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Biomedical subjects

Gilbert R Thompson

Publications and source records attributed to Gilbert R Thompson.

13 recordsLinked to original sources
PubMed2005

History and development of plant sterol and stanol esters for cholesterol-lowering purposes.

Plant stanol esters provide a novel approach to lowering plasma low-density lipoprotein (LDL) cholesterol by dietary means. Their development was preceded by a long period of research into the cholesterol-lowering properties of plant sterols and, recently, plant stanols. Both classes of compound competitively inhibit the absorption of cholesterol and thus lower its level in plasma. Initial impressions were that stanols were more effective and safer than sterols, but the negative outcome of a study led to the recognition that the lipid solubility of free stanols was very limited. This was overcome by esterifying them with fatty acids, with the resultant stanol esters being freely soluble in fat spreads. This led to the launch of Benecol (margarine; Raisio Group, Raisio, Finland) in 1995. The coincident publication of the year-long North Karelia study conclusively demonstrated the long-term LDL-lowering efficacy of plant stanol esters. Variables that might influence the efficacy of stanol esters include dose, frequency of administration, food vehicle in which the stanol ester is incorporated, and background diet. The effective dose is 1 to 3 g/day, expressed as free stanol, which, in placebo-controlled studies, decreased LDL cholesterol by 6% to 15%. This effect is maintained, appears to be similar with once-daily or divided dosage, and is independent of the fat content of the food vehicle. Short-term studies suggest that equivalent amounts of plant sterol and stanol esters are similarly effective in lowering LDL, the main difference being that plasma plant sterol levels increase on plant sterols and decrease on plant stanols. The clinical significance of these changes remains to be determined.

Adsorption↗
PubMed2005

Comparison of efficacy of plant stanol ester and sterol ester: short-term and longer-term studies.

Published data suggest that the cholesterol-lowering effect of dietary plant sterol esters is less marked in longer-term than in short-term studies, whereas plant stanol esters maintain their efficacy. To investigate this further, healthy subjects and patients with familial hypercholesterolemia (FH) receiving statins were randomized to receive plant sterol ester 1.6 g/day or plant stanol ester 1.6 g/day or 2.6 g/day for 2 months. There was no difference among the 3 groups in the pooled low-density lipoprotein (LDL)-lowering response of FH patients and healthy subjects, but the effect of plant sterol diminished at 2 months and was not significantly different from baseline. This was accompanied by increases in serum plant sterols and a significant decrease in 7alpha-hydroxy-4-cholesten-3-one, a marker of bile acid synthesis, especially in FH patients not taking bile acid sequestrants. In contrast, plant stanol esters lowered significantly both LDL cholesterol and plant sterols at 2 months and had no effect on bile acid synthesis. Slight decreases in serum lipid-soluble antioxidants occurred with both plant sterol and stanol esters. Our findings suggest that absorption of dietary plant sterols downregulates bile acid synthesis, which attenuates their cholesterol-lowering efficacy. We conclude that plant stanol esters are preferable for the long-term management of hypercholesterolemia.

Bile Acids and Salts↗
PubMed2005

Additive effects of plant sterol and stanol esters to statin therapy.

Plant sterol and stanol esters each have similar additive effects in lowering low-density lipoprotein cholesterol when combined with statins. They differ in that plasma plant sterols increase when plant sterol esters are used for this purpose, especially in patients with familial hypercholesterolemia, but decrease when plant stanol esters are used.

Cholesterol, LDL↗
PubMed2004

Current management of severe homozygous hypercholesterolaemias.

PURPOSE OF REVIEW: This review focuses on recent advances in the management of patients with homozygous familial hypercholesterolaemia, autosomal recessive hypercholesterolaemia and familial defective apolipoprotein B. RECENT FINDINGS: Autosomal recessive hypercholesterolaemia has been described as a 'phenocopy' of homozygous familial hypercholesterolaemia. Although the clinical phenotypes are similar, autosomal recessive hypercholesterolaemia seems to be less severe, more variable within a single family, and more responsive to lipid-lowering drug therapy. The cardiovascular complications of premature atherosclerosis are delayed in some individuals and involvement of the aortic root and valve is less common than in homozygous familial hypercholesterolaemia. Apheresis is still the treatment of choice in homozygous familial hypercholesterolaemia and in autosomal recessive hypercholesterolaemia patients in whom maximal drug therapy does not achieve adequate control. In addition to the profound cholesterol-lowering effects of apheresis, other potentially beneficial phenomena have been documented: improved vascular endothelial function and haemorheology, reduction in lipoprotein (a) and procoagulatory status, and a decrease in adhesion molecules and C-reactive protein. SUMMARY: Patients with severe homozygous hypercholesterolaemia illustrate the natural history of atherosclerosis within a condensed timeframe. Effective cholesterol-lowering treatment started in early childhood is essential to prevent onset of life-threatening atherosclerotic involvement of the aortic root and valve, and the coronary arteries. Noninvasive methods for regular monitoring of the major sites involved in the atherosclerotic process are necessary in patients with no symptoms or signs of ischaemia. Management of patients with severe homozygous hypercholesterolaemia continues to be a major challenge.

Adolescent↗
PubMed2003

LDL apheresis.

Low density lipoprotein (LDL) apheresis provides a safe and effective means of treating patients with homozygous familial hypercholesterolaemia (FH). It also has a role in preventing the progression of coronary artery disease in heterozygotes and others with severe dyslipidaemia who are refractory to or intolerant of high doses of lipid-lowering drugs. Established methods involve either adsorption of apolipoprotein B-containing lipoproteins by affinity columns containing anti-apolipoprotein B antibodies or dextran sulphate, or their precipitation at low pH by heparin, in each instance after first separating plasma from blood cells with a cell separator. The most recently developed method enables lipoproteins to be adsorbed directly from whole blood, using polyacrylate columns. All 4 methods have proved to be similarly efficient when used weekly or biweekly to lower LDL cholesterol and Lp(a) without unduly reducing HDL cholesterol. Economic constraints restrict the use of LDL apheresis to the treatment of potentially fatal disorders such as FH, where there is clear evidence of benefit compared with conventional therapy. Widening the indications to include the treatment of other dyslipidaemic disorders such as steroid-resistant nephrotic syndrome, post-transplant donor vessel disease, stroke and prevention of re-stenosis after coronary angioplasty requires evidence from controlled trials that is currently lacking.

Cholesterol, LDL↗
PubMed2003

Plasma markers of cholesterol homeostasis and apolipoprotein B-100 kinetics in the metabolic syndrome.

OBJECTIVE: The metabolic syndrome is characterized by defective hepatic apolipoprotein B-100 (apoB) metabolism. Hepato-intestinal cholesterol metabolism may contribute to this abnormality. RESEARCH METHODS AND PROCEDURES: We examined the association of cholesterol absorption and synthesis with the kinetics of apoB in 35 obese subjects with the metabolic syndrome. Plasma ratios of campesterol and lathosterol to cholesterol were used to estimate cholesterol absorption and synthesis, respectively. Very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein apoB kinetics were studied using stable isotopy and mass spectrometry. Kinetic parameters were derived using multicompartmental modeling. RESULTS: Compared with controls, the obese subjects had significantly lower plasma ratios of campesterol, but higher plasma ratios of lathosterol (p < 0.05 in both). This was associated with elevated VLDL-apoB secretion rate (p < 0.05) and delayed fractional catabolism of IDL and low-density lipoprotein-apoB (p < 0.01). In the obese group, plasma ratios of campesterol correlated inversely with VLDL-apoB secretion (r = -0.359, p < 0.05), VLDL-apoB (r = -0.513, p < 0.01) and IDL-apoB (r = -0.511, p < 0.01) pool size, and plasma lathosterol ratio (r = -0.366, p < 0.05). Subjects with low cholesterol absorption had significantly higher VLDL-apoB secretion, VLDL-apoB and IDL-apoB pool size, and plasma lathosterol ratio (p < 0.05 in both) than those with high cholesterol absorption. DISCUSSION: Subjects with the metabolic syndrome have oversecretion of VLDL-apoB and decreased catabolism of apoB-containing particles and low absorption and high synthesis rates of cholesterol. These changes in cholesterol homeostasis may contribute to the kinetic defects in apoB metabolism in the metabolic syndrome.

Adult↗
PubMed2003

Relationships between cholesterol homoeostasis and triacylglycerol-rich lipoprotein remnant metabolism in the metabolic syndrome.

The dysmetabolic syndrome of insulin resistance and visceral obesity is characterized by elevated plasma concentration of triacylglycerol-rich lipoprotein (TRL) remnants that may be related to increased cardiovascular risk. Perturbed hepato-intestinal cholesterol metabolism may play a contributory role in this abnormality. We therefore investigated the association between plasma markers of cholesterol absorption and synthesis with TRL remnant metabolism in 35 men with the metabolic syndrome (MS). Plasma campesterol:cholesterol and lathosterol:cholesterol ratios were measured as estimates of cholesterol absorption and synthesis respectively. Remnant metabolism was assessed by measuring remnant-like particle-cholesterol (RLP-C), apolipoprotein (apo)B-48 and the fractional catabolic rate (FCR) of a labelled remnant-like emulsion. Compared with controls, subjects with the MS had significantly lower plasma campesterol:cholesterol ratio, but higher lathosterol:cholesterol ratio ( P <0.05). Plasma RLP-C and apoB-48 concentrations were also higher ( P <0.01) and the remnant-like emulsion FCR was lower ( P <0.05). The plasma campesterol:cholesterol ratio was inversely correlated ( P <0.05) with plasma triacylglycerols ( r =-0.346), RLP-C ( r =-0.443), apoB-48 ( r =-0.427) and plasma lathosterol:cholesterol ratio ( r =-0.366); the campesterol:cholesterol ratio was also positively correlated with the remnant-like emulsion FCR ( r =0.398, P <0.05). In multiple regression analysis, the significant correlations between plasma campesterol:cholesterol ratio and plasma triacylglycerols, RLP-C, apoB-48 and FCR of the remnant-like emulsion were independent of age, dietary energy and plasma lathosterol. Our findings suggest that in subjects with the MS alterations in cholesterol absorption and synthesis may be closely linked with the kinetic defects in TRL metabolism.

Apolipoprotein B-48↗
PubMed2002

Goals of statin therapy: three viewpoints.

The "lipid hypothesis" is now universally recognized as a law. Few issues in medicine are as completely resolved as the question of whether reducing serum cholesterol increases longevity. However, there are a few questions that remain, and the most important uncertainty is to what extent cholesterol should be reduced. The medical community, in partnership with government and industry, has contributed many excellent trials demonstrating the effects in patients with elevated cholesterol (above the mean). Where should our goal of therapy be? Until data is available from several large, ongoing trials, we do not have a final answer. We asked three investigators, Drs. Gilbert Thompson, Christopher Packard, and Neil Stone, who have all been integrally involved in the accumulation of our present database, to argue three different possible answers.

Goals↗
PubMed2002

Coronary calcification and predicted risk of coronary heart disease in asymptomatic men with hypercholesterolaemia.

OBJECTIVE: To document the relationship between coronary calcification and coronary risk assessed clinically in asymptomatic patients with hypercholesterolaemia. DESIGN: Prospective observational study. SETTING: Health screening clinic. PATIENTS: A total of 286 asymptomatic men aged 45-64 with plasma cholesterol >or= 6.5 mmol/l. INTERVENTIONS: Electron beam computed tomography to measure coronary calcium score. MAIN OUTCOME MEASURES: The Framingham equation was used to separate subjects into groups with either low 10-year risk of coronary artery disease ( or= 20%). Coronary calcium score was assessed in each group. RESULTS: The mean log calcium score was significantly higher in the 97 high-risk men than in the 189 low-risk men (1.58 +/- 0.84 versus 1.00 +/- 0.85, < 0.001). Arithmetic means (158 versus 55), and the proportion with a score > 400 (11% versus 2%, p < 0.01) were also greater. However, 27% of the high-risk group had a low calcium score ( or= 20% in 10 years have minimal coronary calcification. They may therefore represent a subset at lower risk of disease. However, uncertainties about the predictive power of coronary calcification for coronary events must be resolved before electron beam computed tomography can be used to select high-risk patients for primary prevention.

Age Factors↗