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)

VLDL overproduction by enhanced hepatic FFA flux is a major characteristic of familial combined hyperlipidemia (FCHL). The postprandial complement component 3 (C3) response has been associated with impaired postprandial FFA metabolism in FCHL. We investigated the effects of 16 weeks of treatment with atorvastatin on postprandial C3 and lipid changes in 12 FCHL patients. Atorvastatin significantly lowered fasting plasma C3 and triglyceride (TG) in FCHL. Fasting TG and insulin sensitivity were the best predictors of fasting and postprandial C3. Postprandial triglyceridemia and C3 response, estimated as area under the curve (AUC), were significantly lowered by atorvastatin by 19% and 12%, respectively, albeit still elevated, compared with 10 matched controls. Postprandial FFA-AUC and postheparin plasma lipolytic activities remained unchanged after atorvastatin, suggesting no major effect on lipolysis. After atorvastatin, postprandial hydroxybutyric acid-AUC, which was elevated in untreated FCHL patients, was decreased, reaching values similar to those in controls. The present data show reduction of postprandial hepatic FFA flux in FCHL by atorvastatin, providing an additional mechanistic explanation for the reduction of VLDL secretion reported previously for atorvastatin. This was accompanied by a decrease in fasting plasma C3 concentrations and a blunted postprandial C3 response to an acute oral fat load.
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PMID:Effects of atorvastatin on fasting and postprandial complement component 3 response in familial combined hyperlipidemia. 1292 26

Hyperhomocysteinemia is regarded as an independent risk factor for cardiovascular disease. Lipid-lowering agents, such as fibrates, can modify homocysteine levels. However, less is known about the effect of statin therapy on homocysteine. The authors compared the effects of atorvastatin (40 mg/day), simvastatin (40 mg/day), and micronized fenofibrate (200 mg/day) on the serum concentrations of total homocysteine, vitamin B12, and folic acid in patients with primary hyperlipidemia. A total of 128 patients with primary hyperlipidemia (total cholesterol > 240 mg/dL and triglycerides < 350 mg/dL) were assigned to atorvastatin, simvastatin, or fenofibrate. Serum lipid and metabolic parameters were measured at baseline and at 6 and 12 weeks of treatment. Homocysteine correlated positively with serum creatinine and uric acid levels and inversely with serum folic acid levels. All treatment modalities reduced total, low-density lipoprotein (LDL) cholesterol, and triglyceride concentrations. High-density lipoprotein (HDL) cholesterol levels significantly increased only in the fenofibrate-treated patients (47.9 +/- 12.5 vs. 50.7 +/- 12.6 vs. 51.2 +/- 12.8 mg/dL, p < 0.01). Atorvastatin and fenofibrate treatment resulted in a significant reduction of serum uric acid levels (5.3 +/- 1.6 vs. 4.9 +/- 1.4 vs. 4.8 +/- 1.4 mg/dL, p < 0.0001 for atorvastatin; 5.6 +/- 1.6 vs. 4.3 +/- 1.4 vs. 4.4 +/- 1.4 mg/dL, p < 0.0001 for fenofibrate). Homocysteine levels were significantly increased only by fenofibrate (10.3 +/- 3.3 vs. 14.1 +/- 3.8 vs. 14.2 +/- 3.6 microU/L, p < 0.001) but did not change from baseline following statin treatment. Neither statins nor fenofibrate had any effect on serum vitamin B12 and folic acid levels. In contrast to fenofibrate, therapeutic dosages of atorvastatin and simvastatin have a neutral effect on serum homocysteine levels, which is in favor of their "cardioprotective" properties.
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PMID:Comparative effects of atorvastatin, simvastatin, and fenofibrate on serum homocysteine levels in patients with primary hyperlipidemia. 1295 39

Kinetics of apo B and apo AI were assessed in 8 patients with mixed hyperlipidemia at baseline and after 8 weeks of atorvastatin 80 mg q.d. and micronised fenofibrate 200 mg q.d. in a cross-over study. Both increased hepatic production and decreased catabolism of VLDL accounted for elevated cholesterol and triglyceride concentrations at baseline. Atorvastatin significantly decreased triglyceride, total, VLDL and LDL cholesterol and apo B concentrations (-65%, -36%, -57%, -40% and -33%, respectively, P<0.05). Kinetic analysis revealed that atorvastatin stimulated the catabolism of apo B containing lipoproteins, enhanced the delipidation of VLDL1 and decreased VLDL1 production. Fenofibrate lowered triglycerides and VLDL cholesterol (-57% and -64%, respectively, P<0.05) due to enhanced delipidation of VLDL1 and VLDL2 and increased VLDL1 catabolism. Changes of HDL particle composition accounted for the increase of HDL cholesterol during atorvastatin and fenofibrate (18% and 23%, P<0.01). Only fenofibrate increased apo AI concentrations through enhanced apo AI synthesis (45%, P<0.05). We conclude that atorvastatin exerts additional beneficial effects on the metabolism of apo B containing lipoproteins unrelated to an increase in LDL receptor activity. Fenofibrate but not atorvastatin increases apo AI production and plasma turnover.
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PMID:Effects of atorvastatin versus fenofibrate on apoB-100 and apoA-I kinetics in mixed hyperlipidemia. 1452 53

Both atorvastatin and fenofibrate are known to lower postprandial chylomicrons and chylomicron remnants. However, until now it has not been investigated which of the two drugs is more effective in one and the same patient and, secondly, whether these drugs exert different effects on chylomicron remnants of different sizes. To this end 12 patients with mixed hyperlipidemia were treated in a crossover study with 40 mg atorvastatin or with 200 mg micronized fenofibrate once daily for 6 weeks. Oral fat loading was given before and after each treatment. Chylomicron remnants of various sizes were determined by fluorometric determinations of retinyl palmitate after lipoprotein separation by size-exclusion chromatography. As expected, atorvastatin was more effective than fenofibrate on total and LDL-cholesterol (P < 0.05). Fenofibrate, in contrast, was more effective on all triglyceride-rich lipoproteins in both the fasting and the postprandial state. The stronger effect of fenofibrate affected not only chylomicrons and VLDL but also chylomicron remnants. It reduced large chylomicron remnants by 66% at 6h and by 74% at 8 h. The action of atorvastatin was less pronounced, with corresponding reductions of 42 and 65% (P < 0.05 only after 8 h). Fenofibrate was even more effective on small chylomicron remnants, yielding reductions of 47, 74, and 66% at 4, 6, and 8 h. Atorvastatin, in contrast, gave reductions of 30 and 26% after 6 and 8 h, the effect reaching statistical significance only after 6h. Fenofibrate is therefore more effective than atorvastatin in lowering all triglyceride-rich lipoproteins, including large and small chylomicron remnants.
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PMID:Chylomicron remnants of various sizes are lowered more effectively by fenofibrate than by atorvastatin in patients with combined hyperlipidemia. 1464 9

At the beginning of atherosclerosis before evidence of morphological lesions or plaques, vascular distensibility or arterial compliance decreased gradually. This endothelial dysfunction is regarded as an early feature of atherosclerosis. In a randomized, double-blind study design, group 1 (12 patients; 7 males, 5 females) with serum LDL-C levels higher than 170 mg/dL and without any other risk factor for atherosclerosis received three months of 20 mg/day atorvastatin treatment while group 11 (8 males, 4 females) with the same characteristics received 80 mg/day. Baseline and posttreatment serum lipid fractions and arterial compliance were measured. Arterial compliance was measured noninvasively in the left common carotid artery with color Doppler ultrasound. Atorvastatin reduced total cholesterol (TC), LDL-C, and triglyceride levels by 32% (P < 0.001), 40.8% (P < 0.001), and 19% (P < 0.001), respectively, and increased HDL-C by 6.9%, (P = 0.002) in the first group. In the second group these reductions were 38.5% (P < 0.001), 46.2% (P < 0.001), and 26.78% (P < 0.001), respectively, and the increase in HDL was 7.8% (P = 0.03). It was observed that the decrease in serum TC, LDL-C and triglyceride levels were significantly higher in the second group than the first group. With atorvastatin, the distensibility coefficient (DC) and compliance coefficient (CC) increased from 18.7 +/- 3.4 to 21.3 +/- 2.9 10(-3) x kPa(-1) (P < 0.001) and from 0.69 +/- 0.05 to 0.77 +/- 0.03 mm2 x kPa(-1) (P < 0.001) in the first group while they changed from 18.3 +/- 3.6 to 21.9 +/- 3.0 10(-3) x kPa(-1) (P < 0.001) and from 0.70 +/- 0.04 to 0.81 +/- 0.01 mm2 x kPa(-1) (P < 0.001) respectively, in the second group. DC and CC increased in both groups, but the differences between the groups were not significant. High doses of atorvastatin reduce blood lipid levels more than conventional doses, however, the change in compliance is not dose-dependent. As endothelial dysfunction is regarded as an early feature of atherosclerosis, there would be no need to administer aggressive doses in a patient without any risk factors other than hyperlipidemia.
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PMID:Effects of low and high doses of atorvastatin on arterial compliance. 1471 Nov 90

Dyslipidemia, characterized by elevated serum levels of triglycerides and reduced levels of total cholesterol, low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol, has been recognized in patients with human immunodeficiency virus (HIV) infection. It is thought that elevated levels of circulating cytokines, such as tumor necrosis factor-alpha and interferon-alpha, may alter lipid metabolism in patients with HIV infection. Protease inhibitors, such as saquinavir, indinavir and ritonavir, have been found to decrease mortality and improve quality of life in patients with HIV infection. However, these drugs have been associated with a syndrome of fat redistribution, insulin resistance, and hyperlipidemia. Elevations in serum total cholesterol and triglyceride levels, along with dyslipidemia that typically occurs in patients with HIV infection, may predispose patients to complications such as premature atherosclerosis and pancreatitis. It has been estimated that hypercholesterolemia and hypertriglyceridemia occur in greater than 50% of protease inhibitor recipients after 2 years of therapy, and that the risk of developing hyperlipidemia increases with the duration of treatment with protease inhibitors. In general, treatment of hyperlipidemia should follow National Cholesterol Education Program guidelines; efforts should be made to modify/control coronary heart disease risk factors (i.e. smoking; hypertension; diabetes mellitus) and maximize lifestyle modifications, primarily dietary intervention and exercise, in these patients. Where indicated, treatment usually consists of either pravastatin or atorvastatin for patients with elevated serum levels of LDL-C and/or total cholesterol. Atorvastatin is more potent in lowering serum total cholesterol and triglycerides compared with other hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, but it is also associated with more drug interactions compared with pravastatin. Simvastatin and lovastatin are significantly metabolized by cytochrome P450 enzymes (CYP3A4) and are therefore not recommended for coadministration with protease inhibitors. A fibric acid derivative (gemfibrozil or fenofibrate) should be used in patients with primary hypertriglyceridemia. However, it must be kept in mind that protease inhibitors, such as nelfinavir and ritonavir, induce enzymes involved in the metabolism of the fibric acid derivatives and may, therefore, reduce the lipid-lowering activity of coadministered gemfibrozil or fenofibrate. In certain patients HMG-CoA reductase inhibitors may be used in combination with fibric acid derivatives but patients should be carefully monitored for liver and skeletal muscle toxicity. Select patients may experience improvements in serum lipid levels when their offending protease inhibitor(s) is/are exchanged for efavirenz, nevirapine, or abacavir; however each patient's virologic and immunologic status must be taken closely into consideration.
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PMID:Management of protease inhibitor-associated hyperlipidemia. 1472 85

Dyslipidaemia is common in patients with Type 2 diabetes and is held to be responsible for considerable CVD-related morbidity and mortality. Patients with Type 2 diabetes are at high risk from complications associated with atherosclerosis and should therefore receive preventive interventions. At the level of the adipocyte, impaired insulin action leads to increased rates of intracellular hydrolysis of triglycerides with the release of NEFA. The rise in NEFA provides substrate for the liver that, in the presence of impaired insulin action and relative insulin deficiency, is associated with complex alterations in plasma lipids: * Plasma VLDL levels are raised. (i). Increased VLDL levels are associated with post-prandial hyperlipidaemia that is compounded by impaired LPL activity. The latter may be independently associated with CAD. (ii). Remnant particles can deliver more cholesterol to macrophages than LDL-C particles. Thrombogenic alterations in the coagulation system also ensue from hypertriglyceridaemia. * Plasma HDL-C levels are reduced. (i). The reduction in cardioprotective HDL-C means a reduction of cholesterol efflux from the tissues--the first step in reverse cholesterol transport to the liver from peripheral tissues. (ii). The antioxidant and antiatherogenic activities of HDL-C are reduced when circulating levels are low. * LDL-C particles become small and dense. Small, dense LDL-C particles are held to be more atherogenic than their larger, buoyant counterparts because they (a) are more liable to oxidation and (b) may more readily adhere to and subsequently invade the arterial wall. The atherogenicity of LDL-C may also be enhanced by nonenzymatic glycation. Metabolic and lipid abnormalities can often be improved with lifestyle changes, including dietary modification, weight loss, smoking cessation and increased exercise. Although attainment of better glycaemic control may improve diabetic dyslipidaemia, pharmacological intervention is usually required. Several large-scale clinical trials, including 4S and more recently HPS, have clearly demonstrated the benefits of statins in reducing cardiovascular events. By virtue of their high absolute risk of CVD, many patients with Type 2 diabetes may achieve a greater risk reduction than their non-diabetic counterparts. For example, in 4S there was a 43% reduction in total mortality risk among patients with diabetes compared with 29% for non-diabetics and a reduced risk of MI by 55% vs. 32% for diabetic and non-diabetics, respectively. In the diabetic subgroup in HPS, there were reductions of approximately 25-30% in the risk of first major vascular events. More recently, the lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) was halted early because of a significant reduction in cardiovascular events compared with placebo. Surprisingly an analysis of subgroups failed to show significance among the diabetic population, although the sample size, shortened follow-up period and higher drop-in statin use among diabetics on placebo may have affected results. The Collaborative Atorvastatin Diabetes Study (CARDS), involving 2800 patients with Type 2 diabetes, was halted 2 years early in June 2003 because patients allocated atorvastatin had significant reductions in MI, stroke and surgical procedures compared with those receiving placebo. The UKPDS demonstrated that the appearance and progression of certain microvascular complications of Type 2 diabetes could be reduced by treatment directed at hyperglycaemia and hypertension. In addition, correction of dyslipidaemia in patients with diabetes is important in reducing the high toll from macrovascular disease. The subjects in the HPS had similar lipid profiles to the participants in UKPDS, suggesting that additional benefit would accrue from a therapeutic assault on the main cardiovascular risk factors simultaneously. We now have firm evidence that appropriate use of statins in patients with Type 2 diabetes can significantly reduce cardiovascular morbidity and mortality.
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PMID:Lipoprotein abnormalities and their consequences for patients with type 2 diabetes. 1498 18

The combined dyslipidaemia that accompanies the nephrotic syndrome increases the cardiovascular risk and appears to worsen long-term renal function. Our aim was to determine the efficacy and safety of 10 mg atorvastatin in the control of dyslipidaemia in these patients. We carried out a prospective, open, 6 month study of 10 patients with primary or secondary nephrotic syndrome (proteinuria >3.5 g/day, hypoalbuminaemia, oedema and hyperlipidaemia). The changes in lipids and plasma lipoproteins were measured, as well as the safety profile (transaminases, creatine phosphokinase, fibrinogen and antithrombin III activity) and parameters of renal function. The addition of 10 mg atorvastatin daily for 6 months resulted in a 41% reduction in low density lipoprotein (LDL) cholesterol and 31% in triglycerides (both P < 0.05), and a 15% increase in high density lipoprotein (HDL) cholesterol (NS). The drug was well tolerated and there was no change in the safety profile or deterioration in renal function. In fact, the levels of proteinuria fell in all but one patient (6.2 +/- 2.6 vs 4.8 +/- 2.5 g/24 h; P < 0.05). Atorvastatin, at the above dose, and for the time used proved to be a safe drug that effectively reduced dyslipidaemia in patients with nephrotic syndrome.
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PMID:Atorvastatin in dyslipidaemia of the nephrotic syndrome. 1501 35

Familial combined hyperlipidemia (FCHL) patients have an impaired catabolism of postprandial triglyceride (TG)-rich lipoproteins (TRLs). We investigated whether atorvastatin corrects the delayed clearance of large TRLs in FCHL by evaluating the acute clearance of Intralipid (10%) and TRLs after oral fat-loading tests. Sixteen matched controls were included. Atorvastatin reduced fasting plasma TG (from 3.6 +/- 0.4 to 2.5 +/- 0.3 mM; mean +/- SEM) without major effects on fasting apolipoprotein B48 (apoB48) and apoB100 in large TRLs. Atorvastatin significantly reduced fasting intermediate density lipoprotein (Svedberg flotation, 12-20)-apoB100 concentrations. After Intralipid, TG in plasma and TRL showed similar kinetics in FCHL before and after atorvastatin treatment, although compared with controls, the clearance of large TRLs was only significantly slower in untreated FCHL, suggesting an improvement by atorvastatin. Investigated with oral fat-loading tests, the clearance of very low density lipoprotein (Sf20-60)-apoB100 improved by 24%, without major changes in the other fractions. The most striking effects of atorvastatin on postprandial lipemia in FCHL were on hepatic TRL, without major improvements on intestinal TRLs. Fasting plasma TG should be reduced more aggressively in FCHL to overcome the lipolytic disturbance causing delayed clearance of postprandial TRLs.
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PMID:Effects of atorvastatin on the clearance of triglyceride-rich lipoproteins in familial combined hyperlipidemia. 1557 46

Serum levels of lipids and lipoproteins were examined in individuals with hyperlipidemia treated with atorvastatin or colestimide and in healthy volunteers. Modified low-density lipoprotein (LDL) was measured by its faster electrophoretic mobility and expressed as charge modification frequency (CMF). Serum levels of total cholesterol (t-chol), triglyceride (TG), very low-density lipoprotein (VLDL)-chol, low-density lipoprotein (LDL)-chol, and CMF were significantly higher in hyperlipidemia, but there was no significant difference in serum high-density lipoprotein (HDL)-chol levels between hyperlipidemic and healthy subjects. Treatment with atorvastatin resulted in significant decreases of serum t-chol, TG, and LDL-chol levels but not serum HDL-chol and VLDL-chol. Treatment with colestimide significantly reduced serum t-chol, HDL-chol, and LDL-chol levels but not those of TG and VLDL-chol. CMF was significantly reduced by treatment with atorvastatin but not by colestimide. Atorvastatin significantly reduced plasma levels of thrombomodulin, thrombin antithrombin complex (TAT) and tissue type plasminogen activator-plasminogen activator inhibitor-I complex. Colestimide moderately prolonged activated partial thromboplastin time and reduction of TAT. Based on its actions of lowering modified LDL and improving hemostatic abnormalities, we postulate that atorvastatin might inhibit the onset of ischemic diseases.
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PMID:Effects of atorvastatin on serum lipids, lipoproteins, and hemostasis. 1560 78


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