| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Cholesterol readings: biological variation and analytical accuracy Zoltek, R. P. (1993), Am Clin Lab 12(10): 12-4. |
| Cholesterol redistribution within human platelet plasma membrane: evidence for a stimulus-dependent event Boesze-Battaglia, K., S. T. Clayton, et al. (1996), Biochemistry 35(21): 6664-73. Abstract: The fluorescent analog NBD-phosphatidylethanolamine and the analogs of cholesterol NBD-cholesterol and cholestatrienol were used to study the distribution of these lipids within the plasma membrane bilayer of human platelets. The probes were incorporated into platelets using phosphatidylcholine donor vesicles. The distribution of NBD lipid and of cholestatrienol in the platelet plasma membrane bilayer was followed by quenching with dithionite and TNBS, respectively. The t1/2 of cholestatrienol incorporation into platelet membranes was 39 min, and approximately 65% of the probe was quenched by addition of TNBS. When platelets were exposed to collagen or to ADP, a portion of the probe became inaccessible to quenching. Within 2 min of stimulation by collagen (10 micrograms/mL), the percentage of cholestatrienol fluorescence quenched by TNBS decreased to 45%. The fluorescent probe was not found to be associated either with the intracellular membranes or in the extracellular media after collagen stimulation. Similar data were obtained with NBD-cholesterol, but the decrease in accessibility of this probe to quenching was considerably slower. The redistribution of endogenous membrane cholesterol was also measured using cholesterol oxidase. Exposure of platelets to collagen decreased the accessibility of endogenous membrane cholesterol to enzymatic oxidation with cholesterol oxidase. Taken together, the foregoing observations are consistent with the stimulus-dependent translocation of cholesterol out of the outer monolayer. Coincident with the redistribution of cholesterol is the reciprocal movement of NBD-phosphatidylethanolamine into the outer monolayer. In the presence of the chaotropic agents urea and guanidine HCl, the movement of cholestatrienol upon collagen stimulation was prevented, but the redistribution of NBD-phosphatidylethanolamine was still detected. We propose that cholesterol translocates to the inner platelet monolayer following collagen stimulation, but the possibility that the sterol moves laterally within the outer membrane monolayer cannot be rigorously excluded. |
| Cholesterol reducing food certainly is useful Stalenhoef, A. F. (1997), Ned Tijdschr Geneeskd 141(52): 2543-5. Abstract: The effect of a low-cholesterol diet in open intervention studies depends in the long run on motivation, knowledge and dedication. The mean decrease of the serum cholesterol level is 10% (range: 0-20). Epidemiological and cohort studies clearly prove a connection between the intake of saturated fat, the serum cholesterol level and the risk of coronary heart disease and death. High-fat food slows down the clearance of the degradation products rich in cholesterol which appear in the blood after a meal and which are highly atherogenic (these products are not found at a fasting cholesterol assay). Cholesterol-reducing nutrition has additional useful effects, for instance on the blood pressure and the coagulation. The recommendations for healthy, low-cholesterol nutrition for the population as a whole apply particularly to patients with a high risk of coronary heart disease. Although advice given to individuals often has a disappointing effect, influencing the life pattern should be included in the strategy to reduce the risk of coronary heart disease. |
| Cholesterol reduction and clinical benefit. Are there limits to our expectations? Fager, G. and O. Wiklund (1997), Arterioscler Thromb Vasc Biol 17(12): 3527-33. Abstract: Encouraging intervention trials drive our expectations toward more aggressive cholesterol-lowering therapies, lower target levels, and less severe hypercholesterolemia. Available studies may predict which patients, degrees of total cholesterol (TC) reduction, and baseline and target levels of TC provide the most clinical benefit. Data were pooled from seven primary and nine secondary controlled trials with major coronary heart disease (CHD) events as primary endpoints. The analysis showed that we can expect large reductions in CHD from TC reduction in primary and secondary prevention. However, the reduction is much larger in subjects with high TC and/or previous CHD events. The percent reduction in CHD increased exponentially with increasing percent TC reductions, which predicted > 70% of the change in CHD. Consequently, we cannot expect cost-effective clinical benefits from mean reductions in TC > 15 (LDL cholesterol > 20%). The TC level at the study endpoint correlated with CHD incidence irrespective of the study group and explained almost 45% of CHD incidence. The relationship was progressive and leveled off at a TC level below about 150 mgdL (3.9 mmol/L) (LDL cholesterol approximately equal to 110 mg/dl approximately equal to 2.8 mmol/L). Little extra clinical benefit can be expected from further reductions. We can expect an average 2% reduction in CHD events per percent reduction in TC. We can also expect a 2-fold greater clinical benefit among subjects with high initial TC levels than among those with low levels. Finally, we can expect that the cholesterol-attributable risk is reset to that predicted by the TC level achieved within 4 to 6 years. |
| Cholesterol reduction and coronary prevention Prabhakaran, D. (1997), Natl Med J India 10(1): 24-5. |
| Cholesterol reduction and death from non-coronary causes: evidence from randomised controlled trials MacMahon, S. (1994), Aust N Z J Med 24(1): 120-3. Abstract: An overview of randomised trials of cholesterol reduction (26 trials, 50,000 patients, net cholesterol reduction approximately 10%) provides clear evidence of a reduction in the incidence of coronary heart disease (CHD) after just a few years of treatment. Overall, the observed reduction in CHD death (9% +/- 3) was only half as large as the reduction in non-fatal myocardial infarction (19% +/- 4), although both were statistically significant (2p < 0.005). In these trials, 60% of all deaths were from CHD, and since treatment reduced these by about 9%, the expected reduction in total deaths was about 5-6%. This expected reduction falls within the 95% confidence interval of the observed effect of cholesterol reduction on total mortality in these trials. There were small excesses of deaths from cancer and deaths from trauma among patients allocated active treatment. However, in no single trial, nor in the trials collectively, were these increases individually statistically significant. Furthermore, the increases did not appear to be specific to any one agent nor were the increases consistent between trials of the same agent. These observations suggest that the small excesses of non-coronary deaths observed in the cholesterol reduction trials may have occurred by chance. Evidence from ongoing longer-term studies of treatments producing larger cholesterol reductions will be useful in further delineating the effects, if any, of such treatments on non-coronary mortality. |
| Cholesterol reduction and increased cardiovascular fitness following a 12 weeks brisk walking Paillard, T., C. Lafont, et al. (2002), J Nutr Health Aging 6(2): 138-40. Abstract: The effects of a walking training programme were assesed on 10 healthy, active men aged 63-69 years. Serum lipids, pulse and blood pressure, maximum oxygen consumption (VO2 max) and anthropometric parameters, were measured before and after this programme. There was a significant fall in LDL (p<0.02) and mean diastolic BP (p<0.005). In spite of the subjects's initial good level of fitness there was still an 8% rise in the mean VO2 max of the group. There was also a significant loss of body fat (P<0.01). These positive physiological effects suggest that brisk walking can be considered as a a useful activity for improving the fitness and general health in this age-range. |
| Cholesterol reduction and its impact on coronary artery disease and total mortality Holme, I. (1995), Am J Cardiol 76(9): 10C-17C. Abstract: A sample of 42 randomized cholesterol-lowering trials represented by 32 data points were subjected to a metaregression analysis. The logarithmic odds ratio (InOR) of total mortality outcome or incidence of coronary artery disease (CAD) were used as dependent variables and regressed against the net amount of total cholesterol reduction between treatment groups in each trial. Analyses were weighted by variance of OR. Adjustments were also made for single and multifactor trials and for total mortality risk level in the control/placebo group as well as for treatment modality. Analyses were performed both with and without inclusion of trials using 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors as treatment modality. A statistically significant dose-response relationship was found between InOR and the amount of cholesterol reduction for both endpoints and in both groups of trials. These findings were essentially unaltered by various adjustments for potential confounders or by various sensitivity analyses. The results of the Scandinavian Simvastatin Survival Study (4S) fell close to the regression lines for both outcome measures, and inclusion of other statin trials strengthened the significance of this dose-response compared with previous metaregression analyses without inclusion of statin trials. The type of treatment was significantly associated with both endpoints. Fibrate trials did significantly worse on all-cause mortality than statin trials and other drug trials (except hormone). The baseline cholesterol level was also significantly predictive of CAD incidence as a trial outcome; efficacy increased with increased level of baseline cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Cholesterol reduction and mortality Christensen, T. G. (1994), Ugeskr Laeger 156(31): 4477-9. |
| Cholesterol reduction and non-illness mortality: meta-analysis of randomised clinical trials Muldoon, M. F., S. B. Manuck, et al. (2001), Bmj 322(7277): 11-5. Abstract: OBJECTIVE: To investigate the association between cholesterol lowering interventions and risk of death from suicide, accident, or trauma (non-illness mortality). DESIGN: Meta-analysis of the non-illness mortality outcomes of large, randomised clinical trials of cholesterol lowering treatments. STUDIES REVIEWED: 19 out of 21 eligible trials that had data available on non-illness mortality. INTERVENTIONS REVIEWED: Dietary modification, drug treatment, or partial ileal bypass surgery for 1-10 years. MAIN OUTCOME MEASURE: Deaths from suicides, accidents, and violence in treatment groups compared with control groups. RESULTS: Across all trials, the odds ratio of non-illness mortality in the treated groups, relative to control groups, was 1.18 (95% confidence interval 0.91 to 1.52; P=0.20). The odds ratios were 1.28 (0.94 to 1.74; P=0.12) for primary prevention trials and 1.00 (0.65 to 1.55; P=0.98) for secondary prevention trials. Randomised clinical trials using statins did not show a treatment related rise in non-illness mortality (0.84, 0.50 to 1.41; P=0.50), whereas a trend toward increased deaths from suicide and violence was observed in trials of dietary interventions and non-statin drugs (1.32, 0.98 to 1.77; P=0.06). No relation was found between the magnitude of cholesterol reduction and non-illness mortality (P=0.23). CONCLUSION: Currently available evidence does not indicate that non-illness mortality is increased significantly by cholesterol lowering treatments. A modest increase may occur with dietary interventions and non-statin drugs. |
| Cholesterol reduction and stroke Smith, G. D., M. Egger, et al. (1994), Ann Intern Med 120(1): 88-9. |
| Cholesterol reduction and stroke occurrence: an overview of randomized clinical trials Di Mascio, R., R. Marchioli, et al. (2000), Cerebrovasc Dis 10(2): 85-92. Abstract: We performed a meta-analysis of randomized clinical trials of more than 6 months duration to describe how fatal and nonfatal strokes are related to cholesterol lowering and to the type of intervention. A total of 41 individual trials including approximately 80,000 subjects and followed for an average of about 4 years were included in the overview. There was a 16% (95% CI, 7-25%) reduction in risk of stroke among treated patients compared to control patients (test for heterogeneity, p = 0.76). When trials that used different interventions were separately examined, a significant reduction in stroke occurrence was observed only for those using statins as active treatment (risk reduction 23%; 95% CI 13-33%). A variance-weighted regression analysis of the logarithmic odds ratios for stroke incidence against the percentage of cholesterol reduction indicated that a reduction of fatal and nonfatal stroke can be obtained for a cholesterol reduction of 9% (95% CI 6.8-13.6%). The combined data of primary and secondary prevention trials indicate that a large reduction of blood cholesterol, achievable with statin drugs, can reduce the incidence of stroke. |
| Cholesterol reduction and the risk for stroke in men. A meta-analysis of randomized, controlled trials Atkins, D., B. M. Psaty, et al. (1993), Ann Intern Med 119(2): 136-45. Abstract: OBJECTIVE: Reducing serum cholesterol lowers the risk for ischemic heart disease, but its effects on other vascular diseases are unknown. Published trials were reviewed to determine the effect of cholesterol-lowering interventions on fatal and nonfatal stroke. DESIGN: Meta-analysis of randomized, controlled trials. DATA IDENTIFICATION: A literature search of English-language studies examining the effect of modified diets or medications on cardiovascular end points from 1965 to 1992 using MEDLINE and a review of references of five quantitative overviews of cholesterol reduction and coronary disease. DATA ANALYSIS: Thirteen studies met three eligibility criteria: patients randomized to intervention or control; fatal or nonfatal stroke reported separately; and end points assessed without knowledge of treatment status. Heterogeneity among studies and overall effects of treatment on fatal and nonfatal stroke were estimated using the Mantel-Haenszel-Peto method to combine independent study results. The influence of various study designs and interventions was explored using subgroup comparisons. RESULTS: For fatal stroke, the overall odds ratio associated with cholesterol-lowering interventions in 13 trials was 1.32 (95% Cl, 0.94 to 1.86), and the odds ratio for the 10 single-intervention trials was 1.34 (Cl, 0.91 to 1.96). Among eight trials reporting nonfatal events, the summary odds ratio for nonfatal stroke for treated participants compared with controls was 0.88 (Cl, 0.70 to 1.11), and the odds ratio for total strokes was 0.98 (Cl, 0.80 to 1.19). Among three trials using clofibrate, treatment significantly increased the risk for fatal stroke (odds ratio, 2.64; Cl, 1.42 to 4.92) but not for nonfatal stroke (odds ratio, 0.87; Cl, 0.61 to 1.26). Regression analysis showed no statistical association between the magnitude of cholesterol reduction and the risk for fatal stroke. CONCLUSIONS: Lowering serum cholesterol through modified diets or medications does not reduce stroke mortality or morbidity in middle-aged men. Clofibrate appears to increase the risk for fatal strokes, but the mechanism for this effect is unknown. |
| Cholesterol reduction and total mortality Vasan, R. S. (1991), Circulation 84(6): 2604. |
| Cholesterol reduction by different plant stanol mixtures and with variable fat intake Gylling, H. and T. A. Miettinen (1999), Metabolism 48(5): 575-80. Abstract: Our aim was to investigate (1) whether different campestanol/sitostanol mixtures in margarine differ in reducing serum cholesterol, and (2) whether sitostanol ester in butter decreases serum cholesterol and alters cholesterol absorption and metabolism. Twenty-three postmenopausal women replaced 25 g dietary fat with (1) sitostanol ester-rich (campestanol to sitostanol ratio 1:11) and (2) campestanol ester-rich (campestanol to sitostanol ratio 1:2) rapeseed oil margarine, (3) butter, and (4) sitostanol ester-rich (campestanol to sitostanol ratio 1:13) butter. The respective scheduled stanol intake was 3.18, 3.16, and 2.43 g/d. The 6-week margarine periods and, after an 8-week washout, 5-week butter periods were double-blind and in random order. Serum cholesterol precursor sterols (indicators of cholesterol synthesis) and plant sterols (indicators of cholesterol absorption) were quantified with gas-liquid chromatography (GLC). Low-density lipoprotein (LDL) cholesterol was reduced by 8% and 10% with the sitostanol and campestanol ester-rich margarines versus baseline (P <.05 for both) and high-density lipoprotein (HDL) cholesterol was increased by 6% and 5% (P <.05), so the LDL/HDL cholesterol ratio was reduced by 15% (P <.05 for both). Sitostanol ester-rich butter decreased LDL cholesterol 12% and the LDL/HDL cholesterol ratio 11% (P <.05 for both) versus the butter period. The serum proportions of plant sterols and cholestanol were similarly reduced and those of cholesterol precursor sterols were similarly increased during all periods (P <.05 for all). Serum proportions of sitostanol and campestanol were slightly increased, indicating that their absorption related to their dietary intake. During all stanol interventions, serum vitamin D and retinol concentrations and alpha-tocopherol to cholesterol ratios were unchanged, whereas those of alpha- and beta-carotenes were significantly reduced. We conclude that varying the campestanol to sitostanol ratio from 1:13 to 1:2 in margarine and in butter similarly decreased cholesterol absorption, LDL cholesterol, and the LDL/HDL cholesterol ratio such that the serum lipids became less atherogenic. |
| Cholesterol reduction by glucomannan and chitosan is mediated by changes in cholesterol absorption and bile acid and fat excretion in rats Gallaher, C. M., J. Munion, et al. (2000), J Nutr 130(11): 2753-9. Abstract: Glucomannan, a viscous polysaccharide, and chitosan, a derivative of chitin, have both been demonstrated to lower cholesterol in animals. However, the mechanism of cholesterol lowering has not been established for either material. This study was conducted to determine the effect of glucomannan (G), chitosan (CH), or an equal mixture of the two (G + CH) on cholesterol absorption and fat and bile acid excretion. Rats were fed a modified AIN-93G diet for 18 d containing 0.125 g/100 g cholesterol and initially 10 g/100 g of the test materials or cellulose (C) as the control. However, the concentration of test materials and cellulose was reduced to 7.5 g/100 g after 1 wk due to lower weight gain compared with controls. Total liver cholesterol was significantly reduced in G, CH and G + CH groups compared with the C group. The intestinal contents supernatant viscosity of the C and the CH groups was negligible, whereas both G and G + CH produced high viscosities. Cholesterol absorption, measured by the fecal isotope ratio method, was significantly reduced from 37.5% in the C group to 20.2% in G, 18.2% in G + CH and 9.4% in CH. Daily fecal fat excretion did not differ between the C and G groups, but was significantly greater in G + CH and CH compared with the C and G groups. Daily fecal bile acid excretion was significantly greater in the CH and G + CH groups compared with the C and G groups. These results suggest that G lowered liver cholesterol by a viscosity-mediated interference of cholesterol absorption. In contrast, CH appears to lower cholesterol through a different mechanism. |
| Cholesterol reduction following health screening in general practice Kanstrup, H., J. Refsgaard, et al. (2002), Scand J Prim Health Care 20(4): 219-23. Abstract: OBJECTIVES: To evaluate changes in plasma cholesterol following health screening and health discussions in general practice. DESIGN: Randomised prospective population-based study conducted over a period of 5 years. SETTING: Primary care, all general practitioners (GPs) in a well-defined area. SUBJECTS: A random sample of inhabitants aged 30-49 years in January 1991, registered with a local GP was invited to participate. The participants (1507 persons, or 75.4% of the 2000 invited) were randomly allocated to two intervention groups and a control group. MAIN OUTCOME MEASURES: Plasma cholesterol, percentage of subjects with plasma cholesterol higher than 7 mmol/l. RESULTS: After 5 years of intervention, plasma cholesterol in the whole population was significantly lower in the intervention groups compared to the control group. The decrease was most pronounced (0.5 mmol/l) in subjects at high cardiovascular risk. The percentage of high-risk individuals with a cholesterol level higher than 7 mmol/l was significantly lower in the intervention groups compared to the control group (9.8% vs 6.2%, p = 0.04), corresponding to a 37% reduction. CONCLUSIONS: The study shows that the health checks had a measurable impact on plasma cholesterol levels, the most pronounced effect is seen among individuals at high cardiovascular risk. |
| Cholesterol reduction improves myocardial perfusion abnormalities in patients with coronary artery disease and average cholesterol levels Mostaza, J. M., M. V. Gomez, et al. (2000), J Am Coll Cardiol 35(1): 76-82. Abstract: OBJECTIVES: We sought to evaluate whether pravastatin treatment increases myocardial perfusion, as assessed by thallium-201 single-photon emission computed tomographic (SPECT) dipyridamole testing, in patients with coronary artery disease (CAD) and average cholesterol levels. BACKGROUND: Previous studies in hypercholesterolemic patients have demonstrated that cholesterol reduction restores peripheral and coronary endothelium-dependent vasodilation and increases myocardial perfusion. METHODS: This was a randomized, placebo-controlled study with a cross-over design. Twenty patients with CAD were randomly assigned to receive 20 mg of pravastatin or placebo for 16 weeks and then were crossed over to the opposite medication for a further 16 weeks. Lipid and lipoprotein analysis and dipyridamole thallium-201 SPECT were performed at the end of each period. The SPECT images were visually analyzed in eight myocardial segments using a 4-point scoring system by two independent observers. A summed stress score and a summed rest score were obtained for each patient. Quantitative evaluation was performed by the Cedars-Sinai method. The magnitude of the defect was expressed as a percentage of global myocardial perfusion. RESULTS: Total and low density lipoprotein cholesterol levels during placebo were 214 +/- 29 mg/dl and 148 +/- 25 mg/dl, respectively. These levels with pravastatin were 170 +/- 23 mg/dl and 103 +/- 23 mg/dl, respectively. The summed stress score and summed rest score were lower with pravastatin than with placebo (7.2 +/- 2.3 vs. 5.9 +/- 2.3, p = 0.012 and 3.2 +/- 1.6 vs. 2.4 +/- 2.2, p = 0.043, respectively). Quantitative analysis showed a smaller perfusion defect with pravastatin (29.2%) as compared with placebo (33.8%) (p = 0.021) during dipyridamole stress. No differences were found at rest. CONCLUSIONS: Reducing cholesterol levels with pravastatin in patients with CAD improves myocardial perfusion during dipyridamole stress thallium-201 SPECT. |
| Cholesterol reduction in cyclosporine-treated renal transplant patients: effect on platelet-derived growth factor levels and platelet activation Rigatto, O., D. Rush, et al. (1997), Transplant Proc 29(6): 2591-2. |
| Cholesterol reduction in single and multifactor randomized trials: relationship to CHD incidence and total mortality as found by meta analysis of twenty-two trials Holme, I. (1992), Blood Press Suppl 4: 29-34. Abstract: This paper reports on a meta analysis in twenty-two randomized both single and multifactor trials regarding the effect of designed cholesterol reduction on total mortality and CHD incidence. Per cent reduction in CHD incidence was 2.5 for every per cent associated net reduction in total cholesterol, but was only 0.74% for total mortality. Since total net reduction in cholesterol was about 5% in all trials combined, the number of participants was far too small to demonstrate a significant expected reduction of 4% in total mortality. However, the 4% reduction lies just outside the observed 95% confidence limits of the overall estimate of effect on total mortality (OR = 1.02; CL 0.97, 1.07). It is concluded that cholesterol reduction must be much larger than 5% to be able to reduce the relative risk of CHD substantially and total mortality moderately. |