Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

A common pattern of dyslipidemia is elevated levels of plasma triglyceride, borderline high total cholesterol, reduced high-density lipoprotein, and increased apolipoprotein B. This pattern of dyslipidemia frequently is associated with premature coronary heart disease. Nicotinic acid is the drug of first choice for this pattern. In this study, gemfibrozil and lovastatin were compared for their effects on the overall lipoprotein profile in 13 men with this type of dyslipidemia. Both drugs significantly reduced very-low-density lipoprotein and intermediate-density lipoprotein cholesterol levels, and both modestly raised high-density lipoprotein cholesterol levels. Gemfibrozil therapy, however, failed to reduce total cholesterol or total apolipoprotein B levels, whereas lovastatin therapy lowered levels of total cholesterol by 28%, low-density lipoprotein cholesterol by 33%, and total apolipoprotein B by 32%. Moreover, lovastatin therapy caused greater declines in lipoprotein cholesterol ratios than gemfibrozil therapy. Lovastatin thus seems to have certain advantages over gemfibrozil for treatment of elevated plasma triglyceride levels accompanied by borderline high total cholesterol and raised apolipoprotein B levels; therefore, lovastatin therapy should be considered as one approach for management of this condition.
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PMID:Primary hypertriglyceridemia with borderline high cholesterol and elevated apolipoprotein B concentrations. Comparison of gemfibrozil vs lovastatin therapy. 223 67

Familial dyslipidemic hypertension (FDH) is a syndrome recently described from sibships selected for early familial hypertension and found to have one or more of three fasting lipid abnormalities [high triglycerides, low high density lipoprotein (HDL) cholesterol, high low density lipoprotein (LDL) cholesterol]. In further analyses of these same 131 hypertensive subjects, apolipoprotein A-I and B, fasting plasma insulin (adjusted for body mass index), and detailed anthropometrics were different in two subgroups of FDH. Of 63 FDH patients, 19 met the criteria for familial combined hyperlipidemia (FCHL); 44 did not, but still had high triglyceride and/or low HDL cholesterol levels. When compared to 20 normolipidemic hypertensive patients, the 19 hypertensive patients with FCHL had 196% higher very low density lipoprotein cholesterol (p = 0.0001), 33% higher apolipoprotein B (p = 0.0002), smaller LDL particles (p = 0.007), and 73% higher fasting insulin (p = 0.003), but no significant differences in body mass index or skinfold thicknesses. The other 44 FDH patients without FCHL had 33% lower HDL (p = 0.0001), with only 8% lower apolipoprotein A-I levels (p = 0.20); significantly higher subscapular skinfolds (p = 0.02), weights (p = 0.002), body mass index (p = 0.006), knee widths (p = 0.0007), and wrist circumferences (p = 0.0009); smaller, denser LDL subfractions (p = 0.001); and increased apolipoprotein B levels (p = 0.01) compared to the normolipidemic hypertensive group. Increased fasting insulin levels were similar to the normolipidemic group and significantly lower than the FCHL group after adjustment for body mass index, suggesting a relationship between obesity and fasting insulin levels only in the non-FCHL group. We conclude that FDH consists of at least two subgroups: 1) FCHL with high apolipoprotein B, small LDL particles, and increased fasting plasma insulin levels, and 2) a less well-defined residual having upper central obesity with low HDL cholesterol and high triglyceride levels. Elevated insulin levels found in both groups, but possibly originating through different physiological mechanisms, may provide the pathophysiological connections between dyslipidemia, obesity, and hypertension.
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PMID:Apolipoprotein, low density lipoprotein subfraction, and insulin associations with familial combined hyperlipidemia. Study of Utah patients with familial dyslipidemic hypertension. 249 19

High circulating levels of coagulation factor VII (FVII) are known to be associated with elevated concentrations of blood lipids. More specifically, hypertriglyceridemia is correlated with raised FVII coagulant activity (FVIIc). Recently, evidence has been described which suggests that elevation in FVIIc might reflect an increase in the total concentration of FVII, as evaluated by quantitation of FVII antigen (FVIIag). It is also known that FVIIc represents a risk factor for cardiovascular death, but the prediction of cardiovascular risk based on triglyceride estimation is the subject of conflicting results. Since dyslipidemia featuring abnormal triglyceride metabolism is pathophysiologically heterogeneous, we analyzed the possible relationships between FVII and triglyceride further and under standardized postprandial conditions. For this purpose we studied FVIIc and FVIIag in relation to triglyceridemia after a standardized test meal. Our results confirm that FVIIc and FVIIag levels are strongly correlated with each other (r = 0.714; p = 0.01). In addition, both were significantly increased (p less than 0.02) in patients who exhibited abnormal triglyceride levels 8 h after a standardized test meal, as compared to those who displayed normal triglyceridemia. Furthermore, we found that apolipoprotein B levels were also increased in such patients. The deficient postprandial catabolism of triglycerides, therefore, appears to be related to an increase in total FVII concentration, suggesting that some association between the metabolism of triglyceride-rich lipoproteins and FVII might underlie the mechanism of the elevation in FVII. Given the important contribution of FVII to hypercoagulability, then our results may be relevant to the understanding of the role of postprandial triglyceride in atherogenesis and in consideration of the circadian prevalence of cardiovascular thrombosis.
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PMID:Coagulation factor VII and plasma triglycerides. Decreased catabolism as a possible mechanism of factor VII hyperactivity. 274 28

A one-year clinical trial with pantethine was conducted in 24 patients with established dyslipidemia of Fredrickson's types II A, II B, and IV, alone or associated with diabetes mellitus. The treatment was well tolerated by all patients with no subjective complaints or detectable side effects. Blood lipid assays repeated after 1, 3, 6, 9, and 12 months of treatment revealed consistent and statistically significant reductions of all atherogenic lipid fractions (total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B) with parallel increases of high-density lipoprotein cholesterol and apolipoprotein A. The results were equally good in patients with uncomplicated dyslipidemia and in those with associated diabetes mellitus. The authors conclude that pantethine (a drug entity related to the natural compound, pantetheine) represents a valid therapeutic support for patients with dyslipidemia not amenable to satisfactory correction of blood lipids by diet alone.
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PMID:Effectiveness of long-term treatment with pantethine in patients with dyslipidemia. 309 58

Early changes in lipid metabolism and appearance of atherosclerosis risk factors play a key role in the development of cardiovascular disease of chronic renal failure (CRF). In the effort to evaluate the effects of protein restricted diet on dyslipidemia, we studied 122 patients with CRF (S-creatinine 1.3-9 mg/dl); 58.2% of whom were on antihypertensive drugs treatment. Patients had been separated into 6 groups: group 1 was kept on a free diet; groups 2, 3, 4, 5, 6 were kept on a protein-restricted diet from 12, 24, 36, 48, 60 months, respectively. We found hypertriglyceridemia, pathologic levels of esterified cholesterol in high density lipoprotein (HDL-C) and pathologic apolipoprotein A1/B ratio in group 1; the comparison with other groups--whose values were normal range after 12, 24 months of treatment--showed significant differences. The lipidic parameters were independent of the duration of CRF and of patients' age. Serum creatinine showed a significant correlation with tryglicerides and HDL-C values only in group 1. Total cholesterol and apolipoprotein B were significantly greater in hypertensives than in normotensives. In our opinion, a moderate restriction in protein intake could be effective in preventing and in halting the early alterations of lipid metabolism in CRF.
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PMID:Effect of protein-restricted diet on serum lipids and atherosclerosis risk factors in patients with chronic renal failure. 335 2

Serum lipoproteins are important risk factor variables for coronary artery disease (CAD). Studies of a large population of young individuals show changes in lipoproteins in childhood are race- (black-white) and sex-specific and certain changes occur during growth phases. White boys show adverse changes in lipoprotein levels during sexual maturation that mark them at high risk for CAD. Further, low-density lipoprotein particles are relatively apolipoprotein B enriched in white children, especially boys, a characteristic associated with low levels of high-density lipoprotein cholesterol. The impact of apolipoprotein E genotype on serum lipoproteins seen in adults is already apparent in children, which may be helpful in identifying a high-risk group. Observations of child-parent associations in terms of parental myocardial infarction and levels of lipoprotein variables in the offspring suggest that childhood profiles of lipoprotein (a), apolipoprotein A-I, and apolipoprotein B may be helpful as markers of future CAD. Clustering of increased levels of truncal fat, insulin, and blood pressure is often seen in young adults with an adverse lipoprotein profile. This clustering is related to subtle abnormalities in carbohydrate and lipid metabolism and obesity in childhood. The fact that lipoprotein levels persist from childhood to young adulthood underscores the importance of detection and management of dyslipidemia early in life.
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PMID:Childhood lipoprotein profiles and implications for adult coronary artery disease: the Bogalusa Heart Study. 750 26

Renal insufficiency is frequently associated with both quantitative and qualitative abnormalities in lipid and hemorheologic profiles. Although this may lead to increased risk of cardiovascular disease, a number of studies have also shown dyslipidemia to be a significant risk factor for the progression of renal insufficiency in human chronic renal disease. This double-blind, placebo-controlled trial aimed to assess the effect of fluvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on these parameters in dyslipidemic patients with or without chronic renal insufficiency. After a 6-week placebo run-in, 42 patients who had been previously stratified into 2 groups on the basis of creatinine clearance levels (0.5-1.0 mL/sec or > 1.0-1.5 mL/sec) were randomized to treatment with fluvastatin (40 mg daily) or matching placebo. Significant differences (on analysis of variance with repeated measures) were seen between fluvastatin and placebo treatment groups for changes in total cholesterol (-15% vs 1%, respectively; p < 0.001), low density lipoprotein cholesterol (LDL-C; -21% vs -5%; p < 0.001), very low density lipoprotein cholesterol (-14% vs 14%; p = 0.017), very low density lipoprotein triglycerides (-1% vs 29%; p = 0.014) and total triglycerides (-7% vs 24%; p < 0.001). These effects on cholesterol levels were reflected in a significant decrease in apolipoprotein B levels with fluvastatin therapy (p < 0.001). Apolipoprotein A-I levels increased (p = 0.054) despite no significant change in the levels of high density lipoprotein cholesterol. Response to therapy did not differ between the 2 renal function groups for any of the lipid, lipoprotein, and apolipoprotein variables. Hemorheologic parameters were not altered with fluvastatin therapy, regardless of renal function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fluvastatin for dyslipoproteinemia, with or without concomitant chronic renal insufficiency. 760 9

Cigarette smoking has been associated with increased upper body fat deposition, as estimated by the waist to hip ratio, which has been shown to be associated with glucose intolerance and dyslipidemia in nonsmoking subjects. Whether smoking is at the origin of central adiposity and its related metabolic disturbances is unclear. Moreover, it is controversial whether smoking influences fuel metabolism. Therefore, young healthy male volunteers smoking more than 10 cigarettes/day for more than 5 yr (n = 14) were compared with nonsmokers (n = 13) matched for age, sex, body mass index, alcohol consumption, physical activity, as well as family history for hypertension, diabetes, obesity, and coronary heart disease. After an overnight fast, blood was drawn for chemistry, body composition was assessed by dual energy x-ray absorptiometry, and fuel metabolism was determined by indirect calorimetry. Nicotine uptake was estimated by 24-h urinary excretion of cotinine. Lean and fat body mass as well as their respective segmental distribution (i.e. arms, trunk, legs, and head), total bone mineral content, resting energy expenditure, and fat, carbohydrate, and protein oxidation were similar between smokers and nonsmokers. In contrast, 24-h urinary cotinine excretion (72.0 +/- 11.4 vs. 0.8 +/- 0.2 mumol/L.24 h; P < 0.001), plasma glucose (4.62 +/- 0.09 vs. 4.25 +/- 0.1 mmol/L; P < 0.01), total cholesterol (4.87 +/- 0.15 vs. 4.27 +/- 0.16 mmol/L; P < 0.02), low density lipoprotein cholesterol (3.05 +/- 0.19 vs. 2.43 +/- 0.16 mmol/L; P < 0.02), and apolipoprotein B concentrations (1.09 +/- 0.11 vs. 0.83 +/- 0.03 mmol/L; P < 0.03) were all higher in smokers than in nonsmokers. In smokers, 24-h urinary cotinine excretion positively correlated with the waist to hip ratio (r = 0.58; P = 0.03) and negatively with hip circumference (r = 0.87; P < 0.001). Moreover, 24-h cotinine excretion positively correlated with fat oxidation (r = 0.57; P = 0.03), but was independent of the other metabolic parameters studied. These results suggest that the dyslipidemia and glucose intolerance observed in smokers are not related to either central obesity or the amount of nicotine inhaled, but, rather, are due to some other component in cigarette smoke. In contrast, in smokers, fat oxidation increases with increasing nicotine uptake, a fact that might account for the often observed weight gain after cessation of smoking, thus suggesting different mechanisms of action of tobacco consumption on cholesterol and glucose metabolism on one side and fat oxidation on the other.
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PMID:Impact of chronic cigarette smoking on body composition and fuel metabolism. 760 76

High levels of low-density lipoprotein cholesterol (LDL) (hypercholesterolemia) are commonly present in the nephrotic syndrome. Another pattern of dyslipidemia in nephrotic patients is an elevation of both cholesterol and triglyceride levels (combined hyperlipidemia). It has been postulated that the underlying cause of nephrotic dyslipidemia is an hepatic overproduction of apolipoprotein B (apo B)-containing lipoproteins. To examine this hypothesis, the metabolism of LDL-apo B was compared between nephrotic patients with hypercholesterolemia and with combined hyperlipidemia. Thirteen patients (7 with hypercholesterolemia, and 6 with combined hyperlipidemia) underwent measurements of turnover rates of autologous LDL apo B. The results were compared to normolipidemic controls and to patients with primary combined hyperlipidemia previously studied in our laboratory. Nephrotic patients with hypercholesterolemia generally had: (a) lower fractional catabolic rates of LDL apo B than normolipidemic healthy individuals; (b) LDL particles enriched in cholesterol; but (c) no overproduction of LDL apo B. In contrast, patients with combined hyperlipidemia were found to have: (a) high fractional catabolic rates for LDL apo B compared to normolipidemic controls; (b) cholesterol-poor LDL particles; and (c) markedly elevated production rates for LDL. Also, for the group as a whole, there was a positive correlation between plasma triglyceride levels and fractional catabolic rates. These data indicate that the metabolism of LDL is strikingly different between the two forms of nephrotic dyslipidemia. Although there may be common mechanisms contributing to LDL levels in nephrotic patients, there also appears to be a divergence of mechanisms depending on whether hypertriglyceridemia is associated with hypercholesterolemia.
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PMID:Metabolism of low density lipoproteins in nephrotic dyslipidemia: comparison of hypercholesterolemia alone and combined hyperlipidemia. 772 44


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