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)

Fibrates are hypolipaemic agents with a broad spectrum of action and long-term safety. They reduce the cardiovascular mortality and morbidity and can induce also regression of coronary atherosclerosis. They lower the plasma concentration of total and LDL-cholesterol, triacylglycerols, and produce a rise of HDL-cholesterol. Moreover they can reduce the level of fibrinogen, lipoprotein/a/, PAI-1, uric acid and the concentration of highly atherogenic small dense LDL3. Their effect is mediated by activation of "peroxisome proliferator-activated receptors" (PPARs) in the cell nucleus. At present we find on the market second generation fibrates as well as modern micronized medicaments of the third generation. They are indicated for treatment of patients with hypertriglyceridaemia, combined hyperlipidaemia and diabetic dyslipidemia.
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PMID:[Present status of fibrates in the treatment of hyperlipoproteinemias]. 1104 65

We describe the case of a young HIV-positive patient undergoing three-drug antiretroviral therapy that included a protease inhibitor for 9 months, who was admitted to the hospital with an acute myocardial infarction. A coronary angiogram revealed occlusion caused by a thrombus in the proximal third of the anterior descending artery. Complete recanalization was obtained after an angioplasty was performed. At the time of the infarction, only the triglyceride levels were found to be high. Metabolic alterations associated with the prolonged use of protease inhibitors have been described such as an increase in the triglyceride and cholesterol serum levels, diabetes, resistance to insulin, lipodystrophy, and pancreatitis. The consequences of chronic hyperlipidemia are well known in the medical literature, especially premature coronary artery disease. No family history of coronary artery disease was identified in this patient. Whether the genesis of this localized coronary thrombosis was due to a change in the metabolism of the vascular endothelium caused by the protease inhibitors, or by related dyslipidemia, is still to be determined. In this case, the data suggest a strong link between coronary insufficiency and prolonged use of the protease inhibitor.
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PMID:Acute Myocardial Infarction in a 34-Year-Old HIV-Positive Female Patient While Undergoing Active Antiretroviral Therapy Containing a Protease Inhibitor. 1108 68

Current approaches to the treatment of lipid disorders are inadequate for a substantial number of patients with severe hyperlipoproteinemia, isolated low high-density lipoprotein (HDL) cholesterol levels, or other molecular disorders of lipoprotein metabolism. Therefore, dyslipidemias remain important targets for the development of novel therapies. Gene therapy is a logical therapeutic approach to monogenic lipoprotein disorders, such as homozygous familial hypercholesterolemia, familial lipoprotein lipase deficiency, familial lecithin-cholesterol acyltransferase deficiency, and abetalipoproteinemia, for which current therapies are inadequate. Gene therapy could also be used to increase expression of certain proteins, such as apolipoprotein A-I as a strategy to raise HDL cholesterol levels or apoE as a strategy for severe combined hyperlipidemia. With further progress in the development of vectors, gene therapy for severe dyslipidemia is likely to become a clinical reality.
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PMID:Gene therapy for dyslipidemia: clinical prospects. 1112 93

The high triglyceride (TG) and low high density lipoprotein (HDL) cholesterol dyslipidemia has been associated with increased postprandial lipemia. Although fasting TG is a powerful predictor of postprandial hyperlipidemia, the role of hypoalphalipoproteinemia in postprandial TG metabolism is uncertain. We have studied postprandial lipemia among 63 men with low fasting plasma HDL cholesterol concentrations (<0.9 mmol/L), but with either low (<2.0 mmol/L) or high (>2.0 mmol/L) fasting plasma TG levels. A significant relationship was noted between postprandial TG response and fasting HDL cholesterol concentration (r = -0.43; P: < 0.0005). We also found that men with high TG/low HDL dyslipidemia (high TG and low HDL cholesterol; n = 16) were characterized by abdominal obesity as well as increased visceral adipose tissue accumulation, whereas normolipidemic controls (low TG and high HDL cholesterol; n = 26) and men with isolated low HDL cholesterol concentrations (low TG and low HDL cholesterol; n = 17) were not characterized by features of the insulin resistance syndrome (visceral obesity, hyperinsulinemia, and hypertriglyceridemia). Although controls and men with isolated low HDL cholesterol levels had similar postprandial lipemic responses, men with the high TG/low HDL dyslipidemia had a marked increase in their postprandial TG responses to the fat load compared with the other subgroups (P: < 0. 001). Men with the high TG/low HDL dyslipidemia were also characterized by higher concentrations of apolipoprotein (apo) B-48 and B-100 particles (chylomicron remnants and very low density lipoproteins, respectively) before and during the postprandial period compared with the other subjects. These results suggest that low HDL cholesterol concentration is a heterogeneous metabolic phenotype that it is not associated with postprandial hyperlipidemia unless accompanied by other features of the insulin resistance syndrome.
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PMID:Metabolic heterogeneity underlying postprandial lipemia among men with low fasting high density lipoprotein cholesterol concentrations. 1113 11

The epidemiological, etiopathogenetic, laboratory and clinical features of serum lipid abnormalities occurring in the course of HIV disease are still poorly understood (especially when the supporting role of single antiretroviral compounds is considered), while limited literature data are to date available regarding the management of HIV-related dyslipidemia, as well as the efficacy and safety of dietary-exercise programs, and that of selected hypolipidemic agents. At this time, a careful monitoring of serum lipid profile is needed during combination antiretroviral therapy including protease inhibitors, in order to suggest a diet and hypolipidemic treatment when applicable, and to prevent clinical sequelae related to long-term dyslipidemia. The selection of an appropriate hypolipidemic agent is difficult, since no controlled studies are available in this field, and possibly increased risks of pharmacologic interactions, toxicity and impaired patient's adherence should be taken into consideration. Waiting for specific guidelines for the treatment of hypertriglyceridemia and hypercholesterolemia in the setting of HIV infection, all available literature reports dealing with the management of HIV-associated hyperlipidemia are briefly discussed, on the basis of personal clinical experience.
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PMID:Management of dyslipidemia in patients with HIV disease. 1116 60

The arteriosclerotic damage of the arterial endothelium is initiated by risk factors like dyslipidemia, hypertension, diabetes mellitus, and smoking, which account for the majority of vascular morbidity and mortality. Interventional studies confirmed the causative role of hyperlipidemia, particularly of the modified LDL-cholesterol. A large number of epidemiological and interventional studies identified hypertension as another risk factor and showed the correlation between lowering blood pressure and the reduction in micro- and macrovascular complications. Diabetes mellitus decreases the life expectancy on average by 10 years, mainly due to cardiovascular disease. However, intensive control of blood glucose and blood pressure achieved a significant and clinically important reduction in death and complications related to diabetes. Smoking is a main risk factor for peripheral arterial disease and causes advanced arterial lesions in the younger people. Novel risk factors have been identified and contribute to the elucidation of the atherogenic process.
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PMID:[Risk factors for arteriosclerosis]. 1121 73

Familial combined hyperlipidemia (FCHL) is a common genetic dyslipidemia predisposing to premature coronary heart disease (CHD). We previously identified a locus for FCHL on human Chromosome (Chr) 1q21-q23 in 31 Finnish FCHL families. We also mapped a gene for combined hyperlipidemia (Hyplip1) to a potentially orthologous region of mouse Chr 3 in the HcB-19/Dem mouse model of FCHL. The human FCHL locus was, however, originally mapped about 5 Mb telomeric to the synteny border, the centromeric part of which is homologous to mouse Chr 3 and the telomeric part to mouse Chr 1. To further localize the human Hyplip1 homolog and estimate its distance from the peak linkage markers, we fine-mapped the Hyplip1 locus and defined the borders of the region of conserved synteny between human and mouse. This involved establishing a physical map of a bacterial artificial chromosome (BAC) contig across the Hyplip1 locus and hybridizing a set of BACs to both human and mouse chromosomes by fluorescence in situ hybridization (FISH). We narrowed the location of the mouse Hyplip1 gene to a 1.5-cM region that is homologous only with human 1q21 and within approximately 5-10 Mb of the peak marker for linkage to FCHL. FCHL is a complex disorder and this distance may, thus, reflect the well-known problems hampering the mapping of complex disorders. Further studies identifying and sequencing the Hyplip1 gene will show whether the same gene predisposes to hyperlipidemia in human and mouse.
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PMID:Fine mapping of Hyplip1 and the human homolog, a potential locus for FCHL. 1125 74

Familial combined hyperlipidemia (FCHL) is the most frequent genetic lipid abnormality in humans, with a 5- to 10-fold increased risk of early myocardial infarction. Familial combined hyperlipidemia has been proposed as the leading cause of dyslipidemia in familial dyslipidemic hypertension (FDH). It was the objective of this study to quantify and analyze the simultaneous occurrence of hypertension and hyperlipidemia in FCHL families. We assessed blood pressure (BP) and hyperlipidemia in 27 families with FCHL (235 relatives and 140 spouses, aged 30 to 60 years). Hypertension was defined as a BP more than 140/90 mm Hg, or the use of antihypertensive medication. Multiple backward linear regression analysis was used to derive a biological formula describing BP in FCHL families. One-third of 27 FCHL families were diagnosed with FDH. Sixty-four of 235 (27.2%) relatives had dyslipidemic hypertension (DH), compared to 20 of 140 (14.3%) spouses (P = .005); odds ratio = 2.25 (95% confidence interval 1.29-3.91). Multiple linear regression analysis showed that age, FCHL status, and waist circumference significantly contributed to systolic blood pressure (SBP) in female FCHL relatives. In conclusion, in FCHL we defined age, waist circumference, and hyperlipidemia as predictors of SBP. This study indicates that visceral adipose tissue strongly contributes to the high prevalence of DH in FCHL families. Reduction of visceral fat should be tested as a potential therapeutic intervention for hyperlipidemia and hypertension in FCHL individuals.
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PMID:Familial dyslipidemic hypertension syndrome: familial combined hyperlipidemia, and the role of abdominal fat mass. 1133 82

We have developed a stable isotope breath test for the assessment of chylomicron remnant metabolism and report the results from the breath test in human subjects selected for disorders of chylomicron or remnant metabolism. In type I hyperlipemia, the phenotype is extreme hypertriglyceridemia due to a lack of lipoprotein lipase activity, which causes the failure of remnant formation. The type III dyslipidemia phenotype is caused by the inefficient removal of chylomicron remnants from plasma, generally because of homozygosity for apolipoprotein E2 alleles. The breath test was predicted to be abnormal in type III hyperlipemia, whereas a priori in type I hyperlipemia defective remnant clearance was not anticipated. Subjects were injected with lipid emulsions prepared with a composition similar to normal chylomicron remnants. The emulsions contained cholesteryl ester incorporating the stable nonradioactive isotope (13)C in the fatty acid moiety. End exhalation breath was collected at intervals after intravenous injection of the remnant-like emulsions and analyzed for (13)C enrichment by isotope-ratio mass spectrometry. Compared with the group of normolipemic men, the fractional catabolic rate of remnants measured by the breath test was significantly decreased (P = 0.006) in subjects with type III dyslipidemia. In the group with type I hyperlipemia, the fractional catabolic rate was not different (P = 0.233) from the control group. Therefore, the underlying capacity for remnant catabolism was normal in this group of markedly hypertriglyceridemic subjects. By short-circuiting the step of lipolysis, the remnant-like emulsion breath test provides direct information about remnant clearance and metabolism, which should assist in investigations of postprandial lipid metabolism.
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PMID:Chylomicron remnant metabolism in familial dyslipidemias studied with a remnant-like emulsion breath test. 1135 77

Elevated plasma lipoprotein levels play a crucial role in the development of coronary artery disease. Genetic factors strongly influence the levels of plasma lipoproteins, but the genes and sequence variations contributing to the most common forms of dyslipidemias are not known. We used GeneChip probe arrays to resequence the coding regions of 10 key genes of lipid metabolism. The sequences of these genes were analyzed in 80 dyslipidemic individuals. Fourteen nonsynonymous and twenty-two synonymous single nucleotide changes were identified that could be confirmed by conventional sequencing. Seven of the fourteen nonsynonymous sequence variants were polymorphisms with allele frequency >1% in the general population. The remaining seven were not found in normolipidemic controls (25 Caucasians and 25 African-Americans). The relationship between nonsynonymous sequence variations and various dyslipidemias was explored in association and family studies. No evidence was found for coding sequence variations in any of the 10 genes contributing to dyslipidemia. Only a single sequence variation, a missense mutation in the low density lipoprotein receptor gene, co-segregated with hyperlipidemia in the proband's family. This study illustrates some of the difficulties associated with identifying sequence variations contributing to complex traits.
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PMID:Sequence diversity in genes of lipid metabolism. 1138 Oct 31


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