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Biomedical subjects

J M Bard

Publications and source records attributed to J M Bard.

At least 55 records · Page 3Linked to original sources
PubMed1994

Fluvastatin efficacy and tolerability in comparison and in combination with cholestyramine.

The aim of this study was to investigate the new synthetic HMG-CoA reductase inhibitor, fluvastatin, for efficacy, safety and tolerability in comparison to cholestyramine. One hundred fifty one primary hypercholesterolaemic patients participated in this double-blind, parallel-group, randomized study. During the first 12 weeks of the study, fluvastatin (20 mg and 40 mg daily) was compared with cholestyramine (16 g per day). In the subsequent, 6-week part of the study, the comparative efficacy, safety and tolerability of 20 mg fluvastatin, combined with cholestyramine (4 g, 8 g, or 16 g) were assessed. Fluvastatin (40 mg) reduced LDL cholesterol by 28.0%, triglycerides by 10.5% and increased HDL cholesterol by 3.7%. Cholestyramine (16 g) reduced LDL cholesterol by 35.0%, but raised triglycerides and HDL cholesterol by 12.3% (p < 0.01) and 3.7% respectively. The combination of fluvastatin 20 mg and cholestyramine (4 g, 8 g and 16 g) induced the following reductions in LDL cholesterol: 30.4%, 35.6% and 46.6% respectively. There was no significant change in triglycerides in either group although HDL cholesterol was raised by 4.9%, 8.3% and 7.2% respectively. One patient treated with fluvastatin and two treated with cholestyramine were withdrawn from the study due to elevation of liver transaminases. The most frequent subjective adverse effects in both treatment groups were mild, transient gastrointestinal complaints. Thus, fluvastatin was effective as a lipid-lowering agent; the effect was further enhanced when fluvastatin was combined with cholestyramine.

Anticholesteremic Agents↗
PubMed1994

Evidence of non-deficient low-density lipoprotein receptor patients in a pool of subjects with clinical familial hypercholesterolemia profile.

For this study, we selected 41 adult patients with the classic clinical diagnosis of heterozygous familial hypercholesterolemia (FH), which is characterized by a low-density lipoprotein (LDL) cholesterol level above the 95th percentile, xanthomas, and/or personal or familial cardiovascular history. We used an indirect immunocytofluorimetric assay to classify these 41 subjects according to LDL receptor function on lymphocytes. We found that LDL receptor activity was normal in nine patients. A large study of plasma lipid, lipoprotein, and apolipoprotein levels found no significant difference between patients with and without LDL receptor defect. Familial defective apolipoprotein (apo) B-100 (FDB) and LDL-binding defects were not found in the nine patients without LDL receptor defect. These results suggest that other defects in the regulation of lipoprotein metabolism are capable of giving rise to a clinical and biochemical disorder indistinguishable from classic FH.

Adult↗
PubMed1994

Location of probucol in lipoproteins inferred from compositional analysis of lipoprotein particles. An in-vitro study.

The location of labelled probucol in lipoprotein particles was investigated in-vitro. Human serum was incubated for 4 h at 37 degrees C with [14C]probucol to incorporate probucol into lipoproteins. Serum lipoprotein particles were then isolated according to their apolipoprotein markers by sequential immunoaffinity chromatography at 4 degrees C, and probucol concentration was determined in each lipoprotein fraction. Analysis of probucol distribution vs lipoprotein components revealed that probucol in particles strongly correlated with phospholipid concentration. Analysis of probucol distribution vs lipoprotein physical characteristics showed that probucol strongly correlated with the surface area of the monolayer surrounding the lipidic core of particles constituting phospholipids and free cholesterol. These data support the hypothesis that probucol is preferentially located in the phospholipid/free cholesterol monolayer surrounding the lipid core, in the vicinity of cholesteryl ester at the core surface or in the vicinity of hydrophobic areas of apolipoprotein that faces the monolayer.

Humans↗
PubMed1994

Impact of apolipoprotein E polymorphism on lipoproteins and risk of myocardial infarction. The ECTIM Study.

Human apolipoprotein (apo) E, a polymorphic protein with three common alleles, epsilon 2, epsilon 3, and epsilon 4, plays an important role in lipoprotein metabolism. This article describes the association of this polymorphism with lipids, apolipoproteins, and lipoproteins with a particular regard to lipoprotein particles, as defined by their apolipoprotein content, as well as the risk of myocardial infarction in a multicenter population-based case-control study (ECTIM study). In the ECTIM study, 574 male patients aged 25 to 64 were examined 3 to 9 months after myocardial infarction in four regions participating in the World Health Organization MONICA project: Belfast (Northern Ireland) and Lille, Strasbourg, and Toulouse (France). Control subjects (n = 722) were randomly selected from the regional populations. The distribution of apoE phenotypes was significantly different across the four control samples (P = .04), with a higher frequency of the epsilon 4 allele in Belfast (14.3%) than in Toulouse (8.2%). The association of apoE polymorphism with biological measurements was studied in the control groups (n = 640) after men with coronary heart disease or those taking hypolipidemic drugs were omitted, with the apoE3/3 phenotype as a reference after adjustment for concomitant factors. Individuals carrying the epsilon 2 allele had lower levels of plasma cholesterol, low-density lipoprotein cholesterol (LDL-C), and apoB and higher levels of triglycerides, very-low-density lipoprotein cholesterol (VLDL-C), apoC-III, apoE, lipoprotein (Lp) C-III:B, and Lp E:B. However, the effect of the epsilon 2 allele on triglyceride, VLDL-C, apoE, and Lp E:B parameters was heterogeneous across the populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Plasma apolipoprotein concentrations in young adults with a parental history of premature coronary heart disease and in control subjects. The EARS Study. European Atherosclerosis Research Study.

The European Atherosclerosis Research Study (EARS) is a multicenter collaborative project within the European community. Its main objective is to study in young individuals the biological expression of a paternal history of premature coronary heart disease and to analyze the relative contribution of genetic and environmental factors to this expression. This study was carried out in 14 centers in 11 European countries, where the offspring of fathers who suffered a documented myocardial infarction before the age of 55 years (cases) were compared with age- and sex-matched control subjects. Plasma apolipoproteins A-I, B, A-II, A-IV, and E and lipoprotein (Lp) A-I lipoparticles were measured in this student population. Comparison of the values between cases and control subjects showed significantly higher apo B levels in cases compared with control subjects, and these differences were homogeneous throughout Europe. Regional differences were observed for apo E levels with an increasing north-south gradient, which was inversely related to that observed for triglycerides. A stepwise regression analysis including the lipid and apolipoprotein variables showed that apo B and triglycerides were the strongest discriminators between offspring of fathers with premature coronary heart disease and control subjects.

Adult↗
PubMed1994

Effect of fluvastatin on plasma apolipoprotein-B-containing particles, including lipoprotein(a). European Fluvastatin Study Group.

Epidemiological studies have demonstrated an association between apolipoprotein-(apo)-B containing particles [lipoprotein (Lp) (a), LpE:B; LpC-III:B] and coronary heart disease (CHD). The effect of fluvastatin, a novel competitive inhibitor of HMG-CoA reductase, on these plasma lipoprotein levels was studied in patients with hypercholesterolaemia after 14 weeks of standard dietary therapy. The results of a placebo-controlled, dose-response study and of the combined data of the European double-blind, controlled studies on the effect of fluvastatin are presented. The patients were selected according to the following criteria of inclusion: plasma low-density-lipoprotein (LDL) cholesterol levels > 160 mg dL-1 and premature CHD and/or two associated risk factors, or LDL cholesterol > 190 mg dL-1 and no CHD, plus triglycerides < 300 mg dL-1. All measurements were performed at the Pasteur Institute Central Laboratory. Lp(a), LpE:B and LpC-III:B particles were measured by double-site ELISA. In the placebo-controlled, dose-response study, 429 subjects were randomly assigned to one of the following treatment groups: placebo, fluvastatin 2.5 mg q.p.m., 5 mg q.p.m., 10 mg q.p.m. and 20 mg q.p.m. Treatment with fluvastatin for 6 weeks was associated with a dose-dependent reduction of LDL cholesterol, apoB, LpE:B and LpCIII:B levels. In addition, treatment with fluvastatin 5 mg and 20 mg q.p.m. was associated with a significant reduction in median Lp(a) concentrations (3.2%, P < 0.05 and 6.4%, P < 0.05 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Polymorphisms of the apolipoprotein B and E genes and their relationship to plasma lipid variables in healthy Chinese men.

In this study we have analysed the apolipoprotein (Apo) E polymorphism and polymorphisms of the ApoB gene, including the ApoB/XbaI and ApoB/4311 diallelic polymorphisms and a hypervariable region (HVR) situated in the 3' region of the gene (ApoB/3'HVR), in a sample of healthy male subjects from Taiyuan (northern People's Republic of China). In comparison to Caucasian populations, in the Chinese sample, the XbaI2 allele (presence of cutting site; frequency 6.1%; and 95% confidence interval, 3.3-8.9) and the long HVR alleles (9.4%; 6.0-12.8) were rare, whereas the ApoB/4311 (Ser) allele (70.8%; 65.4-76.2) and the 34-repeat allele of the HVR (HVR34; 62.4%; 56.8-68.0) were frequent. In subjects having none, one, or two HVR34 alleles, the mean levels of plasma triglycerides were 2.32 +/- 1.44 (SD), 1.45 +/- 0.74, and 1.75 +/- 1.07 g/l, respectively (P < 0.007). Similar trends were observed for very low density lipoprotein (VLDL) cholesterol, LpE:B, and LpCIII:B. The frequencies of the ApoE alleles were similar to those reported in other populations of Asian origin; E2 (7.4%; 4.2-10.6), E3 (84.4%; 80.2-88.6), and E4 (8.2%; 5.0-11.4). Individuals carrying the E2 allele had a lower mean level of ApoB than E33 individuals: 0.87 +/- 0.16 and 1.00 +/- 0.22 g/l, respectively (P < 0.007). Individuals carrying the E4 allele had higher levels of ApoE than E33 individuals: 0.140 +/- 0.084 and 0.094 +/- 0.052 g/l, respectively (P < 0.004); similar trends were observed for VLDL cholesterol, triglycerides, LpE:B, and LpCIII:B. The ApoB/HVR34 and ApoE/E4 polymorphisms accounted for 10% to 15% of the variability of the plasma levels of VLDL cholesterol, ApoE, triglycerides, LpE:B, and LpCIII:B. Several lipid variables appeared to be favourably affected by specific forms of ApoB and ApoE that are particularly frequent in this Chinese population.

Adult↗
PubMed1993

Distribution of lipid variables in subjects in Belfast, Northern Ireland and Taiyuan, P R China.

To compare the plasma lipid, lipoprotein and apolipoprotein profiles of people of Chinese and European origin, a sample of 151 male Chinese subjects was selected from Taiyuan, Shanxi Province, P R China to 202 broadly age-matched subjects in Belfast who were selected as controls in a case-control study of myocardial infarction. Mean total cholesterol (TC) was 6.15 mmol/l in Belfast and 4.28 mmol/l in Taiyuan. Low density lipoprotein cholesterol (LDL) was much higher in Belfast. High density lipoprotein cholesterol (LDL) was also higher in Belfast than in Taiyuan but the ratio of HDL to TC was lower in Belfast than Taiyuan. Triglyceride (TG) levels were similar and this was reflected in the relatively high level of apolipoprotein E (apo E) in the Chinese sample.

Adult↗
PubMed1993

The relationship between the phospholipid fatty acid composition of red blood cells, plasma lipids, and apolipoproteins.

This study examined the relationship between the fatty acid composition of red blood cell phospholipids and lipid markers of atherosclerotic risk in an urban male population aged 45 to 66 years. There was a surprisingly significant positive association between the docosahexaenoic acid ([DHA] 22:6n-3) content of erythrocyte phospholipids and the following risk markers: plasma cholesterol (P < .01), low-density lipoprotein (LDL) cholesterol (P < .01), apolipoprotein (apo) B (P < .05), and apo B-containing lipoprotein particles (P < .05) recognized by a monoclonal antibody (LpBL3). On the other hand, phospholipid alpha-linolenate was positively correlated with apo A-I and high-density lipoprotein (HDL) cholesterol levels (P < .05), while arachidonate showed an inverse relationship with plasma cholesterol (P < .05). There was a negative association between palmitoleic acid and apo B (P < .01) and LpBL3 (P < .001); the latter showed a negative association with stearic acid (P < .001). These interesting findings emphasize the beneficial effect on atherosclerotic risk markers of dietary n-6 polyunsaturated and monounsaturated fatty acids, and suggest that long-chain n-3 polyunsaturated fatty acids (DHA) could have an adverse effect on some of the lipid risk markers.

Apolipoproteins↗
PubMed1993

Lipoprotein metabolism in marasmic children of northern Mauritania.

Lipid metabolism in marasmus has been poorly studied compared with that in kwashiorkor. Published studies show normal or high plasma triglycerides and low cholesterol concentrations. We studied some plasma lipid indexes, including total, HDL, and LDL cholesterol; triglycerides; apolipoproteins A-I, A-II, B, C-III, and E; and lipoprotein particles containing apo A-I, apo A-I and A-II (Lp A-I:A-II) Lp C-III:B, and Lp E:B in Mauritanian marasmic children compared with a control group. We found in patients low total, HDL, and LDL cholesterol and normal Lp A-I concentrations, which suggest that the cholesterol reverse transport system is not altered. We observed normal triglyceride concentrations and significantly increased Lp C-III:B and Lp E:B, which are triglyceride-rich particles. These data suggest that the marasmic state led to quantitative and structural modifications of the triglyceride-rich lipoproteins, defined by their apolipoprotein composition, and was probably related to undercatabolism.

Anthropometry↗
PubMed1993

High density lipoprotein subfractions, apolipoprotein A-I containing lipoproteins, lipoprotein (a), and cholesterol ester transfer protein activity in alcoholic women before and after ethanol withdrawal.

We studied 11 female alcoholics before and after ethanol withdrawal of 2 weeks and 10 healthy normolipidaemic, nonalcoholic women of similar age. In alcoholic women the HDL2 mass was increased by 63% (P < 0.01) on admission and normalized (P < 0.01) during abstention. The concentrations of HDL3 cholesterol and its mass remained unchanged throughout the study. Consistently with the fall of HDL2 gradient gel electrophoresis analyses also demonstrated decrease of the cholesterol concentration of HDL2b and HDL2a (P < 0.05) during alcohol withdrawal. On admission the apo A-II concentration was increased by 48% (P < 0.01) and it was normalized (P < 0.001) during abstention. Among apo A-I containing lipoproteins the most prominent change occurred in Lp A-I:A-II, which fell by 32% (P < 0.01) during 1 week's alcohol withdrawal. During abstention the lipoprotein (a) concentration increased in 10 out of 11 women. In patients cholesteryl ester transfer (CETP) activity increased by 35% (P < 0.01) during 1 week of ethanol withdrawal. On admission postheparin plasma lipoprotein (LPL) and hepatic lipase activities were increased by 25% (P = NS); during 1 week's abstention they both returned to the control level (P < 0.05- < 0.01). In conclusion, chronic alcoholic women display multiple changes of lipoprotein metabolism which are rapidly reversed during abstinence. In contrast to alcoholic men, studied previously by us using the same study design and methods, there was no significant elevation of HDL3 cholesterol and apo A-I. The data suggest that alcohol interferes with several regulatory steps of HDL metabolism which are partly gender dependent.

Adult↗
PubMed1993

HDLs and alimentary lipemia. Studies in men with previous myocardial infarction at a young age.

The plasma concentration, particle size, and chemical composition of high density lipoproteins (HDLs) are associated with the metabolism of triglyceride-rich lipoproteins (TGRLs). During alimentary lipemia there is active exchange of lipids and apolipoproteins between HDL and apolipoprotein B-containing lipoproteins. Whereas HDL has been assigned a protective role against the development of atherosclerosis, alimentary lipemia has been proposed to represent a potentially atherogenic state. We examined plasma HDL concentration, particle size, and composition and their relations to postprandial TGRLs in 32 postinfarction patients and 10 healthy control subjects after intake of a standardized oral fat load of a mixed-meal type. All patients had undergone coronary angiographies in connection with the myocardial infarction and around 5 years thereafter. The plasma HDL cholesterol concentration decreased significantly in response to the oral fat load, particularly in hypertriglyceridemic patients, with a concomitant increase of HDL triglycerides. A limited and reversible yet consistent increase of HDL particle size (1-2%) was seen 6 hours after intake of the oral fat load on nondenaturing gradient gel electrophoresis (GGE) in both patients and control subjects. Virtually no changes in the plasma concentration of HDL GGE subclasses, lipoproteins containing apolipoprotein A-I but no apolipoprotein A-II (LpA-I), or lipoproteins containing both apolipoproteins A-I and A-II (LpA-I:A-II) were induced in the postprandial state despite massive increases of large very low density lipoprotein (VLDL) and large chylomicron remnant levels (determined as apolipoproteins B-100 and B-48 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis). Strong inverse correlations with fasting plasma HDL cholesterol and the larger HDL GGE subspecies were found for large postprandial VLDL and large chylomicron remnants, whereas the corresponding relations for small VLDL and small chylomicron remnants were weaker. The relations of both large and small VLDL and chylomicron remnants to HDL cholesterol were confined to subjects in the lower fasting plasma HDL cholesterol range (< 1.2 mmol/l). None of the HDL parameters measured, either in the fasting or in the postprandial state (HDL cholesterol, HDL triglycerides, HDL GGE subclasses, LpA-I, and LpA-I:A-II), were related to the development of coronary atherosclerosis, whereas the postprandial plasma levels of small chylomicron remnants, which showed weak negative correlations with HDL, related positively to the progression of coronary atherosclerosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Parental history of early myocardial infarction is associated with decreased levels of lipoparticle AI in adolescents.

A family history of coronary heart disease (CHD) is a known risk factor for CHD. To investigate the possible role of lipoprotein particles in the relationship between family history of CHD and risk of CHD, we performed a case-control study in a sample of adolescents. The case group consisted of 97 adolescents whose parents had suffered a verified myocardial infarction before the age of 55 years. The control group was composed of 194 subjects without any family history of CHD. One case patient was matched to two control subjects for gender, age, and body mass index. In both groups, plasma lipid variables were measured, including total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C) low-density lipoprotein cholesterol, apolipoprotein (apo)AI, apoB, apoAI-containing lipoprotein particles without apoAII (LpAI) and with apoAII, and apoB-containing lipoprotein particles with apoE and with apoCIII. Adolescents with a family history of early myocardial infarction had lower plasma levels of HDL-C (P < .0001), apoAI (P < .01), and LpAI (P < .0001) than control subjects (adjusted for gender, age, body mass index, smoking habits, and oral contraceptive use). No other differences were statistically significant between case and control subjects. The analysis was repeated separately for male and female subjects. In young men, the best predictor of family history of early myocardial infarction was the LpAI plasma level, whereas in young women it was the HDL-C plasma level. Decreased levels of HDL-C and LpAI lipoprotein particles explain part of the relationship between parental history of early myocardial infarction and CHD risk.

Adolescent↗
PubMed1993

Familial hypoalphalipoproteinemia in premature coronary artery disease.

Hypoalphalipoproteinemia (HA) is a common finding in patients with premature coronary artery disease. To characterize the common familial forms of HA, we studied 102 families of probands with premature coronary artery disease; 40 probands (39.2%) had HA. Of these, 25 had at least one first-degree relative affected with HA; 11 had familial hypertriglyceridemia with HA (FTgHA); 10 had familial combined hyperlipidemia (FCH); and 4 had familial HA (FHA) with no other lipoprotein abnormalities. In the remaining 15 families, no lipoprotein abnormalities were observed in first-degree relatives. We measured apolipoprotein (apo) A-I, B, C-III, and E levels as well as lipoprotein particle (Lp) levels of LpA-I (containing apoA-I only), LpA-I:A-II (containing both apoA-I and A-II), LpB:E, and LpB:C-III. Compared with a reference group of healthy men (n = 103) and women (n = 106), probands with familial forms of HA had lower high-density lipoprotein cholesterol levels by selection criteria. Triglyceride levels were higher in FTgHA and FCH probands than in the reference group or FHA subjects. Despite selection of FTgHA and FCH by low-density lipoprotein (LDL) cholesterol, the latter was not significantly different between the three groups and the reference group. ApoA-I levels were decreased in FCH, FHA, and FTgHA probands, and LpA-I and LpA-I:A-II were lower in FHA and FTgHA probands. ApoB levels were significantly higher in all familial HA groups compared with the reference group, being highest in FCH individuals, but not significantly higher between FCH, FTgHA, or FHA probands. LpB:E levels were higher in the FCH and FTgHA groups than in the reference group. There were no significant differences between groups for apoE, apoC-III, and LpB:C-III. LDL particle size was smaller in all three forms of FHA, which, in combination with higher apoB levels, reflects an increased number of smaller, denser LDL particles. Affected children had, on average, higher apoB and LpB:E levels than nonaffected siblings. Our data suggest that common forms of FHA in subjects with coronary artery disease represent a spectrum of overlapping disorders characterized by an increase in apoB-containing lipoproteins, especially LpB:E particles, and smaller, denser LDL particles. When using appropriate age- and gender-adjusted cutpoints, approximately half the offspring (in young adulthood) appeared to be affected.

Adult↗
PubMed1993

Heterogeneity of high density lipoprotein particles.

Human high density lipoprotein (HDL) contains at least two types of lipoprotein-containing A-I particles: one contains both apolipoproteins (apo) A-I and A-II (Lp A-I:A-II) as main protein components, whereas in the other, apo A-II is absent (Lp A-I). The two subpopulations have different metabolisms and physiological roles. Studies indicate that apo A-II is an antagonist of cholesterol efflux. Lp A-I but not Lp A-I:A-II is increased in women compared with men. The lower apo A-I levels in patients with coronary artery disease reflect a decrease in Lp A-I. Lp A-I also is decreased in children with a family history of coronary artery disease, and increased in elderly subjects. Despite cholesterol intake remaining constant, a high polyunsaturated:saturated fat diet leads to a decrease in Lp A-I but not Lp A-I:A-II. Chronic alcohol consumption induces an increase in Lp A-I:A-II and a decrease in Lp A-I, although short bouts of drinking produce increases in both Lp A-I and Lp A-I:A-II. Hypolipidemic drugs have specific effects on discrete apo A-I particles.

Alcoholism↗