Biomedical subjects

P Marques-Vidal

Publications and source records attributed to P Marques-Vidal.

48 records · Page 3Linked to original sources

PubMed1995

Distribution, fatty acid composition and apolipoprotein A-I immunoreactivity of high density lipoprotein subfractions in myocardial infarction.

The lipoprotein profile, the HDL subfractions and the apolipoprotein (apo) A-I conformation of HDL were determined in 119 patients with myocardial infarction and 119 controls, paired for age. Apo A-I conformation was assessed by its immunoreactivity towards two monoclonal antibodies, 5F6 and 3G10. HDL phospholipid levels and fatty acid composition were also determined. HDL and HDL3 cholesterol, apo A-I, LpA-I and LpA-I:A-II levels were significantly lower in patients than in controls, whereas the levels of total and LDL-cholesterol and of apo B were not different. Apo A-I immunoreactivity against MAb 5F6 was significantly better in patients than in controls, while the immunoreactivity against 3G10 was similar. Paired stepwise logistic regression showed only apo A-I, HDL3 cholesterol and 5F6 immunoreactivity to be significantly related to myocardial infarction. After adjustment for HDL cholesterol, lower levels of HDL phospholipids and polyunsaturated fatty acids (PUFA) were found in patients compared with controls. Hence, of all HDL markers, apo A-I and HDL3 cholesterol appear to be the most informative. Also, lower HDL phospholipid and PUFA content may explain a different apo A-I conformation in patients with myocardial infarction.

Adult↗

PubMed1995

Cardiovascular risk factors and alcohol consumption in France and Northern Ireland.

The levels of different lipid, lipoprotein and haemostatic variables were assessed in 615 control subjects of the ECTIM Study, defined by five groups of alcohol consumption: non-drinkers, 0 < or = 15 g/day, 15 < . < or = 36 g/day, 36 < . < or = 66 g/day and > 66 g/day. After adjustment for age, body mass index, cigarette consumption and country, alcohol consumption was associated with an increase in HDL-cholesterol (0.47 +/- 0.02 to 0.59 +/- 0.01 g/l in non-drinkers and > 66 g/day consumers, mean +/- S.E.M., P < 0.0001), apolipoproteins A-I and A-II (1.37 +/- 0.03 to 1.60 +/- 0.03 g/l and 0.32 +/- 0.01 to 0.41 +/- 0.01 g/l, respectively, P < 0.0001), LpA-I, LpA-I:A-II (0.46 +/- 0.01 to 0.50 +/- 0.01 g/l and 0.75 +/- 0.02 to 0.91 +/- 0.02 g/l, respectively, P < 0.001) and PAi-1 activity (134 +/- 11 to 177 +/- 11 U/ml, P < 0.001). Conversely, no increases were found for total and LDL-cholesterol, triglycerides, apolipoproteins B and C-III, LpE:B, LpC-III:B, fibrinogen and factor VII. Hence, among the lipid and haemostatic variables studied, only HDL parameters and PAi-1 activity were increased by alcohol consumption.

Adult↗

PubMed1995

Medical treatment of myocardial infarction in France and Northern Ireland. Results from the ECTIM study. Enquête cas-Témoins de l'Infarctus du Myocarde.

As part of the ECTIM Study, the medical treatment given to male patients (25-64 years) 3 to 9 months after myocardial infarction (MI) were analysed in France and Northern Ireland. On univariate analysis, hypolipidaemic drugs, angiotensin-converting enzyme inhibitors and antiarrhythmic drugs were found to be prescribed more frequently in France, while beta-blockers were more common in Northern Ireland. No differences were found for diuretics, calcium channel blockers, antithrombotic and anti-anginal drugs, although the Northern Irish patients were mainly on antiplatelet drugs and nitrates, while the French patients received nitrates and non-nitrates, as well as oral anticoagulants and antiplatelet drugs in similar amounts. These differences remained after adjustment for personal history of diabetes, hyperlipidaemia, hypertension, and previous myocardial infarction, but the beta-blocker prescription was no longer significant. When the French centres were analysed, patients from Strasbourg were more frequently on oral anticoagulants and diuretics and less frequently on antiplatelet drugs, while patients from Toulouse had fewer anti-anginal drugs. Hence, although the current guidelines for secondary prevention of myocardial infarction are generally well applied in France and Northern Ireland, significant differences exist regarding the choice of the active drug.

Adult↗

PubMed1995

Alcohol intake modulates the effect of a polymorphism of the cholesteryl ester transfer protein gene on plasma high density lipoprotein and the risk of myocardial infarction.

A polymorphism of the CETP gene (CETP/TaqIB) with two alleles B1 (60%) and B2 (40%) has been investigated in relation to lipid variables and the risk of myocardial infarction in a large case-control study (ECTIM) of men aged 25-64. No association was observed between the polymorphism and LDL or VLDL related lipid variables. Conversely, B2 carriers had reduced levels of plasma CETP (P < 0.0001) and increased levels of HDL cholesterol (P < 0.0001) and of other HDL related lipid variables. The effects of the polymorphism on plasma CETP and HDL cholesterol were independent, suggesting the presence of at least two functional variants linked to B2. A search for these variants on the coding sequence of the CETP gene failed to identify them. The effect of B2 on plasma HDL cholesterol was absent in subjects drinking < 25 grams/d of alcohol but increased commensurably, with higher values of alcohol consumption (interaction: P < 0.0001). A similar interaction was not observed for plasma CETP. The odds-ratio for myocardial infarction of B2 homozygotes decreased from 1.0 in nondrinkers to 0.34 in those drinking 75 grams/d or more. These results provide the first demonstration of a gene-environment interaction affecting HDL cholesterol levels and coronary heart disease risk.

Adult↗

PubMed1995

Relationships of plasminogen activator inhibitor activity and lipoprotein(a) with insulin, testosterone, 17 beta-estradiol, and testosterone binding globulin in myocardial infarction patients and healthy controls.

The relationships between plasminogen activator inhibitor (PAi) activity and lipoprotein(a) [Lp(a)] and insulin, testosterone, 17 beta-estradiol, and testosterone binding globulin (TEBG) were assessed in 42 myocardial infarction male patients and 74 healthy controls. Patients had higher levels of insulin than did controls (87 +/- 30 vs. 75 +/- 28 pmol/L, respectively; P < 0.04), and no differences were found in levels of PAi activity, testosterone, 17 beta-estradiol, and TEBG. Lp(a) levels greater than 0.3 g/L were more frequent in patients than in controls (P < 0.002). In all subjects, PAi activity levels were significantly and positively correlated with body mass index (r = 0.20, P < 0.05), triglycerides (r = 0.38, P < 0.0001), and insulin (r = 0.27, P < 0.005) and were negatively correlated with testosterone (r = -0.28, P < 0.005) and TEBG (r = -0.42, P < 0.001). Stepwise multiple regression analysis showed triglyceride, insulin, and TEBG levels to be significantly related to PAi activity. No significant correlations were found between Lp(a) levels and all hormonal variables studied and between Lp(a) and PAi activity (r = -0.06, P < 0.58). These results suggest that TEBG is significantly and independently related to PAi levels.

Adult↗

PubMed1995

[Antiaggregants, aspirin, myocardial infarction and coronary deaths in the Haute-Garonne area].

The aim of this study was to determine changes in treatment of myocardial infarction between 1986 and 1989 in the Haute-Garonne region and, in particular, to assess the role of aspirin and antiaggregant therapy. The cases of 416 patients admitted to hospital for myocardial infarction in 1986 and 1989 were reviewed. During this period the prescription of acetylsalicyclic acid during the acute phase of myocardial infarction increased threefold (26.4 vs 72.9%; p < 0.001) and fivefold when associated with fibrinolytics, coronary bypass or angioplasty. Similarly, the prescription of aspirin at the time of hospital discharge doubled (from 32.6 to 69.5%; p < 0.001). The dosage of aspirin decreased from 500 mg and more per day in 1986 to a dosage of 250 mg or 100 mg per day in 1989. The most commonly prescribed preparation is lysine acetylsalicylate. The hospital mortality in the Haute-Garonne between 1985 and 1989 has decreased as observed in the Haute-garonne centre of the MONICA project. During the same period, the prescription of aspirin in association with angioplasty, bypass surgery and fibrinolytics, has undergone a remarkable increase. The changes observed during this period of observation are in perfect accord with results already published of therapeutic trials of antithrombotic agents in the acute phase or the post-infarction period (ISIS 2).

Aspirin↗

PubMed1994

Synergistic effects of angiotensin-converting enzyme and angiotensin-II type 1 receptor gene polymorphisms on risk of myocardial infarction.

We reported from our previous multicentre case-control study that the deletion (D) polymorphism of the gene encoding angiotensin-converting enzyme (ACE) was associated with increased risk of myocardial infarction. The main function of ACE is to convert angiotensin I into angiotensin II, which exerts its known cellular actions through the angiotensin II AT1 receptor subtype (AGT1R). We have now investigated the role of a common polymorphism of the AT1 receptor gene (an A-->C transversion at position 1166 of AGT1R) and looked for an interaction between ACE and AGT1R gene polymorphisms on the risk of myocardial infarction. We analysed DNA from 613 patients with myocardial infarction and 723 age-matched population controls. We found a significant interaction between ACE and AGT1R gene polymorphisms; the odds ratio for myocardial infarction associated with the ACE DD genotype was 1.05 (95% CI 0.75-1.49) for subjects without the AGT1R C allele, 1.52 (1.06-2.18) in AC heterozygotes, and 3.95 (1.26-12.4) in CC homozygotes (test for trend, p < 0.02). Among patients defined as low risk by traditional risk factors (serum apolipoprotein B < 1.25 g/L, body-mass index < 26 kg/m2) the interaction was even stronger (odds ratios 1.64 [0.68-3.92], 7.03 [2.61-19.0], and 13.3 [p = 0.05], respectively). These findings, if confirmed, could have clinical implications for the prevention and treatment of coronary heart disease.

Adult↗

PubMed1994

[Characteristics of patients with coronary disease and aspirin prescription in Haute-Garonne].

The MONICA Haute-Garonne Centre studied the incidence of myocardial infarction and death from coronary heart disease in 1,762 cases between 1985 and 1989. Changes in treatment were analysed in the subgroup of 416 patients admitted to hospital for myocardial infarction in 1986 and in 1989. The incidence of myocardial infarction decreased in men from 218.4 to 183.9 per 100,000 inhabitants (p < 0.01) and decreased nonsignificantly in women from 19.3 to 23.2 per 100,000 inhabitants (NS). The decreased incidence of myocardial infarction in men was exclusively due to a decrease by one-third of the incidence of infarction in patients with diagnosed coronary heart disease. Although the community mortality remained stable, the hospital mortality decreased by one half in man between 1985 and 1989 (21% versus 10%, respectively, p < 0.001). Between 1986 and 1989, the prescription of acetylsalicylic acid during the acute phase increased threefold (26.4% versus 72.9%, p < 0.001) and increased fivefold when coprescribed with fibrinolytics. Similarly, the prescription of aspirin on discharge from hospital doubled (from 32.6% to 69.5%, p < 0.001). The dosage of aspirin decreased from 500 mg or more per day in 1986 to a daily dose of approximately 250 mg in 1989. Lysine acetylsalicylate was the form most widely prescribed. In this population, patients treated by antithrombotics (aspirin or fibrinolytics) had a more favourable prognosis than patients not receiving any of these treatments. The changes observed in this study population are in line with the published results of therapeutic trials on antithrombotics in the acute phase of myocardial infarction and in the postinfarction phase (GISSI2, ISIS2).

Adult↗

PubMed1994

Hepatic lipase promotes the uptake of HDL esterified cholesterol by the perfused rat liver: a study using reconstituted HDL particles of defined phospholipid composition.

The role of hepatic triacylglycerol lipase (H-TGL) in promoting the liver uptake of high density lipoprotein (HDL) free and esterified cholesterol was studied in a recirculating rat liver perfusion, a situation where the enzyme is physiologically expressed and is active at the vascular bed. For this purpose, reconstituted HDL of defined phospholipid composition were prepared, containing either 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, a substrate for H-TGL, or 1-O-hexadecyl-2-oleoyl-sn-glycero-3-phosphocholine, a non-hydrolyzable analog. Reconstituted HDL were then used in the perfused rat liver system. The main results are the following. 1) Reconstituted HDL were obtained by sonication of lipids and apolipoproteins and isolated by ultracentrifugation in the 1.07-1.21 g/ml density interval. Reconstituted HDL containing either diacylphosphatidylcholine or alkyl-acyl-phosphatidylcholine were similar in terms of chemical composition, apparent size, and apolipoprotein A-I immunoreactivity, and were comparable to native HDL3. 2) Reconstituted HDL were labeled with free [14C]cholesterol and [3H]cholesteryl ether, a non-hydrolyzable tracer of esterified cholesterol, and were perfused through the rat liver. Liver uptake of [3H]cholesteryl ether was 2.5-fold higher from reconstituted HDL containing diacylphospholipid than from HDL reconstituted with alkyl-acyl-phospholipids. Liver uptake of free [14C]cholesterol was identical in both cases. 3) H-TGL-depleted rat livers were obtained by a 12-min preperfusion in the presence of heparin, displacing 90% of the enzymatic activity. The residual activity in the perfusate was inhibited by a specific antibody directed against rat H-TGL. Liver uptake of [3H]cholesteryl ether from reconstituted HDL containing diacylphospholipid was reduced by 35% in hepatic lipase-depleted livers compared to controls. On the other hand, hepatic lipase depletion had no effect on the liver uptake of esterified cholesterol from HDL reconstituted with alkyl-acyl-phospholipids. The above findings support a role for the phospholipase A1 activity of H-TGL in stimulating the delivery of HDL esterified cholesterol to liver cells.

Animals↗

PubMed1994

[Measurement errors and linear regression].

The consequences of a measurement error of known variance in the explanatory variable of a linear regression were assessed. On the average, the ordinary least squares (OLS) method underestimated the regression slope, the bias increasing with the variance of the measurement error and the strength of the relationship. Simulation results showed that the corrected-for-the-error estimate slightly overestimated the slope, the bias increasing with the variance of the measurement error and the strength of the relationship, but rapidly decreasing when the number of observations increased. In all cases the corrected estimate has a larger variance than the OLS estimate, Nevertheless, the mean square deviation of the corrected estimate to the "true" slope value can be smaller than the OLS one, even for a relatively small number of observations (< or = 100). In those conditions, the corrected estimate might be preferred when a "good estimation" of the regression slope is needed. Whereas a measurement error in the dependent variable, does not bias the slope estimator, when it is independent of the error in the explanatory variable, this is not the case when both measurement errors are correlated. An example of the need to correct for such a correlation is given.

Bias↗

PubMed1991

Hepatic lipase-mediated hydrolysis versus liver uptake of HDL phospholipids and triacylglycerols by the perfused rat liver.

Hepatic triacylglycerol-lipase-mediated hydrolysis and liver uptake of high-density lipoprotein (HDL) lipid components were studied in a recirculating rat liver perfusion, a situation where the enzyme is physiologically expressed and active at the vascular bed. Human native HDL were labelled with tri-[3H]oleoylglycerol, [N-methyl-3H]dipalmitoylphosphatidylcholine (DPPC), 1-palmitoyl,2-[14C]linoleoylphosphatidylcholine (PLPC), 1-palmitoyl,2-[14C]linoleoylphosphatidyl-ethanolamine (PLPE) and 1-palmitoyl,2-[14C]palmitoylphosphatidylethanolamine (DPPE). (1) Relative degradation rates of phosphatidylethanolamine molecular species were 2- to 10-fold higher than those of phosphatidylcholine. Considering [14C] PLPC and [14C] PLPE as representative of HDL phosphatidylcholine and phosphatidylethanolamine, respectively, the amounts of lysophosphatidylcholine and lysophosphatidylethanolamine generated after a 60 min perfusion were comparable. The enzyme showed a clear preference for the molecular species bearing an unsaturated fatty acid at the 2 position of glycerol; this was the most pronounced in the case of phosphatidylethanolamine molecular species. (2) Relative liver uptake of HDL-phosphatidylethanolamine was 4- to 5-fold higher than that of HDL-phosphatidylcholine, irrespective of the constitutive fatty acids. Nevertheless, mass estimation indicated that 3 times more molecules of phosphatidylcholine than of phosphatidylethanolamine were transferred. No correlation could be found between the relative degradation rates of phospholipids and their relative liver uptake, indicating a dissociation between the two processes. (3) Perfusate decay and relative liver uptake of labelled HDL-triacylglycerol were higher than that of any phospholipid class. No circulating radiolabelled free fatty acids accumulated in the perfusate, but they were found acylated into liver cell phospholipids and triacylglycerols. (4) A prior 10-12-min washout of the liver vascular bed with heparin removed over 80% of the hepatic lipase activity, as assessed by specific immunoinhibition. Hepatic lipase-depleted liver displayed impaired phospholipid hydrolysis and triacyglycerol uptake, whereas the transfer of HDL phospholipids to liver tissue was unaffected.

Animals↗

PubMed1990

Kinetic evidence for phosphatidylethanolamine and triacylglycerol as preferential substrates for hepatic lipase in HDL subfractions: modulation by changes in the particle surface, or in the lipid core.

Human HDL subfractions, HDL2 (d: 1.085-1.125) and HDL3 (d: 1.125-1.19) labelled with 2-[14C]linoleoylphosphatidylethanolamine and tri-[3H]oleoylglycerol, were incubated with partially purified hepatic triacylglycerol lipase, isolated from human post-heparin plasma. Kinetics of hydrolysis of these two HDL-lipid substrates were followed and were compared to those previously obtained on phosphatidylcholine (G. Simard et al (1989) Biochim. Biophys. Acta 1001, 225-233). (1) The apparent Km obtained for HDL-triacylglycerol was half that for HDL-phosphatidylethanolamine, but the estimated Vmax was higher for the latter. Hence, despite a lower affinity, more molecules of phosphatidylethanolamine than of triacylglycerol were found hydrolysed. A strong correlation was observed between the hepatic lipase activity added and the maximal degradation rates for phosphatidylethanolamine measured in HDL2 and HDL3. (2) A linear relationship was observed in both HDL2 and HDL3 between the respective degradations of the two substrates. The number of phosphatidylethanolamine molecules hydrolysed exceeded that of triacylglycerol by 30% in HDL2 and by 70% in HDL3. HDL2 were 2- and 4-times more reactive than HDL3 for the hydrolysis of phosphatidylethanolamine and triacylglycerol, respectively, taking the Vmax/Km ratio as an indicator of catalytic efficiency. In both HDL subfractions, the calculated Vmax/Km value was 30-50-fold higher for PE and TG than for PC. (3) HDL particles were modified either on their surface by selective enrichment in free cholesterol or in their inner-core by replacement of esterified cholesterol by triacylglycerol in presence of a source of neutral lipid transfer activity. A mild cholesterol enrichment stimulated the phosphatidylethanolamine and triacylglycerol reactivities by 30-60% towards hepatic lipase, whereas increasing the triacylglycerol concentration in HDL was followed by a proportional increase in the amounts of triacylglycerol hydrolysed with no effect on phospholipid degradation.

Cholesterol↗