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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Univariate and bivariate analyses of cholesterol and triglycerides are performed after appropriate age adjustment on 247 individuals in 33 families where the probands have elevations of cholesterol, low density lipoprotein and triglycerides, and type IIb lipoprotein phenotype. Mixture of lognormal distributions are fitted by maximum likelihood to the data. Best fitting single and mixtures of lognormal distributions are compared with empirical cumulative plots, and the likelihood-ratio criterion is used to test for significance. A mixture of two lognormal distributions fits significantly better than one lognormal distribution for cholesterol but not for triglycerides. When a mixture of bivariate lognormals is fitted to the data, only one local maximum is found, suggesting action of a single genetic determinant in this sample. The best cutoff line is almost parallel to the triglyceride axis, indicating the relatively high involvement of cholesterol compared to triglycerides in separating the normal and abnormal groups. Using the best linear function, the difference in the two bivariate means is found to account for 61% of the total variation in log cholesterol and log triglycerides. To determine if the results are due to enrichment of the sample with familial hypercholesterolemia syndrome, seven families where the proband and/or any relative has tendon xanthomas are removed and the analyses repeated on the remaining 26 kindreds. The results of these analyses are virtually the same as those of the total sample. Also, a subsample of 21 families in which the proband and at least one additional kindred member are affected is analyzed in the same manner with similar results. For comparison, data from a study of families with combined hyperlipidemia [1] are analyzed in an analogous manner, bearing in mind that the populations sampled are probably different. Fitting a mixture of two bivariate distributions and finding the best cutoff to these data indicate that triglycerides are more involved in separating the two groups. Probably because of major differences in ascertainment, the distribution of lipid levels in oour patient group is practically indistinguishable from that of hypercholesterolemia, and the Seattle data [1] are more nearly similar to hypertriglyceridemia. It may be premature to consider familial combined hyperlipidemia as an entity distinct from both hypercholesterolemia and hypertriglyceridemia. We hope it will eventually be possible to analyze these data using a refined genetic model that includes both major gene and polygenic effects and to combine this form of analysis with quantitative tissue culture methods.
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PMID:Bivariate analyses of cholesterol and triglyceride levels in families in which probands have type IIb lipoprotein phenotype. 16 68

A subnormal activity of postheparin plasma hepatic lipase was demonstrated in nine of 16 patients with familial type II hypercholesterolemia. On the other hand, in patients with combined hyperlipidemia (type II b) the hepatic lipase activity was mostly in upper normal range. The postheparin plasma lipoprotein lipase activity was normal in both patient groups. It is suggested that the low hepatic lipase activity may have a role in the patholgenesis of one form of familial hypercholesterolemia.
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PMID:Low postheparin plasma hepatic lipase activity in familial type IIa hyperlipoproteinemia. 18 Aug 67

Fasting serum cholesterol and triglyceride levels were measured in 131 randomly selected adult members of a Lebanese Community of Western New York. Mean cholesterol levels (males, 217 mg%; females 234 mg%) were higher than those reported from the Lebanon but similar to those reported in most other populations. Mean triglyceride levels (males, 153 mg%; females, 115 mg%) were higher than those reported in most other populations. Twenty-three subjects were hyperlipidemic on the basis of age and frequency distribution adjusted serum lipid levels above the 90th percentile. Clinical and family studies carried out on 13 of these 23 hyperlipidemic subjects suggested that 77% had monogenic hyperlipidemia and 23% primary non-monogenic hyperlipidemia. A high frequency of familial hypercholesterolemia (minimum estimate 0.7%) was found, in keeping with the high frequency of the disorder in Lebanon. The study serves to emphasize the difficulties in defining hyperlipidemia, in establishing a specific diagnosis in the individual patient, and in distinguishing between optimum and normal serum lipid levels.
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PMID:Hyperlipidemia in a Lebanese community: difficulties in definition, diagnosis and decision on when to treat. 27 66

Since the cloning of the human LDL receptor (LDLR) gene, familial hypercholesterolemia (FH) can be diagnosed by recombinant DNA technology either using restriction enzyme mapping to detect major rearrangements of the gene or using restriction fragment length polymorphisms (RFLPs) and linkage analysis in family studies. Genotypes and haplotypes of four RFLPs (StuI, ApaII 5', PvuII, NcoI) were used to study the inheritance of the detective LDLR gene in three families. Diagnosis of FH based on the lipid levels alone was not possible because in these kindreds both parents exhibit elevated lipid levels. However, in two families using haplotype analysis, elevated cholesterol levels in certain relatives could be attributed to the inheritance of a defective LDRL gene and thereby distinguished from hypercholesterolemia due to familial combined hyperlipidemia. In the third family where both hypercholesterolemic parents carried a defective LDLR gene, a case of homozygous FH could be excluded in a child by demonstrating the inheritance of a normal LDLR gene.
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PMID:Diagnosis of familial hypercholesterolemia using DNA haplotype analysis in three large families with two hyperlipidemic parents. 135 52

Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused by a deficiency in the receptor that clears low density lipoprotein (LDL) from the serum (reviewed in Ref. 1 and 2). Patients with one abnormal LDL receptor allele have moderate elevations in plasma LDL and suffer premature coronary artery disease (CAD). Approximately 5% of all patients under 45 who have had a myocardial infarction carry this trait. Patients with two abnormal LDL receptor genes (homozygous deficient patients) have severe hypercholesterolemia and life-threatening coronary artery disease in childhood. Strategies for treating patients with FH are directed at lowering the plasma level of LDL. In heterozygotes, this is accomplished through the administration of drugs that stimulate the expression of LDL receptor from the normal allele (2). This therapeutic approach is not effective in the treatment of homozygous deficient patients, especially those that retain less than 2% of residual LDL receptor activity. Partial amelioration of hyperlipidemia has been achieved in some homozygous deficient patients by diverting the portal circulation through a portacaval anastomosis (3) and by chronic plasmapheresis therapy (4). A more direct approach has been to correct the deficiency of hepatic LDL receptor by transplanting a liver that expresses normal levels of LDL receptor. Three patients that survived this procedure normalized their serum LDL-cholesterol (5-9). We have used an authentic animal model for FH, the Watanabe Heritable Hyperlipidemic rabbit (WHHL), to develop gene therapies for the homozygous form of FH (10-13). The WHHL rabbit has a mutation in its LDL receptor gene which renders the receptor completely dysfunctional (12) leading to severe hypercholesterolemia, diffuse atherosclerosis, and premature death. The potential efficacy of gene therapy for FH is supported by a series of studies we have performed in the WHHL rabbit in which we have achieved metabolic improvement (14-18). Liver tissue was removed from WHHL rabbits and used to isolate hepatocytes and establish primary cultures. A functional rabbit LDL receptor gene was transduced into a high proportion of hepatocytes using recombinant retroviruses, and the genetically corrected cells were transplanted into the animal from which they were derived. Transplantation of the genetically corrected, autologous hepatocytes was associated with a 30-40% decrease in serum cholesterol that persisted for the duration of the experiment (4 months, Ref. 18). Recombinant derived LDL receptor RNA was detected in liver for at least 6 months. There was no apparent immunological response to the recombinant derived LDL receptor.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ex vivo gene therapy of familial hypercholesterolemia. 139 Oct 38

The primary and secondary prevention of cardiovascular diseases and, therefore, the therapy of hyperlipidemia is essential in strategies to lower morbidity and mortality from coronary heart disease (CHD), the most relevant atherosclerosis-associated disease. These programs imply not only a medical but also an economic challenge to our health system. That is why all therapeutic measures have to be evaluated regarding their cost-effectiveness. A cost-effectiveness profile was calculated for all the therapies of hyperlipidemia (nutritional therapy, dietetic nutritionals, drugs and LDL-apheresis) with respect to the following parameters: total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides. The daily costs of all interventional measures are compared to the success rate, whereby an index of daily therapy costs and 1% change per lipid parameter was calculated. Nutritional therapy is by far the cheapest, and LDL-apheresis the most expensive but also the most effective and reliable therapeutic measure. It has to be considered, however, that dietary intervention can be very successful in overnutrition while in rare cases of severe homozygous familial hypercholesterolemia there is no therapeutic alternative to LDL-apheresis. Life-style modifications, such as changing nutritional habits, may contribute towards reducing or removing one or more risk factor(s) (e.g. malnutrition is associated with overweight, hyperlipoproteinemia (HLP), hyperinsulinemia (syndrome X), hyperfibrinogenemia and hypertension). But neither health politicians nor the population seem to be conscious of the fact that life-style changes help to reduce medical expenditure. Considering the fact that nearly every medical service is getting more and more expensive, the need to introduce financial regulations is evident.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Economic aspects of therapy for lipid metabolism disorders]. 150 39

In people with diabetes, glycation of apolipoproteins correlates with other indices of recent glycemic control, including HbA1. For several reasons, increased glycation of apolipoproteins may play a role in the accelerated development of atherosclerosis in diabetic patients. Recognition of glycated LDL by the classical LDL receptor is impaired, whereas its uptake by human monocyte-macrophages is enhanced. These alterations may contribute to hyperlipidemia and accelerated foam-cell formation, respectively. Glycation of LDL also enhances its capacity to stimulate platelet aggregation. The uptake of VLDL from diabetic patients by human monocyte-macrophages is enhanced. This enhancement may be due, at least in part, to increased glycation of its lipoproteins. Glycation of HDL impairs its recognition by cells and reduces its effectiveness in reverse cholesterol transport. Glycation of apolipoproteins may also generate free radicals, increasing oxidative damage to the apolipoproteins themselves, the lipids in the particle core, and any neighboring macromolecules. This effect may be most significant in extravasated lipoproteins. In these, increased glycation promotes covalent binding to vascular structural proteins, and oxidative reactions may cause direct damage to the vessel wall. Glycoxidation, or browning, of sequestered lipoproteins may further enhance their atherogenicity. Finally, glycated or glycoxidized lipoproteins may be immunogenic, and lipoprotein-immune complexes are potent stimulators of foam-cell formation.
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PMID:Lipoprotein glycation and its metabolic consequences. 152 39

The effects of gemfibrozil and lovastatin treatment on composition and hydrated density distribution of high-density lipoprotein (HDL) were studied in 21 patients with heterozygous familial hypercholesterolemia with the use of HDL density gradient ultracentrifugation. At baseline the patients with familial hypercholesterolemia had a markedly reduced or missing HDL2 subfraction and their HDL3 was more dense with reduced content of cholesteryl ester and increased content of triglyceride compared with HDL of control subjects with normal lipid values. Gemfibrozil and lovastatin caused primarily similar alterations in HDL components in HDL2 and HDL3 subfractions. Both agents increased apolipoprotein AI and apolipoprotein AII concentrations significantly in HDL2, whereas the apolipoprotein changes in HDL3 were relatively smaller. The difference between the effects of these two agents was related to the HDL lipid composition. Gemfibrozil increased the cholesterol concentrations of HDL2 and HDL3 (p less than 0.05 for both), and lovastatin caused significant increases in HDL2 (p less than 0.05) and HDL3 phospholipids (p less than 0.01). The observed similarity of qualitative alterations in HDL subfractions produced by these two agents in patients with familial hypercholesterolemia differs from those reported in other types of hyperlipidemia and is probably a consequence of the basic abnormalities in HDL that are characteristic of familial hypercholesterolemia.
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PMID:Effects of lovastatin and gemfibrozil on high-density lipoprotein subfraction density and composition in patients with familial hypercholesterolemia. 161 16

Atherosclerosis is a fundamental cause of life-threatening disorders, such as ischemic heart disease or stroke. Therefore, prevention and treatment of atherosclerosis is a matter of importance. In atherosclerotic lesions, there are many foam cells which contain large amounts of cholesteryl ester. In particular, most of these foam cells in the early stage of atherosclerosis derive from monocytes/macrophages. Today, foam cell transformation of macrophages in subendothelial space is considered to occur by a mechanism in which macrophages take up oxidized low density lipoprotein. We have already discovered that atherosclerosis of Watanabe heritable hyperlipidemic rabbits, an animal model for hereditary hyperlipidemia and severe atherosclerosis, could be prevented by probucol. This drug was originally developed as an antioxidant, and the mechanism of prevention of atherogenesis with this drug is considered that it prevents oxidative modification of LDL. On the other hand, probucol also causes regression of xanthoma in patients with familial hypercholesterolemia. This effect implies that probucol can be effective for treatment of atheromatous lesions, because xanthoma is a lesion which consists of macrophage-derived foam cells. However, the precise mechanism of probucol in causing regression of xanthoma has not been clarified. Considering these observations, we paid special attention to the oxidative modification of high density lipoprotein (HDL). HDL makes contact with foam cells in subendothelial space and stimulates efflux of cholesterol. This is the very place where oxidative modification of LDL is considered to occur. Therefore, it is rational to attempt to determine what would happen when HDL is oxidized and whether probucol could prevent oxidative modification of HDL.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Studies on atherosclerosis with an animal model]. 161 1

Hyperlipidemia may play a role in the progression of diabetic and other renal diseases. Low density lipoprotein (LDL) and other proteins including extracellular matrix components undergo nonenzymatic glycation in vivo. We examined the effects of glycation of LDL as occurs in diabetes (4 to 8%) on binding and uptake by mesangial cells and their proliferation. The glycation of LDL (g-LDL) significantly decreased its binding and uptake by mesangial cells by 15 to 20%, indicating that glycated LDL binds to the LDL receptor, but with lower affinity than LDL. Both LDL and g-LDL modestly stimulated [3H] thymidine incorporation into mesangial cells at 5 to 10 micrograms/ml. Native, oxidized (Ox-LDL) and glycated LDL all bound to the extracellular matrix generated by rat mesangial cells in culture. The binding of LDL, Ox-LDL and g-LDL to mesangial matrix was two to four times higher than to mesangial cells. Binding of LDL and g-LDL was significantly higher to glycolaldehyde modified matrix, which serves as an in vitro model for nonenzymatic glycation end-product cross-linking of matrix which occurs in long-standing diabetes. Based on these findings, we propose that glycation of LDL decreases its binding and uptake by the LDL receptor of mesangial cells and may slow its catabolism. Furthermore, LDL bound to extracellular mesangial matrix can undergo oxidation and generate cytotoxic LDL components. This process may be further enhanced by advanced glycation of the mesangial matrix in diabetes, contributing to glomerular pathology.
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PMID:Interactions of LDL and modified LDL with mesangial cells and matrix. 161 32


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