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)

This study was designed to evaluate the therapeutic effectiveness of 3 different pharmacologic lipid-lowering regimens in the treatment of patients with clustered lipid risk factors. Sixty-five patients with low high-density lipoprotein (HDL) levels and hypertriglyceridemia were randomized to 1 of 3 treatment arms: pravastatin/niacin, pravastatin/magnesium, or pravastatin/placebo. After 18 weeks, patients in the pravastatin/niacin group had a -41% change in the total cholesterol/HDL ratio compared with -13% in the pravastatin/magnesium arm and -16% in the pravastatin/placebo group. The HDL2 and HDL3 subfractions, as well as the apolipoprotein A-I levels, were increased significantly only in the pravastatin/niacin arm. The levels of small dense low-density lipoprotein (LDL) cholesterol (LDL3) were decreased to a greater extent in the pravastatin/niacin arm (-43%) than in either the pravastatin/magnesium (-13%) or the pravastatin/placebo (-20%) arm. Only the pravastatin/niacin regimen significantly diminished postprandial lipemia (-32% change in the remnant particle triglyceride concentration and decreased very-low-density lipoprotein remnant levels). Thus, in this group of patients with clustered risk factors, the combination of pravastatin and niacin resulted in significant improvements in HDL and triglyceride levels, total cholesterol to HDL ratio, small dense LDL levels, and postprandial lipemia. Pravastatin alone or in combination with magnesium resulted in less significant changes that were largely limited to LDL cholesterol reduction.
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PMID:Effects of pravastatin with niacin or magnesium on lipid levels and postprandial lipemia. 765 48

A new animal model of hyperlipidemia is being developed using the nonionic surfactant poloxamer 407 (P-407). We investigated the impact of pravastatin on P-407-induced hyperlipidemia. Twenty rats received P-407 300 mg intraperitoneally to induce hyperlipidemia, and 20 control rats received saline injection. Pravastatin was administered orally to an equal number of rats in both groups using three different regimens. A fourth group did not receive pravastatin. At 24 hours after injection, total cholesterol levels in two of the pravastatin groups were 28% and 34% lower than those in animals that did not receive pravastatin (p < or = 0.01). At 48 hours, triglyceride levels were significantly lower in all pravastatin groups (21-44%) versus animals not receiving pravastatin. Pravastatin diminished the effects of P-407 on lipoproteins. This new animal model may be useful in screening for investigational antihyperlipidemic agents.
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PMID:Effects of pravastatin on plasma lipid concentrations in poloxamer 407-induced hyperlipidemic rats. 773 51

Hyperlipidemia is a significant risk factor for atherosclerotic vascular disease. We have shown previously that pancreas transplantation (PTX) improves but does not normalize lipids in most PTX recipients. We studied whether pravastatin was effective in treating 10 patients with elevated low density lipoprotein (LDL)-cholesterol (LDL-C) following PTX. Seven men and 3 women were studied. Six received combined kidney-pancreas transplantations, while 4 received PTX alone. Age at time of PTX was 37.2 +/- 2.2 years (mean +/- SEM), and 4 had established coronary artery disease before PTX. Mean cholesterol (C), LDL-C, triglycerides (TG), and high density lipoprotein (HDL)-cholesterol (HDL-C) were 236 +/- 12, 142 +/- 6, 222 +/- 50, and 49 +/- 4 mg/dl before PTX. The LDL to HDL ratio was 3.0 +/- 0.3. After PTX, excluding the first 45 days, mean C, LDL-C, and HDL-C increased to 278 +/- 10, 178 +/- 7, and 63 +/- 6 mg/dl (all P < or = 0.05), respectively. TG, LDL to HDL ratio, and weight were unchanged. Pravastatin (11.7 +/- 0.8 mg/day, mean +/- SEM) was initiated 250 +/- 53 days after PTX. During therapy, C and LDL-C decreased on average to 231 +/- 10 and 134 +/- 8 mg/dl, respectively (both P < 0.01), while HDL did not change. The decreases in C and LDL-C were unexplained by a decrease in weight, cyclosporine dose or concentration, or increase in serum creatinine. However, prednisone dose decreased over the same interval, so a contribution from this variable cannot be excluded. No evidence of toxicity was identified during therapy. This is one of the first reports demonstrating that pravastatin is a safe and effective treatment for elevated C and LDL-C in patients following PTX. However, pravastatin did not increase HDL or decrease TG, as observed in the nontransplantation setting. Whether pravastatin or any hypolipidemia therapy can prevent cardiovascular events or mortality following PTX remains to be established.
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PMID:Pravastatin reduces serum cholesterol and low density lipoprotein concentrations following pancreas transplantation. 799 64

The hyperlipidemia of the nephrotic syndrome is characterized by an elevation of total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC), with a normal or low high-density lipoprotein cholesterol (HDLC), and an increase in triglycerides (TGs) later in the course of the disease. If sustained, this lipid profile probably places these patients at increased risk for cardiovascular disease. Despite extensive trials of diet and drug therapy in patients with primary hyperlipidemias, few such trials exist in patients with the nephrotic syndrome. We conducted a randomized, prospective, double-blind, placebo-controlled trial to investigate the efficacy and safety of pravastatin, the newest cholesterol synthesis inhibitor, in the treatment of the hyperlipidemia of the nephrotic syndrome. After dietary modification was implemented, 13 patients received pravastatin and eight received placebo. All patients were maintained on a low-fat, low-cholesterol diet for the duration of the trial (24 weeks). The dose of pravastatin was increased from the initial 20 mg/d to 40 mg/d at week 10 or 18 if TC remained elevated (> 50th percentile). A bile acid sequestrant was added at week 18 if TC remained elevated and if the patient was already receiving the maximal pravastatin dosage. Dietary modification did not significantly change the lipid profile. Pravastatin (20 mg/d) reduced TC by 22% from a baseline of 301 +/- 28 mg/dL (P < 0.05) and LDLC by 28% from a baseline of 222 +/- 28 mg/dL (P < 0.05). When used at 40 mg/d (in six patients) no further change in the lipid profile was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of hyperlipidemia in the nephrotic syndrome: the effects of pravastatin therapy. 832 77

Familial combined hyperlipidemia (FCHL) is a heterogeneous disorder characterized by multiple lipoprotein phenotypes, a high risk for coronary heart disease, and predominance among the LDL fraction of smaller and denser particles. We report on an FCHL kindred (the M-kindred) in which decreased VLDL- and LDL-apoB elimination rates rather than enhanced production rates were the main kinetic abnormalities. Lipoprotein levels and metabolic parameters of all apoB-containing lipoproteins (including light and dense LDLs) were determined during placebo and pravastatin treatment periods. ApoB metabolism was studied by endogenous labeling with stable isotopes and a multicompartmental model. Five members of the M-kindred participated. The study was doubly blinded, randomized, and placebo controlled. Treatment periods of 6 weeks were separated by 2-week washout periods. All subjects had high apoB levels, 2 had a mixed lipemia, 1 had hypercholesterolemia, and 2 had hypertriglyceridemia. Familial dysbetalipoproteinemia, hypercholesterolemia, and defective apoB-100 were excluded by genetic, testing. Kinetic parameters were remarkably similar in the five study subjects during the placebo period, despite their diverse plasma lipid profiles. Compared with nine normolipidemic control subjects, low VLDL-apoB fractional catabolic rates (FCRs) (3.6 +/- .1 versus 9.3 +/- 2.9 pools per day) and low LDL-apoB FCRs (0.19 +/- 0.05 versus 0.41 +/- 0.13 pool per day) were observed in every case. The majority of the LDL particles were identified in the denser fraction (d = 1.036 to 1.063 g/mL). A clear precursor-product relationship was observed from VLDL to IDL to light LDL to dense LDL, ie, there was no "metabolic channeling." Light LDL had significantly higher FCR than dense LDL (0.82 +/- 0.21 versus 0.22 +/- 0.08 pool per day). VLDL-apoB production rates were normal (19.7 +/- 6.0 versus 21.6 +/- 6.1 mg/kg per day for control subjects). In contrast, in two subjects drawn from two other FCHL kindreds (the C- and K-kindreds), VLDL-apoB production rates were increased (35.6 and 32.1 mg/kg per day, respectively). In these two, more "typical" FCHL subjects, FCRs of LDL-apoB were near normal (0.351 and 0.311 pool per day, respectively). Pravastatin (20 mg/d) resulted in significantly lower plasma cholesterol (265 +/- 30 to 218 +/- 16 mg/dL, P < .01), LDL cholesterol (186 +/- 31 to 145 +/- 15 mg/dL, P < .03), and apoB levels (168 +/- 14 to 125 +/- 16 mg/dL, P < .01) in the five FCHL subjects of the M-kindred. No changes were observed in plasma HDL cholesterol, apoA-I, or lipoprotein(a). Pravastatin significantly increased the LDL-apoB FCR (from 0.19 +/- 0.05 to 0.34 +/- 0.04 pool per day). The FCRs of both LDL subclasses increased with treatment. No pravastatin-induced changes were seen in apoB production rates.
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PMID:A familial combined hyperlipidemic kindred with impaired apolipoprotein B catabolism. Kinetics of apolipoprotein B during placebo and pravastatin therapy. 901 40

Pravastatin treatment of combined hyperlipidemia lowers low-density lipoprotein effectively; nicotinic acid lowers remnant cholesterol and raises high-density lipoprotein. A combination of these 2 drugs may be indicated for optimal treatment of lipoprotein abnormalities in combined hyperlipidemia.
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PMID:Comparison of pravastatin with crystalline nicotinic acid monotherapy in treatment of combined hyperlipidemia. 916 13

To study exogenous sterol metabolism during the suppression or stimulation of cholesterol biosynthesis induced by treatments for hyperlipidemia, we determined plasma plant sterol concentrations before and after administration of an HMG-CoA reductase inhibitor, pravastatin, and compared these with changes in these plasma sterol levels by the bile-sequestrating resin, cholestyramine. The effects of the drugs were also studied in a sitosterolemic patient who has had increased plasma levels of plant sterols. Plasma cholesterol levels determined by the HPLC method were decreased significantly after administration of pravastatin. Plasma plant sterol (sitosterol and campesterol) as well as cholestanol concentrations were also significantly reduced. Cholestyramine administration decreased plasma levels of cholesterol, but did not change those of plant sterols in the hypercholesterolemic subjects. Pravastatin had little effect in a sitosterolemic patient on plasma levels of sterols, where cholestyramine decreased the plasma levels of both cholesterol and cholestanol. These results indicate that treatment with the HMG-CoA reductase inhibitor decreases plasma plant sterol concentrations, and suggest that the increased plasma plant sterol levels in sitosterolemia might not be due to the decreased cholesterol biosynthesis in vivo.
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PMID:Effects of an HMG-CoA reductase inhibitor, pravastatin, and bile sequestering resin, cholestyramine, on plasma plant sterol levels in hypercholesterolemic subjects. 922 10

Monumental advances in the field of lipid metabolism and its relationship to atherosclerotic cardiovascular disease have been achieved during the last half century. Epidemiologic studies have defined lipid disorders as highly significant independent risk factors for coronary heart disease, along with diabetes mellitus, hypertension and smoking. Primary and secondary prevention studies including the Coronary Primary Prevention Trial, Helsinki Heart Study, and the Coronary Drug Project have shown that lowering the atherogenic low density lipoproteins (LDL) and very low density lipoproteins (VLDL) whilst raising the high density lipoproteins (HDL) significantly decreases the risk for coronary disease. Striking evidence that aggressive therapy (to sharply lower LDL and raise HDL with newer drugs) prevents progression and induces regression of coronary narrowing has been obtained in numerous recent studies using quantitative coronary arteriography. An interesting and unexpected lesson learned from these arteriographic studies was that a highly significant reduction within months in several studies in coronary events was out of proportion to improvements in luminal narrowing. Recently, three major clinical trials to assess the effects of cholesterol reduction by the newly discovered HMG CoA reductase inhibitors (statins) have been published. Pravastatin significantly reduced coronary events in hypercholesterolemic patients [mean LDL-Chol. = 5.0 mM/L (192 mg/dl)] without a history of myocardial infarction. In a secondary prevention study, simvastatin also reduced coronary complications in hypercholesterolemic patients [mean LDL-Chol. = 4.9 mM/L (190 mg/dl)] with pre-existing coronary disease. Very recently, pravastatin treatment significantly reduced coronary events and stroke in patients with a history of myocardial infarction and average cholesterol levels [mean LDL-Chol. = 3.6 mM/L (139 mg/dl)], representing the majority of patients with coronary disease. In all these studies, reduction in cardiovascular events was approximately one-third. In subgroup analyses, men, women, elderly, smokers and hypertensives benefited from cholesterol lowering. There was no significant increase in non-cardiovascular causes of death. In the United States of America, the National Cholesterol Education Program (NCEP) Adult Treatment Panel, representing major health organizations, developed national guidelines on the detection, evaluation and treatment of high blood cholesterol in adults. In a given patient, the Panel recognizes the importance of weighing all cardiovascular disease risk factors including age (men > 45 years, postmenopausal women), family history of premature coronary disease, smoking, hypertension, diabetes and HDL-Cholesterol (< 35 mg/dl) in determining how aggressive therapy should be. The patient with manifest coronary heart disease (CHD) is given a special position as such patients are at highest risk for recurrent events. Major goals of therapy are to lower the LDL-Cholesterol to 2.6 mM/L (< 100 mg/dl) in the CHD patient. In non-CHD patients with two or more risk factors, the LDL-Cholesterol goal is 3.4 mM/L (130 mg/dl). In those with fewer risk factors, the goal is 4.2 mM/L (160 mg/dl). These guidelines should be modified as appropriate for Singapore. Patients with elevated triglycerides usually have low HDL-Cholesterol levels and often represent a heterogeneous group who may have other concurrent abnormalities including the presence of small dense LDL, insulin resistance, hypertension, obesity, overt diabetes and combined hyperlipidemia. Such patients merit individualized treatment. The prevalence of this syndrome may be more common in Singapore and requires further investigation. Current therapeutic guidelines emphasize the need for weight loss and dietary restriction of total and especially saturated fat (< 7% to 10% total calories), cholesterol (< 200 to 300 mg/day), and exercise. (ABSTRACT TRUNCATED)
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PMID:Cholesterol and atherosclerosis: a contemporary perspective. 939 24

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase and angiotensin-converting enzyme (ACE) reduce experimental atherosclerosis by different mechanisms. To determine whether dual-drug therapy additively retards the progression of early lesions, control hyperlipidemic hamsters were compared with those treated with pravastatin, captopril, and pravastatin plus captopril. After 8 weeks of treatment, pravastatin (34 mg/kg/day) reduced plasma total cholesterol and triglycerides by 41 and 84%, respectively, whereas captopril (100 mg/kg/day) reduced normal blood pressure by 21%. The combination of pravastatin and captopril (33 and 100 mg/kg/day) decreased plasma total cholesterol and triglycerides by 44 and 84%, and blood pressure was decreased by 14%. In the aortic arch, pravastatin reduced macrophage-foam cell size and fatty streak area by 21 and 31%, respectively, whereas captopril decreased macrophage-foam cell number and fatty streak area by 34 and 35%. Pravastatin plus captopril decreased macrophage-foam cell number, foam cell size, and fatty streak area by 38, 24, and 67%. ACE inhibitors were previously reported to retard atherosclerosis without affecting blood pressure, suggesting that these agents acted on the artery wall. Therefore the expression of arterial ACE was determined in normal and atherosclerotic hamster aortas. ACE messenger RNA (mRNA) and protein were detected in endothelial cells, intimal macrophage-foam cells and medial smooth-muscle cells of atherosclerotic arteries indicating an upregulation of ACE expression with hyperlipidemia and atherosclerosis. In conclusion, dual-therapy with pravastatin and captopril produced an additive reduction in fatty streak area compared with either drug alone and suggested that atherogenesis can be retarded beyond the level achieved with monotherapy. The presence of ACE in endothelial cells and intimal macrophage-foam cells provides cellular targets for captopril to directly modify the formation of early atherosclerotic lesions.
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PMID:Enhanced reduction of atherosclerosis in hamsters treated with pravastatin and captopril: ACE in atheromas provides cellular targets for captopril. 967 17

According to the NCEP resins and nicotinic acid were selected as drugs of choice to treat hypercholesterolemia. Gemfibrozil and nicotinic acid were recommended for patients with HDL cholesterol below 35 mg/dl. Current concepts of efficacy and side effects lead to the following recommendations. a) type IIa severe hypercholesterolemia (LDL > 220 mg/dl): HGMC inhibitors or combined therapy with resins and nicotinic acid, fenofibrate, or bezafibrate. b) Moderate hypercholesterolemia (LDL < 220 mg/dl): bezafibrate and/or acipimox if HDL is < 35 mg/dl; fenofibrate, bezafibrate and/or acipimox if HDL > 35 mg/dl. As second line drugs, the HGMC inhibitors. c) Type IIb hyperlipidemia: first line, acipimox; second line, fibrates associated to acipimox. d) Type III hyperlipidemia: first line, fibrates; second line, an association of HGMC inhibitors and fibrates or acipimox. e) Type IV moderate hyperlipidemia (TG < 500 mg/dl): first line, acipimox, second line, fibrates alone or in association with acipimox. As general remarks, lovastatin has been effective and well tolerated in 98% of cases. Pravastatin seems to have very little side effects. Acipimox, a nicotinic acid derivative is especially effective in elevating HDL2b levels and decreasing LDL III. Given its adequate tolerance, acipimox has replaced nicotinic acid.
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PMID:[Pharmacologic treatment of dyslipidemias: Analysis of initiation recommendations and drug selection]. 972 1


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