| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Assessing population-based programs to reduce blood cholesterol level and saturated fats Vartiainen, E., G. Heath, et al. (1991), Int J Technol Assess Health Care 7(3): 315-26. Abstract: This article reviews seven community-based programs for prevention of cardiovascular disease and their effects on blood cholesterol levels and saturated fat intake. In two programs, cholesterol levels were reduced more in the intervention area than in the reference area. In two other programs, cholesterol increased less in the intervention area than in the reference area. In one program, cholesterol levels initially fell in the intervention group and increased in the reference group; after the first 4 years, the levels also started to increase in the intervention group. The final two programs reduced cholesterol equally in both groups. Only two programs reported on the intake of saturated fats; in both, intake of saturated fat was reduced more in the intervention area than in the reference populations. In one program area, total intake of fat was reduced more than in the reference area. Published data do not allow us to draw conclusions regarding which components of the programs were most important. These studies show that the average blood cholesterol level can be affected in a general population. |
| Assessing possible hazards of reducing serum cholesterol Law, M. R., S. G. Thompson, et al. (1994), Bmj 308(6925): 373-9. Abstract: OBJECTIVE--To assess whether low serum cholesterol concentration increases mortality from any cause. DESIGN--Systematic review of published data on mortality from causes other than ischaemic heart disease derived from the 10 largest cohort studies, two international studies, and 28 randomised trials, supplemented by unpublished data on causes of death obtained when necessary. MAIN OUTCOME MEASURES--Excess cause specific mortality associated with low or lowered serum cholesterol concentration. RESULTS--The only cause of death attributable to low serum cholesterol concentration was haemorrhagic stroke. The excess risk was associated only with concentrations below about 5 mmol/l (relative risk 1.9, 95% confidence interval 1.4 to 2.5), affecting about 6% of people in Western populations. For noncirculatory causes of death there was a pronounced difference between cohort studies of employed men, likely to be healthy at recruitment, and cohort studies of subjects in community settings, necessarily including some with existing disease. The employed cohorts showed no excess mortality. The community cohorts showed associations between low cholesterol concentration and lung cancer, haemopoietic cancers, suicide, chronic bronchitis, and chronic liver and bowel disease; these were most satisfactorily explained by early disease or by factors that cause the disease lowering serum cholesterol concentration (depression causes suicide and lowers cholesterol concentration, for example). In the randomised trials nine deaths (from a total of 687 deaths not due to ischaemic heart disease in treated subjects) were attributed to known adverse effects of the specific treatments, but otherwise there was no evidence of an increased mortality from any cause arising from reduction in cholesterol concentration. CONCLUSIONS--There is no evidence that low or reduced serum cholesterol concentration increases mortality from any cause other than haemorrhagic stroke. This risk affects only those people with a very low concentration and even in these will be outweighed by the benefits from the low risk of ischaemic heart disease. |
| Assessing risk using different cholesterol-screening methods Bowden, R. G., P. M. Kingery, et al. (2004), Public Health 118(3): 225-9. Abstract: The purpose of this study was to compare total capillary, total venous, risk ratio, high-density lipoprotein and low-density lipoprotein measures of cholesterol to determine whether total capillary cholesterol is a valid measure to use in cholesterol screening. An announcement and a registration form were distributed with employee paychecks announcing a cholesterol-screening programme. Capillary and venous samples were collected from screening participants (n=285). Results indicated false negatives in total capillary cholesterol in 17.21-34.4% of cases compared with other methods of cholesterol measurement. Due to the high number of misclassifications, health educators should not use total capillary cholesterol as a predictor of risk for heart disease, nor as a measure for referral during cholesterol screenings. |
| Assessing the observed relationship between low cholesterol and violence-related mortality. Implications for suicide risk Kaplan, J. R., M. F. Muldoon, et al. (1997), Ann N Y Acad Sci 836: 57-80. Abstract: Health advocacy groups advise all Americans to restrict their dietary intake of saturated fat and cholesterol as an efficacious and safe way to lower plasma cholesterol concentrations and thus reduce the risk of coronary heart disease and other atherosclerotic disorders. However, accumulating evidence suggests that naturally low or clinically reduced cholesterol is associated with increased nonillness mortality (principally suicide and accidents). Other evidence suggests that such increases in suicide and traumatic death may be mediated by the adverse changes in behavior and mood that sometimes accompany low or reduced cholesterol. These observations provided the rationale for an ongoing series of studies in monkeys designed to explore the hypothesis that alterations in dietary or plasma cholesterol influence behavior and that such effects are potentiated by lipid-induced changes in brain chemistry. In fact, the investigations in monkeys reveal that reductions in plasma cholesterol increase the tendency to engage in impulsive or violent behavior through a mechanism involving central serotonergic activity. It is speculated that the cholesterol-serotonin-behavior association represents a mechanism evolved to increase hunting or competitive foraging behavior in the face of nutritional threats signaled by a decline in total serum cholesterol (TC). The epidemiological and experimental data could be interpreted as having two implications for public health: (1) low-cholesterol may be a marker for risk of suicide or traumatic death and (2) cholesterol lowering may have adverse effects for some individuals under some circumstances. |
| Assessing the plasma pharmacokinetics, tissue distribution, excretion and effects on cholesterol pharmacokinetics of a novel hydrophilic compound, FM-VP4, following administration to rats Wasan, K. M., K. D. Peteherych, et al. (2001), J Pharm Pharm Sci 4(3): 207-16. Abstract: PURPOSE: The purpose of this project was to 1) assess the disposition kinetics of 3H-cholesterol following co-administration with a novel hydrophilic compound, FM-VP4, and 2) determine the pharmacokinetics, tissue distribution and excretion of 3HFM-VP4 following single oral (150 mg/kg which includes 100 mCi of radiolabel) and intravenous (15 mg/kg which includes 10 mCi of radiolabel) doses. METHODS: Following an overnight fast (12-16 h) and 48 h post-surgery, adult male Sprague Dawley rats were divided into six treatment groups (n=4/group). Groups received single oral doses of 25 mCi/ml 3Hcholesterol alone or with 5, 10, 20, 50 and 100 mg/kg FM-VP4 at 0700 h. Ten percent Intralipid was used to solubilize and co-administer 3H-cholesterol and FM-VP4. LC-MS analysis confirmed minimal cholesterol and vegetable stanol content within 10% Intralipid. Thin layer chromatography was used to confirm that the majority of radioactivity measured in plasma was associated with either esterified or unesterified cholesterol. In a second study pharmacokinetics of 3HFM-VP4 were studied following intravenous or orally gavaged doses (n=8). Tissues, urine and feces were also collected in FM-VP4 kinetics study to measure tissue distribution of radioactivity. Plasma 3H-cholesterol and 3HFM-VP4 were tested for radioactivity. RESULTS: FM-VP4 co-administration significantly decreased 3H-cholesterol AUC0-48h and Cmax, and increased CL/F and Vd/F of 3H-cholesterol as compared to controls in a dose-dependent manner. Following oral administration of 3HFM-VP4, the majority of radioactivity following was recovered in the feces and gastrointestinal (GI) tract. The compound exhibited an oral bioavailability of 6.5%. Following IV administration, a two-compartment pharmacokinetic model was observed and the majority of the radioactivity was recovered in the GI tract. CONCLUSIONS: FM-VP4 reduces plasma concentration of 3H-cholesterol in fasting rats. 3HFM-VP4 has a very low oral bioavailability. |
| Assessing the value and affordability of cholesterol reduction in the managed care setting Gonzalez, E. R. and B. S. Kannewurf (1998), Am J Manag Care 4(4 Suppl): S226-33; quiz S234-5. |
| Assessment of between-instrument variations in a HPLC method for serum lipoproteins and its traceability to reference methods for total cholesterol and HDL-cholesterol Usui, S., M. Nakamura, et al. (2000), Clin Chem 46(1): 63-72. Abstract: BACKGROUND: The main purpose of this study was to evaluate the between-instrument variation of the HPLC method for the measurement of total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), VLDL-cholesterol (VLDL-C), chylomicron cholesterol (CM-C), LDL size, and HDL size. Furthermore, the accuracy of the HPLC was assessed for the determination of TC and HDL-C, compared with CDC reference methods. METHODS: We used four HPLC instruments with different column-load numbers from 250 to 5000. For accuracy assessment of TC and HDL-C, we used the reference methods recommended by the CDC. RESULTS: The values measured by the four instruments were highly correlated with each other (mean r = 0.965), and the absolute mean differences were 4-43 mg/L for TC, 4-30 mg/L for HDL-C, 0-48 mg/L for LDL-C, 7-66 mg/L for VLDL-C, 0-7 mg/L for CM-C, 0.1-0.3 nm for LDL size, and 0-0.1 nm for HDL size. For TC, the HPLC instruments showed high correlation and good agreement with the reference method: r = 0.997; total error <6.6%; absolute mean bias <1.2%. For HDL-C, the results from the HPLC method were significantly higher (10.8% absolute mean bias) than those of the CDC reference method, in spite of good correlation between the two methods (r = 0.998). CONCLUSIONS: The between-instrument variation in serum lipoprotein analysis by HPLC was confirmed to be very small. This method met the US National Cholesterol Education Program's performance criteria for TC but not for HDL-C. |
| Assessment of current National Cholesterol Education Program guidelines for total cholesterol triglyceride, HDL-cholesterol, and LDL-cholesterol measurements Caudill, S. P., G. R. Cooper, et al. (1998), Clin Chem 44(8 Pt 1): 1650-8. Abstract: We examine the effect of systematic bias and random error, quality control, and intraperson biological variation on the National Cholesterol Education Program (NCEP) clinical classifications for reported lipid measurements. We consider misclassification to occur if a true lipid homeostatic set point is within a desirable range but the reported lipid value is in a high-risk range, or if a true lipid homeostatic set point is in a high-risk range but the reported lipid value is in a desirable range. To evaluate the overall adequacy of the NCEP guidelines to ensure correct patient classification, we construct operating characteristic curves for total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. We demonstrate that if laboratories are meeting the NCEP guidelines for inherent bias and analytic precision and are using standard quality-control (QC) procedures incorporating at least two QC samples per analytical run from each of two QC pools (for a total of 4 QC samples), the current NCEP guidelines are adequate to ensure (probability >0.90) correct patient classifications regardless of the size of the systematic bias of the laboratory or increased random analytic error. Thus we suggest that at least two concentrations of QC material be included in the QC scheme to ensure that the measurement system is operating within desired specifications across the entire range of desirable and high-risk lipid concentrations and to ensure with high probability that patients are correctly classified. |
| Assessment of high-density lipoprotein cholesterol in hypertriglyceridemic sera Rosental, S. B., F. D. Brites, et al. (1993), Clin Chem 39(6): 1350-2. |
| Assessment of interlaboratory performance in external proficiency testing programs with a direct HDL-cholesterol assay Rifai, N., T. G. Cole, et al. (1998), Clin Chem 44(7): 1452-8. Abstract: Direct assays for the determination of HDL-cholesterol (HDL-C) have recently become available. The methods are precise, require small sample volume, and appear to be less affected by increased triglycerides than traditional precipitation methods. In this study, we describe the inter- and intralaboratory variability of the Boehringer Mannheim Corporation direct HDL-C assay and its performance in external proficiency testing surveys. A comparison study among three laboratories, using different analyzers and 85 serum specimens, showed a correlation coefficient (r) of 0.99. The direct HDL-C assay also showed good agreement with the ultracentrifugation-dextran sulfate-Mg2+ method (r = 0.98) and the Cholesterol Reference Method Laboratory Network-Designated Comparison Method (a = 0.98x + 4.75 mg/L, r = 0.98). Total error at medical decision levels ranged from -0.8% to +11.1%. Furthermore, this assay performed adequately in the College of American Pathologists and the ALERT surveys as well as the CDC Lipid Standardization Program and met all performance criteria of regulatory agencies. |
| Assessment of LDL particle size by triglyceride/HDL-cholesterol ratio in non-diabetic, healthy subjects without prominent hyperlipidemia Maruyama, C., K. Imamura, et al. (2003), J Atheroscler Thromb 10(3): 186-91. Abstract: Small, dense low-density lipoprotein (LDL) is an atherogenic lipoprotein because of its susceptibility to oxidative modification. However, evaluating LDL size requires highly sophisticated techniques. We investigated potentially convenient biochemical parameters for assessing the presence of small, dense LDL. Thirty-nine male subjects, who had been involved in a work-site health promotion program, were recruited. Subjects were divided into two groups: normal LDL size (> 25.5 nm, Normal LDL group) and small LDL ( |
| Assessment of modes of action and efficacy of plasma cholesterol-lowering drugs: measurement of cholesterol absorption, cholesterol synthesis and bile acid synthesis and turnover using novel stable isotope techniques Stellaard, F. and F. Kuipers (2005), Curr Drug Targets Immune Endocr Metabol Disord 5(2): 209-18. Abstract: Several processes are involved in control of plasma cholesterol levels, e.g., intestinal cholesterol absorption, endogenous cholesterol synthesis and transport and bile acid synthesis. Adaptation of either of these processes allows the body to adapt to changes in dietary cholesterol intake. Disturbances herein may lead to hypercholesterolemia and increase the risk for atherosclerosis. Several approaches are available for plasma-cholesterol lowering therapies, particularly aimed at reduction of low-density lipoprotein (LDL) cholesterol. Currently used therapies aim to decrease (hepatic) cholesterol synthesis, to inhibit cholesterol absorption or to stimulate bile acid synthesis. The latter can be achieved by reducing bile acid absorption to alleviate the negative feedback control exerted by bile acids circulating in the body. Approaches to directly stimulate bile acid synthesis may become available. Novel drugs should be tested on the efficiency to influence their actual targets. Several techniques are available to measure cholesterol absorption, cholesterol synthesis and bile acid synthesis and absorption in vivo in human subjects. The most reliable techniques are based on the use of stable isotopes and mass spectrometry. This paper provides a condensed background on physiological parameters that determine cholesterol homeostasis, and potential new mechanisms of drug action and focuses, especially, on new techniques to monitor the effects of drugs in humans. |
| Assessment of percent cholesterol absorption in humans with stable isotopes Bosner, M. S., R. E. Ostlund, Jr., et al. (1993), J Lipid Res 34(6): 1047-53. Abstract: Dietary cholesterol restriction is a general recommendation for the medical community and emphasizes the importance of intestinal cholesterol absorption and metabolism in humans. However, several methods that may accurately quantify cholesterol absorption utilize radioactive isotopes that are undesirable for younger individuals, women, children, and normal subjects. To eliminate this hazard, we have developed a procedure for measurement of percent cholesterol absorption, based on that of Zilversmit (1972. Proc. Soc. Exp. Med. Biol. 140: 862-865), using stable nonradioactive isotopic tracers of cholesterol. 26,26,26,27,27,27-2Hcholesterol (30 mg) was administered orally and 23,24,25,26,27-13Ccholesterol (15 mg) was administered intravenously on day 0 and percent cholesterol absorption was calculated as the plasma ratio of oral/intravenous isotopic tracer on day 3 as determined by gas chromatography-mass spectrometry with selected ion monitoring. Tracer cholesterol given orally peaked in plasma on day 2 and then slowly declined in parallel with the intravenous tracer. Cholesterol absorption in 16 healthy subjects (on no medication and not ingesting alcohol) consuming a Step One Diet was 53.5% +/- 8.5 SD%. Five subjects underwent repeat testing after 4-6 weeks with excellent replication (SD of difference between tests = 2.8%). No differences in the metabolism of 13C5cholesterol, 2H6cholesterol, and 14Ccholesterol were observed. The use of stable isotopes for the study of percent cholesterol absorption is precise and safe, allowing repeated measurements in normal individuals and thus facilitating clinical investigation of this key component of human cholesterol metabolism. |
| Assessment of split-sample proficiency testing for cholesterol by use of a computer simulation model Bennett, S. T., D. P. Connelly, et al. (1991), Clin Chem 37(4): 497-503. Abstract: We developed a computer model to study the use of patients' specimens to assess compliance of cholesterol measurement performance with the 1992 goals of the Laboratory Standardization Panel of the National Cholesterol Education Program. The model uses Monte Carlo techniques to simulate cholesterol measurements that are subject to both systematic and random error. Split-sample measurements by a clinical laboratory and by a reference laboratory are compared by using linear regression to estimate clinical laboratory bias and imprecision; subsequently, according to specified decision limits, the performance of the clinical laboratory is classified as acceptable or deficient. We have quantified the influence of the bias and imprecision of the clinical laboratory, the imprecision of the reference laboratory, the number of split samples compared, and the decision limits on the accuracy of the classification of clinical laboratory performance. Unless the decision limits are carefully selected and a sufficient number of split samples are used, clinical laboratory performance will be frequently misclassified. |
| Assessment of the risk of cardiovascular disease on the basis of total serum cholesterol in a population of young Danish women and men Voss, A., P. Andersen, et al. (1990), Ugeskr Laeger 152(8): 526-9. Abstract: In this investigation the distribution of total cholesterol in the serum in a population of 364 medical students in the age group 22-32 years is assessed. The average value was 5.27 mmol/l for women and 5.08 mmol/l for men. 5% of the women and 2% of the men had values which exceeded 7.0 mmol/l and were thus in a group where treatment with diet or medicine may be considered, according to the recommendations from the Danish Association for Internal Medicine. In the group investigated here, the authors did not find any significant change in total cholesterol with age and, similarly, no significant seasonal variation was encountered. |
| Assimilation of cholesterol by yeast strains isolated from infant feces and Feta cheese Psomas, E. I., D. J. Fletouris, et al. (2003), J Dairy Sci 86(11): 3416-22. Abstract: Eight yeast strains isolated from infant feces and the traditional Greek Feta cheese, selected for their probiotic properties, were tested along with a commercially available strain of Saccharomyces boulardii for their ability to remove cholesterol from a growth medium (yeast extract glucose peptone broth) supplemented with 0.3% Oxgall. The amount of cholesterol removed during 72 h of growth at 37 degrees C revealed significant variations among the yeast strains examined. Two isolates from infant feces, namely Saccharomyces cerevisiae KK1 and Isaatchenkia orientalis KK5.Y.1 and one isolate from Feta cheese, namely S. cerevisiae 832, along with the commercial strain S. boulardii, were able to remove cholesterol from the growth medium after 48 h of incubation at 37 degrees C. However, Saccharomyces strains proved to be able to remove cholesterol even after 24 h of growth at 37 degrees C. The cholesterol removed from the growth medium was not metabolically degraded but was rather assimilated into the yeast cells. The ability to assimilate cholesterol in vitro and to tolerate low pH levels, gastric juice, and bile indicate that S. cerevisiae 832, and especially S. cerevisiae KK1 and I. orientalis KK5.Y.1 (being more bile and gastric juice tolerant because of their human origin) may be promising candidate strains for use as probiotics. |
| Association analysis of genes involved in cholesterol metabolism located within the linkage region on chromosome 10 and Alzheimer's disease Riemenschneider, M., S. Mahmoodzadeh, et al. (2004), Neurobiol Aging 25(10): 1305-8. Abstract: Epidemiological studies identified a higher risk of developing Alzheimer's disease (AD) among subjects with elevated cholesterol levels. This association may be caused by a modulation of the amyloid precursor protein (APP) processing in response to the cellular cholesterol content. High cholesterol levels may favor the amyloidogenic pathway by inhibition of the alpha-secretase probably leading to elevated beta-Amyloid (Abeta) production. The identification of a linkage peak on chromosome 10q using high Abeta as quantitative trait led us to examine polymorphisms of genes located on chromosome 10 involved in cholesterol metabolism, like Lipase A (LIPA), Cholesterol 25 hydroxylase (CH25H), and FLJ22476, a high density lipoprotein binding related protein. Using 286 patients with AD and 162 controls we analyzed several single nucleotide polymorphisms (SNPs) within LIPA, CH25H, and FLJ22476. None of the polymorphisms showed significant association with AD which contradicts recent findings on CH25H. From our results we conclude that the investigated genetic variations do not contribute to the genetic risk of AD. |
| Association and linkage of LDLR gene variation with variation in plasma low density lipoprotein cholesterol Boright, A. P., P. W. Connelly, et al. (1998), J Hum Genet 43(3): 153-9. Abstract: The role of common variation in the low density lipoprotein (LDL) receptor gene (LDLR) as a determinant of variation in plasma LDL cholesterol in normolipidemic populations is not well established. To address this question, we used both association and linkage analysis to evaluate the relationship between plasma LDL cholesterol and genetic variation in LDLR and in three other candidate genes for lipoprotein metabolism, namely, APOE, PONI, and LPL. We studied a sample of 719 normolipidemic Alberta Hutterites, who comprised 1217 sib pairs. Variation in each of the four candidate genes was significantly associated with variation in plasma LDL cholesterol, but the average effects of the alleles were small. In contrast, sib pair analysis showed that only the LDLR gene variation was linked with variation in plasma LDL cholesterol (P = 0.026). Thus, the common LDLR gene variation was both associated with and linked to variation in plasma LDL cholesterol, suggesting that there is a functional impact of structural variation in LDLR on plasma LDL cholesterol in this study sample. However, the absence of linkage of variation in LDL cholesterol with the other three candidate genes, in particular APOE, is consistent with a lower sensitivity of linkage analysis compared with association analysis for detecting modest effects on quantitative traits. Attributes such as the genetic structure of the study sample, the amount of variance attributable to the locus, and the information content of the marker appear to affect the ability to detect genotype-phenotype relationships using linkage analysis. |
| Association behavior of polyisoprenes having cholesterol and phosphatidylcholine analogous end groups Kostakis, K., S. Mourmouris, et al. (2003), Eur Phys J E Soft Matter 10(1): 55-63. Abstract: Linear polyisoprenes having dimethylamine end groups were prepared by high vacuum anionic polymerization techniques using 3-dimethylaminopropyllithium as the initiator. The amine group was reacted with 2-cholesteryl-2-oxo-1,3,2-dioxaphospholane to provide polymer chains having end zwitterionic groups chemically connected with cholesterol. The association behavior of these end-functionalized polymers was studied in cyclohexane by low angle laser light scattering, dynamic light scattering, and viscometry. The aggregation numbers, Nw were found to decrease by increasing the molecular weight of the precursor polymer, due to excluded volume repulsions. The ability of cholesterol to form liquid crystal mesophases facilitated the association process leading to higher Nw values. The hydrodynamic behavior of the aggregates was similar to that of star polymers. The dependence of the Nw values on the molecular weight of the base polymer, the polydispersity of the associates and the absence of critical micelle concentration, cmc are compatible with the linear head-packing model. |
| Association between a functional variant of the KLOTHO gene and high-density lipoprotein cholesterol, blood pressure, stroke, and longevity Arking, D. E., G. Atzmon, et al. (2005), Circ Res 96(4): 412-8. Abstract: We previously identified a functional variant of KLOTHO, termed KL-VS, that is associated with human aging and early-onset occult coronary artery disease. Here, we determine whether the KL-VS allele influences cardiovascular disease risk factors, cardiovascular events, and ultimately, mortality. A total of 525 Ashkenazi Jews composed of 216 probands (age > or =95 years) and 309 unrelated individuals (ages 51 to 94) were genotyped for the KL-VS allele. In concordance with our previous data in Czech individuals (age > or =79; P<0.01), a heterozygous advantage for longevity was observed for individuals > or =79 years of age (P<0.004). Combined analysis indicates a 1.57-fold (95% CI, 1.23 to 1.98) increased odds ratio (OR) for 5-year survival in two independent populations (P<0.0002). Cardiovascular disease risk factors were assessed through multivariate regression analysis, demonstrating that high-density lipoprotein cholesterol (HDL-C; P<0.05) and systolic blood pressure (SBP; P<0.008) are associated with KL-VS genotype. History of vascular events was analyzed using logistic regression, indicating that after adjustment for traditional risk factors, heterozygous individuals were at significantly lower risk for stroke than wild-type individuals (OR, 5.88; 95% CI, 1.18 to 29.41), whereas homozygous KL-VS individuals had the highest risk (OR, 30.65; 95% CI, 2.55 to 368.00). Similarly, prospective analysis of mortality in probands using Cox regression indicates that wild-type individuals have a 2.15-fold (95% CI, 1.18 to 3.91) and homozygous KL-VS individuals a 4.49-fold (95% CI, 1.35 to 14.97) increase in relative risk for mortality after adjusting for potential confounders. Thus, cross-sectional and prospective studies confirm a genetic model in which the KL-VS allele confers a heterozygous advantage in conjunction with a marked homozygous disadvantage for HDL-C levels, SBP, stroke, and longevity. |