Reduction In Total Cholesterol Levels Research Articles

Effects of isoflavone-supplemented soy yogurt on lipid parameters and atherosclerosis development in hypercholesterolemic rabbits: a randomized double-blind study

BackgroundThere is increasing interest in natural treatments to control dyslipidemia and reduce the risk of cardiovascular disease. Previous studies have demonstrated the beneficial effects of soy yogurt fermented with Enterococcus faecium CRL 183 and of dietary isoflavones on the lipid profile. The purpose of the present study was to investigate the effects of isoflavone-supplemented soy yogurt, fermented with E. faecium CRL183, on lipid parameters and atherosclerosis development in rabbits with induced hypercholesterolemia.MethodsForty-eight rabbits were randomly assigned to eight groups fed on the following diets for 60 days: C - control; IY - isoflavone-supplemented soy yogurt; H - hypercholesterolemic (1.0% cholesterol wt/wt diet); HY - hypercholesterolemic plus soy yogurt; HIY - hypercholesterolemic plus isoflavone-supplemented soy yogurt; HP - hypercholesterolemic plus placebo; HI - hypercholesterolemic plus isoflavone and HE - hypercholesterolemic plus pure culture of E. faecium CRL 183. Serum lipids and autoantibodies against oxLDL (oxLDL Ab) were analyzed on days 0, 30 and 60 of the treatment and the atherosclerotic lesions were quantified at the end of the experiment.ResultsSoy yogurt, soy yogurt supplemented with isoflavones and placebo promoted significant reductions in total cholesterol level (38.1%, 27.0% and 26.6%, respectively). Significant increases in serum HDL-C concentration relative to group H were detected in animals that ingested soy yogurt, with or without the isoflavone supplement (55.2%), E. faecium culture (43.3%) or placebo (35.8%). Intake of soy yogurt and soy yogurt supplemented with isoflavones prevented the rise of oxLDL Ab during the study period. The extent of atherosclerosis in the thoracic and abdominal aortas was reduced in the HIY, HY and HP groups. However, when the whole aorta was analyzed, animals treated with soy yogurt supplemented with isoflavones exhibited the greatest reduction (51.4%, P < 0.05) in atherosclerotic lesion area, compared to group H.ConclusionSoy yogurt could be consumed as an alternative means of reducing the risk of cardiovascular disease by improving the lipid profile and inhibiting oxLDL Ab formation. Our findings also suggest that isoflavone supplementation may enhance the antiatherosclerotic effect of soy yogurt.

Effects of Mirena (levonorgestrel-releasing intrauterine system) and Ortho Gynae T380 intrauterine copper device on lipid metabolism—a randomized comparative study

Background This study aims to assess the effects of levonorgestrel-releasing intrauterine system (LNG-IUS) on lipid metabolism in an Asian population using Ortho Gynae T380 copper containing (nonhormonal) intrauterine device (IUD) as a control. Study Design Ninety-two healthy women requesting IUD for contraception were randomly allocated to the two groups and were followed up at 6-, 12- and 18-month intervals. Serum concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), apolipoprotein A-I (Apo A-I) and apolipoprotein B were measured pre insertion and at each visit following insertion. Results There was a marginally significant reduction in TC level in the LNG-IUS group. HDL-C showed a significant reduction in the LNG-IUS group at 6 months but reverted back to its preinsertion value by 1 year. TG, LDL-C and the cholesterol ratios remained stable. Levels of Apo A-I and B also showed no significant reduction in both groups, and their ratios remained stable and insignificant. Conclusion In this randomized comparative study among our local Asian population, it is assuring to note that the LNG-IUS does not have any adverse effects on lipid metabolism.

Influence of lycopene and vitamin C from tomato juice on biomarkers of oxidative stress and inflammation

A human study was carried out to investigate whether tomato juice, rich in natural lycopene and fortified with vitamin C, is able to reduce several biomarkers of oxidative stress and inflammation and whether the effect can be attributed to lycopene, vitamin C or any other micronutrient. Following a 2-week depletion phase, volunteers were assigned randomly to ingest either tomato juice with (LC) or without (L) vitamin C fortification for 2 weeks (daily dose 20.6 mg lycopene and 45.5/435 mg vitamin C). Plasma and urine were analysed for carotenoids and vitamin C, lipid status, antioxidant capacity, thiobarbituric acid reactive substances (TBARS) and 8-epi-PGF2alpha, protein carbonyls, cytokines IL-1beta and TNFalpha and C-reactive protein (CRP). The consumption of tomato juice led to a reduction in total cholesterol levels (L: 157.6 v. 153.2 mg/dl, P = 0.008; LC: 153.4 v. 147.4 mg/dl, P = 0.002) and that of CRP (L: 315.6 v. 262.3 microg/l, P = 0.017; LC: 319.2 v. 247.1 microg/l, P = 0.001) in both groups. The vitamin C-fortified juice slightly raised the antioxidant capacity in urine and decreased TBARS in plasma and urine. All other markers were affected to a lesser extent or remained unchanged. Cholesterol reduction was correlated with lycopene uptake (P = 0.003), whereas the other effects could not be related with particular micronutrients. Any beneficial effects of tomato consumption for human health cannot be attributed only to lycopene and, as the additional supplementation with ascorbic acid indicates, a variety of antioxidants might be needed to optimize protection against chronic diseases.

Antioxidant effects of simvastatin in primary and secondary prevention of coronary heart disease

The aim of the present study was to determine the effect of simvastatin on the levels of oxidized low-density lipoprotein (ox-LDL) and free radicals in hypercholesterolemic subjects undergoing primary and secondary prevention of coronary heart disease (CHD). Fifteen subjects with hypercholesterolemia and no obvious CHD and 29 subjects with hypercholesterolemia and stable angina received 40 mg of simvastatin daily for 12 weeks. Serum total cholesterol, HDL-cholesterol and triglyceride concentrations were determined by automated enzymatic assays whereas LDL-cholesterol was calculated using the Friedwald formula. The ox-LDL levels were determined by a commercially available ELISA kit. Free radicals were assessed by the Free Radical Analytical System (FRAS). Both in primary and secondary prevention, subjects had borderline levels of free radicals but in neither group there was a significant reduction of free radicals after simvastatin treatment. In subjects undergoing primary prevention of CHD, ox-LDL levels were reduced by 31.1+/-5.0% (P < 0.001) whereas in secondary prevention were reduced by 6.5+/-5.2% (P < 0.02) after simvastatin treatment. The reduction of ox-LDL levels did not correlate with the reduction of total cholesterol levels in either group studied. In both groups, ox-LDL levels were not associated with free radical levels either before or after simvastatin treatment. This study demonstrates that simvastatin can significantly reduce circulating ox-LDL levels both in subjects undergoing primary and secondary prevention of CHD. These results could partly explain the slowing down of the progression of atherosclerosis caused by HMG-CoA reductase inhibitors.

Effect of guar gum supplementation on lipidic and glycidic metabolic control and body mass index in type 2 diabetes

OBJECTIVE: To evaluate the effects of guar gum supplementation in the metabolic control and body mass index (BMI) of type 2 diabetic patients. METHODS: A total of 17 (12 women and 5 men) participants ingested 10 grams of fiber supplement daily for three months. Changes in BMI and the biochemical parameters (fasting glycemia, glycosilated hemoglobin (HbA1c), total plasma cholesterol and triglycerides) were evaluated at the beginning and the end of the study. RESULTS: No changes in mean BMI (p=0.770), mean fasting glycemia (p=0.09) or triglyceride levels were observed. However, significant increases in HbA1c levels were observed (p&lt;0.001) following the ingestion of guar gum supplements. Posterior analysis indicated that the five participants that had the highest mean fasting blood glucose and HbA1c levels, showed a significant reduction in their fasting glycemic levels (p=0.03) at the end of the study. A significant (p&lt;0.001) reduction in total cholesterol levels was observed after three months of guar gum supplementation. CONCLUSION: Guar gum supplementation (10g/day) in the diet of overweight type 2 diabetics, resulting in total fiber ingestion close to 20g per day, did not lead to a spontaneous reduction in body weight. The effect of guar gum on the glycidic metabolic control was inconclusive, but it was shown to be an effective dietetic strategy to reduce blood cholesterol levels.

Pharmacological Profile of SMP-797, a Novel Acyl-Coenzyme A: Cholesterol Acyltransferase Inhibitor with Inducible Effect on the Expression of Low-Density Lipoprotein Receptor

We investigated the pharmacological profile of SMP-797, a novel hypocholesterolemic agent. SMP-797 showed inhibitory effects on acyl-coenzyme A: cholesterol acyltransferase (ACAT) activities in various microsomes and in human cell lines, and hypocholesterolemic effects in rabbits fed a cholesterol-rich diet and hamsters fed a normal diet. In hamsters, the reduction of total cholesterol level by SMP-797 was mainly due to the decrease of low-density lipoprotein (LDL) cholesterol level rather than that of very low-density lipoprotein (VLDL) cholesterol level. Interestingly, SMP-797 increased the hepatic low-density lipoprotein receptor expression in vivo when it decreased the low-density lipoprotein cholesterol level. SMP-797 also increased low-density lipoprotein receptor expression in HepG2 cells like atorvastatin, an HMG-CoA reductase inhibitor, although other acyl-coenzyme A: cholesterol acyltransferase inhibitor had no effect. In addition, SMP-797 had no effect on cholesterol synthesis in HepG2 cells. These results suggested that the increase of low-density lipoprotein receptor expression by SMP-797 was independent of its acyl-coenzyme A: cholesterol acyltransferase inhibitory action and did not result from the inhibition of hepatic cholesterol synthesis. In conclusion, these results suggest that SMP-797 is a novel hypocholesterolemic agent showing a cholesterol-lowering effect in which the increase of hepatic low-density lipoprotein receptor expression as well as the inhibition of acyl-coenzyme A: cholesterol acyltransferase is involved.

Pharmacological Evidence for the Potential of Daucus carota in the Management of Cognitive Dysfunctions

The present study was aimed at investigating the effects of Daucus carota seeds on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. The ethanolic extract of Daucus carota seeds (DCE) was administered orally in three doses (100, 200, 400 mg/kg) for seven successive days to different groups of young and aged mice. Elevated plus maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam-, scopolamine- and ageing-induced amnesia served as the interoceptive behavioral models. DCE (200, 400 mg/kg, p.o.) showed significant improvement in memory scores of young and aged mice. The extent of memory improvement evoked by DCE was 23% at the dose of 200 mg/kg and 35% at the dose of 400 mg/kg in young mice using elevated plus maze. Similarly, significant improvements in memory scores were observed using passive avoidance apparatus and aged mice. Furthermore, DCE reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Daucus carota extract (200, 400 mg/kg, p.o.) reduced significantly the brain acetylcholinesterase activity and cholesterol levels in young and aged mice. The extent of inhibition of brain cholinesterase activity evoked by DCE at the dose of 400 mg/kg was 22% in young and 19% in aged mice. There was a remarkable reduction in total cholesterol level as well, to the extent of 23% in young and 21% in aged animals with this dose of DCE. Therefore, DCE may prove to be a useful remedy for the management of cognitive dysfunctions on account of its multifarious beneficial effects such as, memory improving property, cholesterol lowering property and anticholinesterase activity.

Abca7 Null Mice Retain Normal Macrophage Phosphatidylcholine and Cholesterol Efflux Activity despite Alterations in Adipose Mass and Serum Cholesterol Levels

Mutations in the A class of ATP-binding cassette transporters (ABCA) are causally implicated in three human diseases: Tangier disease (ABCA1), Stargadt's macular degeneration (ABCA4), and neonatal respiratory failure (ABCA3). Both ABCA1 and ABCA4 have been shown to transport lipids across cellular membranes, and ABCA3 may play a similar role in transporting pulmonary surfactant. Although the functions of the other 10 ABCA class transporters identified in the human genome remain obscure, ABCA7-transfected cells have been shown to efflux lipids in response to stimulation by apolipoprotein A-I. In an effort to elucidate the physiologic role of ABCA7, we generated mice lacking this transporter (Abca7-/- mice). Homozygous null mice were produced from intercrosses of heterozygous null mice at the expected Mendelian frequency and developed normally without any obvious phenotypic abnormalities. Cholesterol and phospholipid efflux stimulated by apolipoprotein A-I from macrophages isolated from wild type and Abca7-/- mice did not differ, suggesting that these activities may not be central to the physiological role of the transporter in vivo. Abca7-/- females, but not males, had significantly less visceral fat and lower total serum and high density lipoprotein cholesterol levels than wild type, gender-matched littermates. ABCA7 expression was detected in hippocampal and cortical neurons by in situ hybridization and in brain and white adipose tissue by Western blotting. Induction of adipocyte differentiation from 3T3 fibroblasts in culture led to a marked increase in ABCA7 expression. These studies suggest that ABCA7 plays a novel role in lipid and fat metabolism that Abca7-/- mice can be used to elucidate.

Pravastatin therapy is associated with reduction in coronary allograft vasculopathy in pediatric heart transplantation

Background Hydroxymethylglutaryl CoA reductase inhibitors (statins) have been demonstrated to reduce the risk of developing coronary allograft vasculopathy (CAV) following heart transplantation in adults and are used routinely in many centers. CAV and lipid abnormalities have been reported to be less prevalent in pediatric heart transplant recipients. It is not known whether statins reduce the risk of CAV in this population Methods A retrospective review was performed to analyze the risk factors for developing CAV following pediatric heart transplantation with particular attention to the impact of pravastatin therapy. The study population was comprised of 129 pediatric patients who underwent 142 heart transplants at our institution from 1988 to 2003. The outcome variable was freedom from CAV, CAV being determined by coronary angiography or autopsy. Results CAV was identified in 25 recipients at a median of 3.7 years after transplantation. There were 331 patient-years of pravastatin therapy. Pravastatin therapy resulted in a reduction in total cholesterol levels, 162 ± 29 to 137 ± 20 mg/dl, p = 0.01. In multivariate analysis the use of pravastatin was associated with a lower incidence of CAV ( p = 0.03), whereas an increased frequency of late rejection ( p = 0.003) and earlier year of transplantation ( p = 0.04) were associated with increased risk of CAV. Conclusions The routine use of pravastatin was associated with a lower risk following pediatric heart transplantation. Further studies into the relationship between lipid abnormalities, inflammation and rejection, and the development of CAV in children are warranted.

O suco de berinjela (Solanum melongena) não modifica os níveis séricos de lípides

To compare the effect of eggplant extract on serum lipid levels with that of lovastatin. The study included 21 individuals of both sexes, with total cholesterol (TC) levels > 200 mg/dL, no diabetes, no contraindication for the use of statins, and no use of cholesterol-lowering drugs, divided into the following 3 groups: 1) the eggplant group (B), in which the patients drank 1 glass of eggplant extract with orange juice before breakfast each morning; 2) the statin group (E), in which the patients received 20 mg of lovastatin in the evening after dinner; 3) control group (C), in which the patients received no treatment. Total cholesterol and fractions (HDL, LDL), and triglycerides were measured 3 times at 3-week intervals. The baseline lipid levels were similar in the 3 groups. After 6 weeks, a significant reduction in TC levels (from 245.29 +/- 41.69 to 205.71 +/- 46.45; P=0.02) and in LDL-cholesterol levels (from 170.83 +/- 41.76 to 121.29 +/- 44.90; P=0.008) was observed in group E. In group B, total cholesterol (from 230.60 +/- 19.30 to 240.20 +/- 16.22; P=0.27) and LDL-cholesterol (from 139.60 +/- 21.49 to 154.40 +/- 9.66; P=0.06) showed no statistically significant variation, as in group C. No significant variation was observed in the HDL-cholesterol and triglyceride levels in the 3 groups throughout the study. The eggplant extract with orange juice is not to be considered an alternative to statins in reducing serum levels of cholesterol.

Reversal of glucose intolerance by by pioglitazone in high fat diet-fed rats.

The present study was undertaken to determine the effect of pioglitazone (3, 10 and 30 mg/kg p.o.), an insulin sensitizer, on glucose intolerance in high fat diet- (HFD) fed rats (a nongenetic model of insulin resistance). In addition, the effect of pioglitazone (3, 10 and 30 mg/kg p.o.) on diet-induced changes in body weight, plasma glucose, insulin, triglyceride and total cholesterol levels were also determined. The feeding of HFD for 4 weeks produced a significant increase in body weight, total fat pad weight, basal/fasting plasma glucose, insulin, basal triglyceride (TG) and total cholesterol (TC) levels in male rats. Furthermore, the rats fed HFD exhibited fasting hyperglycemia and hyperinsulinemia as well as enhanced glycemic response to exogenously administered glucose (2 g/kg p.o.) during an oral glucose tolerance test (OGTT) at the end of 4 weeks of dietary manipulation, indicating that the rats had developed insulin resistance and glucose intolerance. Treatment with pioglitazone (10 and 30 mg/kg p.o.) once daily for 2 weeks significantly diminished the elevated basal plasma insulin and TG levels in HFD-fed rats. In addition, a statistically significant reduction in TC level was observed only with the high dose of pioglitazone (30 mg/kg p.o.). However, pioglitazone had no significant effect on body weight, total fat pad weight and basal plasma glucose level. Pioglitazone (10 and 30 mg/kg p.o.) significantly reduced fasting hyperglycemia and reversed oral glucose intolerance to normal in HFD-fed rats compared with control normal rats. The above findings suggest that pioglitazone has potent insulin-sensitizing and lipid-lowering properties in a HFD-fed rat model. In conclusion, the present study demonstrates that the adult male rats on a HFD for 4 weeks exhibited the characteristic features of obesity, insulin resistance and glucose intolerance, namely increased body weight, increased total fat pad weight, mild basal/fasting hyperglycemia, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia and impaired oral glucose tolerance, that closely resemble the human prediabetic obese insulin-resistant and glucose-intolerant state. Further treatment with pioglitazone once daily for 2 weeks significantly ameliorated changes in basal plasma insulin, TG and TC, and reversed oral glucose intolerance to normal in HFD-fed rats, suggesting its potential in the treatment of insulin resistance and glucose intolerance associated with abnormal lipid metabolism.

Association of nitrotyrosine levels with cardiovascular disease and modulation by statin therapy.

Formation of nitric oxide-derived oxidants may serve as a mechanism linking inflammation to development of atherosclerosis. Nitrotyrosine, a specific marker for protein modification by nitric oxide-derived oxidants, is enriched in human atherosclerotic lesions and low-density lipoprotein (LDL) recovered from human atheroma. To determine whether systemic levels of nitrotyrosine are associated with the prevalence of coronary artery disease (CAD) and are modulated by hydroxymethylglutaryl coenzyme-A reductase inhibitor (statin) therapy. A case-control and interventional study at 2 urban tertiary-care referral centers; recruitment for each was from June 1, 2001, until January 1, 2002. For the case-control study, 100 case-patients with established CAD and 108 patients with no clinically evident CAD were recruited consecutively. In the interventional study, participants aged 21 years or older with hypercholesterolemia (LDL cholesterol > or =130 mg/dL [> or =3.5 mmol/L]) underwent nutrition and exercise counseling. Those whose levels did not decrease with 6 to 8 weeks were enrolled in the study (n = 35). For 12 weeks, they received 10 mg/d of oral atorvastatin therapy. In the case-control study, the association between systemic levels of protein-bound nitrotyrosine, CAD risk, and presence of CAD. In the interventional study, the change in nitrotyrosine, lipoprotein, and C-reactive protein (CRP) levels. Nitrotyrosine levels were significantly higher among patients with CAD (median 9.1 micromol/mol [interquartile range, 4.8-13.8 micromol/mol] tyrosine vs 5.2 micromol/mol [interquartile range, 2.2-8.4 micromol/mol]; P<.001). Patients in the upper quartile of nitrotyrosine (29%; P<.001) had a higher odds of CAD compared with those in the lowest quartile (unadjusted odds ratio, 6.1; 95% confidence interval, 2.6-14.0; P<.001). In multivariate models adjusting for Framingham Global Risk Score and CRP, upper quartiles of nitrotyrosine remained associated with CAD (odds ratio, 4.4; 95% confidence interval, 1.8-10.6; P<.001). Statin therapy reduced nitrotyrosine levels significantly (25%; P<.02) with a magnitude similar to reductions in total cholesterol levels (25%; P<.001) and LDL particle number (29%; P<.001) yet were independent of alterations in lipoproteins and inflammatory markers like CRP. The findings from this preliminary study indicate that nitrotyrosine levels are associated with the presence of CAD and appear to be modulated by statin therapy. These results suggest a potential role for nitric oxide-derived oxidants as inflammatory mediators in CAD and may have implications for atherosclerosis risk assessment and monitoring of anti-inflammatory actions of statins.

Utilidad de la pravastina en la dislipidemia del trasplante cardíaco

Patients undergoing cardiac transplantation are at increased risk of dyslipidemia (60% to 80%). Lipid-lowering treatment in these patients should be aggressive given the known role of dyslipidemia in chronic transplant rejection. The objective of this study was to evaluate the efficacy and safety of pravastatina therapy and its effect upon cyclosporine levels in a population of dyslipidemic cardiac transplant patients.A total of 20 cardiac transplant patients were enrolled in this 39-week length prospective observational study. Patients had serum cholesterol levels exceeding 200 mg/dl, and received pravastatin therapy at the adequate dose to obtain an optimal lipid profile without significant adverse effects. Pravastatin, at a mean dose of 50 18 mg/day, produced a significant reduction in total cholesterol levels (from 291 32 to 203 25 mg/dl, p < 0.05), LDL cholesterol (from 187 34 to 102 15 mg/dl, p < 0.05) and an increase in HDL-cholesterol levels (from 48 16 to 55 14, p < 0.05). A slight asymptomatic increase in CPK levels was observed but no differences in cyclosporine levels. Pravastatin has shown to be an effective and safe therapy in dyslipidemic cardiac transplant patients.

Mejoría de la función endotelial al reducir las concentraciones lipídicas en pacientes con hipercolesterolemia y arterias coronarias normales

In patients with coronary risk factors the presence of endothelial dysfunction in epicardial arteries has been documented. The purpose of this study was to determine whether endothelial dysfunction, documented hypercholesterolemic patients and angiographically normal coronary arteries, improves by reduction and normalization of lipid levels. In 10 patients with hypercholesterolemia and normal coronary angiography, the endothelium-dependent coronary vasomotion was studied by intracoronary infusion of acetylcholine into the left anterior descending coronary artery. Vasomotion changes in response to acetylcholine were analyzed by quantitative angiography. Five patients without coronary risk factors and normal coronary arteries formed the control group. Patients with hypercholesterolemia were treated with lipid-lowering therapy (diet and lovastatin) and endothelial function was reevaluated after 24 +/- 4 months. In the initial study, hypercholesterolemic patients compared with the control group showed a vasoconstrictor response to serial doses of acetylcholine(10(-6) M, 10(-5) M, 10(-4)M) indicative of endothelial dysfunction (study group: -0.3 +/- 10%, -6 +/- 4%, -18 +/- 10% vs control group: -0.6 +/- 6%, -2 +/- 6%, 3+/-6%; p < 0.01 to 10(-4) M acetylcholine dose. During follow-up hypercholesterolemic patients who a significant reduction in total cholesterol levels and LDL. Compared to first study, at follow-up, there was an improvement in the response to acetylcholine (-0.4 +/- 4%, -3 +/- 6%, -3 +/- 10%; p<0.001 vs basal values at 10(-4) M acetylcholine concentration). Reduction in total cholesterol during follow-up was related to the improvement in the vasoconstrictor response to acetylcholine (r=0.53; p< 0.05). In patients with hypercholesterolemia and angiographycally normal coronary arteries with documented endothelial dysfunction, the reduction and normalization of lipid levels during follow-up may improve endothelium-dependent coronary vasomotion.

Use of simvastatin treatment in patients with combined hyperlipidemia in clinical practice. For the Simvastatin Combined Hyperlipidemia Registry Group.

To describe and understand current care of simvastatin-treated patients with combined hyperlipidemia in routine clinical practice. A 6-month prospective observational study. Demographics, simvastatin dosage, cardiac risk factors, and lipid profile were collected from August 1997 to December 1998 at 20 sites (230 patients) across the United States. Overall mean percentage of reduction in total cholesterol levels was 27% (P<.001), low-density lipoprotein cholesterol (LDL-C) was 35% (P<.001), and triglyceride values was 28% (P<.001). Among those patients with low baseline high-density lipoprotein cholesterol (HDL-C) values (<0.91 mmol/L [<35 mg/dL]) (N = 49), there was a 17% increase in HDL-C (P< or =.001); 35% of these patients achieved National Cholesterol Education Program HDL-C goal (ie, < or =0.91 mmol/L [> or =35 mg/dL]). Coronary heart disease (CHD) patients were given significantly higher initial doses (mean, 15.1 mg) compared with non-CHD patients (mean, 11.5 mg) (P< or =.001). Overall, 74% of patients achieved LDL-C goal (52% on starting dose, 22% after 1 titration). Among those patients who were not at goal and had a follow-up lipid profile result available, only 1 patient (2%) was at the maximum dose (80 mg); 69% were receiving 20 mg or less. Approximately 63% of patients with CHD, 80% of patients with 2 or more risk factors, and 91% of patients with fewer than 2 risk factors achieved LDL-C goal. Multiple factors contribute to LDL-C goal achievement in a usual care setting. A significant opportunity exists to increase the number of patients who achieve LDL-C goal by appropriate dose titration and/or give patients a higher initial dose of simvastatin.

Use of simvastatin treatment in patients with combined hyperlipidemia in clinical practice

OBJECTIVE To describe and understand current care of simvastatin-treated patients with combined hyperlipidemia in routine clinical practice. DESIGN A 6-month prospective observational study. Demographics, simvastatin dosage, cardiac risk factors, and lipid profile were collected from August 1997 to December 1998 at 20 sites (230 patients) across the United States. RESULTS Overall mean percentage of reduction in total cholesterol levels was 27% (P or =35 mg/dL]). Coronary heart disease (CHD) patients were given significantly higher initial doses (mean, 15.1 mg) compared with non-CHD patients (mean, 11.5 mg) (P< or =.001). Overall, 74% of patients achieved LDL-C goal (52% on starting dose, 22% after 1 titration). Among those patients who were not at goal and had a follow-up lipid profile result available, only 1 patient (2%) was at the maximum dose (80 mg); 69% were receiving 20 mg or less. Approximately 63% of patients with CHD, 80% of patients with 2 or more risk factors, and 91% of patients with fewer than 2 risk factors achieved LDL-C goal. CONCLUSIONS Multiple factors contribute to LDL-C goal achievement in a usual care setting. A significant opportunity exists to increase the number of patients who achieve LDL-C goal by appropriate dose titration and/or give patients a higher initial dose of simvastatin.

AHA Science Advisory. Monounsaturated fatty acids and risk of cardiovascular disease. American Heart Association. Nutrition Committee.

This report summarizes our current understanding of how monounsaturated fatty acids (MUFAs) affect risk for cardiovascular disease (CVD). This is a topic that has attracted considerable scientific interest,1 2 3 in large part because of uncertainty regarding whether MUFA or carbohydrate should be substituted for saturated fatty acids (SFAs) and the desirable quantity of MUFA to include in the diet. MUFAs are distinguished from the other fatty acid classes on the basis of having only 1 double bond. In contrast, polyunsaturated fatty acids (PUFAs) have 2 or more double bonds, and SFAs have none. The position of the hydrogen atoms around the double bond determines the geometric configuration of the MUFA and hence whether it is a cis or trans isomer. In a cis MUFA, the hydrogen atoms are present on the same side of the double bond, whereas in the trans configuration, they are on opposite sides. The American Heart Association Nutrition Committee recently published a scientific statement regarding the relationship of trans MUFA to CVD risk,4 and the present statement, therefore, will be limited to a discussion of dietary cis MUFAs, of which oleic acid ( cis C18:1) comprises ≈92% of cis MUFAs. In the United States, average total MUFA intake is 13% to 14% of total energy intake, an amount that is comparable to (or slightly greater than) SFA intake. In contrast, PUFAs contribute less (ie, 7% of energy). The major emphasis of current dietary guidelines involves replacing SFAs with complex carbohydrates to achieve a total fat intake of ≤30% of calories. There is evidence suggesting that the substitution of MUFA instead of carbohydrate for SFA calories may favorably affect CVD risk.5 6 7 The American Heart Association dietary guidelines for healthy American adults recommend a diet that provides <10% of calories from SFA, up …

Pravastatin versus simvastatin in hyperlipidemic patients with type 2 diabetes mellitus

This study investigated the effects of pravastatin and simvastatin in hypercholesterolemic patients with type 2 diabetes mellitus. Pravastatin and simvastatin were administered at the initial dosages approved in Japan (10 mg/d and 5 mg/d, respectively) to 40 patients using a crossover design. Pravastatin and simvastatin significantly reduced serum total cholesterol (TC) levels and low-density lipoprotein cholesterol (LDL-C) levels. However, the percentage reduction in TC levels was significantly greater with simvastatin than with pravastatin (−19 ± 7% vs −15 ± 9%, respectively; P < 0.05). Similarly, the percentage reduction in LDL-C levels was significantly greater with simvastatin than with pravastatin (−30 ± 11% vs −22 ±12%, respectively; P < 0.001). The percentage of patients who attained the therapeutic goal of LDL-C ≤120 mg/dL and TC ≤200 mg/dL with simvastatin was significantly greater than that with pravastatin (46% vs 21% and 23% vs 13%, respectively; P < 0.05). Neither pravastatin nor simvastatin had any effect on high-density lipoprotein cholesterol, triglycerides, fasting plasma glucose, or glycosylated hemoglobin A 1c. No abnormal laboratory test results or adverse events were reported during treatment with either drug. Because both pravastatin and simvastatin significantly reduced TC and LDL-C levels without influencing control of blood glucose level, these drugs, especially simvastatin, might be safe and useful for treating hyperlipidemic patients with type 2 diabetes mellitus.

Effects of Mediterranean Diet on Lipid Levels and Cardiovascular Risk in Renal Transplant Recipients

Background: Renal transplant recipients have an increased incidence of cardiovascular disease. These patients present abnormalities of lipoprotein profile which are persistent and involve an increasing number of individuals, suggesting the opportunity of an early therapeutic intervention. Methods: We evaluated the effects of a 10- to 12-week diet based on the American Heart Association step-one diet criteria, modified with an increased intake of monounsaturated fats and alimentary fibers, on lipid profile and lipid-related cardiovascular risk in 78 normolipidemic and hyperlipidemic renal transplant recipients. Results: Diet led to a significant reduction in total cholesterol levels by 10%, triglycerides by 6.5%, low-density lipoprotein (LDL)-cholesterol by 10.4% and LDL-cholesterol/high-density lipoprotein (HDL)-cholesterol ratio by 10%, whereas HDL-cholesterol levels remained unchanged. Dividing renal transplant recipients into risk classes according to the National Cholesterol Expert Program guidelines and LDL-cholesterol levels, we observed a progressively increasing reduction in total cholesterol and LDL-cholesterol levels among ‘desirable LDL-cholesterol’, ‘borderline high-risk LDL-cholesterol’ and ‘high-risk LDL-cholesterol’ patients, while HDL-cholesterol levels did not change in any group and the LDL-cholesterol/HDL-cholesterol ratio significantly decreased in ‘borderline high-risk LDL-cholesterol’ and in ‘high-risk LDL-cholesterol’ patients (respectively by 6.8%, p < 0.05, and by 21.1%, p < 0.0001). Reduction in triglyceride levels was statistically significant only in subjects with ‘desirable LDL-cholesterol’ (by 12.3%, p < 0.01). Patients in the ‘desirable LDL-cholesterol’ class increased from 28 (35.9% of total patients) before diet to 45 (57.7% of total patients, p < 0.01), while subjects in the ‘high-risk LDL-cholesterol’ class reduced from 24 (30.8% of total patients) to 8 (10.2% of total patients, p < 0.005). Conclusion: These data suggest the possibility of a nutritional hypolipidemic approach in renal transplant recipients, even if normolipidemic. Dietetic treatment determined an inversion in the typical trend of renal transplant recipients, reducing instead of increasing the number of subjects with hypercholesterolemia, permitting the selection of individual candidates for further pharmacological treatment by carefully evaluating risk/benefit costs.

Lipids and stroke: neglect of a useful preventive measure?

The epidemiological studies linking lipid variables and stroke are reviewed. These studies indicate that serum total cholesterol (TC) levels are associated positively with thrombotic and negatively with haemorrhagic strokes. Relationships for other lipid fractions are not as clearly defined. The results of trials with lipid lowering drugs suggest that only statins effectively reduce the incidence of stroke. Differences between trial results may be due to variation in the extent of reduction of TC levels. Possible underlying mechanisms for benefit and the apparent superiority of statins are also discussed. The reduction in the risk of thrombotic stroke with statins is most evident through meta-analyses (p < 0.001) and less impressive in individual trials (p < 0.03). This difference is largely attributable to the small number of events in trials primarily aimed at evaluating ischaemic heart disease (IHD) reduction. This also means that benefit may be limited to those with established IHD. IHD and thrombotic stroke share common risk factors and patients with one condition are at high risk of developing the other. Therefore, one additional reason for using statins in these patients is that these drugs can effectively prevent IHD-related events including deaths.