Therapy of severe familial heterozygous hypercholesterolemia by low-density lipoprotein apheresis with immunoadsorption: effects of the addition of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors to therapy

To establish whether additional therapy with 3-hydroxy-3-methylglutaryl (HMG) coenzyme A (CoA) reductase inhibitors enhances the low-density lipoprotein (LDL) cholesterol lowering effect of LDL apheresis with immunoadsorption in the treatment of patients with familial heterozygous hypercholesterolemia and coronary artery disease we studied eight patients initially on immunoadsorption therapy alone for 3 years. The adding of HMG CoA reductase inhibitors decreased pretreatment LDL cholesterol from 6.76 +/- 0.98 to 4.97 +/- 0.98 mmol/l and posttreatment LDL cholesterol from 2.33 +/- 0.80 to 1.94 +/- 0.67 mmol/l and increased pre- and posttreatment high-density lipoprotein (HDL) cholesterol by 0.08 and 0.13 mmol/l respectively. The LDL/HDL ratio was reduced from 4.0 to 2.8 (prior to any therapy the ratio was 13.4). The increase in LDL cholesterol between weekly treatments was less steep under the combined therapy. At the same time the treated plasma volume during LDL apheresis could be decreased from 5070 +/- 960 to 4370 +/- 1200 ml. We conclude that in patients with severe familial heterozygous hypercholesterolemia LDL apheresis should be combined with HMG CoA reductase inhibitors.     

Drug therapy of severe hypercholesterolemia

Lowering of plasma cholesterol and particularly of LDL cholesterol has been shown to be an effective way of primary and secondary prophylaxis of coronary heart disease. A broad range of drugs is available (bile acid binding resins, HMG CoA reductase inhibitors, fibrates, nicotinic acid, probucol, beta-sitosterol) for therapy. The choice of the drug is based on the efficacy, possible side effects and proven effects on coronary heart disease.     

Retinoic acid enhances fibrinolytic activity in-vivo by enhancing tissue type plasminogen activator (t-PA) activity and inhibits venous thrombosis

BACKGROUND: Simvastatin and pravastatin are both competitive inhibitors of the rate limiting enzyme for cholesterol biosynthesis (HMG CoA) reductase, but data from individual clinical trials suggest significant differences in potency for cholesterol reduction between the two drugs. AIM: To assess any differences in efficacy and safety between simvastatin and pravastatin in a direct, comparative study. METHODS: A double-blind, double-dummy, randomised study design was used, involving 48 patients with primary hypercholesterolaemia. Following a 6 week placebo baseline period, patients were randomly allocated to treatment with either simvastatin or pravastatin, commencing at a dose of 10 mg daily. The dose levels were titrated up to the recommended maximum effective dose of 40 mg daily at 6 weekly intervals if LDL cholesterol levels remained > or = 3.4 mmol/L. After 18 weeks of therapy, all patients were transferred to simvastatin therapy for a further 6 weeks, continuing at their week 18 dose level. Patients complied with a standard lipid lowering diet (containing < 30% of energy as total fat) throughout the study period. RESULTS: Over the 18 week direct comparison of the two drugs, there was a significant difference (p < 0.001) in response between simvastatin and pravastatin for reduction in levels of total cholesterol (32% vs 21% respectively), LDL cholesterol (38% vs 27%) and apolipoprotein B levels (34% vs 23%). No significant difference in drug effect was seen for the small reduction in levels of apolipoprotein AI (5% vs 6% respectively), nor for the increased levels of apolipoprotein AII (14% vs 11%) and HDL cholesterol (11% vs 7%). Lp(a) levels remained unchanged. When pravastatin was replaced with simvastatin for the final 6 weeks of the study in the 23 patients initially randomised to pravastatin, there were further reductions (p < 0.01) in total and LDL cholesterol, and apolipoprotein B. These results establish the advantage of simvastatin over pravastatin in terms of efficacy, for the treatment of primary hypercholesterolaemia.     

ERK2 signalling from internalised epidermal growth factor receptor in broken A431 cells

In this review the indications for the available treatments for dyslipidemias in the prevention of coronary heart disease (CHD) are considered, and their efficacy according to the latest studies is analyzed. As data sources the authors used the main multicenter studies performed in the last twenty years to evaluate primary and secondary prevention of CHD by correcting dyslipidemias as well as the results of meta-analyses of these studies. All treatments considered were found effective in preventing CHD morbidity and mortality to some extent. In particular, the combination of diet with niacin or hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors seems to give the best results. These drugs induce a marked reduction of total and low-density lipoprotein (LDL) cholesterol and an increase of high-density lipoprotein (HDL) cholesterol concentrations. The use of diet, niacin, and HMG CoA reductase inhibitors reduces total as well as specific mortality. Treatment of dyslipidemia to prevent CHD depends on the pattern and severity of dyslipidemia, the presence of overt CHD, and the patient's response to diet. Pharmacologic treatment should be started only after dietary modifications have been tried and must be combined with diet. Drug side effects must also be considered, for they may affect patient compliance. High levels of total and LDL and low levels of HDL cholesterol are major risk factors for coronary atherosclerosis. Correcting lipid abnormalities can reduce the risk of development or progression of CHD. Diet and drugs are the main instruments available to normalize lipid levels. The choice of drug to combine with diet must be based on its specific effects on lipid metabolism, side effects, and efficacy in reducing CHD.     

Ursodeoxycholic acid treatment in cholesterol gallstone disease: effects on hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, biliary lipid composition, and plasma lipid levels

The present study was undertaken to characterize the effects of ursodeoxycholic acid on biliary lipid metabolism in man. Fifteen gallstone patients were treated with ursodeoxycholic acid at a daily dosage of 15 mg per kg body weight for about 4 weeks before cholecystectomy. At operation a liver biopsy, together with gallbladder and hepatic bile, were obtained. Eighteen untreated gallstone patients undergoing cholecystectomy served as controls. During treatment with ursodeoxycholic acid, hepatic bile became unsaturated with cholesterol in all patients investigated. The total biliary lipid concentration remained unchanged. The hepatic cholesterol concentration decreased by about 20%. No significant change in the microsomal HMG CoA reductase activity was observed (38.5 +/- 6.7 pmol . min-1 . mg protein-1 vs 38.3 +/- 4.7 pmol . min-1 . mg protein-1 in the controls; means +/- SEM). Plasma concentrations of total cholesterol were reduced by about 10%, and those of high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol by about 15%. Plasma triglyceride levels remained essentially unchanged during treatment. We conclude that, similar to chenodeoxycholic acid therapy, ursodeoxycholic acid treatment results in unsaturation of fasting hepatic bile. In contrast to the changes seen during chenodeoxycholic acid feeding, however, the unsaturation of hepatic bile during ursodeoxycholic acid treatment is not primarily related to a decreased hepatic HMG CoA reductase activity. Furthermore, while chenodeoxycholic acid tends to increase plasma LDL levels, such changes are not seen during ursodeoxycholic acid treatment.     

Treatment strategies for management of serum lipids: lessons learned from lipid metabolism, recent clinical trials, and experience with the HMG CoA reductase inhibitors

The Adult Treatment Panel (ATP) guidelines, published initially in 1988 and revised in 1993, are based on sentinel observations and early clinical trials in support of treating and preventing coronary artery disease by cholesterol lowering. With the conclusion of several large long-term trials using HMG CoA reductase inhibitors for primary and secondary coronary prevention, the ATP II recommendations, which remain remarkably accurate, can be supplemented with more evidence-based strategies. Increasing evidence suggests that thoughtful lipid management for coronary prevention should include a more complete assessment of lipoproteins with an emphasis on apolipoproteins, triglycerides, and very low-density (VLDL) remnant particles, LDL particle size, and lipoprotein(a). This review summarizes clinically relevant lipid metabolism with an emphasis on the concept of atherogenic plasma lipids, discusses the clinical benefits and specific uses of each of the lipid-lowering drug classes, and provides an analysis of recent cholesterol-lowering primary and secondary coronary prevention trials from which a new treatment strategy can be derived.     

The pharmacological effects of certain compounds on lipoprotein(a)

Lipoprotein(a) represents a cholesterol ester, LDL-like particle with apo B-100 linked to apo (a). Lp(a) is a fascinating subject of research because of its presumed association with atherosclerotic cardiovascular disease. The reported results do not encourage optimism. Drugs like niacin or fibrates when used alone have been attended by mixed results. Neither clofibrate nor bezafibrate, which reduce the VLDL concentration, affect LP(a) levels. Neither the ion-exchange resin cholestyramine, nor the HMG CoA reductase inhibitor lovastatin reduce the serum concentration of Lp(a). But, we must keep in mind that drugs used to lower plasma Lp(a) levels were designed for apo B and not apo B-apo(a) containing particles. Thus, it may be necessary to develop drugs specifically targeted to Lp(a).     

Attenuation of plasma low density lipoprotein cholesterol by select 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in mice devoid of low density lipoprotein receptors

Low density lipoprotein (LDL) reduction independent of LDL receptor regulation was investigated using HMG-CoA reductase inhibitors in LDL receptor-deficient mice. In males, LDL cholesterol dose-dependently decreased with atorvastatin treatment after 1 week. As untreated mice grew older, their LDL cholesterol progressively rose above basal levels, but was quelled with atorvastatin treatment. In females, atorvastatin treatment time-dependently decreased LDL cholesterol levels and induced hepatic HMG-CoA reductase activity. Unlike males, cholesterol-lowering effects of the drug were sustained in females. Lovastatin, simvastatin, and pravastatin also reduced total and LDL cholesterol; however, additional studies in females demonstrated that atorvastatin caused the greatest dose-dependent and sustained effect after 2 weeks. In females, hepatic HMG-CoA reductase mRNA inversely correlated with LDL cholesterol lowering, with atorvastatin showing the greatest increase in mRNA levels (17.2-fold), followed by lovastatin (10.7-fold), simvastatin (4.1-fold), and pravastatin (2.5-fold). Atorvastatin effects on lipoprotein production were determined after acute (1 day) or chronic (2 week) treatment prior to intraperitoneal injection of Triton WR1339. Acute treatment reduced cholesterol (-29%) and apoB (-16%) secretion, with no change in triglyceride secretion. In contrast, chronic treatment elevated cholesterol (+20%), apoB (+31%), and triglyceride (+57%) secretion. Despite increased cholesterol and apoB secretion, plasma levels were reduced by 51% and 46%, respectively. Overall, under acute or chronic conditions, apoB paralleled cholesterol secretion rates, and triglyceride to cholesterol secretion ratios were elevated by 38% and 32%, respectively. We propose that atorvastatin limits cholesterol for lipoprotein assembly, which is compensated for by triglyceride enrichment. In addition, with either acute or chronic atorvastatin treatment, apoB-100 secretion was blocked, and compensated for by an increased secretion of apoB-48. The apoB-48 particles produced are cleared by LDL receptor-independent mechanisms, with an overall effect of reducing LDL production in these mice. These studies support the idea that HMG-CoA reductase inhibitors modulate lipoprotein levels independent of LDL receptors, and suggest they may have utility in hyperlipidemias caused by LDLreceptor disorders.     

Early onset of reduced morphine analgesia by ingestion of sweet solutions

In this study we show that proliferation of cycling tumor-transformed human fibroblasts (line 90VAV1) is blocked specifically in G1 by HMG CoA reductase inhibition. This inhibition also resulted in a drastic depression of N-linked glycosylation, measured as incorporation of radioactive glucosamine into acid-insoluble material. Following addition of mevalonate to cells arrested by HMG CoA reductase inhibitors, the depression of N-linked glycosylation was overcome and the cells initiated DNA synthesis. However, if the mevalonate-induced increase in protein glycosylation was prevented, due to addition of tunicamycin (an inhibitor of N-linked glycosylation), the cells were not able to proliferate. If instead tunicamycin was added 4 h after the addition of mevalonate, the cells synthesized DNA normally. Upon addition of tunicamycin, to cycling cells the progression through G1 was blocked in a similar way to that following HMG CoA reductase inhibition. Taken together, our data provide strong evidence for involvement of N-linked glycosylation in the mevalonate-controlled cell cycle progression and growth activation of tumor-transformed human fibroblasts.     

Tetradecylthioacetic acid incorporated into very low density lipoprotein: changes in the fatty acid composition and reduced plasma lipids in cholesterol-fed hamsters

The mechanism behind the hypolipidemic effect of tetradecylthioacetic acid (CMTTD, a non-beta-oxidizable 3-thia fatty acid) was studied in hamsters fed a high cholesterol diet (2%), which resulted in hyperlipidemia. Treating hyperlipidemic hamsters with CMTTD resulted in a progressive hypocholesterolemic and hypotriacylglycerolemic effect. Decreased plasma cholesterol was followed by a 39% and 30% reduction in VLDL-cholesterol and LDL-cholesterol, respectively. In contrast, the HDL-cholesterol content was not affected, thus decreasing the VLDL-cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios. 3-Hydroxy-3-methylglutaryl- (HMG) CoA reductase activity and its mRNA level were unchanged after CMTTD administration. Also, the LDL receptor and LDL receptor-related protein (LRP-4) mRNAs were unchanged. The decrease in plasma triacylglycerol was accompanied by a 45% and 56% reduction in VLDL-triacylglycerol and LDL-triacylglycerol, respectively. The hypolipidemic effect of CMTTD was followed by a 1.4-fold increase in mitochondrial fatty acid oxidation and a 2.3-fold increase in peroxisomal fatty acid oxidation. CMTTD treatment led to an accumulation of dihomo-gamma-linolenic acid (20:3n-6) in liver, plasma, very low density lipoprotein, and heart. Noteworthy, CMTTD accumulated more in the heart, plasma, and VLDL particles compared to the liver, and in the VLDL particle alpha-linolenic acid (18:3n-3) decreased whereas eicosatetraenoic acid (20:4n-3) increased. In addition, linoleic acid (18:2n-6) and the total amount of polyunsaturated fatty acids decreased, the latter mainly due to a decrease in n-6 fatty acids. The present data show that CMTTD was detected in plasma and incorporated into VLDL, liver, and heart. The relative incorporation (mol%) of CMTTD was heart > VLDL > liver. In conclusion, CMTTD causes both a hypocholesterolemic and hypotriacylglycerolemic effect in hyperlipidemic hamsters.     

Delaware RNs'' reasons for nonparticipation in continuing education

BACKGROUND: Acipimox, a derivative of nicotinic acid, lowers serum lipid levels by reducing the production of very-low-density and low-density lipoproteins (LDL). METHODS: We studied the additional lipid-lowering effect of high doses of acipimox in 12 patients with severe familial hypercholesterolemia (FH) who were on treatment with an HMG CoA reductase inhibitor, in some cases in combination with a resin. RESULTS: There was a significant reduction in total serum cholesterol (-9%), LDL-cholesterol (-9%) and serum triglycerides (-21%) when the standard doses of acipimox (750 mg/day) was added to treatment with simvastatin (and a resin). However, higher doses had no further hypolipidemic effect. In concordance with the reduction of serum cholesterol and LDL-cholesterol there was a significant decrease in apolipoprotein (apo)-B (-11%). There was no change in HDL-cholesterol, apo-A1 and lipoprotein(a). Acipimox in high doses up to 2250 mg/d was well tolerated except for initial gastric complaints and of flushing; because of these side effects one patient dropped out of the study. CONCLUSIONS: Acipimox in high doses, which were well tolerated, has no additional lowering effect on LDL-levels compared to the standard dose in patients with severe FH who are already treated with simvastatin.     

Effect of the vaccines for children program on inner-city neighborhood physicians

PURPOSE: Atorvastatin (Lipitor) was developed as an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase for treatment of serum lipid disorders. Other reductase inhibitors (RIs) induce cataracts in dogs exposed to relatively high levels of the drugs for extended periods of time. The purpose of these studies was to assess the cataractogenic potential of atorvastatin, when administered for up to 2 years in beagle dogs. METHODS: Atorvastatin was administered at doses up to 150 mg/kg/day in 2-week, 13-week or 104-week studies. A 52-week interim sacrifice and a reversal group in which dosing was terminated at week 52 and the dogs sacrificed at week 64, was included in the 104-week study. RESULTS: Serum cholesterol was significantly lowered in all studies. No clinical or histologic evidence of drug-induced cataracts was found in any study. Lens biochemical analyses in the 13-week study revealed no statistically significant changes in lenticular weight, reduced or oxidized glutathione content, adenosine nucleotide content, glucose-6-phosphate dehydrogenase activity or phosphofructokinase activity in any treatment group. Modest (11-17%) and transient decreases in lens protein, potassium and glucose content were noted in the 13-week study and at week 52 (glucose only) in the 104-week study, at the doses > or = 40 mg/kg. CONCLUSIONS: These studies demonstrated that, in spite of marked reduction in serum cholesterol, atorvastatin was not cataractogenic in dogs at any tested dose. We conclude that atorvastatin differs from other RIs in this regard.     

Association of an acute reduction in lipoprotein(a) with coronary artery restenosis after percutaneous transluminal coronary angioplasty

BACKGROUND: Lipoprotein(a) [Lp(a)], which structurally resembles-tissue-type plasminogen, is reported to be associated with coronary atherosclerosis. We examined whether the acute change in Lp(a) by percutaneous transluminal coronary angioplasty (PTCA) is related to restenosis after PTCA. METHODS AND RESULTS: We measured serum Lp(a) and other lipid parameters (triglycerides and total, LDL, and HDL cholesterol) before and 1 day after PTCA in 143 procedures and 3 days after and 4 months after PTCA in 62 procedures. Quantitative coronary angiography was performed, and restenosis was defined according to three criteria: (1) clinical recurrence of ischemic symptoms, (2) a final stenosis > 50%, and (3) an absolute decrease in minimal lumen diameter > 1/2 of the acute gain in the dilated segment. Restenosis was recognized in 25.9%, 35.7%, and 38.5% of the cases 4 months after PTCA for each criterion, respectively. Although triglyceride and LDL, HDL, and total cholesterol levels were similar in the restenosis and no-restenosis groups before PTCA, Lp(a) was significantly higher in the restenosis group. We found a significant reduction in Lp(a) in the restenosis but not the no-restenosis group 1 day after PTCA. At 3 days after and 4 months after PTCA, Lp(a) was similar in the two groups. A multivariate-analysis revealed that the absolute change in Lp(a) (before versus 1 day after PTCA) to be the sole significant predictor of restenosis among the clinical, angiographic, and plasma lipid parameters examined. CONCLUSIONS: Lp(a) levels were significantly higher in the restenosis group, and they fell significantly after PTCA in the restenosis group.     

Cerivastatin

Cerivastatin is a synthetic HMG-CoA reductase inhibitor with high liver selectivity, which lowers plasma cholesterol levels by inhibiting endogenous cholesterol synthesis. In vitro, the affinity of cerivastatin for HMG-CoA reductase was higher than that of lovastatin, simvastatin and pravastatin. This higher enzyme affinity was reflected in vivo, with a lower ED50 (dose causing 50% inhibition) for cerivastatin in rats and beagle dogs compared with lovastatin. Cerivastatin 0.2 mg/day significantly reduced low density lipoprotein (LDL)-cholesterol, total cholesterol and triglyceride levels, and increased high density lipoprotein (HDL)-cholesterol levels, in patients with type IIa hypercholesterolaemia. Available data indicate that cerivastatin has a tolerability profile similar to that of other HMG-CoA reductase inhibitors. No drug interactions were observed when cerivastatin was coadministered with digoxin, warfarin, cimetidine or the antacid magnesium/aluminium hydroxide.     

Isolation and analysis of a cDNA clone encoding the small subunit of ADP-glucose pyrophosphorylase from wheat

We measured plasma levels of lipoprotein(a) (Lp(a)) in a sample of 152 Dutch adolescent mono- and dizygotic twin pairs and their parents. The distribution of Lp(a) levels was skewed, with the highest frequencies at low levels and was similar for adult men and women and their children. The relationship of Lp(a) concentrations with other lipoprotein and apolipoprotein risk factors for coronary heart disease and with lathosterol, an indicator of whole-body cholesterol synthesis, was studied dependent on sex and generation. In mothers and children there was a small positive correlation between Lp(a) levels and plasma cholesterol and apolipoprotein (apo) B. In mothers and daughters there also was a correlation between Lp(a) and LDL cholesterol levels. No correlation was found between Lp(a) levels and plasma lathosterol, suggesting that there is no relationship between Lp(a) levels and cholesterol synthesis. Associations among family members, i.e. between monozygotic and dizygotic twins and between parents and offspring were used to study familial transmission of Lp(a) levels. Results showed that almost all of the variance in Lp(a) concentrations was accounted for by genetic heritability. A small, but significant, sex difference in heritability was observed, but heritabilities were the same in parents and offspring. Heritability estimates were 93% for females and 98% for males. No evidence was found for assortative mating or for the influence of a shared family environment. These results indicate that nearly all variance in Lp(a) concentrations that is not accounted for by the apo(a) size polymorphism, is also under genetic control.     

Enhancement of a kappa-opioid receptor agonist-induced analgesia by L-tyrosine and L-tryptophan

To test the possibility that HMG-CoA reductase inhibitors reduce LDL mass by an increased VLDL catabolism, we determined the effect of simvastatin therapy on cellular metabolism of VLDL in 18 patients with primary hypercholesterolaemia. Six months of simvastatin therapy was followed by 26%, 31% and 21% reduction of plasma total cholesterol, LDL-cholesterol and plasma triglyceride levels, respectively. Before therapy, patients' VLDL metabolism in cultured human normal skin fibroblasts was similar to control VLDL. Six months after therapy was initiated, a remarkable 2-5-fold increase in VLDL cell metabolism was found. These effects were even more marked when the VLDL was enriched with exogenous recombinant apo E-3. A comparison of the metabolism of the patients' VLDL to control VLDL and LDL, revealed that simvastatin increased metabolic ratios of 60-70% and 45-95%, respectively. Simvastatin therapy was associated with a decrease of VLDL cholesteryl ester content of 19% and increase of the phospholipid content of 13%. The data strongly indicate that simvastatin therapy stimulates VLDL: cell interactions and catabolism, possibly reflecting alterations of the physico-chemical properties of the particle. It is proposed that in addition to other previously described pathways, HMG-CoA reductase inhibitors decrease LDL mass through a novel mechanism of enhanced VLDL catabolism prior to the conversion to LDL.     

Therapeutic efficiency of lipoprotein(a) reduction by low-density lipoprotein immunoapheresis

This study was performed to investigate the effect of low-density lipoprotein (LDL) immunoapheresis on lipoprotein(a) [Lp(a)] reduction in patients with heterozygous and homozygous familial hyperlipidemia (N=16) and insufficient response to lipid-lowering agents. By desorption of approximately 5,700+/-500 mL of plasma, a mean reduction in total cholesterol of 62% (P < .001) and in LDL-cholesterol of 70% (P < .001) was achieved. Lp(a), which was elevated at study entry in seven of these patients (82.1+/-34.3 mg/dL; range, 48 to 148 mg/dL), was reduced during the initial LDL-apheresis procedure by 74.8%+/-14.1% (P < .001). Long-term apheresis treatment performed at weekly intervals resulted in an mean reduction in Lp(a) pretreatment values to 39.1+/-28.5 mg/dL (-54%; P < .001). Desorbed Lp(a) was measured at the waste of the columns for 31 apheresis treatments. Lp(a) concentration of the column waste was higher in patients with elevated serum Lp(a) pretreatment values as compared with those with Lp(a) serum values within the normal range (elevated Lp(a), 1,420+/-380 mg; without elevated Lp(a), 235+/-190 mg; P < .001). The rate of return of Lp(a) following apheresis treatment scheduled at weekly intervals was comparable to that of LDL-cholesterol.     

The use of an interactive computer program for the education of parents of asthmatic children

OBJECTIVES: To evaluate the effect of a single evening meal (gorging) on plasma lipids and lipoproteins in normal individuals observing the Ramadan Fast. During the Ramadan month, Muslims refrain from food and liquids during the day and eat a large meal after sundown. DESIGN: Sequential measurement of plasma lipids and lipoproteins in Muslims observing the Ramadan Fast and non-fasting individuals. SETTING: The study was conducted in the Bedouin town of Rahat, in the northern Negev area of Israel. SUBJECTS: Twenty-two healthy subjects who fasted during Ramadan and 16 non-fasting laboratory workers, were studied before Ramadan, at week 1, 2 and 4 of the Ramadan month, and again four weeks after the end of Ramadan. RESULTS: Plasma high-density lipoprotein cholesterol (HDL) rose significantly (P < 0.001) at the week 4 measurement, returning to basal levels 4 weeks after the end of Ramadan. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL), very-low density lipoprotein cholesterol (VLDL), and lipoprotein (a) [Lp(a)] did not change significantly. CONCLUSIONS: Plasma HDL increased by 23% after four weeks of gorging. The dietary change did not affect the composition of other lipoproteins, such as LDL, VLDL or Lp(a), other plasma biochemical parameters, or BMI. Prolonged gorging, well tolerated by all individuals, is a very effective non-pharmacological method to increase plasma HDL-cholesterol.     

Capillary adrenoceptors in rat skeletal muscle

Coronary artery disease (CAD) is the most common cause of death in women in the United States. Dyslipidemia is a risk factor for CAD in both men and women. Low levels of high-density lipoprotein (HDL) cholesterol and hypertriglyceridemia, especially in association with a dense low-density lipoprotein (LDL) phenotype, may be of greater importance in women than in men. The relationship between CAD and dyslipidemia and the therapeutic approach to disorders of lipid metabolism in women have unique features because of the effects of exogenous and endogenous hormones on lipid pathways. Estrogen decreases LDL cholesterol and Lp(a) lipoprotein and increases triglyceride and HDL cholesterol levels. Progestogens decrease triglycerides, HDL cholesterol, and Lp(a), and they increase LDL cholesterol. Thus, oral contraceptives increase plasma triglycerides, whereas the effect of these agents on LDL cholesterol and HDL cholesterol levels is related to the androgenicity and dose of progestogen. Postmenopausal hormone replacement therapy increases triglycerides and decreases LDL cholesterol. The effect of hormone replacement therapy on HDL cholesterol is influenced by the addition of progestogen. Although no primary prevention studies have analyzed lipid lowering and CAD in women, secondary prevention studies have suggested that the response to drug treatment and the benefit of lipid lowering are similar in women and in men. Hormone replacement therapy should be considered in the treatment of hypercholesterolemia in postmenopausal women; however, individualization of treatment is important to avoid adverse effects.     

Antiatherothrombotic properties of statins: implications for cardiovascular event reduction

Clinical trials of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors or statin therapy have demonstrated that baseline or treated low-density lipoprotein (LDL) cholesterol levels are only weakly associated with net coronary angiographic change or cardiovascular events. The beneficial effects of statins on clinical events may involve nonlipid mechanisms that modify endothelial function, inflammatory responses, plaque stability, and thrombus formation. Experimental animal models suggest that statins may foster stability through a reduction in macrophages and cholesterol ester content and an increase in volume of collagen and smooth muscle cells. The thrombotic sequelae caused by plaque disruption is mitigated by statins through inhibition of platelet aggregation and maintenance of a favorable balance between prothrombotic and fibrinolytic mechanisms. These nonlipid properties of statins may help to explain the early and significant cardiovascular event reduction reported in several clinical trials of statin therapy.