| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Extracorporeal LDL-cholesterol elimination in the treatment of severe familial hypercholesterolemia Blaha, M. (2003), Acta Medica (Hradec Kralove) 46(1): 3-7. Abstract: The extracorporeal elimination of LDL-cholesterol could be performed using the classic non-selective centrifuge or membrane plasmapheresis. The modern methods are more selective and effective. The atherogenic particules are removed from plasma by active colon or capsula. The methods include: cascade filtration, imunoadsorbtion, heparin-induced precipitation of LDL, thermofiltration, dextran-induced precipitation of LDL and direct adsorption of lipids (DALI). The regular LDL-apheresis is the life-saving technique in the treatment of homozygous familial hypercholesterolaemia. It is used in heterozygous familial hypercholesterolaemia when the patients do not respond to diet and drugs therapy, too. The regular LDL-apheresis treatment may be followed by the decreased frequency of angina pain episodes, the reduction of ECG changes during the bicycle ergometry and significant disappearance of tendinous xantomas. Some prospective randomised studies has shown even in this group of patients, resistant to conventional treatment, a significant regression of atherosclerotic changes. |
| Extracorporeal shock wave lithotripsy in symptomatic cholesterol gallbladder stone patients with a second generation electrohydraulic lithotripter (MPL-9000): experiences with 106 patients over 15 months Swobodnik, W., P. Janowitz, et al. (1992), J Stone Dis 4(3): 208-15. Abstract: One hundred and six patients were treated with a second generation underwater spark discharge lithotripter (Dornier MPL-9000). During the 15-month study period, Kaplan-Meier analysis predicted a stone clearance rate of 16.5% after 4 months, 37% (7 months), 71% (10 months), and 81% (15 months), respectively. Patients with multiple stones had a 5% probability to be free of stones after 13 months of treatment, when compared to 100% in patients with solitary stones smaller than 2 cm (p less than 0.001). Stones with densities below 100 Hounsfield units (HU) on computed tomography disappeared in 75% of the cases within 13 months. Rim calcified stones were cleared in 100% after 10 months of treatment. Fragmentation efficacy proved to be an essential predictive parameter for stone clearance: a fragment size below 5 mm after extracorporeal shock wave lithotripsy resulted in a 100% stone clearance within 13 months regardless of the initial stone number, size, and density. None of the stones fragmented to pieces of more than 10 mm in diameter could be dissolved within the observation period. Obviously, modern generation electrohydraulic lithotripters are effective in stone fragmentation, thus providing the basis for successful bile acid therapy provided the patients are properly selected. |
| Extraction of cholesterol with methyl-beta-cyclodextrin perturbs formation of clathrin-coated endocytic vesicles Rodal, S. K., G. Skretting, et al. (1999), Mol Biol Cell 10(4): 961-74. Abstract: The importance of cholesterol for endocytosis has been investigated in HEp-2 and other cell lines by using methyl-beta-cyclodextrin (MbetaCD) to selectively extract cholesterol from the plasma membrane. MbetaCD treatment strongly inhibited endocytosis of transferrin and EGF, whereas endocytosis of ricin was less affected. The inhibition of transferrin endocytosis was completely reversible. On removal of MbetaCD it was restored by continued incubation of the cells even in serum-free medium. The recovery in serum-free medium was inhibited by addition of lovastatin, which prevents cholesterol synthesis, but endocytosis recovered when a water-soluble form of cholesterol was added together with lovastatin. Electron microscopical studies of MbetaCD-treated HEp-2 cells revealed that typical invaginated caveolae were no longer present. Moreover, the invagination of clathrin-coated pits was strongly inhibited, resulting in accumulation of shallow coated pits. Quantitative immunogold labeling showed that transferrin receptors were concentrated in coated pits to the same degree (approximately sevenfold) after MbetaCD treatment as in control cells. Our results therefore indicate that although clathrin-independent (and caveolae-independent) endocytosis still operates after removal of cholesterol, cholesterol is essential for the formation of clathrin-coated endocytic vesicles. |
| Extraction of excessive malonic dialdehyde and cholesterol from erythrocytes using natural latex Bankova, V. V., I. D. Khodzhaeva, et al. (1992), Gematol Transfuziol 37(4): 37-9. |
| Extravascular circulation of lipoproteins: their role in reverse transport of cholesterol Reichl, D. (1994), Atherosclerosis 105(2): 117-29. Abstract: The transfer of lipoproteins out of plasma into peripheral tissues, their flow through the interstitium and their return to blood has been reviewed. In this context special emphasis has been given to reports dealing with the movement of lipoproteins into and out of the wall of arteries. |
| Extreme decrease of serum total cholesterol and other lipid levels in elderly inpatients Saito, N., Y. Doi, et al. (1998), Nippon Ronen Igakkai Zasshi 35(5): 389-95. Abstract: In this study 112 elderly inpatients (55 men, 57 women) were recruited. 1. Twelve elderly inpatients (5 men, 7 women) aged 82.5 +/- 7.4 years (M +/- SD) were investigated during 3 periods of dietary intake: good intake (period I), tube nutrition (period II) and fasting with intravenous fluid infusion (period III). Calorie, protein, carbohydrate, fat and cholesterol intakes were greater in period I than in periods II and III. Serum total and LDL cholesterols were lowest in period III, when serum HDL cholesterol, triglyceride and total protein were lower in period III than in period I. 2. One hundred elderly inpatients (50 men, 50 women) were divided into 4 groups according to type of decreased serum lipid and a control group. Serum total cholesterol only was decreased in group I, both serum total and HDL cholesterols were decreased in group II, both serum total cholesterol and triglyceride were decreased in group III, all 3 lipids were decreased in group IV and lipid levels did not change in the control group. There were 5 patients in group I, 28 patients in group II, 20 patients in group III, 27 patients in group IV and 20 patients in the control group. The patient's age ranged from 80.3 to 88.4 years and body mass index ranged from 14.7 to 18.4 kg/m2. Serum total protein decreased significantly in groups II-IV, to 5.6 to 5.7 g/dl. Serum total protein, and total cholesterol correlated positively (r = 0.525, p < 0.01), as did Calorie ingestion and serum total cholesterol levels (r = 0.554, p < 0.001). Therefore, severe hypocholesterolemia was accompanied by malnutrition and a decrease in Calorie or cholesterol intake. Serum total cholesterol levels during observation decreased most in group IV, followed by group II similar to serum HDL cholesterol levels. The amount of nutrient intake was smallest in group IV resulting in an extreme lowering of all 3 serum lipid levels. |
| Extrusion and boiling improve rat body weight gain and plasma cholesterol lowering ability of peas and chickpeas Wang, Y. H. and G. H. McIntosh (1996), J Nutr 126(12): 3054-62. Abstract: This study investigated the effect of feeding peas (Pisum sativum) and chickpeas (Cicer arietinum) processed by boiling or extrusion on growth performance, plasma cholesterol concentrations and organ weights of rats. Casein was used as the protein source in the control diets. Complementarity of wheat and legumes on protein quality was also evaluated. Boiled or extruded legumes significantly increased body weight gain (BWG) of rats but not protein efficiency ratio (PER) when compared with raw legumes. Rats fed processed chickpeas and those fed casein had similar BWG, and both groups had greater BWG than rats fed peas. Extruded wheat combined with peas or chickpeas increased sulfur amino acid (SAA) levels in the diets and significantly improved BWG and PER of rats compared with those fed sucrose as an energy source. There was a linear correlation between the SAA to dietary protein ratio and BWG of rats (r = 0.902, P < 0.014), indicating that SAA are the limiting amino acids in legumes. Plasma cholesterol concentrations were lower in rats fed legumes than in those fed casein. Cholesterol-lowering ability was affected by processing method, with extrusion being most effective for peas; boiling and extrusion were equally effective for chickpeas. Raw legume feeding resulted in greater pancreatic and small intestine weight relative to body weight. Chickpea fed rats had lower spleen, thymus and liver relative weights and higher cecum and colon relative weights than rats fed casein. There were no differences in growth, PER, organ relative weight or plasma cholesterol concentration between rats fed extruded legumes and those fed boiled legumes, suggesting that extrusion improves nutritional value of these legumes to the same extent as the traditional boiling method. |
| Ezetimib. A new cholesterol absorption inhibitor Heinzl, S. (2002), Med Monatsschr Pharm 25(7): 229-32. |
| Ezetimibe and cholesterol absorption Lavoie, M. A. (2003), Can J Clin Pharmacol 10 Suppl A: 7A-12A. Abstract: Cholesterol, an important biological lipid and excessive dietary intake, is associated with hypercholesterolemia, a prevalent cardiovascular risk factor. Because cholesterol is essentially a water insoluble molecule, its transport within and absorption from the aqueous medium of the intestine is rather complex. This takes place in a series of orderly and interrelated steps, including emulsification, hydrolysis by specific pancreatic esterases, micellar transport, mucosal absorption, resynthesis in enterocytes and assembly with apolipoproteins to form chylomicrons. Many of these processes are not well characterized at the molecular level. Besides being generally inefficient, cholesterol absorption is highly variable with a between-subject variability that depends in part on genetic factors and an intraindividual variability, which may be modulated by physiological and dietary conditions. All of the sequential steps in intestinal cholesterol absorption can be interfered with by dietary components or drugs and therefore are potential therapeutic targets for rendering cholesterol absorption even more inefficient in an attempt to lower cholesterol levels. |
| Ezetimibe and other azetidinone cholesterol absorption inhibitors Clader, J. W. (2005), Curr Top Med Chem 5(3): 243-56. Abstract: Atherosclerotic coronary artery disease remains a major healthcare concern especially in developed countries. While lowering plasma cholesterol levels via diet, exercise, and pharmacotherapy can reduce this risk of developing coronary artery disease, there remains a need for more effective drug therapies. The azetidinone cholesterol absorption inhibitors typified by ezetimibe represent the first new approach to lipid lowering therapy in more than a decade. This review summarizes the medicinal chemistry of the azetidinone cholesterol absorption inhibitors as a class, with emphasis on factors that contributed both to the discovery of ezetimibe as well as to our overall understanding of S.A.R. trends in this area. |
| Ezetimibe potently inhibits cholesterol absorption but does not affect acute hepatic or intestinal cholesterol synthesis in rats van Heek, M., C. Farley, et al. (2003), Br J Pharmacol 138(8): 1459-64. Abstract: 1. Ezetimibe (1-(4-fluorophenyl)-(3R)-3-(4-fluorophenyl)-(3S)-hydroxypropyl-(4S)-(4-h ydroxyphenyl)-2-azetidinone) and its analog SCH48461 are potent and selective cholesterol absorption inhibitors that inhibit the transport of cholesterol across the intestinal wall, thereby lowering plasma cholesterol. 2. After a dose response for ezetimibe in rats was established, experiments were conducted to determine whether acute administration could alter hepatic or intestinal cholesterol synthesis. To determine whether this class of intestinal cholesterol absorption inhibitors could discriminate between newly synthesized cholesterol in the intestine versus exogenously administered cholesterol, rats were intraduodenally dosed with (14)C-cholesterol and (3)H-mevalonate, and mesenteric lymph was analyzed for radiolabeled cholesterol and cholesteryl ester content. 3. Ezetimibe attenuated diet-induced hypercholesterolemia 60-94% at doses of 0.1-3 mg x kg(-1) in rats. A single administration of ezetimibe did not have a direct effect on intestinal or hepatic cholesterol synthesis, while ketoconazole significantly inhibited cholesterol synthesis after a single dose. The ezetimibe analog, SCH48461, inhibited the movement of exogenously administered cholesterol into lymph, but did not affect the appearance of newly synthesized cholesterol into lymph. 4. These data suggest that this class of cholesterol absorption inhibitors does discriminate by blocking the movement of exogenous cholesterol in the enterocyte before it reaches the intracellular cholesterol pool to be incorporated into intestinal lipoproteins, without affecting the incorporation of newly synthesized cholesterol into intestinal lipoproteins. |
| Ezetimibe selectively inhibits intestinal cholesterol absorption in rodents in the presence and absence of exocrine pancreatic function van Heek, M., C. Farley, et al. (2001), Br J Pharmacol 134(2): 409-17. Abstract: 1. Ezetimibe potently inhibits the transport of cholesterol across the intestinal wall, thereby reducing plasma cholesterol in preclinical animal models of hypercholesterolemia. The effect of ezetimibe on known absorptive processes was determined in the present studies. 2. Experiments were conducted in the hamster and/or rat to determine whether ezetimibe would affect the absorption of molecules other than free cholesterol, namely cholesteryl ester, triglyceride, ethinylestradiol, progesterone, vitamins A and D, and taurocholic acid. In addition, to determine whether exocrine pancreatic function is involved in the mechanism of action of ezetimibe, a biliary anastomosis model, which eliminates exocrine pancreatic function from the intestine while maintaining bile flow, was established in the rat. 3. Ezetimibe reduced plasma cholesterol and hepatic cholesterol accumulation in cholesterol-fed hamsters with an ED(50) of 0.04 mg kg(-1). Utilizing cholesteryl esters labelled on either the cholesterol or the fatty acid moiety, we demonstrated that ezetimibe did not affect cholesteryl ester hydrolysis and the absorption of fatty acid thus generated in both hamsters and rats. The free cholesterol from this hydrolysis, however, was not absorbed (92 - 96% inhibition) in the presence of ezetimibe. Eliminating pancreatic function in rats abolished hydrolysis of cholesteryl esters, but did not affect the ability of ezetimibe to block absorption of free cholesterol (-94%). Ezetimibe did not affect the absorption of triglyceride, ethinylestradiol, progesterone, vitamins A and D, and taurocholic acid in rats. 4. Ezetimibe is a potent inhibitor of intestinal free cholesterol absorption that does not require exocrine pancreatic function for activity. Ezetimibe does not affect the absorption of triglyceride as a pancreatic lipase inhibitor (Orlistat) would, nor does it affect the absorption of vitamin A, D or taurocholate, as a bile acid sequestrant (cholestyramine) would. |
| Ezetimibe, a potent cholesterol absorption inhibitor, inhibits the development of atherosclerosis in ApoE knockout mice Davis, H. R., Jr., D. S. Compton, et al. (2001), Arterioscler Thromb Vasc Biol 21(12): 2032-8. Abstract: Ezetimibe (SCH58235) is a potent, selective, cholesterol absorption inhibitor. The objective of this study was to determine whether ezetimibe reduces plasma cholesterol and inhibits atherogenesis in apolipoprotein E knockout (apoE-/-) mice. Cholesterol absorption was inhibited by >90% at doses of ezetimibe >3 mg/kg in apoE-/- mice. Atherosclerosis and lipoprotein changes were determined in apoE-/- mice fed a high-fat (0.15% cholesterol) "western" diet, a low-fat (0.15% cholesterol) diet, or a semisynthetic cholesterol-free diet with or without ezetimibe (5 mg/kg per day) for 6 months. Ezetimibe reduced plasma cholesterol levels from 964 to 374 mg/dL, from 726 to 231 mg/dL, and from 516 to 178 mg/dL in the western, low-fat, and cholesterol-free diet groups, respectively. The reductions occurred in the very low density and low density lipoprotein fractions, whereas high density lipoprotein cholesterol levels were increased by ezetimibe treatment. Ezetimibe reduced aortic atherosclerotic lesion surface area from 20.2% to 4.1% in the western diet group and from 24.1% to 7.0% in the low-fat cholesterol diet group. Ezetimibe reduced carotid artery atherosclerotic lesion cross-sectional area by 97% in the western and low-fat cholesterol groups and by 91% in the cholesterol-free group. Ezetimibe inhibits cholesterol absorption, reduces plasma cholesterol, increases high density lipoprotein levels, and inhibits the progression of atherosclerosis under western, low-fat, and cholesterol-free dietary conditions in apoE-/- mice. Although apoE-/- mice are more hypercholesterolemic than are humans and low density lipoprotein reductions with ezetimibe are not as pronounced clinically, ezetimibe may inhibit atherogenesis in individuals consuming restricted-fat or western diets. |
| Ezetimibe, a potent cholesterol absorption inhibitor, normalizes combined dyslipidemia in obese hyperinsulinemic hamsters van Heek, M., T. M. Austin, et al. (2001), Diabetes 50(6): 1330-5. Abstract: Ezetimibe potently and selectively inhibits cholesterol absorption in the intestine, thereby reducing plasma cholesterol in preclinical models of hypercholesterolemia. Clinical trials have demonstrated that ezetimibe lowers LDL cholesterol and raises HDL cholesterol in humans. The effect of ezetimibe on other dyslipidemias, particularly hypertriglyceridemia, is not yet known. In the present studies, we assessed the effect of ezetimibe on combined hypercholesterolemia and hypertriglyceridemia in obese hyperinsulinemic hamsters. Hamsters were fed chow, chow with cholesterol (0.12%), or the same cholesterol diet containing different dietary triglycerides (15%) in the absence or presence of 1 mg/kg ezetimibe (in diet) for up to 84 days. Body weight, serum insulin, leptin, glucose, cholesterol, and triglyceride levels were analyzed. Cholesterol and triglyceride levels were also determined in VLDL+IDL, LDL, and HDL. Hamsters maintained on high-fat diets became obese, hyperinsulinemic, hyperleptinemic, hypercholesterolemic, and hypertriglyceridemic. Ezetimibe did not affect body weight, insulin, or leptin, but ablated the combined hypercholesterolemia and hypertriglyceridemia induced by high-fat diets. Ezetimibe normalized VLDL+IDL cholesterol and triglyceride and significantly decreased LDL cholesterol to below chow-fed levels. The ratio of HDL to LDL cholesterol increased significantly with the addition of ezetimibe. Ezetimibe completely eliminated the accumulation of cholesteryl ester and free cholesterol in liver that was induced under the various dietary conditions in the absence of drug. In conclusion, ezetimibe is very effective in correcting the combined dyslipidemia in diet-induced obese hyperinsulinemic hamsters and may be an effective therapy for ameliorating combined dyslipidemia in obese insulin-resistant and/or type 2 diabetic humans. |
| Ezetimibe: a novel cholesterol-lowering agent that highlights novel physiologic pathways Patel, S. B. (2004), Curr Cardiol Rep 6(6): 439-42. Abstract: Ezetimibe is a US Food and Drug Administration-approved novel drug that targets the absorption of cholesterol in the intestine. The identification of this drug has also led to the elucidation of the dietary cholesterol receptor. Ezetimibe is efficacious as a plasma cholesterol-lowering agent as monotherapy, but its greatest utility seems to be as a combination with a low-dose statin, where it results in cholesterol lowering that is equivalent to using maximum-dose statins. It has a very favorable side-effect profile, as well as a lack of drug-drug interactions. In addition, it prevents the absorption of noncholesterol sterols, such as plant sterols. In clinical studies, it has been shown to be highly efficacious in lowering plant sterols in a rare genetic disorder, sitosterolemia. Both the disease, as well as this therapeutic agent, have led to the concept that ezetimibe may be also useful in dissecting the role of these noncholesterol sterols in the pathogenesis of atherosclerosis. |
| Fabrication, characterization and in vitro release of paclitaxel (Taxol) loaded poly (lactic-co-glycolic acid) microspheres prepared by spray drying technique with lipid/cholesterol emulsifiers Mu, L. and S. S. Feng (2001), J Control Release 76(3): 239-54. Abstract: Spray dry technique was applied to produce paclitaxel loaded microspheres of biodegradable poly (lactic-co-glycolic acid) (PLGA) as an alternative delivery system. Various emulsifiers such as L-alpha-dipalmitoyl-phosphatidylcholine (DPPC), cholesterol, polyvinyl alcohol (PVA), gelatin were incorporated in order to achieve high encapsulating efficiency of paclitaxel in the microspheres and desired properties for a sustained release. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) showed that the surface of the microspheres with high ratio of lipid was spherical and smooth. Those made with other emulsifiers had rougher surface with pores. Incorporation of lipid, cholesterol or gelatin can significantly increase the drug content in the microspheres. The differential scanning calorimetry (DSC) result indicated that the paclitaxel trapped in the microspheres existed in an amorphous or disordered-crystalline status in the polymer matrix. The zeta potential of the microspheres was negative in general and was strongly influenced by the type of the emulsifiers used in fabrication. The system formulated with cholesterol was most stable. The release profiles of various formulations with PVA, gelatin as well as low ratio of DPPC showed almost zero-order release kinetics in the first 3 weeks after an initial burst less than 5% in the first day. The release rate then gradually decreased. The microspheres fabricated with high ratio of DPPC exhibited large initial burst. When cholesterol was combined together with DPPC as an emulsifier, the release became faster. |
| Facile synthesis, aggregation behavior, and cholesterol solubilization ability of avicholic acid Mukhopadhyay, S. and U. Maitra (2004), Org Lett 6(1): 31-4. Abstract: reaction: see text Avicholic acid, a major constituent of the bile of several avian species, was synthesized in eight steps from readily available chenodeoxycholic acid in 9% overall yield using Breslow's remote functionalization strategy in a key step. Micelle formation and equilibrium cholesterol solubilization properties were studied for avicholate in aqueous solution. |
| Factor VII activation, apolipoprotein A-I and reverse cholesterol transport: possible relevance for postprandial lipaemia Miller, G. J., C. J. Cooke, et al. (2002), Thromb Haemost 87(3): 477-82. Abstract: Postprandial lipaemia is associated with activation of factor VII (FVII) and efflux of cholesterol from tissues to nascent plasma high density lipoproteins (HDL) containing apolipoprotein A-I (apo A-I). To determine whether FVII activation and cholesterol efflux occur together in other situations, the responses to intravenous infusion of HDL-like apo A-I/phosphatidylcholine discs were measured in 10 healthy men. Disc infusion (40 mg apo A-I/kg body weight) over 4 h was followed by increases in HDL cholesteryl ester and plasma apo A-I (p <0.0001). Significant activation of FVII was apparent during infusion in fasting subjects (p = 0.03), activated FVII averaging 123% of baseline value by 12 h (p <0.0001). Plasma thrombin-antithrombin (TAT) complex increased to 156% of baseline level by 12 h (p >0.05) but individual responses differed considerably. Peak TAT post-infusion was associated inversely with peak HDL triglyceride concentration (p = 0.004). The coagulation responses to disc-infusion may be due to transfer of phosphatidylserine to cell surfaces during cholesterol efflux. |
| Factor VII coagulant activity and cholesterol changes in premenopausal women consuming a long-term cholesterol-lowering diet Brace, L. D., C. Gittler-Buffa, et al. (1994), Arterioscler Thromb 14(8): 1284-9. Abstract: We periodically obtained blood samples from mildly hypercholesterolemic, but otherwise healthy, premenopausal women who were recruited to participate in a study of a long-term, cholesterol-lowering diet. All meals were prepared and most meals were consumed in the study center dining facility. Tests performed on blood samples included fibrinogen, cholesterol, factor VII coagulant activity (VIIc), and other measures of factor VII. We found that when women switched from a typical American diet (37% fat, polyunsaturated fatty acid to saturated fatty acid P/S ratio 0.5, 300 mg cholesterol/d) to a diet lower in fat and cholesterol (American Heart Association phase 2 diet: 30% fat, P/S ratio of 1, 150 to 200 mg cholesterol/d) and maintained that diet for 20 weeks, their plasma cholesterol levels decreased by approximately 6% after 4 weeks and remained at that level until study termination. Likewise, VIIc decreased by approximately 11% while factor VII antigen, total factor VII activity, and fibrinogen concentration did not change appreciably from baseline values. Our results show that premenopausal women benefit from a diet lower in total and saturated fat by a reduction in blood cholesterol and VIIc. Extrapolation from data on men in the Northwick Park Heart Study indicates that the 11% decrease in VIIc activity would correspond to an approximately 30% decrease in risk of mortality from coronary heart disease. |
| Factor VII, cholesterol, and triglycerides. The CARDIA Study. Coronary Artery Risk Development in Young Adults Study Green, D., M. A. Chamberlain, et al. (1997), Arterioscler Thromb Vasc Biol 17(1): 51-5. Abstract: Cross-sectional studies have shown that factor VII coagulant activity (VIIc) is positively associated with plasma total cholesterol (TC), LDL cholesterol, and triglycerides (TG) as well as body mass index (BMI) and diastolic blood pressure. To determine whether changes in VIIc parallel changes in coronary risk factors over a period of 2 years, we examined data from 1514 participants in the Coronary Artery Risk Development in Young Adults Study (CARDIA), an ongoing investigation of lifestyles and evolution of cardiovascular risk factors. Subjects were 23 to 35 years old at the year 5 examination. Cross-sectional analyses at these examinations showed that VIIc was positively correlated (P <.001) with TC and TG in all race/sex groups except for TC in black women at the year 5 examination. Changes in VIIc over the 2-year period were correlated positively with changes in TC in all except black men and TG in all groups; the association of VIIc change with change in TC and TG was reduced only slightly with adjustment for age and BMI at year 5 and 2-year change in BMI. To determine whether the higher levels of VIIc in subjects with higher lipid values were due to activation of the factor or to an increase in the concentration of the factor VII clotting protein, we measured factor VII antigen (VIIag) in a randomly selected subsample of 223 subjects at the year 7 examination. In all sex/race groups, VIIag correlated with VIIc (r =.69 to 0.81). After adjustment for sex and race, the partial correlation coefficient between TG and VIIc was.28 (P =.0001); between TG and VIIag.35 (P =.0001); between TC and VIIc.39 (P =.0001); and between TC and VIIag, 0.43 (P =.0001). No associations were observed between lipid levels and the ratio of VIIc to VIIag. We conclude that the raised VIIc with higher lipid levels occurs in blacks as well as whites, in men and women, persists over time, and represents a true increase in the plasma concentration of this clotting factor. |