UMLS:C0020473 - FACTA Search

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

Serum and biliary lipid metabolism were examined in 13 patients with different types of hyperlipoproteinemia before and after 4 weeks of treatment with either bezafibrate or fenofibrate. In patients with heterozygous familial hypercholesterolemia (FH), bezafibrate (n = 5) and fenofibrate (n = 7) produced a similar significant reduction of total cholesterol, LDL-cholesterol, and triglycerides by 21, 23, and 32%, respectively. In patients with familial combined hyperlipidemia (CHL), only triglycerides decreased markedly. Biliary lipid secretion rates in patients with heterozygous FH were not different from those of young male volunteers, indicating that a reduction of hepatic LDL receptors did not affect hepatic elimination of cholesterol or bile acids. Biliary cholesterol secretion increased significantly from 57 to 75 mg/hr during bezafibrate therapy (n = 8) and from 62 to 71 mg/hr during fenofibrate therapy (n = 9). No consistent change in bile acid or phospholipid secretion was observed. The elevated output of biliary cholesterol increased cholesterol saturation significantly from 147 to 185% and from 152 to 173% during administration of bezafibrate and fenofibrate, respectively. The present study indicates that treatment with bezafibrate or fenofibrate is effective in lowering LDL cholesterol in patients with heterozygous FH, but both drugs increase cholesterol saturation of bile, which might enhance the risk of cholesterol gallstone formation.
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PMID:Biliary lipid secretion in patients with heterozygous familial hypercholesterolemia and combined hyperlipidemia. Influence of bezafibrate and fenofibrate. 376 Jul 7

Low density lipoprotein (LDL) is probably the most atherogenic of all the lipoproteins. Several abnormalities in LDL metabolism seem to be associated with coronary heart disease (CHD) one of them being an elevation of plasma LDL concentration. Recent findings suggest that disorders in the metabolism of LDL could be associated with accelerated atherosclerosis even without elevated LDL levels such as increased flux of LDL and changes in the LDL composition. Elevation of plasma LDL levels can be caused by two factors, first, a decrease in the clearance of LDL and second, an overproduction of this lipoprotein. Catabolism of LDL is largely determined by the LDL receptors as clearly shown in patients with familial hypercholesterolemia (FH). In this inherited disease the patients do not have normal LDL receptors and their LDL levels are remarkably elevated. LDL production is also increased in these subjects. In the rest of the population LDL levels are regulated by both the LDL clearance and production rate. The latter also seems to be related to the LDL receptor activity. The conversion of the LDL precursor, very low density lipoprotein (VLDL) to LDL is the most important factor regulating LDL synthesis. When the LDL receptor activity is low a large fraction of VLDL apolipoprotein B (apoB), the major structural protein in VLDL, is converted to LDL, and LDL production is high. On the other hand, only a small part of VLDL apoB is converted to LDL resulting in low LDL synthesis rate in conditions with high LDL receptor activity. The relationships between production and clearance of LDL are, however, more complex. There are individuals who produce a large number of VLDL and LDL particles but maintain LDL concentrations at a normal level by clearing their LDL very effectively. These subjects obviously have another abnormality in lipoprotein metabolism namely an overproduction of apoB. This disorder has been observed in several conditions like obesity, adult-onset diabetes mellitus, several patients with familial combined hyperlipidemia and some normolipidemic subjects with premature coronary heart disease. In all these conditions increased transport of LDL can be associated with coronary artery disease even in the absence of hypercholesterolemia. This raises the possibility that increased flux of LDL could itself be atherogenic possibly by overloading reverse cholesterol transport. Finally, there is some evidence that LDL particle composition may be important in the process of atherogenesis. High LDL apoB but normal LDL cholesterol levels, hyperapobetalipoproteinemia, has been associated with premature coronary heart disease.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Abnormalities in metabolism of low density lipoproteins associated with coronary heart disease. 390 93

The hyperlipidemia observed in familial hypercholesterolemia can be reduced by portacaval anastomosis. We report the effects of a portacaval shunt on hepatic morphology and biosynthetic pathways crucial to hepatic cholesterol homeostasis in homozygous receptor-negative familial hypercholesterolemia. Portacaval anastomosis was associated with a dramatic change in hepatocyte morphology, 28% reduction in plasma low-density lipoprotein concentration, and a decrease in hepatic total and free cholesterol content by 27 and 75%, respectively. Furthermore, the rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase was decreased by 56%. Finally, the reduced binding of low-density lipoproteins to hepatic membranes preoperatively was increased following the portacaval shunt. These combined results indicate that the changes in circulating lipoprotein concentrations observed after portacaval shunt are due to alterations in the metabolic consequences of the defective recognition of low-density lipoproteins by the liver of familial hypercholesterolemic subjects.
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PMID:The effect of portacaval shunt on hepatic lipoprotein metabolism in familial hypercholesterolemia. 405 99

Although analysis of lipoprotein phenotypes is widely used to diagnose and classify the familial hyperlipidemias, an evaluation of this system as a method for genetic classification has hitherto not been published. The present study of 156 genetically defined survivors of myocardial infarction was therefore designed to examine the relationship between lipoprotein phenotypes and genetic lipid disorders. The lipoprotein phenotypes of each survivor was determined primarily by measurement of his plasma triglyceride and low density lipoprotein (LDL)-cholesterol concentrations; his genetic disorder was identified by analysis of whole plasma cholesterol and triglyceride levels in relatives. The mean levels of LDL-cholesterol discriminated statistically among the three monogenic lipid disorders; it was highest in survivors with familial hypercholesterolemia (261+/-61 mg/100 ml [mean +/-SD]); intermediate in those with familial combined hyperlipidemia (197+/-50); and lowest in those with familial hypertriglyceridemia (155+/-36) (P < 0.005 among the three groups). However, on an individual basis no lipoprotein pattern proved to be specific for any particular genetic lipid disorder; conversely, no genetic disorder was specified by a single lipoprotein pattern. This lack of correlation occurred for the following reasons: (a) individual LDL-cholesterol levels frequently overlapped between disorders; (b) in many instances a small quantitative change in the level of either LDL-cholesterol or whole plasma triglyceride caused qualitative differences in lipoprotein phenotypes, especially in individuals with familial combined hyperlipidemia, who showed variable expression (types IIa, IIb, IV, or V); (c) lipoprotein phenotypes failed to distinguish among monogenic, polygenic, and sporadic forms of hyperlipidemia; (d) clofibrate treatment of some survivors with genetic forms of hyperlipidemia caused their levels of triglyceride and LDL-cholesterol to fall below the 95th percentile, thus resulting in a normal phenotype; and (e) beta-migrating very low density lipoproteins (beta-VLDL), previously considered a specific marker for the type III hyperlipidemic disorder, was identified in several survivors with different lipoprotein characteristics and familial lipid distributions. These studies indicate that lipoprotein phenotypes are not qualitative markers in the genetic sense but instead are quantitative parameters which may vary among different individuals with the same genetic lipid disorder. It would therefore seem likely that a genetic classification of the individual hyperlipidemic patient with coronary heart disease made from a quantitative analysis of lipid levels in his relatives may provide a more meaningful approach than determination of lipoprotein phenotypes.
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PMID:Hyperlipidemia in coronary heart disease. 3. Evaluation of lipoprotein phenotypes of 156 genetically defined survivors of myocardial infarction. 435 58

Primary hyperbetalipoproteinemia (type II hyperlipoproteinemia) is a common disorder associated with premature vascular disease. It is frequently due to genetic abnormalities, some of which are expressed in childhood. We have examined the manner in which that form of hyperbetalipoproteinemia known as familial hypercholesterolemia may be expressed in 236 children aged 1-19 born of 90 matings in which one parent had hyperbetalipoproteinemia of this variety and one parent did not.Two Gaussian populations were fitted to the distribution of both low density lipoprotein cholesterol (C(LDL)) and plasma cholesterol (C) in these children and a likelihood ratio test strongly favored a two over a one population model for both C(LDL) (X(2) = 18.41, P < 0.0005) and C (X(2) = 7.81, P < 0.025). 45% of the children were in the population identified as affected; their mean C(LDL) was 229. The remaining 55% were in the normal population with a mean C(LDL) of 110 which was indistinguishable from that of an unrelated control population, aged 1-19. On the basis of an assumed frequency of hyperbetalipoproteinemia in the general population of 5%, the Edwards' test indicated that a polygenic model of inheritance was highly unlikely (expected, 22%; observed, 45%). The segregation ratio obtained from the derived intersection between the two population curves (C(LDL), 164 mg/100 ml; C, 235 mg/100 ml) was 45/55 (abnormal/normal). The percentage of abnormal children in the first decade (52%) significantly exceeded that in the second (39%) (P < 0.01). The ratios (II/N) were 50/47 and 55/84 in the offspring of affected female and male parents, respectively (X(2) = 3.819, 0.05 < P < 0.10). Only 10% of hyperbetalipoproteinemic children were considered to have hyperglyceridemia. These children, frequently, but not invariably, had a parent with hyperglyceridemia in addition to hyperbetalipoproteinemia (P < 0.05). None of the affected children who were examined had ischemic heart disease (IHD) and 7% had tendon xanthomas. Half of the parents (mean age, 37.4 yr) who were examined had IHD and three-quarters had xanthomas. The data agree well with the hypothesis that hyperbetalipoproteinemia is inherited as a monogenic trait with early expression in these children. More than one genetic defect within the group is not excluded, but retrospective analyses of the 345 first-degree adult relatives of the affected parents indicated that most of the abnormal parents probably represented familial hypercholesterolemia, rather than combined hyperlipidemia, the other most generally recognized form of familial hyperbetalipoproteinemia.
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PMID:Familial hypercholesterolemia (one form of familial type II hyperlipoproteinemia). A study of its biochemical, genetic and clinical presentation in childhood. 436 6

To assess the genetics of hyperlipidemia in coronary heart disease, family studies were carried out in 2520 relatives and spouses of 176 survivors of myocardial infarction, including 149 hyperlipidemic and 27 normolipidemic individuals. The distribution of fasting plasma cholesterol and triglyceride values in relatives, together with segregation analyses, suggested the presence of five distinct lipid disorders. Three of these-familial hypercholesterolemia, familial hypertriglyceridemia, and familial combined hyperlipidemia-appeared to represent dominant expression of three different autosomal genes, occurring in about 20% of survivors below 60 yr of age and 7% of all older survivors. Two other disorders-polygenic hypercholesterolemia and sporadic hypertriglyceridemia-each affected about 6% of survivors in both age groups. The most common genetic form of hyperlipidemia identified in this study has hitherto been poorly defined and has been designated as familial combined hyperlipidemia. Affected family members characteristically had elevated levels of both cholesterol and triglyceride. However, increased cholesterol or increased triglyceride levels alone were also frequently observed. The combined disorder was shown to be genetically distinct from familial hypercholesterolemia and familial hypertriglyceridemia for the following reasons: (a) the distribution pattern of cholesterol and triglyceride levels in relatives of probands was unique; (b) children of individuals with combined hyperlipidemia did not express hypercholesterolemia in contrast to the finding of hypercholesterolemic children from families with familial hypercholesterolemia; and (c) analysis of informative matings suggested that the different lipid phenotypes owed their origin to variable expression of a single autosomal dominant gene and not to segregation of two separate genes, such as one elevating the level of cholesterol and the other elevating the level of triglyceride. Heterozygosity for one of the three lipid-elevating genes identified in this study may have a frequency in the general population of about 1%, constituting a major problem in early diagnosis and preventive therapy.
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PMID:Hyperlipidemia in coronary heart disease. II. Genetic analysis of lipid levels in 176 families and delineation of a new inherited disorder, combined hyperlipidemia. 471 53

Chylomicron (primary particles) were detected by polyvinylpyrollidone (PVP) flocculation in plasma collected after an overnight fast from eight hyperlipemic subjects with broad-beta disease (type III hyperlipoproteinemia). The composition of these chylomicrons was abnormal: relatively poor in triglyceride and rich in cholesterol, giving rise to a triglyceride/cholesterol ratio of < 3.0 in all cases, uniformly below the ratio in chylomicrons from eight fasting subjects with mixed lipemia. By contrast, at the peak of alimentary lipemia following an oral fat load (2 g/kg), chylomicrons from broad-beta subjects had normal, triglyceride-rich composition (triglyceride/cholesterol = 14.0) and resembled chylomicrons from subjects with mixed lipemia, endogenous lipemia, and familial hypercholesterolemia after similar fat loads. As the alimentary lipemia cleared, chylomicrons remaining in broad-beta subjects 14-24 hr after the fat load were again rich in cholesterol. However, a similar degree of cholesterol enrichment was observed in chylomicrons from the subjects with familial hypercholesterolemia, while only a minor increase in cholesterol was recorded in chylomicrons from subjects with mixed or endogenous lipemia. Parallel studies of changes in chylomicron composition during in vitro incubation of whole plasma and of S(f) > 400 with S(f) < 400 lipoproteins from subjects with the different forms of hyperlipoproteinemia revealed equal cholesterol enrichment of chylomicrons from a subject with mixed lipemia and from a subject with broad-beta disease in media of equivalent cholesterol content. These experiments suggested neither excessive avidity of chylomicrons for cholesterol uptake nor excessive influence of S(f) < 400 lipoproteins upon chylomicron composition in broad-beta disease.Thus, results in this study suggest that the cholesterol-rich chylomicrons observed in subjects with broad-beta disease after an overnight fast may originate in the intestine as particles of normal composition (chiefly dietary triglyceride) but assume a composition which is relatively rich in cholesterol through processes of lipolysis and cholesterol transfer among circulating lipoproteins which may not be unique to broad-beta disease.
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PMID:Abnormal lipid composition of chylomicrons in broad-beta disease (type 3hyperlipoproteinemia). 546 Feb 88

Combined drug therapy with cholestyramine and compactin was found to be extremely effective against heterozygous cases of familial hypercholesterolemia. With a single drug regimen, compactin at a dosage of 15 mg/day produced a cholesterol reduction of 23% (70 mg/dl) in cases of combined hyperlipidemia, while twice the dosage (30 mg/day) was needed to produce a comparable effect with heterozygous familial hypercholesterolemia. When compaction was combined with cholestyramine (in a 4 g dose three times a day), the cholesterol-lowering effect of compactin was strongly improved with heterozygous familial hypercholesterolemia; half the dosage of compactin was enough to produce the additive effect compared with the effect produced by each single drug regimen.
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PMID:Combined drug therapy--cholestyramine and compactin--for familial hypercholesterolemia. 650 Jul 69

Cholesteryl ester hydrolase (CEH) activity was measured in freshly isolated mononuclear cells from patients with primary Type II hypercholesterolemia, heterozygous familial hypercholesterolemia (FH) and familial combined hyperlipidemia (CFH). CEH activity was significantly lower in mononuclear cells from Type II patients than in cells from matched normolipidemic individuals. Moreover, the reduced CEH activity in cells from the hypercholesterolemic patients was accompanied by significant accumulation of cholesteryl ester. This pattern of reduced CEH activity and cholesteryl ester accumulation was identical for cells from both the FH and CFH patients. Since low density lipoprotein (LDL) cholesterol concentrations were higher in the Type II patients, we incubated mononuclear cells from normolipidemic individuals with high concentrations of LDL-cholesterol (greater than 150 mg/dl). Under these conditions CEH activity was significantly decreased, cholesteryl ester content increased, and cholesterol linoleate, in particular, accumulated. These data suggest that the intracellular accumulation of cholesteryl esters is determined in part by the extracellular concentrations of LDL-cholesterol and by the activity of CEH within the cells.
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PMID:Cholesteryl ester hydrolase activity in mononuclear cells from patients with type II hypercholesterolemia. 671 78

This study investigates the pedigree of 508 individuals over five generations identified by an individual with hypertriglyceridemia, familial hypercholesterolemia, and a IIb lipoprotein electrophoretic phenotype. The sample of 378 living individuals studied extensively for risk factors and disease status was distributed among maternal (170) and paternal (176) relatives and the codescendants (32) of the index case. It was found that the distributions of the plasma lipid and lipoprotein abnormalities in the different subsets of the kindred were consistent with the presence of two separate hereditary lipid disorders: familial hypercholesterolemia on the paternal side and familial hyperprebetalipoproteinemia on the maternal side. This combination of disorders with a possible contribution from factors influencing glucose metabolism was associated with high frequency of hypercholesterolemia and its clinical manifestations and of cardiovascular morbidity among the codescendants. An interaction effect is suggested as an explanation for the unusually high prevalence of hyperlipidemia among the codescendants and for the presence of a IIb phenotype in the index case.
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PMID:Interaction of two lipid disorders in a large French-Canadian kindred. 682 93

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