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J M Bard

Publications and source records attributed to J M Bard.

At least 37 records · Page 2Linked to original sources
PubMed1997

Relationship between low-density lipoprotein size and apolipoprotein A-I-containing particles: the ECTIM study.

It is now established that small dense low-density lipoproteins (LDLs) are more common among patients with coronary heart disease than among control individuals. Small LDL size is also associated with a high-risk profile, including increased levels of triglycerides and decreased high-density lipoprotein (HDL)-cholesterol. Furthermore, some human HDL particles contain both apolipoprotein (apo) A-I and apoA-II (LpA-I:A-II) while others contain apoA-I but are devoid of apoA-II (LpA-I). We have investigated the relationship between LDL size, measured by non-denaturing gradient-gel electrophoresis, and HDL parameters, particularly LpA-I and LpA-I:A-II levels, in healthy control subjects (n = 408). LDL size was positively and significantly correlated with HDL-cholesterol (r = 0.43), apoA-I (r = 0.32) and LpA-I (r = 0.29), whereas no correlation was observed with apoA-II and LpA-I:A-II. The determination of the mean apoA-I and LpA-I in the quintiles of LDL size distribution revealed a progressive increase in apoA-I and LpoA-I from the first quintile (small LDLs), 137 and 42 mg dL-1 respectively, to the fifth quintile (large LDLs), 161 and 54 mg dL-1 respectively. Conversely, no evolution of apoA-II and LpA-I:A-II was observed. Multivariate analysis showed that not only triglycerides, but also HDL-cholesterol, apoA-I and LpA-I, are determinants of LDL size, depending on the model used. Thus, part of the variation in size of LDLs is associated with the metabolism of HDL independently of that of triglycerides. Thus, a low concentration of LpA-I combined with the presence of small LDLs could contribute to the high-risk profile observed in subjects with small LDLs.

Adult↗
PubMed1996

The Gln/Arg polymorphism of human paraoxonase (PON 192) is not related to myocardial infarction in the ECTIM Study.

Paraoxonase is a high-density-lipoprotein associated enzyme capable of hydrolyzing lipid peroxides, which has been suggested to contribute to atherosclerosis and coronary heart disease (CHD). We studied the Gln/Arg polymorphism affecting codon 192 of human paraoxonase (PON 192) to determine whether this polymorphism, which is associated with serum paraoxonase (PON) activity, represents a risk factor for myocardial infarction (MI). The PON 192 polymorphism was analysed in 642 male patients with myocardial infarction and 701 age-matched controls participating in the ECTIM Study (Etude Cas-Témoins de l'Infarctus du Myocarde). The frequency of the Gln allele was 0.69 in cases and 0.70 in controls (ns). The frequency of the PON 192/Arg allele in 405 MI patients who underwent coronary angiography was 0.295, 0.323 and 0.331, respectively in those with 1, 2 or 3 stenosed arteries (stenosis > 50%) (ns). The mean levels of several plasma lipids, lipoproteins and apolipoproteins were compared between the 3 PON genotypes and no difference was observed. The PON 192 polymorphism was unrelated to MI, the severity of coronary atherosclerosis and to plasma levels of several lipid variables.

Adult↗
PubMed1996

Association between the LPL-D9N mutation in the lipoprotein lipase gene and plasma lipid traits in myocardial infarction survivors from the ECTIM Study.

Using polymerase chain reaction (PCR) based techniques, we have identified individuals in the ECTIM study of myocardial infarction survivors (cases) and healthy matched controls who are carriers for a mutation of the gene for lipoprotein lipase (LPL) which alters amino acid 9 from aspartic acid to asparagine (LPL-D9N). The frequency of carriers in the cases from Belfast and France (3 separate centres) was 2.5 and 3.7%, respectively (mean 3.3%, 95% CI 1.9-4.7) and in the controls 2.0 and 2.9%, respectively (mean 2.7%, 95% CI 1.6-3.8%), but this difference was not statistically significant. In the cases, carriers of the allele for LPL-N9 had higher levels of several plasma lipid traits including total triglycerides (TG) (30%), very low density lipoprotein (VLDL) cholesterol (19%), apo E (24%), apo C-III (17%), lipoprotein particles (Lp) containing both apo E and apo B (LpE:B) (32%), and particles containing both apo C-III and apo B (LpCIII:B) (39%), and this effect was consistent in cases both from Belfast and from the French centres combined. By contrast, in the controls there were no differences in any lipid trait between carriers and non-carriers of the mutation that was consistent between the French centres and Belfast. There were no significant differences in the levels of any measured factor between cases and controls that could explain the different effect on plasma lipid traits associated with the mutation. However, compared to the non-carriers, in both cases and controls who carried the mutation, plasma TG concentrations were higher in those whose body mass index (BMI) was above the mean of the sample (26.0 kg/m2), with statistically significant interaction seen between BMI and genotype and levels of apo C-III, and lipoprotein particles containing both apo C-III and apo B (P < 0.02). The data suggest that carriers for the LPL-N9 mutation have a mild genetic predisposition to developing hyperlipidaemia and an atherogenic lipid profile, but that this requires the presence of other genetic or environmental factors for full expression, one of which appears to be increasing obesity.

Adult↗
PubMed1996

Apolipoprotein AIV of human interstitial fluid is associated with apolipoprotein AI-containing but not with AII-containing particles.

Apolipoproteins and lipoprotein particles from human interstitial fluid and plasma were analyzed. The interstitial fluid was enriched in apolipoproteins AI, AII, and AIV compared with apo B, apo CIII, and apo E, LpAI was found to contain apo AIV which was absent from LpAI: AII. Moreover, the bulk of lecithin-cholesterol acyl-transferase was present in LpAI. The concentration range of these particles was in agreement with those required in vitro for cholesterol efflux. Thus the interstitial fluid contains particles in which two agonists but no antagonists of cholesterol efflux are associated with lecithin-cholesterol acyltransferase activity. This supports apolipoprotein AI- and/or AIV-containing particles playing a critical role in the first step of reverse cholesterol transport.

Adult↗
PubMed1996

The effect of growth hormone on low-density lipoprotein cholesterol and lipoprotein (a) levels in familial hypercholesterolemia.

Severe elevations of low-density lipoprotein (LDL) cholesterol are not always normalized with conventional drugs. Growth hormone decreases LDL cholesterol levels, in part by augmenting liver LDL receptor activity. This increase may be on the order of magnitude of the increase induced by statins. We investigated the effect of growth hormone in familial hypercholesterolemia (FH) in a randomized, double-blind, placebo-controlled study. Thirty-one men with FH aged 20 to 48 years, of whom 81% had a known LDL receptor gene mutation, discontinued all lipid-lowering drugs 6 weeks before the study. Dietary stabilization continued for 5 more weeks, followed by single-blind placebo injections for 1 week. Thereafter, 16 subjects were allocated to recombinant growth hormone 0.05 IU/kg/d and 15 to placebo injected subcutaneously for 12 weeks. Baseline lipid levels were similar in both groups. One subject in the growth hormone group withdrew after 8 weeks due to shoulder pain. Mean compliance among the rest of the subjects was 98%. The mean change in LDL cholesterol was -0.46 mmol/L (95% confidence interval [CI], -1.00 to 0.09 mmol/L) in the growth hormone group versus 0.08 mmol/L (95% CI, -0.55 to 0.71 mmol/L) in the placebo group (difference not significant). No changes occurred in the levels of other lipids, lipoprotein particles, or apolipoproteins, with the exception of lipoprotein(a) [Lp(a)]. The median changes in Lp(a) were 33% (interquartile range, 2% to 53%) and -15% (interquartile range, -22% to 18%) in the growth hormone and placebo groups, respectively (P = .02). We conclude that the effect of growth hormone on LDL cholesterol levels in FH is less than expected, based on its LDL-catabolic effects, and is counteracted by profound increases in Lp(a) levels, resulting in unchanged levels of apolipoprotein B. Thus, growth hormone is probably not useful as adjunctive therapy in FH.

Adult↗
PubMed1996

The effect of metformin on the metabolic abnormalities associated with upper-body fat distribution. BIGPRO Study Group.

OBJECTIVE: The constellation of anomalies associated with insulin resistance is a plausible additional cause of ischemic cardiovascular disease and of NIDDM. To test this hypothesis in a primary prevention trial, the effects of metformin as a potential candidate for intervention in the insulin resistance syndrome (IRS) were evaluated in 324 middle-aged subjects with upper-body obesity. RESEARCH DESIGN AND METHODS: Trial patients were selected on the basis of a high waist-to-hip ratio. They were randomly allocated to receive either metformin or placebo, following a double-blind procedure. After 1 year of treatment, the main clinical and biological parameters of the IRS were assessed and their evolution compared between treatment groups. RESULTS: Compared with placebo, metformin induced a significant weight loss, a better maintenance of fasting blood glucose, total and LDL cholesterol levels, and a greater decrease of fasting plasma insulin concentration. Moreover, tissue-type plasminogen activator antigen, a marker of fibrinolytic impairment, showed a significant decrease under metformin. By contrast, metformin treatment had no significant effect on blood pressure or serum triglyceride and HDL cholesterol concentrations. The main side effect of metformin was diarrhea. CONCLUSIONS: The BIGuanides and Prevention of Risks in Obesity (BIGPRO1) results suggest that metformin would be a suitable candidate for long-term intervention for the prevention of diabetes but that its use in a trial of primary prevention of cardiovascular diseases requires either a reevaluation of its properties toward the most potentially atherogenic anomalies of the IRS or a better definition of the target population.

Adipose Tissue↗
PubMed1996

Apolipoproteins C-III and E in apoB- and non-apoB-containing lipoproteins in two populations at contrasting risk for myocardial infarction: the ECTIM study. Etude Cas Témoins sur 'Infarctus du Myocarde.

Apolipoprotein (apo) C-III and apoE are components of two major classes of plasma lipoproteins, i.e., apoB- and non-apoB-containing lipoproteins. To analyze the relationship between the distribution of apoC-III and apoE among lipoproteins and coronary heart disease, we compared the distribution of these two apolipoproteins in survivors of myocardial infarction (MI) and control subjects, within and between populations at contrasting risk for MI. ApoC-III and apoE concentrations were determined in plasma devoid of apoB-containing lipoproteins by immunoprecipitation using a specific anti-apoB antiserum. These assays referred to apoC-III-Lp non-B and apoE-Lp non-B, respectively. By examining the difference with total plasma apoC-III and apoE levels, we calculated apoC-III and apoE in apoB-containing lipoproteins (apoCIII-LpB and apoE-LpB, respectively). These determinations were performed in control subjects and in survivors of MI, all males aged 25 to 64 years. They were recruited in Northern Ireland and France, countries characterized by a large difference in the incidence of coronary heart disease. In univariate analysis, apoCIII-LpB appeared significantly higher and the apoC-III ratio (apoC-III-Lp non-B/apoC-III-LpB) significantly lower in MI survivors than in control subjects in both countries. ApoE-LpB was higher in MI survivors than in control subjects in Northern Ireland but not in France. The two French and Irish control populations differed for apoC-ILL-Lp non-B, apoC-III ratio, and apoE ratio, which were higher in France than in Northern Ireland, and for apoC-III-LpB, apoE, and apoE-LpB, which were lower. Multivariate analysis showed that no parameter involving apoC-III and apoE was more discriminatory than HDL-cholesterol, cholesterol, and triglycerides or apoA-I, apoB, and triglycerides between controls and MI subjects. In contrast, the apoC-III ratio was a better discriminatory parameter between the two control populations than the listed parameters. The differences between the two control populations are of particular interest because they are not biased by the presence of disease or the large difference of the incidence in coronary heart disease between the two countries. It is suggested that the distribution of apoC-III among lipoproteins may play a role in the different susceptibility of the two populations to the atherogenic process.

Adult↗
PubMed1996

Effects of gender and menopausal status on plasma lipoprotein subspecies and particle sizes.

The risk of coronary heart disease (CHD) is lower in women than in men, but increases in women after menopause. Some of the gender, age, and menopausal-related differences in CHD risk may relate to differences in lipoprotein subspecies. We therefore examined these subspecies in three groups of healthy subjects: premenopausal women (W, n = 72, mean age 41.2 +/- 6.5), postmenopausal women (PMW, n = 74, 55.8 +/- 7.4), and men (M, n = 139, 48.8 +/- 10.7). We measured plasma levels of lipids, lipoprotein cholesterol, apolipoproteins A-I, A-IV, B, C-III, and E, and lipoprotein subspecies Lp A-I, Lp A-I:A-II, Lp B, Lp B:C-III, and Lp B:E, as well as LDL and HDL particle sizes. Our data indicate that women have significantly higher values of HDL-C, apoA-I, apoE, and Lp A-I; larger LDL and HDL particle sizes; and lower values of triglyceride, apoB, and Lp B:C-III particles than men, with no difference in Lp A-I:A-II. Postmenopausal status was associated with significantly higher values of total cholesterol, triglyceride, VLDL-C, and LDL-C; increased levels of apoB, C-III, and E; elevated values of Lp B, Lp B:C-III, and Lp B:E; and lower levels of HDL-C along with smaller HDL particle size. Moreover, we noted a strong correlation between LDL and HDL particle size. Our data are consistent with the concepts that male gender confers decreases in HDL subspecies due to lower Lp A-I levels; while postmenopausal status results in higher levels of all apoB-containing lipoproteins (Lp B, Lp B:C-III, and Lp B:E). The lipoprotein alterations associated with male gender and postmenopausal status would be expected to increase CHD risk.

Adult↗
PubMed1996

Serum Lp AI lipoprotein particles and other antiatherogenic lipid parameters in normolipidaemic obese subjects.

The android pattern of body fat distribution has been shown to increase the risk of metabolic and coronary heart disease. Protective lipid markers against cardiovascular disease were studied in 98 obese normolipidaemic, non diabetic, non-smoker subjects over 18 years of age according to regional distribution of adipose tissue as estimated by the waist ship ratio (WHR) and overall obesity as estimated by the body mass index (BMI). WHR was inversely correlated with Lp AI (r = 0.46) and HDL-cholesterol (r = 0.37). BMI was not correlated with protective lipid parameters but only with triglycerides. After adjustment, Lp AI was lower in men and in upper body obese women (p < 0.05). Lp AI is a better indicator of body fat distribution than HDL-cholesterol or apo AI, and its variations appear to be indirectly related to gender, menopause, and age, thereby influencing body fat distribution (the main factor accounting for Lp AI variation). Lp AI was inversely correlated with WHR in gluteal-femoral obese women but not in abdominally obese women or men, possibly because of a threshold effect.

Adult↗
PubMed1995

Changes in plasma apolipoprotein B-containing lipoparticle levels following therapy with fluvastatin and cholestyramine. European Fluvastatin Study Group.

Epidemiologic studies have demonstrated that apolipoprotein (apo) B-containing lipoparticles (LpE:B, LpC-III:B) are associated with the risk of coronary artery disease whereas apo A-1-containing lipoparticles (LpA-I) are protective against coronary artery disease. The effect on lipoparticle levels of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor fluvastatin, in combination with cholestyramine, was assessed in a double-blind randomized study. A total of 144 patients with primary hypercholesterolemia were recruited, who had successfully completed an original study comparing the effects of fluvastatin and cholestyramine on plasma lipoparticle levels. All subjects fulfilled the following inclusion criteria: plasma low density lipoprotein cholesterol (LDL-C) levels > 160 mg/dL, with premature coronary artery disease and 2 associated risk factors; or LDL-C > 190 mg/dL, no coronary artery disease, and triglycerides < 300 mg/dL, after a lipid-lowering diet. Patients were randomized to 1 of 3 combination therapy groups: fluvastatin 20 mg/day plus cholestyramine 4 g/day; fluvastatin 20 mg/day plus cholestyramine 8 g/day; and fluvastatin 20 mg/day plus cholestyramine 16 g/day. The study length was 6 weeks and patients were examined at 3-week intervals. Fluvastatin plus cholestyramine produced a significant (p < 0.001), dose-dependent reduction in levels of cholesterol (range, -29 to -34%), LDL-C (range, -30 to -44%), apo B (range, -23 to -34%), and apo E (range, -33 to -43%). LpE:B levels were also reduced (range, -19 to -26%), but not significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticholesteremic Agents↗
PubMed1995

Serum lipoprotein profile in Algerian patients with celiac disease.

Celiac disease is characterized by a gluten-induced villous atrophy of the upper small intestine which has an active role in the lipoprotein metabolism. In the present study the lipoprotein profiles of different patients were analyzed to determine the effect of impaired enterocyte function in celiac disease. We compared serum lipid parameters in controls and in celiac disease patients. The major differences between celiac disease patients and the control group were a diminution of cholesterol and phospholipids in HDL and LDL in the former. These differences persisted after treatment; in addition, a lower level of cholesterol in VLDL was observed. Plasma LpAI and apo A-I levels were significantly lower (-17 and -15%) in celiac disease patients than in controls. Both levels remained low after gluten-free diet. In Algerian patients, treatment with gluten-free diet did not give any return towards normal lipids concentrations.

Adolescent↗
PubMed1995

Comparison of the effect of fluvastatin, an hydroxymethyl glutaryl coenzyme A reductase inhibitor, and cholestyramine, a bile acid sequestrant, on lipoprotein particles defined by apolipoprotein composition.

In a double-blind, parallel-group, randomized study, the effects of fluvastatin (FLUV) 20 and 40 mg/d on lipoprotein particle levels were compared with those of cholestyramine (CME) 16 g/d. Lipoparticles were defined by apolipoprotein composition as either those containing both apolipoprotein (apo) B and apo E or CIII (lipoprotein [Lp] E-B or Lp CIII-B) or those containing apo AI alone (Lp AI) or in association with apo AII (Lp AI-AII). After an 8-week dietary stabilization period, 100 hypercholesterolemic patients were treated with FLUV 20 mg/d for 6 weeks and 40 mg/d for an additional 6 weeks and were compared with 48 hypercholesterolemic subjects treated with CME 16 g/d. Treatment with FLUV (40 mg/d) or CME (16 g/d) for 12 weeks was associated with a significant reduction in plasma cholesterol and low-density lipoprotein (LDL) cholesterol and a significant increase in high-density lipoprotein (HDL) cholesterol. However, plasma triglyceride levels decreased following FLUV treatment, whereas they increased with CME. These changes were associated with a significant reduction in the levels of apo B (FLUV, -24%, P < .001; CME, -26%, P < .001), apo E (FLUV, -36%, P < .001; CME, -32%, P < .001), and apo CIII (FLUV, -21%, P < .001; CME, -6%, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Efficacy of sequential hormone replacement therapy in the treatment of hypercholesterolaemia among postmenopausal women.

OBJECTIVES: To test the efficacy of hormone replacement therapy (HRT) and dietary therapy, compared to dietary therapy, in lowering LDL cholesterol levels among postmenopausal women. DESIGN: A prospective parallel randomized study of sequential 17 beta-oestradiol and norethisterone acetate or placebo for 48 weeks. SETTING: A University outpatient lipid clinic. SUBJECTS: A total of 76 postmenopausal women, aged 43-60 years, with LDL cholesterol levels > or = 4.2 mmol 1-1, treated with a lipid-lowering diet. MAIN OUTCOME MEASURES: Levels of lipids, lipoproteins, apolipoproteins, fibrinogen and glucose tolerance. RESULTS: Adherence to the diet was similar in both groups. Total and LDL cholesterol levels were reduced by 14% (95% CI, 11-17%) and 19% (95% CI, 14-23%), respectively, in the HRT group vs. 3% (95% CI, 0-7%) and 5% (95% CI, 0-11%) in the diet group. HRT reduced the levels of apolipoprotein B and lipoprotein(a). Levels of HDL cholesterol, HDL2, HDL3, triglycerides, lipoprotein populations and apolipoproteins AI and AII remained unchanged. No adverse effects on glucose tolerance or on fibrinogen levels were observed. The reduction in LDL cholesterol was positively correlated with initial levels of LDL cholesterol and negatively correlated with body mass index. CONCLUSIONS: HRT is effective in reducing elevated LDL cholesterol levels, and should be considered in the treatment of hyperlipidaemic postmenopausal women, in addition to dietary therapy.

Adult↗
PubMed1995

Modulation of lipoprotein B binding to the LDL receptor by exogenous lipids and apolipoproteins CI, CII, CIII, and E.

We have recently shown that apo B-containing lipoproteins isolated by immunoaffinity chromatography bind to the LDL receptor with an affinity dependent on their apo E or apo CIII content. However, these lipoproteins--LpB:E, LpB:CIII, and LpB:CIII:E--isolated from whole plasma have variable lipid and apolipoprotein contents, and it is difficult to consider each parameter separately, particularly because an increase in the apo CIII content is always associated with an increase in the content of other C apolipoproteins. Therefore, we used affinity-purified LpB free of other apolipoproteins. Lipid content of LpB was increased by incubation with a lipid emulsion, and this triglyceride-enriched LpB was named TG-LpB. Free apo CI, apo CII, apo CIII, and apo E were added to LpB and TG-LpB and their associations to the lipoprotein were assessed by gel filtration, nondenaturing electrophoresis, and immunoblotting. Molar ratios of 6 (apo E), 30 (apo CII), 20 (apo CIII), and 30 (apo CI) for 1 apo B were obtained. The association of apo CII to LpB and TG-LpB induced modifications to the LpB structure and a redistribution of lipids and apolipoproteins on the lipoprotein particles. The binding of these LpBs and TG-LpBs with and without added apo CI, CII, CIII, and E was tested at 4 degrees C on the LDL receptors of HeLa cells. The increased content of lipids reduced TG-LpB binding to the LDL receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein C-I↗
PubMed1995

The effect of diet on lipid, apoprotein and lipoparticle variation in the ECTIM study in Belfast.

The objective of the study was to evaluate the contribution of dietary factors to variation of plasma levels of lipids, apoproteins and lipoparticles in the Northern Ireland population. This study was part of a larger case-control study of the genetic and environmental determinants of myocardial infarction in France and Northern Ireland. A random sample of 175 middle aged men was drawn from the population covered by the Belfast MONICA project register. Habitual diet was assessed by a questionnaire. A blood sample was obtained after an over-night fast for determination of plasma levels of lipids, apoproteins and lipoparticles. All participants had a medical examination and completed a lifestyle questionnaire. In a stepwise regression, after adjusting for co-factors (i) vitamin C and (ii) alcohol consumption were the only nutrients which contributed significantly to the variation in, respectively, (i) Total Cholesterol, LDL Cholesterol and Apolipoprotein B (inverse correlation) and (ii) HDL Cholesterol and LpAI (positive correlation). The amount of variation explained by the final models was modest, ranging from 4% to 15%. In conclusion, in this Northern Ireland population, habitual diet contributes to little of the variation in plasma levels of lipids, apoproteins and lipoparticles.

Adult↗
PubMed1995

Lipoprotein lipase gene polymorphisms: associations with myocardial infarction and lipoprotein levels, the ECTIM study. Etude Cas Témoin sur l'Infarctus du Myocarde.

Several lipoprotein lipase (LPL) gene polymorphisms have been found associated with fasting lipid levels, but their impact on coronary heart disease (CHD) is less clearly established. We investigated associations of LPL polymorphisms (HindIII, PvuII, Ser447-->Ter) and the newly described mutation Asn291-->Ser with the risk of myocardial infarction (MI), severity of atherosclerosis, and fasting plasma lipoprotein concentrations in the ECTIM study (614 patients and 733 controls). The Ter447 allele had a lowering effect on triglycerides (P < 0.01), VLDL-cholesterol (P < 0.05), apoC-III (P < 0.001), LpE:B (P < 0.01), and LpCIII:B (P < 0.05), and a raising effect on apoA-I levels (P < 0.05). The H- allele of the HindIII polymorphism was associated with lower apoC-III (P < 0.01) and higher HDL-cholesterol (P < 0.05) levels. The PvuII and Asn291-->Ser polymorphisms did not exhibit any significant association with the biochemical traits examined. The HindIII genotype distributions differed between cases and controls, the odds ratios for MI associated with H+H+ and H+H- genotypes being 2.05 (P < 0.01) and 1.74 (P < 0.05) by reference to H-H-. The lack of association between Ser447-->Ter and MI suggested that this mutation was unlikely to be the cause of the association found with HindIII. In some cases, the severity of atherosclerosis assessed by coronarography increased with the presence of P+ allele (coronary scores: 1.41, 1.57, and 1.64 in P-P-, P-P+, and P+P+ individuals respectively, P < 0.05). A similar trend on the coronary score was observed with the presence of the Asn291-->Ser mutation (1.58 vs. 1.90, P = 0.06). Our results suggest that the LPL gene is involved in the determination of lipoprotein profiles, the predisposition to CHD, and the severity of atherosclerosis.

Adult↗
PubMed1994

Fluvastatin reduces levels of plasma apo B-containing particles and increases those of LpA-I. European Fluvastatin Study Group.

Epidemiologic studies have demonstrated an association between apolipoprotein (apo) B-containing particles (lipoprotein [Lp] E:B; LpC-III:B) and an inverse association between LpA-I and the risk of coronary artery disease (CAD). The effect of 6 weeks of treatment with fluvastatin (20 and 40 mg/day in the evening), a novel competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, on lipoparticle levels was studied in 423 patients with hypercholesterolemia after 14 weeks of standard dietary therapy. The combined data of the European double-blind controlled studies were used for the analysis. Two independent groups of hypercholesterolemic patients receiving fluvastatin (20 and 40 mg every evening) for 6 weeks were compared with a placebo group. For inclusion, patients had to fulfill the following criteria: plasma low-density lipoprotein (LDL) cholesterol levels > 160 mg/dL and premature CAD and/or two associated risk factors; LDL cholesterol > 190 mg/dL and no CAD; triglycerides < 300 mg/dL. All measurements were performed at the Pasteur Institute Central Laboratory, LpE:B and LpC-III:B were measured by double-site ELISA. Lipoprotein A-I and LpA-I:A-II were determined by differential electroimmunodiffusion. Treatment with 20 and 40 mg of fluvastatin was associated with reductions in plasma apo B (median change: -19.3% and -22.8%, respectively; p < 0.001), LpE:B (-12.5% and -22.6%, respectively; p < 0.001), and LpC-III:B (-3.6% and -36.8%, respectively; p < 0.001) particles compared with placebo. Significant increases in plasma apo A-I (1.7% and 4.8%, respectively; p < 0.001) and antiatherogenic LpA-I (2.3% and 6.9%, respectively; p < 0.001) were also observed. Levels of LpA-I:A-II were not affected by fluvastatin treatment. In conclusion, 6-week treatment with fluvastatin is associated with beneficial antiatherogenic changes in lipoparticle profiles in hypercholesterolemic patients.

Analysis of Variance↗