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PubMed2006

Effect of policosanol on lipid levels among patients with hypercholesterolemia or combined hyperlipidemia: a randomized controlled trial.

CONTEXT: Policosanol is a natural substance derived from sugar cane that is advertised for its lipid-lowering effects as a nonprescription drug. More than 80 placebo-controlled or comparative trials, performed mostly by a single research institute, suggest that policosanol at doses of 5 to 40 mg/d has lipoprotein-lowering effects comparable with statins. OBJECTIVES: To determine the lipoprotein-lowering effects of Cuban sugar cane-derived policosanol and to establish, if effective, dose-dependency up to 80 mg/d in patients with hypercholesterolemia or combined hyperlipidemia. DESIGN, SETTING, AND PARTICIPANTS: A multicenter (lipid outpatient clinics and general practitioners in Germany), randomized, double-blind, placebo-controlled, parallel-group trial conducted from September 29, 2000, to May 10, 2001, of patients with hypercholesterolemia or combined hyperlipidemia having baseline low-density lipoprotein cholesterol (LDL-C) levels of at least 150 mg/dL (> or =3.88 mmol/L) and either no or 1 cardiovascular risk factor other than known coronary heart disease, or baseline LDL-C levels of between 150 and 189 mg/dL (3.88-4.89 mmol/L) and 2 or more risk factors. INTERVENTIONS: Open-label 6-week placebo and diet run-in phase followed by a double-blind 12-week treatment phase after randomization to 5 groups: 10, 20, 40, or 80 mg/d of policosanol or placebo. MAIN OUTCOME MEASURE: The percentage change of LDL-C, with changes in other lipoproteins as secondary outcome measures. RESULTS: A total of 143 patients were randomized to 5 equal groups and were analyzed on an intention-to-treat basis. In none of the 5 treatment groups did LDL-C levels decrease more than 10% from baseline. No statistically significant difference between policosanol and placebo was observed. A nonparametric test analyzing dose-dependency yielded nonsignificant results. In none of the secondary outcome measures, namely total cholesterol, high-density lipoprotein cholesterol (HDL-C), very low-density lipoprotein cholesterol, triglycerides, lipoprotein(a), and ratio of total or LDL-C to HDL-C, were there any significant effects of policosanol. Policosanol was tolerated well without serious adverse events. CONCLUSION: In patients with hypercholesterolemia or combined hyperlipidemia, the sugar cane-derived policosanol in usual and high doses does not demonstrate a reduction in lipid levels beyond placebo. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00288483.

Adult↗
PubMed1999

Long-term safety of pravastatin-gemfibrozil therapy in mixed hyperlipidemia.

BACKGROUND: Combined HMG-CoA reductase inhibitor and fibric acid derivative therapy is often necessary for the effective reduction of concentrations of low-density lipoprotein (LDL) cholesterol and triglycerides in patients with mixed hyperlipidemia; however, the potential risk of myopathy has limited the use of these agents. HYPOTHESIS: This study evaluated long-term safety and efficacy of combined pravastatin and gemfibrozil therapy. METHODS: Eighty-three patients with hyperlipidemia were treated with combined pravastatin and gemfibrozil therapy for a median of 44 months (range 9-78 months). Plasma lipids, serum liver function tests, creatinine, and creatinine kinase (CK) levels were measured every 3 to 4 months. RESULTS: One patient developed myalgia with a normal CK level after 4 months of combination therapy. Three patients had transient elevations in CK levels that ranged from 3 to 5 times the upper limits of "normal" and that returned to normal upon repeat testing. Liver function tests did not change significantly from baseline. In a subset of 26 previously untreated patients, combined pravastatin (mean daily dose 22 mg) and gemfibrozil (mean daily dose 1,154 mg) therapy lowered total cholesterol by 25% (p < 0.001), triglycerides by 53% (p = 0.0001), LDL cholesterol by 14% (p = 0.24), and increased high-density lipoprotein (HDL) cholesterol by 20% (p = 0.012). CONCLUSION: Pravastatin and gemfibrozil therapy is safe and efficacious in patients with mixed hyperlipidemia. The long-term safety results are consistent with other reports on follow-up of shorter duration.

Cholesterol, HDL↗
PubMedDate not supplied

Genetic dissection of familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) is the most common genetic hyperlipidemia in man. FCHL is characterized by familial clustering of hyperlipidemia and clinical manifestations of premature coronary heart disease, i.e., before the age of 60. Although FCHL was delineated about 25 years ago, at present the FCHL phenotype and its complex genetics are not fully understood. Initially, the familial aggregation of high plasma total cholesterol and triglyceride levels, with a bimodal distribution of triglycerides, was taken as evidence of a dominant mode of inheritance. However, it is now clear that the genetics of FCHL is more complex, and it has been suggested that FCHL is heterogeneous. Several approaches can be taken to identify genes contributing to the disease phenotype in complex genetic disorders either by studying the disease in the human situation or by using animal models. Recent reports have shown that a combination of genetic linkage studies, association studies, and differential gene expression studies provides a useful tool for the genetic dissection of complex diseases. Therefore, the genetic strategies that will be used to dissect the genetic background of FCHL are reviewed.

Animals↗
PubMed1996

Comparative pharmacokinetics of theophylline in rabbits and in humans with hyperlipidemia.

UNLABELLED: The study was carried out on male rabbits divided into two groups: a control and an experimental one, fed on a high-fat diet. Humans were also ascribed into two groups: control and those affected with primary, mixed form of hyperlipidemia. The animals and humans were given theophylline intravenously as a single dose. Blood was sampled after 5, 10, 15, 30 and 45 min and 1, 2, 4, 6, 8, 12 and 24 h following theophylline administration. FPIA method was used to determine blood serum concentrations of theophylline. Considerable alterations of theophylline pharmacokinetics in humans suffering from mixed form of hyperlipidemia were observed. Marked decrease in area under the concentration-time curve (AUC), diminished volume of distribution, increased total body clearance, and shortened elimination half-life were observed. On the contrary, in rabbits with alimentary induced lipid metabolism disturbances t1/2 of theophylline was practically unchanged and AUC only slightly increased. IN CONCLUSION: (1) hyperlipidemia affects the pharmacokinetics of theophylline in human beings, (2) rabbit model with dietetary induced lipid metabolic disturbances is not a suitable subject for estimation of pharmacokinetics of xanthine derivatives.

Adult↗
PubMed1982

Behavioral treatment of hyperlipidemia: techniques, results, and future directions.

The present review examines the role of several target behaviors in the treatment of hyperlipidemia, including diet, exercise, cigarette smoking, Type A pattern, and medication adherence. Modification of the typical American diet (high in cholesterol, fat, and sodium) is emphasized in the treatment of hyperlipidemia since a multitude of laboratory, clinical, and epidemiological studies have shown that diet plays a crucial role in the pathogenesis of this condition and an increase in coronary risk. Factors affecting patient compliance such as health beliefs and family support are discussed in terms of their impact on behavior change efforts aimed at reducing plasma lipids through dietary and drug regimens. Intervention studies are reviewed in the behavioral treatment of hyperlipidemia. These programs have focused on diet modification, exercise, and medication adherence to reduce plasma lipids and coronary risk. The role of other target behaviors (i.e., Type A pattern and smoking) is explored not only in determining coronary risk but also in terms of their direct impact on plasma lipids. Further research is necessary to clarify the relationship between these target behaviors and plasma lipid levels and to investigate the effects of innovative family- and group-based intervention procedures in promoting and maintaining habit change related to coronary risk reduction.

Behavior Therapy↗
PubMed1993

Hyperlipidemia in childhood nephrotic syndrome.

Hyperlipidemia is an important characteristic of nephrotic syndrome (NS). Elevation of plasma total cholesterol, or more specifically low-density lipoprotein cholesterol, is the major lipid abnormality in NS, although hypertriglyceridemia may develop as the disorder progresses. The pathophysiology of nephrotic hyperlipidemia is complex. The prevailing view is that both hepatic synthesis of lipids and of apolipoproteins is increased, and that the clearance of chylomicrons and very low-density lipoproteins is reduced. The precise contribution of increased lipogenesis and decreased lipid catabolism to hyperlipidemia, and their relationship to urinary protein loss, hypoalbuminemia and reduced serum oncotic pressure remain controversial. There are two potential risks of elevated plasma lipids: atherosclerosis and progression of glomerular injury. Although neither of these complications has been proved with certainty, there is growing evidence that both may be long-term consequences of NS. Therefore, the diagnosis and treatment of lipid abnormalities, important aspects of the management of nephrotic children, is summarized here to provide pediatric nephrologists with an informed choice.

Child↗
PubMed1996

Is the presence of hyperlipidemia associated with impairment of endothelium-dependent neointimal relaxation after percutaneous transluminal coronary angioplasty?

To determine whether hyperlipidemia affects the endothelium-dependent vasomotor response along the dilated vessel after percutaneous transluminal coronary angioplasty (PTCA), we evaluated 32 patients with one-vessel disease, 3-6 months after successful PTCA without restenosis. Fourteen patients had mild stenotic lesions not subjected to PTCA (non-PTCA sites) in addition to the PTCA sites. Vessel diameter changes at 32 PTCA and 36 non-PTCA sites were assessed by quantitative angiography, before and after intracoronary injection of acetylcholine (20 micrograms to the right and 50 micrograms to the left coronary artery) and of nitroglycerin (0.1-0.3 mg). The acetylcholine response ranged from 46% (dilation) to -100% (constriction). All coronary arteries were dilated in response to nitroglycerin, which suggested preservation of the function of vascular smooth muscle, and the presence of an abnormality in endothelial function in those patients with a constrictor response to acetylcholine. There was a negative correlation between the acetylcholine response and the serum total cholesterol level at PTCA sites (r = -0.37; P = 0.038) and at non-PTCA sites (r = -0.46; P = 0.005). These findings indicate that hyperlipidemia is associated with a loss of endothelium-dependent vasodilation, not only at non-PTCA but also at PTCA sites, at which restoration of endothelial function might have occurred. They also suggest that hyperlipidemia may be related to the functional state of the regenerated endothelium at sites where PTCA had been previously performed.

Acetylcholine↗
PubMed1988

Effects of estrogen-induced hyperlipidemia on the erythrocyte membrane in chicks.

The effects of estrogen-induced hyperlipidemia on plasma lipid peroxidation, fatty acid composition and osmotic fragility of erythrocytes in chickens were studied. Young male chickens implanted with estrogen for three wk developed a marked hyperlipidemia. Plasma levels of triglyceride, cholesterol and phospholipid were elevated 68-, four- and 24-fold, respectively, over controls. There was also a two-fold increase in plasma lipid peroxidation measured by the thiobarbituric acid test. Vitamin E supplement (1,000 IU/kg diet) reduced the plasma lipid peroxidation to the control level, but had no effect on the plasma lipid content. Estrogen-induced hyperlipidemia resulted in changes in the fatty acid composition of membrane lipids of erythrocytes. The major changes were an increase in oleic acid from 10.0% to 14.2% and a decrease in linoleic acid from 31.3% to 26.0%. The erythrocytes with an altered membrane fatty acid composition were found to have an increased osmotic fragility. It was apparent that there was a direct correlation between the oleic acid content and the osmotic fragility of erythrocytes.

Animals↗
PubMed2006

Effect of Taizhi'an capsule combined with Simvastatin on hyperlipidemia in diabetic patients.

OBJECTIVE: To evaluate the effectiveness and safety of Taizhi'an (TZA) capsule combined with Simvastatin (Sim) in treating hyperlipidemia in diabetes mellitus (DM) patients. METHODS: Eighty cases of type 2 DM patients with hyperlipidemia were randomized into two groups, 40 in each group. The patients in the treated group took orally TZA capsules at the dose of 0.9 g 3 times a day and Sim 10 mg at bedtime. And the patients in the control group were treated with Sim 20 mg alone at bedtime. Both regimens lasted for 12 weeks. Before and after the study the changes of blood lipid levels and adverse reaction were investigated. RESULTS: The serum levels of total cholesterol (TC), triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C) were decreased respectively by 28.8%, 18.2% and 26.3% in the treated group; and by 29.4%, 19.4% and 24.6% in the control group. On the contrary, high density lipoprotein-cholesterol (HDL-C) was increased by 23.5% in the treated group and by 29.4% in the control group. All these changes were statistically significant before and after treatment (all P < 0.05), but they did not differ statistically between the two groups (P > 0.05). There was no significant changes in hemoglobin A(1)c (HbA(1)c). Patients in the treated group did not develop any adverse reactions. However, ALT was found to be higher above the normal range in 5% of the patients in the control group. CONCLUSION: In treating hyperlipidemia in DM patients, combination of TZA with Sim 10 mg taken daily achieved satisfactory efficacy which was similar to Sim 20 mg daily alone. But the combination therapy conducted in the treated group proved to be better in safety, and could overcome adverse reactions resulting from Sim that was seen in the control group.

Adult↗
PubMed2004

The lipid-regulating effects of atorvastatin on type 2 elder diabetes patients with hyperlipidemia.

To investigate the effect of atorvastatin on lipid metabolism in type 2 elder diabetes patients with hyperlipidemia, 26 patients with type 2 elder diabetes complicated with hyperlipidemia were treated with atorvastatin (10 mg/d) for 8 weeks. The serum triglyceride (TG), high density protein cholesterol (HDL-C) and low density protein cholesterol (LDL-C) were measured before and after the treatment. Meanwhile, the non-denaturing polyacrylamide gradient gel electrophoresis was used for detection of small-sized LDL(SLDL). Our results showed that TG dropped from 4.88 +/- 0.72 mmol/L to 2.65 +/- 0.32 mmol/L; HDL-C was increased from 0.85 +/- 0.31 mmol/L to 1.28 +/- 0.29 mmol/L; LDL-C was declined from 3.71 +/- 2.98 mmol/L to 2.10 +/- 1.22 mmol/L, sLDL-A was increased from (42.49 +/- 8.1)% to (53.27 +/- 7.5)%; LDL-B was decreased from (57.91 +/- 8.1)% to (46.73 +/- 7.5% ) (P<0.05). The level of blood glucose was not changed at the end of 8th week. It is concluded that atorvastatin has satisfactory lipid-regulating effects on type 2 elder diabetes patients with hyperlipidemia.

Aged↗
PubMed2006

Salicornia herbacea prevents high fat diet-induced hyperglycemia and hyperlipidemia in ICR mice.

Salicornia herbacea L. (Chenopodiaceae) has been used as a seasoned vegetable by living in coastal areas. S. herbacea (SH) has been demonstrated to stimulate cytokine production, nitric oxide release, and to show anti-oxidative effect. In a series of investigations to develop potential anti-diabetic and/or anti-hyperlipidemic agents from Korean indigenous plants, 50% ethanol extract of Salicornia herbacea was found to prevent the onset of the hyperglycemia and hyperlipidemia induced by high fat diet in ICR mice. At 6 week old, the ICR mice were randomly divided into five groups; two control and three treatment groups. The control mice were to receive either a regular diet (RD) or high-fat diet (HFD), and the treatment groups were fed a high fat diet with either 350 mg/kg, 700 mg/kg of SH (SH350 and SH700) or 250 mg/kg of metformin (MT250) for a 10-week period. SH not only reduced body weight but also corrected associated hyperglycemia and hyperlipidemia in a dose dependent manner. SH exerted beneficial effects on the plasma glucose and lipid homeostasis possibly ascribed to its specific effects on lipogenesis related genes (SREBP1a, FAS, GAPT), and PEPCK, glucose 6-phosphatase gene expressions in liver. Ethanol extract of S. herbacea has potential as a preventive agent for type 2 diabetes (and possibly hyperlipidemia) and deserves future clinical trial.

Adipose Tissue↗
PubMed1999

Mutations of the human hepatic lipase gene in patients with combined hypertriglyceridemia/hyperalphalipoproteinemia and in patients with familial combined hyperlipidemia.

Hepatic lipase is an enzyme which hydrolyzes triglycerides from plasma lipoproteins and thus takes part in the metabolism of intermediate density lipoproteins and high-density lipoproteins. The search described here concentrated on mutations of the HL gene in 129 patients with combined hypertriglyceridemia/hyperalphalipoproteinemia and in 184 members of 19 families with familial combined hyperlipidemia. Controls were 100 subjects with favorable lipid values (age 46-51 years). Mutation screening and analysis were performed by temperature-gradient gel electrophoresis, allele-specific restriction genotyping, and sequencing. Six different missense mutations and four different silent mutations were found in the HL gene. The alleles Phe-267 and Gln-343 were detected only once in the patient group with hypertriglyceridemia and hyperalphalipoproteinemia and were not detected in the control group. The allele Met-383 was rare in both patients and controls. We found 9.3% of the patients and only 3.0% of controls to be carrying the Val-73-Met missense mutation. The allele Phe-334 was found in 5.43% of patients and in 2.0% of controls. The difference between the frequencies of these alleles was significant between male patients and male controls (Met-73 P=0.044; Phe-334 P=0.047). Also, the summarized odds ratio of 3.28 (95% confidence interval 1.23-8.73) demonstrates that mutation carriers are significantly more prevalent in the patients. Fifteen carriers of the Met-73 allele were found in six families of the familial combined hyperlipidemia group. Furthermore, six carriers of the Phe-334 allele were found in three families of the same group. In comparison to the controls the summarized odds ratio of 2.45 (95% confidence interval 0.89-6.71) barely missed the level of significance. The linkage between genotype and phenotype was incomplete. These results show an association of the missense mutations Val-73-Met and Leu-334-Phe as susceptibility alleles for combined forms of hyperlipidemia.

Adolescent↗
PubMed2001

Peripheral differential leukocyte counts in humans vary with hyperlipidemia, smoking, and body mass index.

Reports of diverse relationships between blood concentrations of different lipids and peripheral total leukocyte count, and a unique lower peripheral monocyte count in hypercholesterolemia, have driven us to think that in humans, peripheral differential leukocyte counts may be influenced differently by different types of hyperlipidemia. Our subjects were Taipei residents who attended a regular health check program in our hospital in 1998. A total of 3,282 subjects was enrolled, including 1,677 normolipidemic, 960 untreated borderline hyperlipidemic, and 645 untreated hyperlipidemic subjects. By one-way analysis of variance (ANOVA), we found that different types of hyperlipidemia were associated with significant differences in differential leukocyte counts. In hypertriglyceridemia, the total leukocyte count and counts of all leukocyte subtypes were significantly higher than those in normolipidemia. Pure hypercholesterolemia, by contrast, was associated with a significantly lower monocyte count and no significant difference in other leukocyte counts. By two-way ANOVA adjusted for presence and degree of hyperlipidemia, we found significantly higher counts of total leukocytes and of all leukocyte subtypes in smokers, and significantly positive trends in relationships between body mass index (BMI) and counts of all leukocytes, neutrophils, lymphocytes, and monocytes. By multivariate regression analysis including all subjects, the serum triglyceride (TG) level was positively correlated with total leukocyte count and counts of all subtypes except eosinophils. On the contrary, serum high density lipoprotein-cholesterol had a negative correlation with total leukocyte count and with counts of neutrophils, monocytes, and basophils. In these multivariate regression analyses, there was no significant correlation between lipid levels and eosinophil count, whereas smoking was consistently associated with significantly higher counts of all leukocyte subtypes, including eosinophils. BMI had a significantly positive correlation with counts of all leukocytes, neutrophils, lymphocytes, and monocytes.

Body Mass Index↗
PubMed1989

Initial drug therapy for hypertensive patients with hyperlipidemia.

Hypertension and hyperlipidemia are cardiovascular risk factors that commonly coexist. Studies have indicated that it is important to control both risk factors to achieve significant reductions in morbidity and mortality. Recent debate has focused upon whether traditional step I antihypertensive agents can substantially lower these risks because of their effects on plasma lipids. This debate continues to be unresolved. However, for the patient with elevated lipid levels, diuretics and beta-blockers may make the management of the lipid disorder more difficult. Therefore it may be desirable to select alternative step I antihypertensive agents that will not interfere with the therapy for hyperlipidemia. Alternative step I agents include alpha 1-blockers, ACE inhibitors, and calcium channel blockers. These agents either have no effect on plasma lipids or they improve the lipid profile. Generally, these drugs are well tolerated and provide good alternatives for patients with hyperlipidemias. The initial drug of choice can be chosen depending upon other patient variables such as age, race, or concomitant diseases.

Adrenergic alpha-Antagonists↗
PubMed1989

Diabetes mellitus and hypertension in the elderly: concomitant hyperlipidemia and coronary heart disease risk.

Age is an important factor in predicting risk of myocardial infarction (MI). Age is currently treated as an independent variable in assessing risk, but it is also related to other major risk factors including hyperlipidemia, hypertension and diabetes, all of which increase in prevalence with age. Current evidence indicates that a combination of 2 or more of the major risk factors predisposes a person to a high risk of MI. In the experience of the Prospective Cardiovascular Munster study, patients with diabetes alone have twice the risk of MI, but those with diabetes and hyperlipidemia have about a 15-fold increased risk. Similarly, patients with hypertension alone have twice the risk of MI, but those with hypertension combined with hyperlipidemia have approximately a 15-fold increased risk.

Adult↗
PubMed1976

Drug treatment of hyperlipidemia.

The most frequent indication for treatment of hyperlipidemia is for prevention of arteriosclerosis, a suspected but unproved benefit. The cornerstone of treatment of primary hyperlipidemia is diet; drugs may be added to, but do not replace, diet. When a drug is used with any patient, its potential benefits and hazards must be carefully weighed for the given subject. The subjects should be carefully followed and observed for side effects. Plasma lipids should be monitored during the course of treatment. Five drugs have been approved by the U.S. Food and Drug Administration for the treatment of hyperlipidemia: cholestyramine, clofibrate, nicotinic acid, sodium dextrothyroxine and beta-sitosterol. The use, the actions and the side effects of each and of several nonapproved agents are discussed.

Aminosalicylic Acids↗
PubMed1984

Hyperlipidemia in tumor-bearing rats.

Hyperlipidemia occurs in animals bearing tumors but the mechanism of its development is uncertain. We have measured triacylglycerol clearance and production rate in rats bearing a transplantable sarcoma. The plasma content of very-low-density lipoprotein triacylglycerol was increased in these tumor-bearing rats but our data excluded a primary clearance defect because the rate of triacylglycerol accumulation (mg/min) after Triton injection was equal to or greater than in normal control rats, except in cachectic rats with very large tumors. The fractional clearance of injected radioactive triacylglycerols was less in tumor-bearing rats than in controls, but the turnover (mg/min) was probably not decreased in the tumor-bearing rats because of their expanded plasma pool. Also inconsistent with a decreased turnover was our finding of a greater production of radioactive plasma triacylglycerols after injection of a tracer dose of radioactive free fatty acid, and unchanged production in Triton-treated rats. Therefore, in the fasted state, the hyperlipidemia of the tumor-bearing rats was associated with an unchanged or possibly an increased flux of hepatic triacylglycerols and a primary clearance defect was excluded. After fat-feeding, rats with tumors developed a higher post-prandial hyperlipidemia than control rats. Therefore, the clearance mechanism for the plasma triacylglycerols was close to saturation in the fasted state, and the added influx of exogenous triacylglycerols was removed less efficiently in the tumor-bearing rats.

Animals↗
PubMed1992

Gestational hyperlipidemia in the rat is characterized by accumulation of n - 6 and n - 3 fatty acids, especially docosahexaenoic acid.

We have evaluated the relative and quantitative changes in long-chain fatty acids in maternal liver, serum, carcass and conceptus (fetuses plus placentae) during pregnancy in the rat, to ascertain whether previous concern over lower proportions of n - 6 and n - 3 fatty acids in maternal serum could be indicative of suboptimal n - 6 or n - 3 fatty acid status. Gestational hyperlipidemia was characterized by proportional decreases in linoleic, stearic and arachidonic acids but increases in palmitic and docosahexaenoic acids. However, the quantitative amount (microgram/ml) of linoleic, arachidonic and docosahexaenoic acids in serum lipids actually increased 2-5-fold from mid-pregnancy to term. Compared to non-pregnant rats, gestational hyperlipidemia was also associated with a lower proportion but similar quantity of linoleic acid in maternal carcass and adipose stores. We conclude that gestational hyperlipidemia in the rat is characterized by a relative but not quantitative decrease in whole-body stores of n - 6 fatty acids and a marked proportional and quantitative increase in docosahexaenoic acid in maternal organs and in the conceptus.

Adipose Tissue↗