Cholesterol Articles and Abstracts

For medical practitioners and the general public - Cholesterol Journal Article Catalog.

Cholesterol Journal Articles



Record 10601 to 10620
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Reduction of circulating cholesterol and apolipoprotein levels during sepsis
Fraunberger, P., S. Schaefer, et al. (1999), Clin Chem Lab Med 37(3): 357-62.
Abstract: Sepsis with multiple organ failure is frequently associated with a substantial decrease of cholesterol levels. This decrease of cholesterol is strongly associated with mortality suggesting a direct relation between inflammatory conditions and altered cholesterol homeostasis. The host response during sepsis is mediated by cytokines and growth factors, which are capable of influencing lipid metabolism. Conversely lipoproteins are also capable of modulating cytokine production during the inflammatory response. Therefore the decrease in circulating cholesterol levels seems to play a crucial role in the pathophysiology of sepsis. In this review the interaction between cytokines and lipid metabolism and its clinical consequences will be discussed.

Reduction of coronary events by pravastatin--is lowering low-density lipoprotein cholesterol the answer?
Halle, M., A. Bery, et al. (1997), Am J Cardiol 80(5): 683.

Reduction of dietary saturated fatty acids correlates with increased plasma lecithin cholesterol acyltransferase activity in humans
Berard, A. M., H. Dabadie, et al. (2004), Eur J Clin Nutr 58(6): 881-7.
Abstract: OBJECTIVE: Increased HDL-cholesterol (HDL-C) concentrations have been associated with lower coronary heart disease risk. On the other hand, dietary fats are known to influence the fatty acid profile of plasma lipids, including phospholipids that are substrates of lecithin cholesterol acyltransferase (LCAT), an important enzyme in HDL metabolism. The purpose of this study was to examine the association between the saturated fatty acid (SFA) intake and LCAT activity. DESIGN: An interventional study was performed in a monk community of 25 men. SETTING: A French monk community, South West of France. SUBJECTS AND INTERVENTIONS: The basal diet of the study cohort contained SFA in a proportion of 13.5% of their total energy intake (TEI). They were submitted to two experimental isocaloric diets containing either 8.4% of the TEI in SFA (diet A) or 11% (diet B), each lasting 5 weeks. RESULTS: The elevation of SFA in diet B was mainly obtained by decreasing carbohydrates. The only significant difference among total fats between diets A and B was the myristic acid content (0.6 and 1.2% of TEI, respectively). The elevation in SFA in diet B resulted in a significant increase of HDL-C (P<0.04), while plasma apo A-I concentration and LCAT activity both decreased (P<0.02). CONCLUSION: Altogether, these results are consistent with a negative effect of SFA on reverse cholesterol transport.

Reduction of elevated LDL-cholesterol levels of 4- to 10-year-old children through home-based dietary education
Shannon, B. M., A. M. Tershakovec, et al. (1994), Pediatrics 94(6 Pt 1): 923-7.
Abstract: OBJECTIVE. To assess the effects of a home-based, parent-child autotutorial (PCAT) dietary education program on the dietary knowledge, lipid consumption, and plasma low density lipoprotein-cholesterol (LDL-C) of 4- to 10-year-old children with elevated plasma LDL-C. METHODS. "At-risk" children (screening total cholesterol, (TC), exceeded 4.55 mmol/L and average LDL-C from two fasting samples was between 2.77 and 4.24 mmol/L for boys or 2.90 and 4.24 mmol/L for girls) were randomized to the PCAT program (N = 88), for dietary counseling with a registered dietitian (N = 86), or to an at-risk control group (N = 87). Dietary knowledge, diet, and LDL-C of these groups were assessed at baseline and after the educational period (3-month follow-up). The knowledge and diet of a not-at-risk (TC below 4.22 and 4.34 mmol/L for boys and girls, respectively) control group (N = 81) was also assessed and compared with that of the at-risk control group. RESULTS. At the 3-month follow-up, the PCAT children's knowledge scores had increased three times more than those of the counseling and at-risk control groups (P <.001). Mean grams of total and saturated fat consumed by PCAT and counseling groups declined while that of the at-risk control group increased slightly; these differences were significant (P <.05). The mean LDL-C decline of the PCAT group was significantly different (P <.05) from the decline of the at-risk control group (0.26 vs 0.09 mmol/L), and approached significance (P =.07) when compared with that of the counseling group (0.26 vs 0.11 mmol/L). The at-risk control group's knowledge and diet did not differ from that of the not-at-risk group. CONCLUSION. The PCAT program offers a mechanism for providing effective dietary education to children with elevated cholesterol and to their families.

Reduction of high cholesterol levels associated with younger age and longer education in a primary health care programme for cardiovascular prevention
Hellenius, M. L., P. Nilsson, et al. (2005), Scand J Prim Health Care 23(2): 75-81.
Abstract: OBJECTIVE: To study possible social predictors for reduction of hyperlipidaemia in subjects offered lifestyle intervention in primary health care after an opportunistic screening. SETTING: Primary health care in Sollentuna, Sweden. DESIGN: Follow-up study of changes in high lipid levels in men and women aged 20-60 years participating in a voluntary screening and cardiovascular prevention programme. SUBJECTS AND MAIN OUTCOME MEASURES: A total of 1904 individuals had a follow-up visit registered after a mean of 466 days. Men and women with raised lipid levels (serum cholesterol = 6.5 mmol/l, and/or triglycerides = 2.3 mmol/l) at baseline were compared with normolipidaemic participants. Data on social characteristics such as education, occupation, marital status, and income were collected from national censuses. Associations between socioeconomic factors and changes in lipid levels were studied. RESULTS: Men and women with hyperlipidaemia were generally (p < 0.001) older (men 6-8 years, women 8-10 years) and less educated than normolipidaemic subjects. Significant predictors for reducing hypercholesterolaemia were younger age, OR 0.97 (0.95-1.00) for increasing age, and longer education, OR 0.47 (0.24-0.91) for low education (<9 years). Foreign-born subjects were more likely to achieve a high success rate in reducing hypercholesterolaemia, OR 3.43 (1.00-11.8), than the Swedish-born. No significant predictors were detected for reduction of high triglyceride levels. CONCLUSION: A successful reduction of high cholesterol levels was associated with younger age and longer education in a primary health care-based programme for cardiovascular prevention.

Reduction of intracellular cholesterol accumulation in THP-1 macrophages by a combination of rosiglitazone and atorvastatin
Llaverias, G., D. Lacasa, et al. (2004), Biochem Pharmacol 68(1): 155-63.
Abstract: Rosiglitazone and atorvastatin combination therapy has beneficial effects on both glycemic control and plasma lipid levels in type 2 diabetic patients. In the present study, we sought to determine whether this combination can also exert direct antiatherosclerotic effects in macrophages. Our results show that 2 microM rosiglitazone, alone or combined with 5 microM atorvastatin, significantly upregulated the expression of the ATP-binding cassette transporter ABCA1 and of the class B scavenger receptor CLA-1 (CD36 and LIMPII analog), both involved in cholesterol efflux from macrophages. On the other hand, the combination with atorvastatin attenuated the inductive response elicited by rosiglitazone alone on CD36 mRNA (34%, P < 0.05) and protein (16%, P < 0.05), while the uptake of oxidized low density lipoprotein (LDL) remained unaffected. When we examined the effects of the drugs on acetyl-LDL-induced cholesterol accumulation, we found that only the combination of atorvastatin with rosiglitazone caused a net depletion in the cholesteryl ester content of macrophages (35%, P < 0.05). Our data suggest that this reduction was not mediated by effects on proteins that regulate cholesterol flux, but it may be related to the inhibition of cholesteryl ester formation elicited by the statin.

Reduction of LDL cholesterol by 25% to 60% in patients with primary hypercholesterolemia by atorvastatin, a new HMG-CoA reductase inhibitor
Nawrocki, J. W., S. R. Weiss, et al. (1995), Arterioscler Thromb Vasc Biol 15(5): 678-82.
Abstract: This 6-week, double-blind clinical trial evaluated lipid parameter responses to different dosages of atorvastatin in patients with primary hypercholesterolemia. Atorvastatin is a new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor under development. After completing an 8-week placebo-baseline dietary phase, 81 patients were randomly assigned to receive either placebo or 2.5, 5, 10, 20, 40, or 80 mg atorvastatin once daily for 6 weeks. Plasma LDL cholesterol reductions from baseline were dose related, with 25% to 61% reduction from the minimum dose to the maximum dose of 80 mg atorvastatin once a day. Plasma total cholesterol and apo B reductions were also dose related. Previously, reductions in LDL cholesterol of the magnitude observed in this study have been seen only with combination drug therapy. In this study, atorvastatin was well tolerated by hyperlipidemic patients, had an acceptable safety profile, and provided greater reduction in cholesterol than other previously reported HMG-CoA reductase inhibitors.

Reduction of LDL cholesterol by pravastatin does not influence platelet activation in patients with mild hypercholesterolaemia at risk of coronary heart disease
Barrow, S. E., P. D. Stratton, et al. (1991), Br J Clin Pharmacol 32(1): 127-9.
Abstract: The effect of pravastatin on low density lipoprotein (LDL) cholesterol and platelet activation was studied in 16 patients with mild hypercholesterolaemia who had two or more additional cardiovascular risk factors. Patients were treated with either pravastatin (20-40 mg day-1) or placebo for 1 year. Plasma LDL and urinary excretion of 2,3-dinor-thromboxane B2 (an index of platelet activation in vivo) were determined at 0, 3, 6 and 12 months. There was a significant reduction in LDL at 6 and 12 months (2P less than 0.05) but this was not associated with any significant change in thromboxane metabolite excretion.

Reduction of LDL cholesterol in patients with primary hypercholesterolemia by SCH 48461: results of a multicenter dose-ranging study
Dujovne, C. A., H. Bays, et al. (2001), J Clin Pharmacol 41(1): 70-8.
Abstract: SCH 48461, an inhibitor of gastrointestinal absorption of cholesterol, was evaluated for its effects on lipid parameters in patients with primary hypercholesterolemia in a multicenter, double-blind, randomized, parallel-group study. Following the baseline phase, which consisted of a 2- to 10-week drug washout and dietary stabilization phase and a 4-week placebo lead-in (placebo baseline phase), 190 patients were randomized to an 8-week double-blind active drug (SCH 48461 1, 6.25, 25, 100, 200, or 400 mg) or 40 mg lovastatin once daily each morning or placebo treatment phase. By week 2, patients who received SCH 48461 6.25 to 400 mg or lovastatin demonstrated greater reduction from baseline in directly measured low-density lipoprotein cholesterol (LDL-C) levels than patients in the placebo group (p < or = 0.03). Overall, the percent reductions in LDL-C from baseline increased as the dose of SCH 48461 increased, with 0.6% to 15.5% reductions from the minimum dose of 1 mg to the maximum dose of 400 mg. Lovastatin 40 mg/day reduced LDL-C by 30.7% (p < 0.01). Statistically significant decreases were also seen for total cholesterol and apolipoprotein B (apo B) with doses of 25 mg to 400 mg of SCH 48461 and lovastatin. SCH 48461 was well tolerated. There was a similar incidence of adverse events in each SCH 48461- or lovastatin-treated group compared to placebo. This study demonstrated a clinically and statistically significant cholesterol-lowering effect of SCH 48461 in patients with primary hypercholesterolemia.

Reduction of new coronary events and new atherothrombotic brain infarction in older persons with diabetes mellitus, prior myocardial infarction, and serum low-density lipoprotein cholesterol >/=125 mg/dl treated with statins
Aronow, W. S., C. Ahn, et al. (2002), J Gerontol A Biol Sci Med Sci 57(11): M747-50.
Abstract: BACKGROUND: We report the incidence of new coronary events and new atherothrombotic brain infarction (ABI) in older men and women with diabetes mellitus, prior myocardial infarction, and a serum low-density lipoprotein (LDL) cholesterol of >/=125 mg/dl treated with statins and with no lipid-lowering drug. METHODS: The incidence of new coronary events and of new ABI was investigated in an observational prospective study of 529 diabetics, mean age 79 +/- 9 years, with prior myocardial infarction and a serum LDL cholesterol of >/=125 mg/dl treated with statins (279 persons or 53%) and no lipid-lowering drug (250 persons or 47%). Follow-up was 29 +/- 18 months. RESULTS: At follow-up, the stepwise Cox regression model showed that after controlling for other risk factors, the use of statins was associated with a 37% significant independent reduction in the incidence of new coronary events and with a 47% significant independent reduction in the incidence of new ABI. CONCLUSIONS: Use of statins was associated with a 37% significant, independent reduction in new coronary events and a 47% significant, independent reduction in new ABI in older men and women with diabetes mellitus, prior myocardial infarction, and a serum LDL cholesterol of >/=125 mg/dl. Elderly diabetics with prior myocardial infarction and increased serum LDL cholesterol should especially be treated with statins.

Reduction of noise-stress-induced physiological damage by radices of Astragali and Rhodiolae: glycogen, lactic acid and cholesterol contents in liver of the rat
Zhu, B. W., Y. M. Sun, et al. (2003), Biosci Biotechnol Biochem 67(9): 1930-6.
Abstract: Noise is one of the factors that induces critical stress in animals. The contents of glycogen, lactic acid and cholesterol in the liver of noise-stressed rats were analyzed in order to investigate the alleviation of noise-stress-induced physiological damages by traditional medicine using Astragali and Rhodiolae radices. More than 95 dB noise ranging from 2 to 4 kHz reduced the contents of these compounds in the liver of rats not injected with the extract of Astragali or Rhodiolae, but did not change the contents in the liver of rats injected with the Astragali or Rhodiolae extract. These results show that noise induced stress in the rats via a decrease in contents of these compounds in the liver and that Astragali or Rhodiolae maintained the contents of these compounds in the liver of the noise-stressed rats. The results indicate that Astragali or Rhodiolae improved the ability for rats to resist noise stress.

Reduction of plasma 24S-hydroxycholesterol (cerebrosterol) levels using high-dosage simvastatin in patients with hypercholesterolemia: evidence that simvastatin affects cholesterol metabolism in the human brain
Locatelli, S., D. Lutjohann, et al. (2002), Arch Neurol 59(2): 213-6.
Abstract: BACKGROUND: Previous studies have shown that patients with early onset of Alzheimer disease and vascular dementia have higher levels of circulating brain-derived 24S-hydroxycholesterol (cerebrosterol).Two recent epidemiological studies indicated that treatment with inhibitors of cholesterol synthesis (statins) reduces the incidence of Alzheimer disease. OBJECTIVE: To test the hypothesis that treatment with high-dosage simvastatin reduces circulating levels of 24S-hydroxycholesterol. DESIGN: Prospective, 24-week treatment trial for lowering of cholesterol levels. We conducted assessments at baseline, week 6, and week 24. SETTING: An academic outpatient clinical study. PATIENTS: Eighteen patients who met the criteria for hypercholesterolemia. INTERVENTION: Treatment with 80 mg/d of simvastatin at night. MAIN OUTCOME MEASURES: Plasma lipoprotein levels were measured enzymatically; lathosterol, by means of gas chromatography; and 24S-hydroxycholesterol, by means of gas chromatography-mass spectrometry. RESULTS: Simvastatin reduced total plasma cholesterol levels by 36% and 35% after 6 and 24 weeks, respectively (P<.001). Lathosterol levels were reduced by 74% and 72%, respectively, and the ratio of lathosterol to cholesterol, an indicator of whole-body cholesterol synthesis, was reduced by 60% and 61%, respectively (P<.001). Plasma 24S-hydroxycholesterol levels were lowered by 45% and 53%, respectively (P<.001). The ratio of 24S-hydroxycholesterol to cholesterol also decreased significantly (-12% P=.01 and -23% P<.002, respectively). The further reduction of 24S-hydroxycholesterol levels and its ratio to cholesterol from weeks 6 to 24 was also significant (P=.02 for both). CONCLUSIONS: The greater reduction of plasma concentrations of 24S-hydroxycholesterol compared with cholesterol indicates that simvastatin in a dosage of 80 mg/d reduces cholesterol turnover in the brain. The present results might describe a possible mechanism of how long-term treatment with statins could reduce the incidence of Alzheimer disease.

Reduction of plasma cholesterol by Curcuma comosa extract in hypercholesterolaemic hamsters
Piyachaturawat, P., J. Charoenpiboonsin, et al. (1999), J Ethnopharmacol 66(2): 199-204.
Abstract: The influence of the extract of Curcuma comosa Roxb. (Zingiberaceae) on lipid metabolism was investigated in hypercholesterolaemic hamsters. Intragastric administration of the ethyl acetate extract of C. comosa rhizome (0-500 mg/kg per day) to hypercholesterolaemic animals for 7 days decreased both plasma triglyceride and cholesterol levels in a dose-dependent manner. The reduction of plasma cholesterol levels was accompanied by a significant increase in the hepatic cholesterol content while the triglyceride content was not significantly changed. The increase of the hepatic cholesterol content was brought about by an expansion of the free cholesterol pool which specifically augments biliary cholesterol excretion. The C. comosa extract also increased plasma high density lipoprotein (HDL)-cholesterol and decreased plasma low density lipoprotein (LDL)-cholesterol. These results suggest that the C. comosa extract exerts a hypolipidaemic action by acceleration of lipid mobilization from extrahepatic tissue to the liver which subsequently increases excretion of cholesterol via the bile for excretion.

Reduction of plasma cholesterol by lovastatin normalizes erythrocyte membrane fluidity in patients with severe hypercholesterolaemia
Levy, Y., R. Leibowitz, et al. (1992), Br J Clin Pharmacol 34(5): 427-30.
Abstract: The effect of lovastatin on erythrocyte membrane composition and fluidity was investigated in eight patients with severe hypercholesterolaemia (mean LDL-cholesterol of 7.2 mmol l-1). Lovastatin was administered at a dosage of 40-80 mg for 20 weeks and was discontinued for 5 weeks thereafter. Parallel to a 47% fall in plasma LDL cholesterol, there was a significant reduction (P < 0.01) in erythrocyte membrane cholesterol:phospholipid molar ratio, while erythrocyte membrane fluidity assessed by diphenylhexatriene (DPH) fluorescence polarization increased significantly (P < 0.01). Discontinuation of lovastatin resulted in the reversal of erythrocyte membrane composition and fluidity to pre-treatment values.

Reduction of plasma cholesterol levels and induction of hepatic LDL receptor by cerivastatin sodium (CAS 143201-11-0, BAY w 6228), a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, in dogs
Yasunobu, Y., K. Hayashi, et al. (1997), Cardiovasc Drugs Ther 11(4): 567-74.
Abstract: The effects of cerivastatin sodium (BAY w 6228), a new type of inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on plasma cholesterol concentrations and the induction of hepatic LDL receptors were investigated with beagle dogs and Hep G2 cells. Oral administration of cerivastatin (0.01, 0.03, and 0.1 mg/kg per day) for 3 weeks reduced plasma total and very low-density lipoprotein plus low-density lipoprotein (VLDL + LDL) cholesterol concentrations and increased hepatic LDL receptor binding activity in dogs. Scatchard plot analysis revealed a 1.9-fold increase in the maximum binding capacity of hepatic LDL receptors in cerivastatin-treated animals. Similar results were obtained by administration of pravastatin (1.0 and 5.0 mg/kg/day) for 3 weeks. Binding activity of the LDL receptor, as well as receptor mRNA and protein concentrations, were increased in a dose-dependent manner (0.01-1.0 microM) by exposure of Hep G2 cells to cerivastatin. The results suggest that cerivastatin reduces plasma cholesterol concentrations by increasing hepatic LDL receptor expression. The mechanism of lowering cholesterol concentration by cerivastatin was the same as with the other previously examined HMG-CoA reductase inhibitors, but the effects with cerivastatin were apparent at doses much lower than the effective doses of the other drugs. Cerivastatin, therefore, shows potential for clinical use as a potent and efficacious plasma cholesterol-lowering drug.

Reduction of plasma cholesterol levels in normal men on an American Heart Association Step 1 diet or a Step 1 diet with added monounsaturated fat
Ginsberg, H. N., S. L. Barr, et al. (1990), N Engl J Med 322(9): 574-9.
Abstract: The design of diets to achieve optimal changes in plasma lipid levels is controversial. In a randomized, double-blind trial involving 36 healthy young men, we evaluated the effects on plasma lipid levels of both an American Heart Association Step 1 diet (in which 30 percent of the total calories were consumed as fat: 10 percent saturated, 10 percent monounsaturated, and 10 percent polyunsaturated fats, with 250 mg of cholesterol per day) and a monounsaturated fat-enriched Step 1 diet (with 38 percent of the calories consumed as fat: 10 percent saturated, 18 percent monounsaturated, and 10 percent polyunsaturated fats, with 250 mg of cholesterol per day). The effects of these diets were then compared with those of an average American diet, in which 38 percent of the total calories were consumed as fat: 18 percent saturated, 10 percent monounsaturated, and 10 percent polyunsaturated fats, with 500 mg of cholesterol per day. The men consumed the average American diet for 10 weeks before random assignment to one of the two Step 1 diets or to continuation of the average diet for an additional 10 weeks. Caloric intake was adjusted to maintain a constant body weight. As compared with the mean (+/- SD) change in the plasma total cholesterol level in the group that followed the average American diet throughout the study (-0.05 +/- 0.36 mmol per liter), there were statistically significant reductions (P less than 0.025) in the plasma total cholesterol level in the group on the Step 1 diet (-0.37 +/- 0.27 mmol per liter) and in the group on the monounsaturated fat-enriched Step 1 diet (-0.46 +/- 0.36 mmol per liter). There were parallel reductions in the plasma low-density lipoprotein cholesterol levels in these two groups. Neither the plasma triglyceride levels nor the high-density lipoprotein cholesterol concentrations changed significantly with any diet. We conclude that enrichment of the Step 1 diet with monounsaturated fat does not alter the beneficial effects of the Step 1 diet on plasma lipid concentrations.

Reduction of remnant lipoprotein cholesterol concentrations by cilostazol in patients with intermittent claudication
Wang, T., M. B. Elam, et al. (2003), Atherosclerosis 171(2): 337-42.
Abstract: BACKGROUND: Elevated triglyceride-rich lipoproteins and reduced high-density lipoproteins (HDL) are associated with the development of intermittent claudication (IC), a life-limiting symptom of peripheral arterial disease. Cilostazol, a potent platelet inhibitor and vasodilator, lowers triglycerides and increases HDL concentrations in addition to increasing walking distance in patients with intermittent claudication. However, the association of remnant lipoproteins (a more atherogenic subset of triglyceride-rich lipoproteins) and peripheral arterial disease and the effects of cilostazol on remnant lipoproteins have not been studied. METHODS AND RESULTS: We quantified plasma remnant lipoprotein concentrations using the remnant lipoprotein-cholesterol assay (RLP-C). Patients with intermittent claudication (n = 415) had significantly higher remnant lipoprotein concentrations compared to reference subjects (n = 874; 0.31 +/- 0.32 versus 0.24 +/- 0.17 mmol/l, P < 0.001) in addition to elevated total triglyceride (2.67 +/- 1.92 versus 1.92 +/- 1.24 mmol/l, P < 0.001) and reduced high-density lipoprotein (HDL) cholesterol concentrations (1.06 +/- 0.31 versus 1.22 +/- 0.36 mmol/l, P < 0.001). Cilostazol treatment (100 mg, b.i.d.) in patients with intermittent claudication (n = 56) for 6 months resulted in 20% reduction of remnant lipoprotein-cholesterol (from 0.27 +/- 0.21 to 0.22 +/- 0.09 mmol/l, P < 0.05) versus no significant change (from 0.26 +/- 0.17 to 0.27 +/- 0.12 mmol/l) in the placebo group (n = 67). Cilostazol also reduced triglyceride concentrations significantly (from 2.32+/-1.46 to 1.79+/-0.72 mmol/l, P < 0.01, in the cilostazol group versus 2.38 +/- 1.39 to 2.25 +/- 1.19 mmol/l in the placebo group) and increased HDL cholesterol concentrations (from 1.06 +/- 0.23 to 1.24 +/- 0.34 mmol/l, P < 0.001) in the cilostazol group versus no significant change (1.06 +/- 0.34 to 1.09 +/- 0.36 mmol/l) in the placebo group. Pentoxifylline (400 mg, t.i.d.) did not have any significant effects on lipid variables (n = 66). CONCLUSIONS: Remnant lipoprotein concentrations are significantly elevated in patients with intermittent claudication and can be reduced by cilostazol. Reduction of remnant lipoproteins may provide a long-term benefit to the patients with symptomatic peripheral arterial disease.

Reduction of serum cholesterol and hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinol diglucoside isolated from flaxseed
Prasad, K. (1999), Circulation 99(10): 1355-62.
Abstract: BACKGROUND: Secoisolariciresinol diglucoside (SDG) is a plant lignan isolated from flaxseed. Lignans are platelet-activating factor-receptor antagonists that would inhibit the production of oxygen radicals by polymorphonuclear leukocytes. SDG is an antioxidant. Antioxidants studied thus far are known to reduce hypercholesterolemic atherosclerosis. The objective of this study was to determine the effect of SDG on various blood lipid and aortic tissue oxidative stress parameters and on the development of atherosclerosis in rabbits fed a high-cholesterol diet. METHODS AND RESULTS: Rabbits were assigned to 4 groups: group 1, control; group 2, SDG control (15 mg. kg body wt-1. d-1 PO); group 3, 1% cholesterol diet; and group 4, same as group 3 but with added SDG (15 mg. kg body wt-1. d-1 PO). Blood samples were collected before (time 0) and after 4 and 8 weeks of experimental diets for measurement of serum triglycerides, total cholesterol (TC), and LDL, HDL, and VLDL cholesterol (LDL-C, HDL-C, and VLDL-C). The aorta was removed at the end of the protocol for assessment of atherosclerotic plaques; malondialdehyde, an aortic tissue lipid peroxidation product; and aortic tissue chemiluminescence, a marker for antioxidant reserve. Serum TC, LDL-C, and the ratios LDL-C/HDL-C and TC/HDL-C increased in groups 3 and 4 compared with time 0, the increase being smaller in group 4 than in group 3. Serum HDL-C decreased in group 3 and increased in group 4 compared with time 0, but changes were lower in group 3 than in group 4. SDG reduced TC and LDL-C by 33% and 35%, respectively, at week 8 but increased HDL-C significantly, by>140%, as early as week 4. It also decreased TC/LDL-C and LDL-C/HDL-C ratios by approximately 64%. There was an increase in aortic malondialdehyde and chemiluminescence in group 3, and they were lower in group 4 than in group 3. SDG reduced hypercholesterolemic atherosclerosis by 73%. CONCLUSIONS: These results suggest that SDG reduced hypercholesterolemic atherosclerosis and that this effect was associated with a decrease in serum cholesterol, LDL-C, and lipid peroxidation product and an increase in HDL-C and antioxidant reserve.

Reduction of serum cholesterol and low-density lipoprotein cholesterol levels in a juvenile population after isocaloric substitution of whole milk with a milk preparation (skimmed milk enriched with oleic acid)
Estevez-Gonzalez, M. D., P. Saavedra-Santana, et al. (1998), J Pediatr 132(1): 85-9.
Abstract: OBJECTIVE: To study the effects of serum lipid levels by isocaloric substitution of whole milk intake in a group of children with a milk preparation (fat-free milk enriched with oleic acid containing a small amount of cholesterol) that is frequently consumed in our community. DESIGN: A crossover clinical trial was carried out with random selection. There were 88 children of both sexes, ranging in age from 3 to 9 years, selected at a Primary Care Center. The children were divided into two homogeneous groups. The first group consumed whole milk for the first 7-month study period, whereas the second group drank the milk substitute. At the end of the first test period, serum lipid levels were measured. Then the type of diet was reversed: Group 1 children consumed the milk substitute whereas Group 2 children drank whole milk. The rest of their intake did not vary throughout the study. At the end of the second 7-month period we measured serum lipid levels again. The levels of serum lipid evaluated were total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, Apoprotein A1, Apoprotein B, and lipoprotein (a). For the statistical analysis the nonpaired and paired t tests were used. RESULTS: The mean level of cholesterol after taking whole milk was 4.53 mmol/L (175.26 mg/dl), and the mean level after taking the milk preparation was 4.2 mmol/L (162.65 mg/dl), which indicates a 7.2% decrease. The mean level of low-density lipoprotein cholesterol after whole milk intake was 2.73 mmol/L (106.1 mg/dl), whereas after consuming the milk preparation it was 2.47 mmol/L (96.1 mg/dl), which indicates a decrease of 9.5%. Triglycerides were reduced from 0.83 mmol/L (73.53 mg/dl) after whole milk to 0.72 mmol/L (63.79 mg/dl) after the milk substitute, which suggests a 13.25% decrease. High-density lipoprotein cholesterol, apoprotein A1, apoprotein B, and lipoprotein (a) did not undergo any significant change. CONCLUSIONS: To reduce serum levels of total cholesterol and low-density lipoprotein cholesterol, without reducing caloric intake, it may be beneficial to substitute the whole milk customarily consumed by children with a milk preparation of fat-free milk enriched with oleic acid.

Reduction of serum cholesterol in postmenopausal women with previous myocardial infarction and cholesterol malabsorption induced by dietary sitostanol ester margarine: women and dietary sitostanol
Gylling, H., R. Radhakrishnan, et al. (1997), Circulation 96(12): 4226-31.
Abstract: BACKGROUND: Reduction of serum cholesterol decreases mortality in primary and especially in secondary prevention. We investigated how effectively postmenopausal women with a previous myocardial infarction reduced their serum cholesterol with dietary means by using sitostanol ester rapeseed oil margarine, alone and in combination with statins, and to what extent cholesterol metabolism was affected. METHODS AND RESULTS: The first study group consisted of 22 randomly chosen women with angiographically documented coronary artery disease. Baseline studies on home diet were followed by double-blind, randomized, cross-over studies on margarine without and with sitostanol (3 g/d) ester for 7 weeks in random order. A second group of 10 women on simvastatin consumed sitostanol ester margarine for 12 weeks. Sitostanol ester margarine lowered serum total cholesterol by 13% (P<.05) and LDL cholesterol by 20% (P<.01). Sitostanol ester margarine reduced total cholesterol in all patients, LDL cholesterol <2.6 mmol/L (<100 mg/dL) in 32%, and <3.4 mmol/L (<133 mg/dL) in 73% versus none and 27% during the home diet (P<.01 for both). Combined with simvastatin, sitostanol still reduced total and LDL cholesterol by 11+/-3% and 16+/-5% (P<.01 for both). Sitostanol reduced absorption (-45%), increased fecal elimination (+45% as neutral sterols), and stimulated synthesis (+39%) of cholesterol. High cholestanol and plant sterol (high cholesterol absorption) and low baseline precursor sterol proportions (low cholesterol synthesis) predicted high decreases in serum cholesterol. CONCLUSIONS: Dietary use of sitostanol ester margarine normalizes LDL cholesterol in about one third of women with previous myocardial infarction, especially in those with high baseline absorption and low synthesis of cholesterol, and in combination with statins reduces the needed drug dose.


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