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Biomedical subjects

A Gaw

Publications and source records attributed to A Gaw.

At least 37 records · Page 2Linked to original sources
PubMed1999

The design of a prospective study of Pravastatin in the Elderly at Risk (PROSPER). PROSPER Study Group. PROspective Study of Pravastatin in the Elderly at Risk.

The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) is a randomized, double-blind, placebo-controlled trial designed to test the hypothesis that treatment with pravastatin will diminish risk of subsequent major vascular events in a cohort of men and women (70 to 82 years old) with preexisting vascular disease or significant risk of developing this condition. Five thousand eight hundred four men and women in addition to receiving advice on diet and smoking, have been randomized equally to treatment with 40 mg pravastatin/day or matching placebo in 3 centers (Cork, Ireland, Glasgow, Scotland, and Leiden, The Netherlands). Following an average 3.5-year intervention period, a primary assessment will be made of the influence of this therapy on major vascular events (a combination of coronary heart disease, death, nonfatal myocardial infarction, and fatal and nonfatal stroke). A number of additional analyses will also be conducted on the individual components of the primary end point, on men, on women, and on subjects with and without previous evidence of vascular disease. Finally, an assessment will be made of the effects of treatment on cognitive function, disability, hospitalization or institutionalization, vascular mortality, and all-cause mortality.

Aged↗
PubMed1999

Predictors of plasma lipoprotein(a) concentration in the West of Scotland Coronary Prevention Study cohort.

An elevated plasma lipoprotein(a) (Lp(a)) concentration is an independent risk factor for coronary heart disease (CHD). Plasma Lp(a) levels are believed to be predominantly controlled by the APO(a) gene, which encodes the apo(a) glycoprotein moiety of the Lp(a) particle. However, other parameters in the lipoprotein profile as well as co-existing disease states or personal traits have been proposed as co-varieties. In order to examine these potential controlling factors in greater detail than previously possible, 1760 unrelated Caucasian subjects were studied, from which were identified 907 with a single expressing APO(a) allele. This strategy was followed to obviate the difficulty in dealing with the co-expression of different apo(a) isoforms and the resulting compound plasma Lp(a) level. After cube-root transformation of the plasma Lp(a) levels to normalise their distribution, a series of correlates were computed. There was no good correlation between Lp(a) concentration and any other measured lipid or lipoprotein in the lipid profile or with any other variable examined, with the important exception of the length of the expressed apo(a) isoform (r = -0.491, P = 0.0001). We conclude that in this population the plasma Lp(a) concentration is not predicted by the plasma lipid profile, alcohol intake, or smoking status but is predicted, albeit incompletely, by the length polymorphism of the APO(a) gene.

Age Distribution↗
PubMed1998

Evidence based approach for the management of mixed hyperlipidaemia.

There is now a large body of evidence from multiple clinical trials confirming that lowering plasma low density lipoprotein (LDL)-cholesterol results in a clinically significant reduction in coronary heart disease (CHD) risk. These include the Scandinavian Simvastatin Survival Study and the West of Scotland Study. However, further analyses of the Helsinki Heart Study (HHS) have provided additional detail on the relationship between other lipid changes and incidence of CHD. In the HHS, the reduction of CHD events was related not only to the LDL-cholesterol lowering ability of the drug used, but also to its HDL-cholesterol raising and triglyceride lowering effects. Furthermore, a recent comparison of the levels of atheroma regression associated with different drug classes reveals that, while statins produce much greater changes in total and LDL-cholesterol, fibrates have the most marked effect on coronary artery minimum lumen diameter changes. In practice, the overall CHD risk of patients should be reduced by a co-ordinated approach to management of all the correctable risk factors. As part of this approach, the lipid profile should be assessed and normalised initially through the instigation of lifestyle changes, and if necessary, the adjunctive use of lipid regulating drugs. While the lowering of LDL-cholesterol is clearly important, the significance of lowering plasma triglyceride should not be overlooked.

Coronary Disease↗
PubMed1998

Impact of apo(a) length polymorphism and the control of plasma Lp(a) concentrations: evidence for a threshold effect.

Plasma lipoprotein(a) [Lp(a)] levels are believed to be controlled predominantly by the apolipoprotein(a) [APO(a)] gene, which encodes the apo(a) glycoprotein, a key constituent of the Lp(a) particle. Previously, it has been accepted that the plasma Lp(a) level is inversely proportional to apo(a) length. To examine this relationship in greater detail, 1500 unrelated, homogeneous (sex, race, age, plasma lipids) subjects were studied, from which 769 were identified with a single-expressing APO(a) allele. A bimodal frequency distribution of apo(a) isoforms was observed. As expected, there was a general inverse relationship between apo(a) isoform size and Lp(a) level. However, when groups with equivalent single-expressing apo(a) isoforms were studied, it was clear that although smaller isoforms were associated on average with higher levels, they were also associated with the greatest variability in level. After logarithmic transformation of Lp(a) data, the overall contribution of the apo(a) length polymorphism was calculated to be 38%. However, in subjects with apo(a) isoforms of </=20 kringle-4 (K-4) repeats, only 9% of the variability in Lp(a) concentration is explicable on the basis of the apo(a) length polymorphism. In those with apo(a) isoforms of >20 K-4 repeats, the corresponding contribution is 10%. We conclude that the contribution of the apo(a) isoform size to the control of plasma Lp(a) level is considerably lower than previously calculated, because the variability in plasma Lp(a) concentration is not uniform across the apo(a) size spectrum.

Alleles↗
PubMed1996

Genetic factors that contribute to interindividual variations in plasma low density lipoprotein-cholesterol levels.

The interplay of multiple genes and environmental factors generates interindividual variation in plasma low density lipoprotein-cholesterol (LDL-C) concentrations. As a result, it has been difficult to identify individual genes that contribute to variation in plasma LDL-C levels using classical linkage analysis. We have exploited a genetic defect in the gene encoding the LDL receptor that is associated with a dramatically elevated plasma LDL-C level to unmask an allele at another locus that lowers plasma LDL-C levels. The existence of such an allele was implied by the analysis of a human pedigree with familial hypercholesterolaemia in which a third of the familial hypercholesterolaemia heterozygotes had normal levels of LDL-C. To develop an animal model of this LDL-C lowering effect and to identify genes that modify the plasma LDL-C level, we crossed LDL receptor-deficient mice with other strains of mice.

Alleles↗
PubMed1996

Lipid metabolism.

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Coronary Disease↗
PubMed1996

Apolipoprotein B metabolism in primary and secondary hyperlipidaemias.

Important advances in our understanding of apolipoprotein B100 metabolism have been made in the last year. Here we review a diverse group of studies designed to examine the underlying metabolic defects in primary hyperlipidaemia or to define the impact of diseases such as diabetes nephrotic syndrome and thyroid dysfunction on the metabolism of apoB-containing lipoproteins.

Apolipoproteins↗
PubMed1996

Effects of colestipol alone and in combination with simvastatin on apolipoprotein B metabolism.

The effects of colestipol therapy alone (20 g/d) or combined with simvastatin (20 mg/d) were examined in a group of eight male patients with primary moderate hypercholesterolemia (total cholesterol > or = 6.5 mmol/L [> or = 250 mg/dL]) who had undergone coronary artery bypass grafting more than 3 months previously. Colestipol therapy decreased total cholesterol by 14% (P < .001) and LDL cholesterol (LDL-C) by 23% (P < .001), while dual therapy decreased total cholesterol by 38% and LDL-C by 52% (both P < .001 versus baseline). No significant changes were observed in plasma triglyceride, VLDL cholesterol, or HDL cholesterol levels. VLDL subfraction turnovers were conducted at baseline and again on each regimen. ApoB kinetic parameters derived from a multicompartmental model suggested that colestipol therapy resulted in an expansion of the total VLDL apoB pool (36%, P < .05) that was largely due to a fall in the clearance rate of VLDL1 apoB (49%), while the LDL apoB pool decreased 23% as a result of diminished direct LDL input. The model used also revealed that addition of simvastatin to the resin therapy caused increases in the fractional transfer rates of VLDL2 to IDL and IDL to LDL together with a 37% increment in the LDL apoB fractional catabolic rate. Compared with baseline, combined therapy generated falls in both IDL (35%, P = .01) and LDL (37%, P < .04) apoB pools due to enhanced clearance of IDL (214%, P < .03) and reduced total input of LDL (39%, P < .003).

Adult↗
PubMed1995

Metabolism of apolipoprotein B in primary moderate hypercholesterolaemia: effects of acipimox and cholestyramine therapy.

The effects of combined therapy with acipimox (1250 mg/day) and cholestyramine (20 g/day) were examined in a group of 7 subjects with primary moderate hypercholesterolaemia (total cholesterol >=7 mmol/L). Radiolabeled VLDL subfraction turnovers were performed at baseline, during acipimox therapy and during combined therapy. Acipimox and combined therapies lowered plasma low density lipoprotein (LDL)-cholesterol by 20% (P<0.001) and 27% (P<0.001) respectively. The marked fall in LDL-cholesterol associated with acipimox therapy, was due to a reduced production rate of LDL (apolipoprotein) apoB. This is shown to be a result of reduced direct LDL apoB production, reduced IDL to LDL transfer consistent with inhibition of hepatic triglyceride lipase, and with a reduction in the overall throughput of VLDL1 apoB. With combined therapy both reduced production and increased catabolism of apoB containing LDL precursors and of LDL itself have to be invoked to explain the fall in plasma LDL-cholesterol.

Adult↗