Etude multicentrique d'intervention nutritionnelle LipGene (effets de la qualité et de la quantité des acides gras alimentaires chez des sujets présentant un syndrome métabolique)

Le syndrome métabolique n'est pas une maladie spécifique, mais désigne plutôt une association de dysfonctionnements métaboliques modérés liés aux risques cardio-vasculaires: insulino-résistance, hyperglycémie, hyper-triglycéridémie, hypertension et excès de poids. L étude d intervention nutritionnelle LipGene est une étude européenne multicentrique menée sur une cohorte de 486 volontaires présentant un syndrome métabolique d après les critères de la NCEP-ATPIII. Le principal objectif de LipGene est d étudier l impact de la qualité et de la quantité des lipides alimentaires sur de nombreux paramètres liés à l insulino-résistance, principale composante du syndrome métabolique. Les volontaires ont été randomisés dans quatre régimes avec des teneurs variées d AGS, d AGMI, d AGPI et de glucides. L intervention nutritionnelle a duré 12 semaines et a permis d étudier les variations des profils glucidiques, lipidiques, des paramètres inflammatoires et du stress oxydant et les variations de marqueurs liés aux dysfonctions endothéliales. Une des originalités de cette étude est d avoir appliqué avec succès un modèle diététique unique à travers les huit centres européens participants. Le modèle de substitution alimentaire mis en place lors de l intervention nutritionnelle a permis une bonne compliance aux régimes et des objectifs d apports lipidiques et glucidiques atteints dans les 4 groupes de régimes. Après 12 semaines de régime, l état d insulino-résistance des volontaires SM n apparaît pas directement affecté par les 4 régimes mais les effets observés sur les marqueurs de l insulinorésistance semblent très dépendants de la composition lipidique des habitudes alimentaires de base. Nous avons confirmé l effet hypotriglycéridémiant des AGPI n-3 quand, en complément dans un régime pauvre en lipides mais hyperglucidiques, ces acides gras permettaient d atténuer l hypertriglycéridémie généralement observée avec ce type de régime sans supplémentation. Le profil lipidique des sujets SM et notamment leur métabolisme du cholestérol est affecté par les régimes riches en glucides même s ils sont pauvres en lipides. Les taux des marqueurs de l inflammation, de la coagulation ou encore du stress oxydant n ont pas été modifiés par l intervention nutritionnelle. La formation d une sous-cohorte Méditerranéenne a permis quelques études additionnelles. Parmi celles-ci, l étude du dysfonctionnement endothéliale a été réalisée par quantification des microparticules circulantes. Avant analyse de l intervention nutritionnelle sur ces taux de microparticules, il est intéressant de souligner l élévation de microparticules de diverses origines dans notre population SM comparée à une population contrôle ainsi que le lien de corrélation de ces microparticules avec un marqueur du stress oxydant.AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

The Medi-RIVAGE study: reduction of cardiovascular disease risk factors after a 3-mo intervention with a mediterranean-type diet or a low-fat diet

International audienceBackground: Epidemiologic studies link Mediterranean-type diets to a low incidence of cardiovascular disease; however, few dietary intervention studies have been undertaken, especially in primary prevention. Objectives: In the Mediterranean Diet, Cardiovascular Risks and Gene Polymorphisms (Medi-RIVAGE) study, the effects of a mediterranean-type diet (Med group) or a low-fat diet (low-fat group) on risk factors were evaluated in 212 volunteers (men and women) with moderate risk factors for cardiovascular disease. Design: After the 3-mo dietary intervention, changes in many risk factors were evaluated. Dietary questionnaires and plasma nutritional markers were used to test compliance. Results: Although the dietary goals were only partially reached, changes in dietary habits were observed in both groups (n=169): protein, carbohydrate, and fiber intakes increased and fat quality (decreased saturated fat and increased monounsaturated or polyunsaturated fat) improved. BMI, total and triacylglycerol-rich lipoprotein (TRL) cholesterol, triacylglycerols, TRL triacylglycerols, apolipoproteins A-I and B, insulinemia, glycemia, and the homeostasis model assessment score were significantly lower after 3 mo. The reductions in total cholesterol, triacylglycerols, and insulinemia remained significant after adjustment for BMI. There was a trend for a diet-by-time interaction for LDL cholesterol (P= 0.09). Our data predicted a 9% reduction in cardiovascular disease risk with the low-fat diet and a 15% reduction with this particular Mediterranean diet. Conclusion: After a 3-mo intervention, both diets significantly reduced cardiovascular disease risk factors to an overall comparable exten

Ticagrelor Increases Adenosine Plasma Concentration in Patients With an Acute Coronary Syndrome

International audienceObjectives: This study aimed to investigate the impact of ticagrelor on adenosine plasma concentration (APC) in acute coronary syndrome (ACS) patients.Background: Ticagrelor is a direct-acting P2Y12-adenosine diphosphate receptor blocker. The clinical benefit of ticagrelor compared with clopidogrel in ACS patients suggests that the drug has non–platelet-directed properties. Animal and in vitro models suggested that the “pleiotropic” properties of ticagrelor may be related to an interaction with adenosine metabolism.Methods: We prospectively randomized 60 ACS patients to receive ticagrelor or clopidogrel. The APC was measured by liquid chromatography. To assess the mechanism of APC variation, we measured adenosine deaminase concentration, adenosine uptake by red blood cells, and cyclic adenosine monophosphate production by cells overexpressing adenosine receptors. The P2Y12-adenosine diphosphate receptor blockade was assessed by the vasodilator-stimulated phosphoprotein index.Results: Patients receiving ticagrelor had significantly higher APC than patients receiving clopidogrel (1.5 μM [interquartile range: 0.98 to 1.7 μM] vs. 0.68 μM [interquartile range: 0.49 to 0.78 μM]; p < 0.01). The APC was not correlated with vasodilator-stimulated phosphoprotein (p = 0.16). Serum-containing ticagrelor inhibited adenosine uptake by red blood cells compared with clopidogrel or controls (p < 0.01 for both comparisons). Adenosine deaminase activity was similar in serum of patients receiving clopidogrel or ticagrelor (p = 0.1). Ticagrelor and clopidogrel had no direct impact on adenosine receptors (p = not significant).Conclusions: Ticagrelor increases APC in ACS patients compared with clopidogrel by inhibiting adenosine uptake by red blood cells

NOS3 gene polymorphisms are associated with risk markers of cardiovascular disease, and interact with omega-3 polyunsaturated fatty acids

Objective Omega-3 polyunsaturated fatty acids (n-3 PUFA) may protect against the development of cardiovascular disease (CVD). Genotype at key genes such as nitric oxide synthase (NOS3) may determine responsiveness to fatty acids. Gene–nutrient interactions may be important in modulating the development of CVD, particularly in high-risk individuals with the metabolic syndrome (MetS). Methods Biomarkers of CVD risk, plasma fatty acid composition, and NOS3 single nucleotide polymorphism (SNP) genotype (rs11771443, rs1800783, rs1800779, rs1799983, rs3918227, and rs743507) were determined in 450 individuals with the MetS from the LIPGENE dietary intervention cohort. The effect of dietary fat modification for 12 weeks on metabolic indices of the MetS was determined to understand potential NOS3 gene–nutrient interactions. Results Several markers of inflammation and dyslipidaemia were significantly different between the genotype groups. A significant gene–nutrient interaction was observed between the NOS3 rs1799983 SNP and plasma n-3 PUFA status on plasma triacylglycerol (TAG) concentrations. Minor allele carriers (AC + AA) showed an inverse association with significantly higher plasma TAG concentrations in those with low plasma n-3 PUFA status and vice versa but the major allele homozygotes (CC) did not. Following n-3 PUFA supplementation, plasma TAG concentrations of minor allele carriers of rs1799983 were considerably more responsive to changes in plasma n-3 PUFA, than major allele homozygotes. Conclusions Carriers of the minor allele at rs1799983 in NOS3 have plasma TAG concentrations which are more responsive to n-3 PUFA. This suggests that these individuals might show greater beneficial effects of n-3 PUFA consumption to reduce plasma TAG concentrations

Effects of dietary fat modification on oxidative stress and inflammatory markers in the LIPGENE study.

Subjects with the metabolic syndrome (MetS) have enhanced oxidative stress and inflammation. Dietary fat quality has been proposed to be implicated in these conditions. We investigated the impact of four diets distinct in fat quantity and quality on 8-iso-PGF2α (a major F2-isoprostane and oxidative stress indicator), 15-keto-13,14-dihydro-PGF2α (15-keto-dihydro-PGF2α, a major PGF2α metabolite and marker of cyclooxygenase-mediated inflammation) and C-reactive protein (CRP). In a 12-week parallel multicentre dietary intervention study (LIPGENE), 417 volunteers with the MetS were randomly assigned to one of the four diets: two high-fat diets (38 % energy (%E)) rich in SFA or MUFA and two low-fat high-complex carbohydrate diets (28 %E) with (LFHCC n-3) or without (LFHCC) 1·24 g/d of very long chain n-3 fatty acid supplementation. Urinary levels of 8-iso-PGF2α and 15-keto-dihydro-PGF2α were determined by RIA and adjusted for urinary creatinine levels. Serum concentration of CRP was measured by ELISA. Neither concentrations of 8-iso-PGF2α and 15-keto-dihydro-PGF2α nor those of CRP differed between diet groups at baseline (P>0·07) or at the end of the study (P>0·44). Also, no differences in changes of the markers were observed between the diet groups (8-iso-PGF2α, P = 0·83; 15-keto-dihydro-PGF2α, P = 0·45; and CRP, P = 0·97). In conclusion, a 12-week dietary fat modification did not affect the investigated markers of oxidative stress and inflammation among subjects with the MetS in the LIPGENE study

Dietary fat modifications and blood pressure in subjects with the metabolic syndrome in the LIPGENE dietary intervention study

Hypertension is a key feature of the metabolic syndrome. Lifestyle and dietary changes may affect blood pressure (BP), but the knowledge of the effects of dietary fat modification in subjects with the metabolic syndrome is limited. The objective of the present study was to investigate the effect of an isoenergetic change in the quantity and quality of dietary fat on BP in subjects with the metabolic syndrome. In a 12-week European multi-centre, parallel, randomised controlled dietary intervention trial (LIPGENE), 486 subjects were assigned to one of the four diets distinct in fat quantity and quality: two high-fat diets rich in saturated fat or monounsaturated fat and two low-fat, high-complex carbohydrate diets with or without 1·2 g/d of very long-chain n-3 PUFA supplementation. There were no overall differences in systolic BP (SBP), diastolic BP or pulse pressure (PP) between the dietary groups after the intervention. The high-fat diet rich in saturated fat had minor unfavourable effects on SBP and PP in males