Publications
429 results found
Naoumova RP, Watts GF, Kim KD, et al., 1998, Cholesterol synthesis is increased in combined hyperlipidaemia, ATHEROSCLEROSIS, Vol: 138, Pages: S6-S6, ISSN: 0021-9150
Riches FM, Watts GF, Naoumova RP, et al., 1998, Hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 studied with a stable isotope technique in men with visceral obesity, INTERNATIONAL JOURNAL OF OBESITY, Vol: 22, Pages: 414-423, ISSN: 0307-0565
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- Citations: 105
Thompson GR, Naoumova RP, 1998, New prospects for lipid-lowering drugs., Expert Opin Investig Drugs, Vol: 7, Pages: 715-727
The advent of 3-hydroxy-methylglutaryl Co-enzyme A (HMG-CoA) reductase inhibitors has dramatically improved the treatment of dyslipidaemia and the prevention of atherosclerosis over the past 10 years. Similar but less marked benefit had previously been demonstrated for fibrates and bile acid sequestrants, which were first introduced over 30 years ago and are still in use. The discovery that fibrates are ligands for peroxisome proliferator activated receptors (PPARs) may lead to innovations in the future. However, most of the compounds now undergoing clinical trials are either HMG-CoA reductase inhibitors or bile acid sequestrants, which is indicative of the current emphasis on lowering low density lipoprotein (LDL) cholesterol. Drugs in an earlier stage of development include inhibitors of squalene synthase, which have yet to fulfil their initial promise, and of acylcholesterolacyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP). Most of the earlier ACAT inhibitors were poorly absorbed, but compounds with better bioavailability hold considerable promise by virtue of their ability to inhibit ACAT in liver and arterial wall macrophages. MTP inhibitors have the potential to drastically reduce apolipoprotein B (apoB) secretion, but safety issues could negate this advantage. Thus, despite the impact of statins, the development of new lipid-modulating drugs continues to be a dynamic field of research.
Fruchart JC, Brewer HB, Leitersdorf E, 1998, Consensus for the use of fibrates in the treatment of dyslipoproteinemia and coronary heart disease. Fibrate Consensus Group., Am J Cardiol, Vol: 81, Pages: 912-917, ISSN: 0002-9149
The hypolipidemic action of fibrates has recently been shown to involve the activation of peroxisome proliferator activated receptors establishing a molecular mechanism for this class of drugs. Increasing clinical trial evidence supports the efficacy of fibrates in the treatment of dyslipoproteinemias, particularly in patients with hypertriglyceridemia and low high-density lipoproteins.
Thompson GR, 1998, Serum cytokines and cardiovascular risk factors, HEART, Vol: 79, Pages: 422-422, ISSN: 1355-6037
Forbat SM, Naoumova RP, Sidhu PS, et al., 1998, The effect of cholesterol reduction with fluvastatin on aortic compliance, coronary calcification and carotid intimal-medial thickness: a pilot study., J Cardiovasc Risk, Vol: 5, Pages: 1-10, ISSN: 1350-6277
BACKGROUND: Regression of atheroma with reduction of cholesterol levels is recognized to occur, but less is known about reversal of sclerosis. Non-invasive indices of sclerosis have largely been based on carotid ultrasound measurements. OBJECTIVE: To measure aortic compliance, coronary calcification and carotid intimal-medial thickness during reduction of cholesterol level in patients with and without coronary artery disease. METHODS: We studied 64 hypercholesterolaemic patients, 24 with and 40 without coronary artery disease. All were administered fluvastatin for 1 year. Aortic compliance was assessed using magnetic resonance and coronary calcification score was determined by electron beam computed tomography. Carotid intimal-medial thickness in 34 patients was measured by carotid ultrasound means. RESULTS: There was a rise in high-density lipoprotein cholesterol level and falls in total cholesterol level, low-density lipoprotein cholesterol level, low: high-density lipoprotein ratio, triglyceride level and very-low-density lipoprotein cholesterol level. Coronary artery disease patients had a higher coronary calcification score (442 +/- 551) than did other patients (269 +/- 724, P = 0.0002). For both groups there was a small rise in coronary calcification score during the study. Mean aortic compliance rose and blood pressure and carotid intimal-medial thickness fell. Analysis revealed significant correlations between change in mean aortic compliance and changes in high-density lipoprotein level (r = 0.3, P = 0.036), very-low-density lipoprotein level (r = -0.31, P = 0.038) and low: high-density lipoprotein ratio (r = -0.35, P = 0.014). There was no significant difference in these changes between the two patient groups. CONCLUSION: An improvement in aortic compliance over 1 year indicates that increase in high-density lipoprotein level, decrease in very-low-density lipoprotein level and improvement in low: high-density lipoprotein ratio caused by administration of f
Thompson GR, 1998, The clinical case for triglyceride-rich lipoproteins, 11th International Symposium on Atherosclerosis, Publisher: ELSEVIER SCIENCE BV, Pages: 599-603, ISSN: 0531-5131
Thompson GR, 1998, To treat or not to treat dyslipidemia in the asymptomatic elderly, Satellite Symposium on Vascular Disease in the Elderly of the 1997 World Congress in Gerontology, Publisher: PARTHENON PUBLISHING GROUP LTD, Pages: 105-115
Betteridge J, Shepherd J, Thompson G, 1997, Use of statins. Sheffield tables have shortcomings., BMJ, Vol: 315, ISSN: 0959-8138
Thompson GR, 1997, Indian gas of the power of the world, British Medical Journal, Vol: 314, ISSN: 0959-8146
Watts GR, Naoumova RP, Kelly JM, et al., 1997, Inhibition of cholesterogenesis decreases hepatic secretion of apoB-100 in normolipidemic subjects, American Journal of Physiology, Vol: 273, ISSN: 0002-9513
We examined the effect of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on the kinetics of very low-density lipoprotein apolipoprotein B-100 (VLDL apoB) in 13 normolipidemic men in a placebo-controlled crossover study. Simvastatin significantly decreased the plasma concentrations of low-density lipoprotein (LDL) cholesterol by 36%, triglycérides by 26%, mevalonic acid by 34%, and lathosterol by 32%. Hepatic secretion of VLDL apoB was measured using a primed constant intravenous infusion of [l-13C]leucine with monitoring of isotopic enrichment of apoB by gas chromatography-mass spectrometry; fractional turnover rate was derived using a monoexponential function. Simvastatin decreased VLDL apoB pool size by 53% and the hepatic secretion rate of VLDL apoB by 46% but did not significantly alter its fractional catabolism. The change in hepatic VLDL apoB secretion was significantly and independently correlated with changes in plasma mevalonic acid and lathosterol concentrations and the lathosterol-tocholesterol ratio. The data support the hypothesis that the rate of de novo cholesterol synthesis directly regulates the hepatic secretion of VLDL apoB in normal subjects. Copyright ©1997 the American Physiological Society.
Pfohl M, Naoumova RP, Neuwirth C, et al., 1997, Upregulation of cholesterol synthesis after acute reduction of low density lipoprotein by apheresis in normocholesterolaemic subjects: evidence for a threshold effect, ATHEROSCLEROSIS, Vol: 135, Pages: 257-262, ISSN: 0021-9150
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- Citations: 10
Naoumova RP, Pegoraro RJ, Naidu P, et al., 1997, HMG-CoA reductase is not the site of the genetic defect in phytosterolaemia in South Africa., ATHEROSCLEROSIS, Vol: 135, Pages: 23-23, ISSN: 0021-9150
Riches FM, Watts GF, Naoumova RP, et al., 1997, Direct association between the hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 and plasma mevalonic acid and lathosterol concentrations in man, ATHEROSCLEROSIS, Vol: 135, Pages: 83-91, ISSN: 0021-9150
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- Citations: 15
Marais AD, Naoumova RP, Firth JC, et al., 1997, Decreased production of low density lipoprotein by atorvastatin after apheresis in homozygous familial hypercholesterolemia, JOURNAL OF LIPID RESEARCH, Vol: 38, Pages: 2071-2078, ISSN: 0022-2275
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- Citations: 95
Riches FM, Watts GF, Naoumova RP, et al., 1997, Direct association between the hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 and plasma mevalonic acid and lathosterol concentrations in normolipidaemic subjects, ATHEROSCLEROSIS, Vol: 134, Pages: 354-354, ISSN: 0021-9150
Watts GF, Naoumova RP, Kelly JM, et al., 1997, Inhibition of cholesterogenesis decreases hepatic secretion of apolipoprotein B-100 in normolipidaemic subjects, ATHEROSCLEROSIS, Vol: 134, Pages: 356-356, ISSN: 0021-9150
Riches FM, Watts GF, Naoumova RP, et al., 1997, Visceral obesity is associated with hepatic oversecretion of very-low-density lipoprotein apolipoprotein B-100, ATHEROSCLEROSIS, Vol: 134, Pages: 354-354, ISSN: 0021-9150
Naoumova RP, Dunn S, Rallidis L, et al., 1997, Prolonged inhibition of cholesterol synthesis explains the efficacy of atorvastatin, ATHEROSCLEROSIS, Vol: 134, Pages: 130-130, ISSN: 0021-9150
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- Citations: 1
Watts GF, Naoumova RP, Kelly JM, et al., 1997, Inhibition of cholesterogenesis decreases hepatic secretion of apoB-100 in normolipidemic subjects, AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, Vol: 273, Pages: E462-E470, ISSN: 0193-1849
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- Citations: 43
Vos J, de Feyter PJ, Kingma JH, et al., 1997, Evolution of coronary atherosclerosis in patients with mild coronary artery disease studied by serial quantitative coronary angiography at 2 and 4 years follow-up. The Multicenter Anti-Atheroma Study (MAAS) Investigators., Eur Heart J, Vol: 18, Pages: 1081-1089, ISSN: 0195-668X
AIMS: Angiographic studies on the natural course of both focal and diffuse coronary atherosclerosis have not been performed before, but can both be assessed by quantitative coronary angiography. The objective of this study was to describe the natural course of focal and diffuse coronary atherosclerosis over time. METHODS AND RESULTS: In 129 patients with mild coronary artery disease, but not on lipid-lowering medication, three coronary angiograms were made each 2 years apart. Nine hundred and sixty five angiographically diseased and non-diseased segments were analysed by quantitative coronary angiography. Mean lumen diameter and minimal lumen diameter were used as measures of diffuse and focal coronary atherosclerosis. Mean lumen diameter and minimum lumen diameter decreased by 0.02 and 0.03 mm per year. The rate of progression was similar in the angiographically non-diseased, as in the mildly and moderately diseased segments. Progression of diffuse coronary atherosclerosis was largest in severely stenosed lesions (percentage diameter stenosis > or = 50%) and in the right coronary artery with a loss of 0.19 mm and 0.16 mm in mean lumen diameter. Progression of focal disease was most prominent in new and mild lesions and the right coronary artery, with a decrease in minimum lumen diameter of 0.34 mm and 0.22 mm. In most subgroups, progression occurred gradually over time. On a per segment level, progression and the occurrence of new lesions occurred in 4.4% and 4.2%. Regression and disappearance of a lesions was found in 2.3% and 1.9%. On a per patient level, 36% were progressors, 12% had a mixed response, 36% were stable, and 16% were regressors. CONCLUSION: Diffuse and focal coronary atherosclerosis progressed at the same rate in the first and second 2 years in stenosed and non-stenosed segments. The rate of coronary atherosclerosis progression was small, but was higher for focal than for diffuse disease. A minority of lesions progressed and spontaneous regressi
Naoumova RP, Dunn S, Rallidis L, et al., 1997, Prolonged inhibition of cholesterol synthesis explains the efficacy of atorvastatin, JOURNAL OF LIPID RESEARCH, Vol: 38, Pages: 1496-1500, ISSN: 0022-2275
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- Citations: 70
Kitano Y, Thompson GR, 1997, The familial hypercholesterolemia regression study: a randomized comparison of therapeutic reduction of both low-density lipoprotein and lipoprotein(a) versus low-density lipoprotein alone., Ther Apher, Vol: 1, Pages: 187-190, ISSN: 1091-6660
Lipoprotein (a) [Lp (a)] is a risk factor for coronary heart disease (CHD), especially in the presence of a raised low-density lipoprotein (LDL)-cholesterol (LDL-C). To ascertain whether reduction of both LDL and Lp(a) is more advantageous than reduction of LDL alone, patients with heterozygous FH and CHD were selected randomly to receive either LDL apheresis fortnightly plus simvastatin 40 mg/day or colestipol 20 g plus simvastatin 40 mg/day. Quantitative coronary angiography was undertaken before and after 2.1 years. Changes in serum lipids were similar in both groups except for the greater reduction of LDL-C and Lp(a) by apheresis. There were no significant differences in primary angiographic endpoints, and none of the angiographic changes correlated with Lp(a). Although LDL apheresis plus simvastatin was more effective than colestipol plus simvastatin in reducing LDL-C and Lp(a), it was not more beneficial in influencing coronary atherosclerosis. Decreasing Lp(a) seems unnecessary if LDL-C is reduced below 130 mg/dl.
Thompson GR, 1997, What targets should lipid-modulating therapy achieve to optimise the prevention of coronary heart disease?, ATHEROSCLEROSIS, Vol: 131, Pages: 1-5, ISSN: 0021-9150
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- Citations: 46
Thompson GR, 1997, Grand rounds--Hammersmith Hospital. Hazards of running a marathon., BMJ, Vol: 314, Pages: 1023-1025, ISSN: 0959-8138
Thompson GR, Scott J, Walport MJ, et al., 1997, Grand rounds - Hammersmith Hospital - Hazards of running a marathon - Creatine kinase MB can be raised without myocardial infarction, BRITISH MEDICAL JOURNAL, Vol: 314, Pages: 1023-1025, ISSN: 0959-8138
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- Citations: 10
Sidhu P, Forbat S, Naoumova R, et al., 1997, Assessment of lipid-lowering therapy by noninvasive cardiovascular imaging, ATHEROSCLEROSIS, Vol: 128, Pages: 15-15, ISSN: 0021-9150
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- Citations: 1
Naoumova RP, Kim KD, Neuwirth C, et al., 1997, Hypertriglyceridaemia is associated with increased cholesterol synthesis, ATHEROSCLEROSIS, Vol: 128, Pages: 19-19, ISSN: 0021-9150
Thompson GR, Kitano Y, 1997, The role of low density lipoprotein apheresis in the treatment of familial hypercholesterolemia., Ther Apher, Vol: 1, Pages: 13-16, ISSN: 1091-6660
The chief indication for low density lipoprotein (LDL) apheresis is the treatment of homozygous familial hypercholesterolemia (FH), a potentially fatal condition that responds poorly to conventional therapy. Dextran sulfate/cellulose adsorption columns (Kaneka) and on-line heparin precipitation (HELP) are the most popular systems used in LDL apheresis. Weekly or biweekly procedures plus concomitant drug therapy enable LDL cholesterol to be maintained at 30-50% of its untreated level, with regression of xanthomas, arrest of progression of coronary atherosclerosis, and improved life expectancy. However, aortic stenosis may progress despite apheresis and necessitate valve replacement. Better control of hypercholesterolemia results from combining apheresis with a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, atorvastatin. LDL apheresis can also be useful in treating drug-resistant FH heterozygotes with coronary disease. However, the FH Regression Study showed no evidence that reduction by apheresis of both LDL and lipoprotein(a), was more advantageous than reduction by combination drug therapy of LDL alone.
Thompson GR, 1997, First priority is to decrease the severity of hyperchylomicronaemia, BRITISH MEDICAL JOURNAL, Vol: 314, Pages: 62-63, ISSN: 0959-8138
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