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

Current concepts of the pathogenesis of atherosclerosis have been reviewed, emphasizing some of the similarities of the mechanisms and events involved to those in inflammation. Figure 2 is a schematic summary of these events. Hyperlipidemia, or some component of hyperlipidemic serum, as well as other risk factors, are thought to cause endothelial injury, resulting in adhesion of platelets and/or monocytes and release of PDGF (and other growth factors), which leads to smooth muscle migration and proliferation. It is clear that endothelial injury need not be denuding, and in fact may consist of altered endothelial function (dysfunction); adhesion of monocytes, increased permeability of endothelium, and disturbances in growth control can occur without morphologically obvious endothelial injury. Hyperlipidemia, hypertension, smoking, immune injury, and other risk factors may contribute to this endothelial dysfunction in different ways and sometimes in combination. Smooth muscle cells produce large amounts of collagen, elastin, and proteoglycans and these form part of the atheromatous plaque. Hyperlipidemia contributes in a number of ways (as discussed earlier), and indeed, in the severely hypercholesterolemic patient, such as one with familial hypercholesterolemia, is alone sufficient to cause atherosclerosis in the absence of other risk factors. Foam cells of atheromatous plaques are derived both from macrophages and from smooth muscle cells; from macrophages via the beta-VLDL receptor and also possibly by way of LDL modification, recognized by the acetyl-LDL receptor (such as oxidized LDL); and from smooth muscle cells by less certain mechanisms. Extracellular lipid is derived from insudation from the lumen, particularly in the presence of hypercholesterolemia, and also from degenerating foam cells. Cholesterol accumulation in the plaque should be viewed as reflecting imbalance between influx and efflux, and it is possible that high-density lipoprotein is the molecule which helps clear the cholesterol from these accumulations (134). The diagram (right) also depicts the possibility that smooth muscle proliferation may occur without endothelial injury at all. There are several postulated mechanisms for such an occurrence: loss of growth control, direct smooth muscle injury (such as by LDL), and autonomous proliferation by the mechanisms suggested by Benditt. The theoretical scheme presented is based largely on in vitro work, only partly substantiated by experimental and human studies, and does not explain the precise mechanisms by which all risk factors increase the susceptibility to atherosclerosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The pathogenesis of atherosclerosis: atherogenesis and inflammation. 327 59

A study was made of 26 patients suffering from primary hyperlipoproteinemia; 8 belonging to familial hypercholesterolemia (phenotype IIa), 9 to familial combined hyperlipidemia (phenotype IIb, 9 to familial hypertriglyceridemia (phenotype IV). During treatment, which was continued for two years, all patients received a diet consisting of 45% carbohydrates, 33% fats and 22% protein. They were given 400 mg (TID) of Plafibride after breakfast, lunch and dinner. In the three phenotypes studied, significant decreases in cholesterol, triglycerides, glucose, insulin and lecithin were observed, while there was an increase in HDL cholesterol, free fatty acids and lysolecithin. Tolerance to the drug was good, and a study of different serum enzymes revealed no undesirable collateral effects.
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PMID:Plafibride treatment and serum lipids in hyperlipoproteinemias. 332 93

Familial dysalbuminemic hyperthyroxinemia (FDH), an autosomal disorder characterized by an increase in serum albumin binding of thyroxine, has been encountered in a family who was also found to have both familial hypercholesterolemia (FHC) and multiple lipoprotein type hyperlipidemia (MLH). One subject with FHC and two subjects with MLH had FDH. Although some of the laboratory parameters in hyperlipidemic patients with FDH were suggestive of hyperthyroidism, the dialyzable free thyroxine concentrations were in the normal range and the patients were clinically euthyroid. The significance of the occurrence of FDH in hyperlipidemic subjects with hypothyroidism has been discussed, especially in regard to the longer time interval that may be needed to achieve an amelioration of the hypothyroid state during treatment with a normal maintenance dose of thyroxine. Treatment of FDH patients with other drugs may require an altered dosage if the drug binds to the atypical albumin fragments characterizing this disorder.
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PMID:Coexistence of familial dysalbuminemic hyperthyroxinemia with familial hypercholesterolemia and multiple lipoprotein type hyperlipidemia. 340 59

Recent experimental and epidemiologic evidence has dispelled all doubts about the need to treat patients with hyperlipidemia. Therapy should focus on 3 areas: control of concomitant risk factors for atherosclerosis, reduction of lipid levels through diet and, if response to diet proves inadequate, administration of lipid-lowering agents. There are 4 categories of first-line drugs: resins, fibrates, nicotinic acid and probucol. Probucol has a sustained effect, additive to that of a lipid-lowering diet; it can reduce total serum cholesterol and cause xanthoma regression even in patients with receptor-defective homozygous familial hypercholesterolemia. It is effective when used alone and has an additive effect when combined with resins or nicotinic acid. Compared with many other lipid-lowering medications, it is well tolerated. Although the combination of probucol and clofibrate may cause a significant decrease in high density lipoproteins, there is no evidence that this decrease carries any adverse consequences for the underlying disease process.
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PMID:Medical management of hyperlipidemia and the role of probucol. 346 Mar 20

Recent studies have shown that heterogeneity of human plasma low-density lipoproteins (LDL) is, in part, the result of production of different LDL products from two subspecies of intermediate-density lipoproteins (IDL). Cholesterol-enriched forms of both IDL species are found in plasma of patients with atherogenic dyslipidemias (familial hypercholesterolemia and type 3 hyperlipoproteinemia) and have physical properties similar to the major species in plasma of cholesterol-fed monkeys. Patients with familial combined hyperlipidemia have been shown to have increased plasma levels of IDL and of a smaller, denser LDL subclass (LDL-IIIA) that appears to be a metabolic product of the smaller IDL subspecies. Results from the NHLBI Type II Coronary Intervention study have supported a link between the small IDL-LDL pathway and coronary disease, in that 2-year changes in levels of these species were associated with disease progression. Furthermore, therapeutic reductions in IDL levels were correlated with increases in high-density lipoprotein cholesterol. Thus variation in IDL levels might influence coronary disease risk by both a direct effect and indirectly by affecting LDL particle number and possibly high-density lipoprotein metabolism.
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PMID:Relationship of intermediate and low-density lipoprotein subspecies to risk of coronary artery disease. 354 74

The degree of atherosclerotic plaques in the carotid arteries was evaluated in 85 patients with familial hypercholesterolemia and in 43 patients with familial combined hyperlipidemia by means of Duplex scan which recognizes early atherosclerosis. In patients older than 40 years carotid atherosclerosis of moderate degree was associated with coronary heart disease in 90% of cases. The extent of elevated cholesterol, age, cigarette smoking, and hypertension determined the degree of carotid atherosclerosis.
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PMID:Atherosclerosis of the carotid arteries documented by duplex scan as a predictor of coronary artery disease in familial hyperlipidemias. 355 Feb 65

The homozygous Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model for human familial hypercholesterolemia, which has been maintained in a closed colony, has a reproductive ability which is remarkably lower than that of normal rabbits. The present study was undertaken to determine whether this low reproductive ability was associated with hyperlipidemia, since it is not associated with inbreeding depression. WHHL dams with over 600 mg/dl of serum cholesterol level showed a weaning rate of only about 20%, while dams with about 300 mg/dl of cholesterol showed a 64% weaning rate. Both conception and weaning rate seemed to decrease with a rise in serum triglyceride. The weaning age of homozygous offspring from the homozygous WHHL dams was significantly higher than homozygous offspring from heterozygous WHHL dame. The rate of increase in body weight of the offspring from WHHL dams was significantly lower than that of the offspring from heterozygous dams under 24 days of age. We concluded that the low reproductive ability, especially low nursing ability, was associated with hyperlipidemia due to the deficiency of low density lipoprotein receptors.
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PMID:Effects of hyperlipidemia on the nursing ability of WHHL rabbits. 358 13

A child showed a type IIb lipoprotein pattern and triglyceride-enriched cutaneous xanthomas before 1 year of age. The proband and 9 of 18 relatives had elevated plasma levels of low density lipoprotein (LDL) B protein; of these nine relatives, four had elevated LDL of increased density while five had elevated LDL of normal density. Compared with normal LDL, LDL of increased density had less cholesteryl ester and free cholesterol, more apolipoprotein B and triglyceride, and a lower molecular weight and flotation rate (Sf degrees). Patients with LDL of increased density had higher mean plasma levels of triglycerides, very low density lipoproteins, and intermediate density lipoproteins, but lower levels of high density lipoproteins than those with elevated LDL of normal density. Multiple lipoprotein patterns in the father's family suggested the presence of familial combined hyperlipidemia (FCH). The mother of the proband and two of her relatives had type IIa lipoprotein patterns and tendon xanthomas, compatible with familial hypercholesterolemia (FH). High affinity binding, internalization, and degradation of 125I LDL in cultured fibroblasts from the proband and his mother were reduced two- to threefold compared with normal cells, while LDL receptor activity in the proband's father was normal. This unusual proband has apparently inherited both FCH and FH.
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PMID:Hyperapobetalipoproteinemia in a kindred with familial combined hyperlipidemia and familial hypercholesterolemia. 359 67

In familial hypercholesterolemia, structural and functional abnormalities of the receptor for low-density lipoprotein (LDL) lead to hypercholesterolemia and premature atherosclerosis. We have developed a simplified method to identify LDL-receptor defects in peripheral-blood lymphocytes. When lymphocytes are cultured in lipoprotein-depleted medium and endogenous sterol biosynthesis is suppressed with mevinolin, mitogen-stimulated proliferation of lymphocytes is dependent on an exogenous source of cholesterol. Whereas a small concentration of supplemental LDL cholesterol (3 to 4 micrograms per milliliter) permits a maximal response in normal lymphocytes, even high concentrations (10 to 50 micrograms per milliliter) are unable to support the proliferation of lymphocytes from patients with homozygous familial hypercholesterolemia. Thus, functional LDL receptors are necessary to allow lymphocyte proliferation in these cultures. The response of lymphocytes from patients with hyperlipidemia not caused by defective LDL receptors was like that of normal cells. In contrast, the response of lymphocytes from patients with heterozygous familial hypercholesterolemia was intermediate between that of homozygotes and that of normal or hyperlipidemic controls. Our method can therefore be used to identify persons who are heterozygous for abnormalities of LDL receptors.
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PMID:Detection of familial hypercholesterolemia by assaying functional low-density-lipoprotein receptors on lymphocytes. 363 81

Several models for low density lipoprotein (LDL) apo B metabolism were applied to LDL turnover data from subjects with two distinct genetic forms of hyperlipidemia, familial hypercholesterolemia (FH), and familial combined hyperlipidemia (FCHL). Of the first two models tested, there was good agreement between the observed and predicted data for FH in one (model A), and for FCHL in the other (model B). The major difference between these two models is that LDL is kinetically homogeneous in model A and heterogeneous in model B, raising the possibility that LDL subspecies differences may occur between these two disorders. The findings are consistent with LDL homogeneity in FH and LDL heterogeneity in FCHL. Two other integrated models (models C and D) provided good agreement between observed and predicted data in both disorders. Although neither could be rejected outright on the basis of known physiology, parameter estimates were more variable with model D. Analysis of the data using model C was consistent with the known pathophysiologic defect in LDL catabolism in FH and suggests that individuals with FH as well as FCHL have more than one LDL subpopulation in plasma. The urine/plasma (U/P) ratio was shown to be constant from day 4 to day 14 of the study in FH, while in FCHL this value declined in all cases. Thus, determination of LDL fractional catabolic rates (FCR) by the U/P ratio method may be invalid in certain groups of patients. The other traditional method for calculating LDL FCR, the Matthews' analysis, overestimated FCR in some instances, and could lead to systematic errors when used to determine LDL FCR and production rates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Low density lipoprotein metabolism in familial combined hyperlipidemia and familial hypercholesterolemia: kinetic analysis using an integrated model. 373 10


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