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)

Hypoalphalipoproteinemia (HPAL) with mild hypertriglyceridemia (HTG) is associated with increased coronary artery disease (CAD) risk. The aim of this study was to examine the metabolism of postprandial lipoproteins in HPAL/HTG subjects (n = 21). They had a fasting plasma high density lipoprotein (HDL) cholesterol level < 0.9 mmol/l, a triglycerides (TG) level of 2.0-7.1 mmol/l, and a normal low density lipoprotein (LDL) cholesterol level (< 3.7 mmol/l). They were either homozygous for apoprotein E3 (n = 13) or heterozygous for apoprotein E4 (n = 5) or E2 (n = 3). After ingestion of a vitamin A fat load, plasma and chylomicron (CM) retinyl palmitate (RP) response (areas under curves) was three times and non-CM RP response 2.5 times greater than in normolipidemic control subjects (n = 13). There was close correlation between fasting plasma TG level and postprandial RP response in HPAL/HTG subjects (plasma, r = 0.87; CM, r = 0.89; and non-CM, r = 0.84). In control subjects this correlation was present for plasma RP (r = 0.80) and CM RP (r = 0.61) but not for non-CM RP (r = 0.53). In contrast, postprandial RP response was not correlated with fasting plasma HDL cholesterol levels for both groups. There was also no correlation between fasting TG and fasting HDL cholesterol. Postheparin lipoprotein lipase and hepatic lipase activities were slightly higher in HPAL/HTG subjects. The pattern of postprandial change in HDL composition was similar to that in control subjects. These data indicate enhanced postprandial lipemia in the HPAL/HTG syndrome, and this may account for their increased CAD risk.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Delayed clearance of postprandial chylomicrons and their remnants in the hypoalphalipoproteinemia and mild hypertriglyceridemia syndrome. 139 May 90

The postprandial (PP) elevations in triglyceride rich lipoproteins (TRL) are potentially atherogenic. We compared PP lipemia in non insulin dependent diabetes mellitus (NIDDM) with hypoalphalipoproteinemia (HA) and patients with primary HA. Eight males in each group, mean age +/- SD 54 +/- 10 years, were studied for 12 hours after the ingestion of a fat load (65 g of fat/square meter of body surface). Plasma glucose, triglycerides (TG) and cholesterol (C) in plasma and in the different lipoprotein fractions were measured. The PP triglyceridemia was significantly greater in NIDDM patients with HA and correlated with the fasting TG concentrations. The curve pattern of the lipemia (% delta) was otherwise similar in the patients with secondary or primary HA; only the triglyceridemia persisted for a longer period of time in the latter but was otherwise similar to that of the NIDDM patients with lower basal triglyceride values. Patients with primary HA may have a disturbed metabolism of triglyceride rich lipoproteins which have a delayed depuration during the postprandium. Basal HDL-C in patients with HA cannot predict the PP triglyceridemia.
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PMID:[Postprandial lipemia in subjects with primary hypoalphalipoproteinemia and hypoalphalipoproteinemia associated with diabetes]. 148 77

The familial aggregation of lipids [total cholesterol (CH) and triglyceride (TG)] and lipoproteins [high-density lipoprotein cholesterol (HDL) and low-density lipoprotein cholesterol (LDL)] was investigated in families ascertained through both random and nonrandom probands in the Minnesota Lipid Research Clinic Family Study. Nonrandom proband ascertainment was based on single selection through truncation for hyperlipidemia at an earlier screening. A path model was used to investigate the nature of familial resemblance using appropriate adjustments for ascertainment and to determine whether random and hyperlipidemic samples are heterogeneous with regard to the multifactorial model. The results suggest that parameter estimates are consistent with those from previous studies in which only random families were used and that random and nonrandom samples are homogeneous with regard to the path model for CH and LDL. However, for TG and HDL the random and hyperlipidemic samples are significantly heterogeneous. This heterogeneity would be observed if familial hypertriglyceridemia and/or familial hypoalphalipoproteinemia segregates predominantly in the hyperlipidemic rather than in the random sample, as on might expect.
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PMID:Familial aggregation of lipids and lipoproteins in families ascertained through random and nonrandom probands in the Minnesota Lipid Research Clinic Family Study. 188 94

The inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase are highly effective in treating severe elevations of serum cholesterol, and are being widely used for this purpose. In our laboratory, these drugs have been used for the treatment of other forms of dyslipidemia including primary moderate hypercholesterolemia, primary mixed hyperlipidemia, diabetic dyslipidemia, hyperlipidemia of the nephrotic syndrome, and primary hypoalphalipoproteinemia. In these conditions, the HMG CoA reductase inhibitors proved effective in substantially decreasing levels of both low-density lipoproteins and very low density lipoproteins, as well as apolipoprotein B. In some patients, they may even increase levels of high-density lipoproteins. The primary mode of action of HMG CoA reductase inhibitors appears to be to increase the synthesis of hepatic receptors for lipoproteins containing apolipoprotein B, although a reduction in synthesis of these lipoproteins has not been ruled out with certainty. Regardless of mechanisms, drugs of this type appear to have the potential for effective therapy of various forms of dyslipidemia beyond primary severe hypercholesterolemia.
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PMID:Use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in various forms of dyslipidemia. 220 34

CAD results from atherosclerosis, a chronic disease process that has its origin in childhood. Children and adolescents can be at higher risk for CAD by virtue of being from families with premature CAD or familial dyslipoproteinemias. The plasma lipid and lipoprotein levels result from a number of complex metabolic processes that are under the control of genetic and environmental (e.g., diet) influences. The normal ranges of plasma lipids and lipoproteins in children are known, and children and adolescents with dyslipoproteinemia are ordinarily defined as those having levels of plasma total, LDL, or triglyceride above the 95th percentile or with a low HDL cholesterol below the 5th percentile. Children of a parent with documented dyslipoproteinemia or with family history of premature CAD may be screened in the fasting state any time after 2 years of age. Following the exclusion of secondary causes of dyslipoproteinemia, the diagnosis of primary dyslipoproteinemia can be made. Lipoprotein patterns are not diagnostic for a given genotype. Efforts to determine further the biochemical defects responsible for a given phenotype have led to the investigation of gene coding for the apolipoproteins, the key enzymes in the lipoproteins pathways (LPL, HDL, and LCAT) and the receptors that process lipoproteins, such as the LDL receptor and the chylomicron remnant receptor. From a practical standpoint, the diagnosis of the kind of dyslipoproteinemia in a child will depend upon the nature and severity of the dyslipoproteinemia, both in the child (or adolescent) and in parents and siblings. Marked increases in plasma total and LDL cholesterol in the child and in at least one of the parents often reflect the presence of familial hypercholesterolemia, an inherited dominant condition due to a defect in the LDL receptor gene. The triglyceride levels are often normal. If the child has a different dyslipoproteinemia pattern from siblings and parents, then the diagnosis of familial combined hyperlipidemia or hyperapobetalipoproteinemia should be considered. Most children with mild or borderline elevations in total and LDL cholesterol will have polygenic hypercholesterolemia. Triglyceride problems in children and adolescents are relatively uncommon, particularly the more severe hypertriglyceridemia such as that found in lipoprotein lipase and apoC-II deficiency, dysbetalipoproteinemia, and type V hyperlipoproteinemia. High levels of Lp(a) lipoprotein, in isolation or in combination with other dyslipoproteinemia, accelerate risk for CAD. Low levels of HDL cholesterol in the absence of other abnormalities suggest the diagnosis of hypoalphalipoproteinemia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Diagnosis and management of familial dyslipoproteinemia in children and adolescents. 225 50

Cholesteryl ester transfer from solid-phase bound HDL to endogenous plasma HDL or VLDL/LDL was determined in 50 patients with primary disorders of lipid metabolism and 27 normolipidemic subjects. Transfer to the plasma HDL pool was significantly reduced in familial hypercholesterolemia, familial combined hyperlipidemia, hypoalphalipoproteinemia and dysbetalipoproteinemia. Subfractionation of HDL revealed that the lipid transfer to HDL3 was significantly reduced in all patient groups while transfer to HDL2 was increased in those with dysbetalipoproteinemia and familial hypertriglyceridemia. Transfer to LDL and VLDL was increased only in patients with dysbetalipoproteinemia and hypoalphalipoproteinemia. Reduced transfer to HDL occurred in samples with altered HDL composition; particularly where HDL-triglyceride was significantly increased and HDL-cholesteryl esters were reduced. Transfer of cholesteryl ester to HDL3 was significantly decreased in patients with vascular disease. These findings indicate that impaired interaction of cholesteryl ester transfer protein with the HDL3 pool may contribute to the risk of coronary heart disease in patients with specific plasma lipid abnormalities.
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PMID:Relationship between cholesteryl ester transfer activity and high density lipoprotein composition in hyperlipidemic patients. 275 50

Significant risk factors for premature coronary heart disease include: (1) family history, (2) elevated low density lipoprotein (LDL) cholesterol level > or = 160 mg/dl, l, (3) decreased high density lipoprotein (HDL) cholesterol level < 35 mg/dl, l, (4) cigarette smoking, (5) high blood pressure and (6) diabetes mellitus. All of these risk factors are common in patients with premature heart disease. Common familial lipid disorders associated with premature heart disease include familial lipoprotein(a) excess, familial dyslipidemia (elevated triglycerides and decreased HDL cholesterol), familial combined hyperlipidemia (elevations of LDL cholesterol and triglycerides, and often decreased HDL cholesterol), familial hypoapobetalipoproteinemia (elevated apolipoprotein B levels), familial hypoalphalipoproteinemia (low HDL cholesterol levels), and familial hypercholesterolemia (elevated LDL cholesterol levels). All these disorders have been characterized using age and gender specific 90th and 10th percentile values from the normal population. The diagnosis and potential management of these disorders is reviewed.
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PMID:Familial lipoprotein disorders and premature coronary artery disease. 780 28

Large-scale and systemic epidemiological, pathological and experimental studies emphasized and documented the childhood origin of atherosclerosis. There is increasing consensus that lipid levels in children to a large extent determine the rate of coronary artery disease (CAD) in the adult population. Minimal sudanophilic intimal deposits, and the presence of intracellular and extracellular lipid, and a slight increase in interstitial ground substance in 3 years of age or older patients are found. In the Bogalusa Hearth Study aortic fatty streaks were strongly related the antemortem levels of both total cholesterol and low-density lipoprotein cholesterol (LDL-C) independent of race, sex, and age, and were negatively correlated with the ratio of high-density lipoprotein (HDL-C) to low-density plus very-low-density lipoprotein cholesterol (LDL-C+VLDL-C). The potential for primary prevention is real and the strongest piece of evidence for its is the remarkable trend in CHD mortality rates in recent times, rapidly downward in many western countries. A number of factors influence plasma levels of lipid and lipoproteins in newborn, in infants, in children and adolescents and their relevance as possible predictors of adult coronary artery disease. They are certain inherited disorders of dyslipoproteinemia (familial hypercholesterolemia, familial combined hyperlipidemia, hyperapobetalipoproteinemia, and hypoalphalipoproteinemia) and secondary causes of hyperlipidemia (congenital biliary atresia, glycogen storage diseases, hypothyroidism, diabetes mellitus and nephrotic syndrome, etc).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Atherosclerosis and juvenile dyslipidemias]. 818 5

Hypoalphalipoproteinemia (HA) is a common finding in patients with premature coronary artery disease. To characterize the common familial forms of HA, we studied 102 families of probands with premature coronary artery disease; 40 probands (39.2%) had HA. Of these, 25 had at least one first-degree relative affected with HA; 11 had familial hypertriglyceridemia with HA (FTgHA); 10 had familial combined hyperlipidemia (FCH); and 4 had familial HA (FHA) with no other lipoprotein abnormalities. In the remaining 15 families, no lipoprotein abnormalities were observed in first-degree relatives. We measured apolipoprotein (apo) A-I, B, C-III, and E levels as well as lipoprotein particle (Lp) levels of LpA-I (containing apoA-I only), LpA-I:A-II (containing both apoA-I and A-II), LpB:E, and LpB:C-III. Compared with a reference group of healthy men (n = 103) and women (n = 106), probands with familial forms of HA had lower high-density lipoprotein cholesterol levels by selection criteria. Triglyceride levels were higher in FTgHA and FCH probands than in the reference group or FHA subjects. Despite selection of FTgHA and FCH by low-density lipoprotein (LDL) cholesterol, the latter was not significantly different between the three groups and the reference group. ApoA-I levels were decreased in FCH, FHA, and FTgHA probands, and LpA-I and LpA-I:A-II were lower in FHA and FTgHA probands. ApoB levels were significantly higher in all familial HA groups compared with the reference group, being highest in FCH individuals, but not significantly higher between FCH, FTgHA, or FHA probands. LpB:E levels were higher in the FCH and FTgHA groups than in the reference group. There were no significant differences between groups for apoE, apoC-III, and LpB:C-III. LDL particle size was smaller in all three forms of FHA, which, in combination with higher apoB levels, reflects an increased number of smaller, denser LDL particles. Affected children had, on average, higher apoB and LpB:E levels than nonaffected siblings. Our data suggest that common forms of FHA in subjects with coronary artery disease represent a spectrum of overlapping disorders characterized by an increase in apoB-containing lipoproteins, especially LpB:E particles, and smaller, denser LDL particles. When using appropriate age- and gender-adjusted cutpoints, approximately half the offspring (in young adulthood) appeared to be affected.
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PMID:Familial hypoalphalipoproteinemia in premature coronary artery disease. 824 Oct 92

Although there is consensus that lipid variables, especially lipoprotein(a), are heritable and that elevated LDL cholesterol levels should be treated, there are no clear definitions of the common familial lipid disorders associated with premature CHD (lipoprotein(a) excess, FCH, familial dyslipidemia, familial hypoalphalipoproteinemia, familial hypercholesterolemia), nor do we have clear guidelines for the treatment of most of these disorders. Implementation of therapy for elevated LDL cholesterol in familial lipid disorders often has not occurred even in the United States. Before recommendations can be made for subjects with lipoprotein(a) excess and HDL deficiency (who often have combined hyperlipidemia or hypertriglyceridemia), prospective studies documenting benefit of CHD risk reduction must be carried out in subjects with lipoprotein(a) excess and HDL deficiency. One such study is being carried out with gemfibrozil in CHD patients with HDL deficiency. Current data do justify treatment of CHD patients with lipoprotein(a) excess with niacin because niacin has been shown to lower lipoprotein(a) levels as well as lower CHD risk mortality in random CHD patients. With regard to CHD patients with or without HDL cholesterol levels less than 35 mg/dL (0.9 mmol/L), efforts should be made to optimize their lipid profile and reduce their LDL cholesterol levels to less than 100 mg/dL (2.6 mmol/L).
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PMID:Familial lipoprotein disorders and premature coronary artery disease. 828 32


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