| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Multicenter evaluation of a patient-administered test for blood cholesterol measurement McNamara, J. R., G. R. Warnick, et al. (1996), Prev Med 25(5): 583-92. Abstract: BACKGROUND: In order to assess accuracy of a newly developed, noninstrumented, self-administered fingerstick test that measures cholesterol levels in whole blood, the AccuMeter Cholesterol Self-Test was evaluated for home-use by untrained consumers in a multicenter study. METHODS: A total of 486 untrained adult volunteers of varying age, occupation, and educational background were recruited at four sites. Participants received written instructions provided in the kit, access to a telephone "800" number for additional help, and, if necessary, a short instructional video available to consumers on request. Fingerstick cholesterol results obtained by untrained volunteers were compared with paired venous serum results obtained by the Abell-Kendall cholesterol reference method. After application of exclusion criteria, 79.0% (384/486) of subjects had AccuMeter fingerstick results available for comparison with the reference method. RESULTS: Results obtained with the AccuMeter test correlated well with the Abell-Kendall results (r = 0.91). There was a mean overall bias for the AccuMeter of -0.116 +/- 0.528 mmol/liter (-2.2%), with a mean absolute bias of 0.398 +/- 0.367 mmol/liter (7.6%). Biases at the National Cholesterol Education Program cutpoints of 5.20 and 6.20 mmol/liter were -2.2 and -2.5%, respectively. Subjects with high-risk total cholesterol values (> or = 6.20 mmol/liter) were correctly classified 80.0% of the time, with an additional 18.8% placed in the borderline category (5.20-6.20 mmol/liter); 1.2% were inappropriately placed in the desirable category. No subjects were placed in the high-risk category by the AccuMeter test if they had a desirable cholesterol value by the reference method, while 9.8% were placed in this category if they were in fact borderline. CONCLUSIONS: This test appears to be a useful addition to available options in the effort to increase awareness of cholesterol as a heart disease risk factor. A large portion of untrained consumers were able to perform the AccuMeter Cholesterol Self-Test and obtain comparable results to the reference method. This test for the first time allows consumers to determine their own cholesterol values, with a reasonably good degree of accuracy. |
| Multicenter evaluation of four homogenous LDL-cholesterol assays Bayer, P., F. Veinberg, et al. (2005), Ann Biol Clin (Paris) 63(1): 27-41. Abstract: International guidelines emphasize the importance of LDL cholesterol (LDL-C) assay in the care and follow-up of patients with cardiovascular risk. Most studies and common practice use Friedewald's formula for LDL-C calculation. The accuracy of the result depends closely on the precision of the input parameters (total cholesterol, triglycerides (TG) and HDL cholesterol), and discrepancies between calculated LDL-C and measurement by reference methods appear when TG exceed 4.5 mmol/L, or in the presence of abnormal lipoproteins. These restrictions and uncertainties in calculations have prompted the recent development of direct and homogeneous methods that fit all analyzers. A multicenter evaluation of four direct assays of LDL-C (Daiichi, Denka Seiken, Kyowa, Wako) was carried out on 45 serum samples (TG below 3.1 mmol/L) in eight laboratories using different analyzers. For three methods (Daiichi, Kyowa, Wako), the interlaboratory reproducibility was markedly improved relative to that of calculation. A strong correlation was found for all new methods when compared with a beta-quantification assay. Average bias in Denka Seiken assays was greater than Kyowa's and Daiichi's (although less dispersed for the latter) and for Wako all bias were positive. The relationship between bias variations and the lipid parameters of the samples was studied. Three methods, Daiichi, Kyowa and Wako, revealed a significant positive correlation between bias and serum VLDL-C/TG ratio, clearly indicating that cholesterol enrichment of VLDL was a source of variability in these assays. Specificity of the four methods was tested in situation of dyslipidemia by spiking isolated lipoproteins (chylomicrons, VLDL and HDL). This experiment revealed differences in behavior, most evidently upon addition of VLDL. No method was truly specific, but up to 8 mmol/L of TG the variations were acceptable. In the presence of type III hyperlipoproteinemia, however, only the Denka Seiken method was reliable. Linearity up to 20 mmol/L (Daiichi, Denka Seiken) or 14 mmol/L (Kyowa, Wako) of LDL-C allows these tests to be used in main routine cases. New direct assays are an obvious technological advance in terms of analytical performance and conveniency. Their use for the diagnosis and follow-up of hyperlipidemic patients offers an alternative that overcomes the limitations of the Friedewald calculation. |
| Multicenter evaluation of Reflotron direct dry-chemistry assay of high-density lipoprotein cholesterol in venous and fingerstick specimens Warnick, G. R., G. J. Boerma, et al. (1993), Clin Chem 39(2): 271-7. Abstract: The Reflotron HDL Cholesterol test (Boehringer Mannheim GmbH) directly separates and analyzes high-density lipoprotein (HDL) cholesterol in plasma collected with EDTA in an integrated dry-reagent system suitable for alternative site testing of lipoproteins. We describe a multicenter evaluation of this test by two US and six European laboratories experienced in lipid analysis. Each laboratory compared the Reflotron with the same conventional wet-chemistry method, Boehringer phosphotungstate-Mg2+ precipitation with enzymatic cholesterol assay. Imprecision was within accepted guidelines, with CVs of < or = 8% for fresh and frozen plasmas (median CV 1.7-3.9%) and for lyophilized sera (median CV 3.8-4.7%), similar to those of the conventional method. Results of linear-regression analysis were as follows: Reflotron HDL Cholesterol = 1.03 conventional - 3.9 mg/L, r = 0.987. The Reflotron results were somewhat low in the two US laboratories, demonstrating the need for general standardization of methods for measuring HDL cholesterol. Results from capillary fingerstick plasma agreed well with those from venous-derived plasma; capillary = 1.04 venous + 4.5 mg/L, r = 0.967. The system is relatively insensitive to interference from hemoglobin (< or = 0.75 g/L), ascorbic acid (< or = 0.3 g/L), bilirubin (< or = 50 mg/L), cholesterol (< or = 3.5 g/L), and triglycerides (< or = 4 g/L). The relative ease of operation and the rapid availability of results (within 90 s for plasma collected in EDTA) make the method appropriate for use by well-trained, but not necessarily technical, operators in the physician's office or other alternative sites. |
| Multicenter evaluation on different analyzers of three methods for direct HDL-cholesterol assay Egloff, M., D. Leglise, et al. (1999), Ann Biol Clin (Paris) 57(5): 561-72. Abstract: Most frequently, in routine laboratories, C-HDL is measured in the supernatant after precipitation of apolipoprotein B-containing lipoproteins by the sodium phosphotungstate/magnesium chloride reagent (PTA). This method involves precipitation, centrifugation and decantation steps which prevent full automation of the measurement and decrease the accuracy of the results. Recently, three direct assays for C-HDL including alpha-cyclodextrin sulphate (alpha-CD), polyanions/detergents (PA-D) or antibodies anti-beta-lipoproteins (AC) have been commercialized, in which all steps are fully managed by automated analyzers. These new methods have been compared to the conventional procedure (PTA), in multicenter studies among six laboratories using different analyzers. The C-HDL values measured by the alpha-CD and PA-D assays correlated well with those of the PTA method (r > 0.98), on most of the analyzers. With the AC assay, only the results obtained with the Hitachi 717 analyzer were correlated with C-HDL values of the PTA method. The linearity and specificity studies were evaluated in the laboratory A on a Kone Specific analyzer. The alpha-CD and PA-D assays were linear for C-HDL values from 0 to 5.56 mmol/l, as observed by increasing amounts of HDL2 + HDL3 or serum without lipoprotein isolated by ultracentrifugation. The specificity of these two methods was evaluated simultaneously, by adding various amounts of lipoproteins isolated by sequential ultracentrifugation. No interference was observed when adding chylomicrons up to 13.4 mmol/l of triglycerides for both methods. Inversely, increased C-HDL values were observed with added VLDL from 6 mmol/l of triglycerides for the PA-D assay and from 8 mmol/l for the alpha-CD assay. No interference was observed with added LDL up to 11.5 mmol/l of C-LDL for the alpha-CD assay and up to 6.7 mmol/l for the PA-D assay. In conclusion, the present multicenter evaluation demonstrates that the new procedures for the direct automation of C-HDL are easy and accurate and most of them correlated well with the classical precipitation method. In addition the study provides arguments for a choice between the different direct C-HDL methods. |
| Multicentre evaluation of a non-wipe system for the rapid determination of total cholesterol in capillary blood, Accutrend Cholesterol on Accutrend GC Gottschling, H. D., W. Reuter, et al. (1995), Eur J Clin Chem Clin Biochem 33(6): 373-81. Abstract: Accutrend Cholesterol, a non-wipe test for the determination of total cholesterol in capillary blood, was evaluated at four clinical centres. Cholesterol determinations with the Accutrend system using capillary blood were compared with results obtained with the cholesterol oxidase/p-aminophenazone (CHOD-PAP) method using the respective capillary sera. Triacylglycerols, uric acid and haematocrit were determined to evaluate potential interference. Imprecision measurements were performed with venous blood. To examine the reproducibility of results from lot to lot, three different lots of test strips were included in these investigations. Results with Accutrend Cholesterol agree with those of the comparison method within systematic differences of +2.5% to -3.2%, depending on the lot. There was no interference by triacylglycerols up to 10.28 mmol/l (900 mg/dl), by uric acid 60 to 400 mumol/l (1 mg/dl to 7 mg/dl), or by haematocrits between 0.35 and 0.54. Impression data show coefficients of variation of generally less than 5%. Thus Accutrend Cholesterol proved to be a reliable system for the determination of total cholesterol. |
| Multidrug permeases and subcellular cholesterol transport Ioannou, Y. A. (2001), Nat Rev Mol Cell Biol 2(9): 657-68. Abstract: Studies of Niemann-Pick C (NPC) and Tangier diseases have led to the identification of the causative genes, NPC1 and ABCA1, respectively. Characterization of their protein products shows that NPC1 and ABCA1 are permeases that belong to two different superfamilies of efflux pumps, which might be important in subcellular lipid and cholesterol transport. |
| Multidrug resistance (MDR1) P-glycoprotein enhances esterification of plasma membrane cholesterol Luker, G. D., K. R. Nilsson, et al. (1999), J Biol Chem 274(11): 6979-91. Abstract: Class I P-glycoproteins (Pgp) confer multidrug resistance in tumors, but the physiologic function of Pgp in normal tissues remains uncertain. In cells derived from tissues that normally express Pgp, recent data suggest a possible role for Pgp in cholesterol trafficking from the plasma membrane to the endoplasmic reticulum. We investigated the esterification of plasma membrane cholesterol under basal conditions and in response to sphingomyelinase treatment in transfected and drug-selected cell lines expressing differing amounts of functional class I Pgp. Compared with parental NIH 3T3 fibroblasts, cells transfected with human multidrug resistance (MDR1) Pgp esterified more cholesterol both without and with sphingomyelinase. Esterification also was greater in drug-selected Dox 6 myeloma cells than parental 8226 cells, which express low and non-immunodetectable amounts of Pgp, respectively. However, no differences in total plasma membrane cholesterol were detected. Transfection of fibroblasts with the multidrug resistance-associated protein (MRP) did not alter esterification, showing that cholesterol trafficking was not generally affected by ATP-binding cassette transporters. Steroidal (progesterone, dehydroepiandrosterone) and non-steroidal antagonists (verapamil, PSC 833, LY335979, and GF120918) were evaluated for effects on both cholesterol trafficking and the net content of 99mTc-Sestamibi, a reporter of drug transport activity mediated by Pgp. In Pgp-expressing cells treated with nonselective and selective inhibitors, both the kinetics and efficacy of inhibition of cholesterol esterification differed from the antagonism of drug transport mediated by Pgp. Thus, although the data show that greater expression of class I Pgp within a given cell type is associated with enhanced esterification of plasma membrane cholesterol in support of a physiologic function for Pgp in facilitating cholesterol trafficking, the molecular mechanism is dissociated from the conventional drug transport activity of Pgp. |
| Multidrug resistance P-glycoprotein is not involved in cholesterol esterification Issandou, M. and T. Grand-Perret (2000), Biochem Biophys Res Commun 279(2): 369-77. Abstract: The aim of the present paper is to reinvestigate the role of multidrug resistance P-glycoprotein MDR1 and MDR-associated protein (MRP1) in cholesterol esterification using well-characterized inhibitors. Using specific substrate efflux assay, we show that GF120918 (0.2 microM) and probenecid (5 mM) were specific inhibitors of MDR1 and MRP1, respectively. In HepG2 cells, neither of them affect the esterification of cholesterol derived from the uptake of cholesterol-rich lipoprotein, while both verapamil (100 microM) and progesterone (100 microM) were able to inhibit cholesterol esterification. Similar results were obtained with verapamil, progesterone, and GF120918 in the MDR1-overexpressing cells MCF7/ADR. The capacity of progesterone to reduce cholesterol esterification is not correlated with its ability to inhibit MDR1 but is rather due to direct inhibition of acyl-CoA:cholesterol acyltransferase (ACAT). We conclude that the esterification of cholesterol is not correlated with MDR1 or MRP1 activity, thus excluding their role in the intracellular transport of endocytosis-derived cholesterol. |
| Multidrug resistance: a role for cholesterol efflux pathways? Liscovitch, M. and Y. Lavie (2000), Trends Biochem Sci 25(11): 530-4. Abstract: Multidrug resistance (MDR) severely impairs the efficacy of cancer chemotherapy. Several protein transporters that mediate drug export have been identified, but additional adaptations appear to be necessary for full-fledged drug resistance. The cell surface density of caveolae and the expression of the caveolar coat protein caveolin are dramatically increased in MDR cancer cells. Acquisition of MDR might thus be accompanied by upregulation of caveolin-dependent cholesterol efflux pathways, raising the possibility that these same pathways are utilized for delivering drugs from intracellular compartments to the plasma membrane, where drugs can be extruded from the cells by drug efflux ATPases. The upregulation of caveolin mandates a phenotypic change of MDR cells in terms of their cholesterol homeostasis and is accompanied by loss of important features of the transformed phenotype of MDR cancer cells. |
| Multifactorial treatment of hypertensive men at high cardiovascular risk and low-density lipoprotein cholesterol affinity to human arterial proteoglycans Fagerberg, B., O. Wiklund, et al. (1996), Eur J Clin Invest 26(11): 960-5. Abstract: The purpose of this work was to examine in an open, randomized parallel-group study whether an intervention programme directed towards hypercholesterolaemia, smoking and diabetes mellitus in treated hypertensive men was associated with less complex formation between low-density lipoprotein (LDL) and human arterial proteoglycans than was the case with usual care. The intervention consisted mainly of non-pharmacological treatment, but drug therapy could be instituted to achieve the treatment goals in the intervention group. The intervention programme was associated with a significant reduction in body mass index, and 46% of the patients were on lipid-lowering medication at the follow-up examination. The net differences were (intervention--usual care): change in serum LDL-cholesterol, -0.48 mmol L-1 (95% confidence interval -0.84 to -0.11 mmol L-1), precipitated LDL-cholesterol, -5.5 micrograms (95% CI -9.0 to -1.1 micrograms). The latter remained after adjustment for the difference in serum LDL-cholesterol between groups. Our conclusion is that the multifactorial risk factor treatment programme was associated with a reduced tendency of LDL to form complexes with human arterial proteoglycans. |
| Multilayer structures in lipid monolayer films containing surfactant protein C: effects of cholesterol and POPE Malcharek, S., A. Hinz, et al. (2005), Biophys J 88(4): 2638-49. Abstract: The influence of cholesterol and POPE on lung surfactant model systems consisting of DPPC/DPPG (80:20) and DPPC/DPPG/surfactant protein C (80:20:0.4) has been investigated. Cholesterol leads to a condensation of the monolayers, whereas the isotherms of model lung surfactant films containing POPE exhibit a slight expansion combined with an increased compressibility at medium surface pressure (10-30 mN/m). An increasing amount of liquid-expanded domains can be visualized by means of fluorescence light microscopy in lung surfactant monolayers after addition of either cholesterol or POPE. At surface pressures of 50 mN/m, protrusions are formed which differ in size and shape as a function of the content of cholesterol or POPE, but only if SP-C is present. Low amounts of cholesterol (10 mol %) lead to an increasing number of protrusions, which also grow in size. This is interpreted as a stabilizing effect of cholesterol on bilayers formed underneath the monolayer. Extreme amounts of cholesterol (30 mol %), however, cause an increased monolayer rigidity, thus preventing reversible multilayer formation. In contrast, POPE, as a nonbilayer lipid thought to stabilize the edges of protrusions, leads to more narrow protrusions. The lateral extension of the protrusions is thereby more influenced than their height. |
| Multinucleated variant endothelial cells (MVECs) have a greater capacity for LDL cholesterol uptake than typical mononuclear endothelial cells (TECs) Tokunaga, O., T. Satoh, et al. (2002), J Atheroscler Thromb 9(1): 35-41. Abstract: The existence of large endothelial cells in the human aorta, especially on atherosclerotic lesions has been reported. They have multiple nuclei and are called "multinucleated variant endothelial cells (MVECs)". In the present study caveolin expression was demonstrated in both MVECs and small typical endothelial cells (TECs). Caveolin was expressed diffusely as fine particles, and caveoles were expressed as prominent accumulations of caveolin in the cytoplasm. LDL was bound to the endothelial surface. With double immunostaining for caveolin and LDL, the location of LDL corresponded to the immunoreactive caveoles. Over time, large dots of LDL appeared in MVECs, whereas a few fine particles remained in TECs. An electron microscopic chase study of LDL-gold uptake identified many LDL-gold particles in plasmalemmal vesicles and in endosomes or lysosomes of MVECs, but only a few particles were found in TECs. Gold containing vesicles often were located near the abluminal surface. The number of LDL-gold particles was 4.5 times greater per unit area in MVECs than in TECs. Some of the gold particles were located in the subendothelial collagen matrix. These findings indicate that MVECs have a greater capacity of LDL cholesterol uptake followed by transport to the subendothelial matrices than TECs, and that MVECs contribute to the development and advancement of atherosclerotic lesions. |
| Multiple cholesterol embolism mimicking periarteritis nodosa Cosserat, J., O. Bletry, et al. (1992), Presse Med 21(12): 557-64. Abstract: Ten men aged 56 to 84 were hospitalized with a diagnosis of periarteritis nodosa, whereas they had multiple cholesterol embolism. The diagnosis was corrected post mortem in the first 3 patients and subsequently in live patients. The particularly misleading clinical manifestations were neurological (polyneuritis in 5 cases, mononeuritis in 1, central nervous system disorders in 3), pulmonary (alveolar haemorrhage in 2 cases, respiratory failure of unknown mechanism in 4) and pericardial (2 cases). Five patients had eosinophilia (more than 500 eosinophils/mm3). The elements that led to the correct diagnosis were the presence of vascular risk factors in all 10 patients (but hyperlipidaemia in only one), severe complications of the atheromatous disease in all cases, a precipitating or aggravating factor in 8 patients (anticoagulant therapy in 7, arteriography in 6) and the finding of purple or necrotic toes (6 cases). Histological (5 cases) and/or ophthalmological (2 cases) evidence was obtained in only 6 patients. Seven patients died 1 to 3 years after the onset of the disorders. Studies on low-density lipoprotein metabolism are in progress to determine the mechanism of clinical manifestations unexplainable by embolism. |
| Multiple inhibitory effects of garlic extracts on cholesterol biosynthesis in hepatocytes Gebhardt, R. (1993), Lipids 28(7): 613-9. Abstract: Exposure of primary rat hepatocytes and human HepG2 cells to water-soluble garlic extracts resulted in the concentration-dependent inhibition of cholesterol biosynthesis at several different enzymatic steps. At low concentrations, sterol biosynthesis from 14Cacetate was decreased in rat hepatocytes by 23% with an IC50 (half-maximal inhibition) value of 90 micrograms/mL and in HepG2 cells by 28% with an IC50 value of 35 micrograms/mL. This inhibition was exerted at the level of hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase) as indicated by direct enzymatic measurements and the absence of inhibition if 14Cmevalonate was used as a precursor. At high concentrations (above 0.5 mg/mL), inhibition of cholesterol biosynthesis was not only seen at an early step where it increased considerably with dose, but also at later steps resulting in the accumulation of the precursors lanosterol and 7-dehydrocholesterol. No desmosterol was formed which, however, was a major precursor accumulating in the presence of triparanol. Thus, the accumulation of sterol precursors seems to be of less therapeutic significance during consumption of garlic, because it requires concentrations one or two orders of magnitude above those affecting HMG-CoA reductase. Alliin, the main sulfur-containing compound of garlic, was without effect itself. If converted to allicin, it resulted in similar changes of the sterol pattern. This suggested that the latter compound might contribute to the inhibition at the late steps. In contrast, nicotinic acid and particularly adenosine caused moderate inhibition of HMG-CoA reductase activity and of cholesterol biosynthesis suggesting that these compounds participate, at least in part, in the early inhibition of sterol synthesis by garlic extracts. |
| Multiple intrahepatic cholesterol stones Sanabria, J. R., P. A. Clavien, et al. (1993), Can J Surg 36(3): 255-60. Abstract: The authors report a case of multiple intrahepatic cholesterol stones found in an asymptomatic patient who had undergone cholecystectomy 12 years before. Biochemical abnormalities and radiologic and pathologic findings are noted. The patient underwent liver resection with Roux-en-Y choledochojejunostomy and received ursodeoxycholic acid postoperatively. Recovery was uncomplicated, and the patient was well at 1-year follow-up. Intrahepatic cholesterol lithiasis is rare but can be diagnosed preoperatively. Treatment depends on the presence of complications and the distribution of the stones. |
| Multiple mechanisms mediate cholesterol-induced synaptogenesis in a CNS neuron Goritz, C., D. H. Mauch, et al. (2005), Mol Cell Neurosci 29(2): 190-201. Abstract: Neurons undergo a complex differentiation process that endows them with the ability to generate electrical signals and to transmit them via synaptic connections. There is increasing evidence that glial cells regulate specific aspects of neuronal differentiation including synapse formation, but the underlying mechanisms are not well understood. Here, we show how glia-derived cholesterol promotes the development of synapses in microcultures of highly purified retinal ganglion cells (RGCs) from postnatal rats. We identify dendrite differentiation as rate limiting step for glia-induced synaptogenesis and we show that this process requires cholesterol. Furthermore, we show that cholesterol enhances directly presynaptic differentiation and that it is essential for continuous synaptogenesis and for the stability of evoked transmitter release. These results reveal new roles of cholesterol in neuronal differentiation and underline the importance of neuron-glia interactions during brain development. |
| Multiple rare alleles contribute to low plasma levels of HDL cholesterol Cohen, J. C., R. S. Kiss, et al. (2004), Science 305(5685): 869-72. Abstract: Heritable variation in complex traits is generally considered to be conferred by common DNA sequence polymorphisms. We tested whether rare DNA sequence variants collectively contribute to variation in plasma levels of high density lipoprotein cholesterol (HDL-C). We sequenced three candidate genes (ABCA1, APOA1, and LCAT) that cause Mendelian forms of low HDL-C levels in individuals from a population-based study. Nonsynonymous sequence variants were significantly more common (16% versus 2%) in individuals with low HDL-C ( |
| Multiple roles of cholesterol in hedgehog protein biogenesis and signaling Beachy, P. A., M. K. Cooper, et al. (1997), Cold Spring Harb Symp Quant Biol 62: 191-204. |
| Multiple, independently regulated pathways of cholesterol transport across the intestinal epithelial cells Iqbal, J., K. Anwar, et al. (2003), J Biol Chem 278(34): 31610-20. Abstract: The present study provides a new understanding about the mechanisms involved in cholesterol absorption by the intestinal cells. Contrary to general belief, our data show that newly absorbed cholesterol is neither immediately available for secretion with apoB lipoproteins nor exclusively secreted as part of chylomicrons. Based on our data, cholesterol transport by enterocytes can be broadly classified into two independently modulated, apoB-dependent and -independent, pathways. Cholesterol secretion by the apoB-dependent pathway is induced by oleic acid, is repressed by microsomal triglyceride transfer protein inhibitors, and occurs only with larger apoB-containing lipoproteins. ApoB-independent pathways do not require microsomal triglyceride transfer protein and involve efflux mediated by ABCA1, high density lipoprotein assembly, and possibly other unknown mechanisms. There are at least two different metabolic pools of cholesterol. The newly absorbed and pre-absorbed cholesterol are preferentially secreted via apoB-independent and apoB-dependent pathways, respectively. In contrast to compartmentalization for secretion, these two metabolic pools are equally accessible for cellular esterification. The esterified cholesterol is mainly secreted by the apoB-dependent pathway, whereas both the pathways are involved in the secretion of free cholesterol. Thus, enterocytes transport exogenous cholesterol by several independently regulated pathways raising the possibility that targeting of apoB-independent pathways may result in selective inhibition of cholesterol transport without affecting triglyceride transport. |
| Multivariate analysis of cholesterol distribution for monitoring the risk of coronary heart disease Percy, D. F. and T. J. Hine (1993), Stat Med 12(10): 967-74. Abstract: The screening of people for potential coronary heart disease and the monitoring of subjects considered at risk have been performed for some time by measuring total serum cholesterol and its constituent lipoproteins. However, these measurements vary substantially within subjects, making such assessments imprecise. It has been suggested that greater consistency can be achieved by analysing the joint distribution of the individual lipoproteins or of transformed variables derived from them. In this paper we present the results of a laboratory experiment to investigate these ideas with a view to improving current methods of monitoring patients at risk. Nested, random-effects, multivariate analysis of variance and the log-ratio analysis of compositions are used to include information on all three lipoproteins simultaneously, and ratios of generalized variances are used to assess and compare the different response variables. The multivariate approach is seen to be far superior to the usual methods. Recommendations are made for routine monitoring and the practical implications are discussed. |