroke, which is recognized to be a polygenic disease. Management of these risk factors is crucial for primary prevention of stroke, which is the leading cause of death or disability all over the developed countries.
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PMID:[Risk factors for cerebral infarction: current topics and new developments]. 1278 67

The association of elevated lipoprotein (a) (Lp(a)) with an increased risk for coronary events is clearly established. This increased risk may in part be due to the activation of monocytes as major cells involved in atherogenesis. High concentrations of plasma Lp(a) were shown to influence the gene expression of human blood monocytes and in the present study we demonstrate a reduced abundance of the lysosomal acid lipase (LAL) mRNA in monocytes of patients with coronary disease and selective Lp(a) hyperlipidemia. This is also supported by in vitro studies where purified Lp(a) but not low-density lipoprotein (LDL) was shown to downregulate mRNA levels of the LAL in control monocytes. A correlation of Lp(a) serum levels and the proinflammatory cytokine IL-6 was recently also described. Therefore, we investigated whether Lp(a) is capable to enhance the release of this acute phase cytokine from human blood monocytes. Purified Lp(a) led to an increased secretion of IL-6, but not TNF-alpha arguing against a general activation of these cells. The association of reduced LAL activity with the premature development of coronary artery disease has been demonstrated in patients with hypercholesterolemia, and in the present study we show for the first time that LAL expression is suppressed in monocytes from patients with Lp(a) hyperlipidemia and by purified Lp(a). In addition, increased levels of IL-6 also predict future cardiovascular events and IL-6 secretion was also induced by purified Lp(a).
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PMID:Lipoprotein (a) downregulates lysosomal acid lipase and induces interleukin-6 in human blood monocytes. 1297 90


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