128 results on '"Després, Jean-Pierre"'
Search Results
2. List of contributors
- Author
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Abdesselam, Ines, primary, Agarwal, Monica, additional, Ajie, Mandala, additional, Bakermans, Adrianus J., additional, Bauwens, Matthias, additional, Boesch, Chris, additional, Brady, Emer M., additional, Brady, Michael, additional, Brethauer, Stacy A., additional, Bulte, Daniel, additional, Christ, Emanuel, additional, Dekkers, Ilona A., additional, de Mutsert, Renée, additional, de Roos, Albert, additional, Després, Jean-Pierre, additional, English, Wayne J., additional, Fischli, Stefan, additional, Flynn, Charles R., additional, Gaborit, Bénédicte, additional, Gulsin, Gaurav S., additional, Henson, Joseph, additional, Higuchi, Ryota, additional, (Onno) Holleboom, A.G., additional, Jansen, Philip, additional, Jermendy, György, additional, Jiang, Janey, additional, Joles, Jaap A., additional, Just, Ivica, additional, Keller, J.J., additional, Klepochová, Radka, additional, Krebs, Michael, additional, Kreis, Roland, additional, Krššák, Martin, additional, Lamb, Hildo J., additional, Levelt, Eylem, additional, Lin, Ling, additional, Loher, Hannah, additional, MacCannell, Amanda, additional, Maurovich-Horvat, Pál, additional, Menzel, Christopher P., additional, Murakami, Daisuke, additional, Nadolsky, Karl, additional, Nguyen, Isabel T.N., additional, Numans, Mattijs E., additional, O'Neill, Sean M., additional, Paulus, Andreas, additional, Pijl, Hanno, additional, Rayner, Jennifer J., additional, Robson, Matthew, additional, Ruissen, M.M., additional, Saito, Yuichi, additional, Sala, Michiel, additional, Scherer, Thomas, additional, Schoonakker, Marjolein P., additional, Seidell, Jacob C., additional, Senn, Janina, additional, Severin, Sonia, additional, Stienstra, Rinke, additional, Straw, Sam, additional, Triay Bagur, Alexandre, additional, Tronieri, Jena Shaw, additional, Tushuizen, Maarten E., additional, Valet, Philippe, additional, van den Burg, Elske L., additional, van Peet, Petra G., additional, van Son, Koen C., additional, Verhaar, Marianne C., additional, and Wolf, Peter, additional
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- 2023
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3. Influences of the phosphatidylcholine transfer protein gene variants on the LDL peak particle size
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Dolley, Guillaume, Berthier, Marie-Thérèse, Lamarche, Benoît, Després, Jean-Pierre, Bouchard, Claude, Pérusse, Louis, Vohl, Marie-Claude, Dolley, Guillaume, Berthier, Marie-Thérèse, Lamarche, Benoît, Després, Jean-Pierre, Bouchard, Claude, Pérusse, Louis, and Vohl, Marie-Claude
- Abstract
Background: The small, dense LDL phenotype is associated with an increased cardiovascular disease risk. A genome-wide scan performed on 236 nuclear families of the Quebec Family Study (QFS) revealed a quantitative trait locus (QTL) affecting LDL peak particle size (LDL-PPD) and density on the 17q21 region. This region contains the phosphatidylcholine transfer protein gene (PCTP). In the liver, phosphatidylcholine transfer protein binds specifically phosphatidylcholine suggesting a role for this protein in the formation of HDL and possibly VLDL phospholipid membranes. Objectives: To test the association between two coding polymorphisms (c.29A>C (Glu10Ala) and c.188G>A (Cys63Tyr)) in PCTP gene and the LDL-PPD. Methods: LDL-PPD was measured by non-denaturating 2–16% polyacrylamide gradient gel electrophoresis on 623 QFS subjects. Results: After adjustment for age and sex, carriers of the c.29C allele showed larger LDL-PPD than A/A homozygotes (p < 0.05). These results remained significant when LDL-PPD was further adjusted for the effects of BMI and triglyceride levels (p < 0.04). We also observed a three-fold lower risk of having the small (LDL-PPD <256 Å), dense LDL phenotype in subjects carrying the c.29C allele, when compared to A/A homozygotes (OR = 0.35 (95% CI: 0.14–0.91; p = 0.03)). Conclusion: PCTP gene variants are associated with LDL-PPD.
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- 2021
4. Relative contribution of low-density lipoprotein receptor and lipoprotein lipase gene mutations to angiographically assessed coronary artery disease among French Canadians
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Perron, Patrice, Gaudet, Daniel, Julien, Pierre, Tremblay, Gérald, Vohl, Marie-Claude, Després, Jean-Pierre, Gagné, Claude, Moorjani, Sital, Bergeron, Jean, Perron, Patrice, Gaudet, Daniel, Julien, Pierre, Tremblay, Gérald, Vohl, Marie-Claude, Després, Jean-Pierre, Gagné, Claude, Moorjani, Sital, and Bergeron, Jean
- Abstract
Men with low-density lipoprotein receptor gene mutations causing familial hypercholesterolemia (FH) are at high risk of premature coronary artery disease (CAD). The dyslipidemic state found among patients who are heterozygous for mutations in the lipoprotein lipase (LPL) gene may also increase the risk of CAD. In the present study, the association of the heterozygous forms of low-density lipoprotein receptor gene mutations causing FH as well as of LPL gene mutations causing (P207L and G188E) or not causing (D9N and N291S) complete loss of LPL activity with angiographically assessed CAD was estimated in a cohort of 412 French Canadian men aged <60 years who consecutively underwent coronary angiography for the investigation of retrosternal pain. The frequency of FH as well as of LPL gene mutations tended to increase with the number of narrowed coronary arteries. However, CAD occurred earlier in FH patients than in partly LPL-deficient patients. Indeed, the proportion of men affected by FH was of 16.4% in those <45 years of age, and solely 4.3% among those between 56 and 60 years of age (p <0.0001). In contrast, the LPL gene defect was found in only 4.0% of men aged <45 years, whereas this prevalence reached 8.3% among those aged 56 to 60 years. In multivariate analyses, the association of LPL with CAD was not independent of age, high-density lipoprotein cholesterol concentrations, and other covariates included at baseline, and was not affected by the type of mutation in the LPL gene. In contrast, FH was associated with CAD with minimal contribution of other cardiovascular risk factors. However, the relation between FH and CAD was at least partly dependent on plasma apolipoprotein B concentrations. In the different regression models, fasting insulin and plasma high-density lipoprotein cholesterol concentrations were important covariates of CAD, whether or not patients were affected by FH or LPL deficiency. In conclusion, the association of LPL gene mutations with CAD w
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- 2020
5. Visceral obesity attenuates the effect of the hepatic lipase −514C > T polymorphism on plasma HDL-cholesterol levels in French-Canadian men
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St-Pierre, Julie, Gaudet, Daniel, Miller-Felix, Isabelle, Lamarche, Benoît, Paradis, Marie-Ève, Vohl, Marie-Claude, Després, Jean-Pierre, Bergeron, Jean, St-Pierre, Julie, Gaudet, Daniel, Miller-Felix, Isabelle, Lamarche, Benoît, Paradis, Marie-Ève, Vohl, Marie-Claude, Després, Jean-Pierre, and Bergeron, Jean
- Abstract
The dyslipidemic state of visceral obesity is characterized by increased plasma triglyceride (TG) levels, low HDL-cholesterol concentrations and alterations in LDL composition and concentration. A functional, non-coding −514C>T single nucleotide polymorphism (SNP) of the hepatic lipase gene (LIPC) has been related to variation in HDL-cholesterol concentrations. Objectives: To investigate the hypotheses that the LIPC −514C>T polymorphism may be associated with a deteriorated lipoprotein-lipid profile and that environmental factor, such as abdominal obesity, alters this association. Methods: A total of 235 French-Canadian men from the greater Quebec City area were assigned into three groups on the basis of their LIPC −514C>T SNP, including 149 CC homozygotes, 75 CT heterozygotes, and 11 TT homozygotes. Results: In the present study, the highest values of BMI, waist circumference, and accumulation of visceral adipose tissue (VAT) were observed among TT homozygotes (p<0.05). After adjustment for age and BMI, TT homozygotes still showed higher plasma apolipoprotein (apo) AI and HDL-TG concentrations than the two other groups (p<0.05). When the two genotype groups (CC vs CT/TT) were further divided on the basis of VAT accumulation using a cut-off point of 130 cm2 (high vs low) it appears that irrespective of the genotype subjects with low VAT had higher HDL2-cholesterol concentrations (p<0.0001). However, lean carriers of the T allele had higher plasma HDL2-cholesterol levels than lean CC homozygotes. The beneficial effect of the T allele on plasma HDL2-cholesterol levels was abolished in the presence of visceral obesity (VAT>130 cm2). Conclusion: In summary, the presence of visceral obesity attenuates the impact of the LIPC −514C>T polymorphism on plasma HDL2-cholesterol levels.
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- 2020
6. Detection of a major gene effect for LDL peak particle diameter and association with apolipoprotein H gene haplotype
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Bouchard, Claude, Feitosa, Mary F., Pérusse, Louis, Lamarche, Benoît, Bossé, Yohan, Rice, Treva, Vohl, Marie-Claude, Rao, D. C. (Dabeeru C.), Després, Jean-Pierre, Bouchard, Claude, Feitosa, Mary F., Pérusse, Louis, Lamarche, Benoît, Bossé, Yohan, Rice, Treva, Vohl, Marie-Claude, Rao, D. C. (Dabeeru C.), and Després, Jean-Pierre
- Abstract
Low-density lipoprotein (LDL) size, a coronary heart disease risk factor, is influenced by both genetic and environmental factors. Results from the Quebec Family Study (QFS) revealed that the LDL peak particle diameter (LDL-PPD) aggregates in families with a heritability coefficient above 50% and is affected by a major quantitative trait locus on chromosome 17q (LOD=6.8). Complex segregation analyses have consistently demonstrated a major gene effect influencing LDL size. In the present study, we report a similar analysis in the QFS cohort, which suggests that a major gene explains 23% of the variance in age-body mass index and triglyceride-adjusted LDL-PPD. The most intuitive positional candidate gene on chromosome 17q is the apolipoprotein H gene. Direct sequencing of the promoter, coding regions, and exon-intron splicing boundaries of this gene revealed the presence of three missense mutations and two polymorphisms in the untranslated regions. Using family-based association tests, none of these variants was individually associated with LDL-PPD. However, analysis of the haplotypes constructed from the three missense mutations, suggested that one particular haplotype (frequency=20.9%) was associated with a significant increase in LDL-PPD trait values (p=0.046). Taken together, these results suggest the presence of a major gene effect influencing LDL-PPD and a positive association with a positional candidate gene located on chromosome 17q. Replication of the association between apolipoprotein H gene haplotype and LDL-PPD is required before reaching firm conclusion.
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- 2020
7. Relation of the “Hypertriglyceridemic Waist” phenotype to earlier manifestations of coronary artery disease in patients with glucose intolerance and type 2 diabetes mellitus
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St-Pierre, Julie, Perron, Patrice, Gaudet, Daniel, Brisson, Diane, Vohl, Marie-Claude, Santuré, Marta, Després, Jean-Pierre, St-Pierre, Julie, Perron, Patrice, Gaudet, Daniel, Brisson, Diane, Vohl, Marie-Claude, Santuré, Marta, and Després, Jean-Pierre
- Abstract
This study tested the hypothesis that the “hypertriglyceridemic waist” phenotype (waist girth >90 cm [35.4 inches] in men and >85 cm [33.5 inches] in women, along with a plasma triglyceride concentration of ≥2.0 mmol/L [177 mg/dl]) as a covariate of metabolic syndrome features (hyperinsulinemia, hyperapolipoprotein B, and small low-density lipoprotein particles), is predictive of premature coronary artery disease (CAD) among patients with glucose intolerance or type 2 diabetes. Glucose intolerance and type 2 diabetes were assessed after an oral glucose tolerance test among 1,190 men and women using the American Diabetes Association criteria. Glycemic control was evaluated using hemoglobin A1c levels. CAD was considered present on the basis of a clinical history of retrosternal pains on exertion, electrophysiologically and clinically documented myocardial infarction, or angiographic evidence of coronary lesions. More than 53% of men (n = 103) with a waist circumference ≥90 cm (35.4 inches) and nearly 80% of women (n = 122) with a waist circumference ≥85 cm (33.5 in.) with triglyceride levels ≥2 mmol/L (177 mg/dl) were diagnosed with glucose intolerance or type 2 diabetes. Survival models revealed that those with glucose intolerance or type 2 diabetes with the “hypertriglyceridemic waist” phenotype experienced their first CAD symptoms 5 years earlier than those without this phenotype. This elevated and earlier risk of CAD was statistically significant (hazard ratio 2.0, 95% confidence interval 1.2 to 3.7, p = 0.02). In conclusion, the “hypertriglyceridemic waist” phenotype, an inexpensive and simple tool identifying subjects with metabolic syndrome features, is a significant marker of CAD manifestations occurring at an earlier age in those with glucose intolerance or type 2 diabetes.
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- 2020
8. Contribution of receptor negative versus receptor defective mutations in the LDL-receptor gene to angiographically assessed coronary artery disease among young (25–49 years) versus middle-aged (50–64 years) men
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Perron, Patrice, Gaudet, Daniel, Vohl, Marie-Claude, Moorjani, Sital, Després, Jean-Pierre, Tremblay, Gérald, Couture, Patrick, Gagné, Claude, Perron, Patrice, Gaudet, Daniel, Vohl, Marie-Claude, Moorjani, Sital, Després, Jean-Pierre, Tremblay, Gérald, Couture, Patrick, and Gagné, Claude
- Abstract
Elevated plasma LDL-cholesterol (LDL-C) levels are associated with an increased risk of coronary artery disease (CAD). Familial hypercholesterolemia (FH), a monogenic trait due to mutations in the LDL-receptor (R) gene is characterized by raised plasma LDL-C levels and premature CAD. The aim of the present investigation, derived from the study of a population of 1465 unrelated men aged 25 to 64 years, was to compare the expression of CAD assessed by coronary angiography in young (aged 25–49 years) versus middle-aged (50–64 years) heterozygous FH patients of French Canadian descent. Furthermore, the relationship of binding-defective versus receptor negative mutations in the LDL-R to premature CAD (B50 years) was examined and compared with men displaying a normal plasma lipoprotein-lipid profile. From the original study sample, a total of 100 men met the clinical criteria of heterozygous FH. Among them, 30 were carriers of a receptor negative mutation (deletion \15 kb or point mutations Y468X or R329X) whereas 64 were carriers of a receptor defective mutation (W66G, E207K or C646Y). As expected, in both age groups (25–49 years vs. 50–64 years), carriers of a receptor negative mutation had higher plasma cholesterol and LDL-C levels than carriers of a defective allele or men with a normal plasma lipoprotein-lipid profile. In addition, the mean number of diseased vessels (with\50% stenosis) was higher in men aged 50–64 years compared to those aged 25–49 years. In the two age groups, FH patients were characterized by a higher number of stenosed coronary vessels than the normal phenotype group. Within each group (either receptor negative, receptor defective or normal phenotype) plasma cholesterol, LDL-C, HDL-C, triglyceride and apolipoprotein B levels were similar irrespective of age (25–49 years vs. 50–64 years). Finally, multiple logistic regression analyses revealed that compared to non-FH men, the relative odds of being affected by CAD before the age of 50 years was 7.
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- 2020
9. Investigation of LRP8 gene in 1p31 QTL linked to LDL peak particle diameter in the Quebec family study
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Bouchard, Claude, Pérusse, Louis, Dolley, Guillaume, Lamarche, Benoît, Vohl, Marie-Claude, Després, Jean-Pierre, Bouchard, Claude, Pérusse, Louis, Dolley, Guillaume, Lamarche, Benoît, Vohl, Marie-Claude, and Després, Jean-Pierre
- Abstract
The small, dense LDL phenotype is associated with an increased cardiovascular disease risk. A genome-wide scan performed on 236 nuclear families of the Quebec Family Study (QFS) revealed a quantitative trait locus affecting LDL peak particle diameter (LDL-PPD) and density on the 1p31 region. This region contains the low-density lipoprotein receptor-related protein 8 (LRP8) gene. LRP8, a receptor for apolipoprotein (apo) E, modulates apoE levels, thus contributing to plasma cholesterol and triglyceride (TG) concentrations. We investigate the effects of LRP8 polymorphisms on LDL-PPD, on the relative proportion of small LDL (< 255 Å) and the absolute concentration of cholesterol among the small LDL particles. LRP8 rs5174 was associated with LDL-PPD and estimated cholesterol concentrations in the small LDL particles adjusted for the effects of age and sex (p = 0.008, p = 0.04, respectively). LRP8 rs3820198 was associated with total and LDL-cholesterol levels as well as with apoB concentrations adjusted for the effects of age and sex (p = 0.005, p = 0.004 and p = 0.01, respectively) but not with LDL size-related variables. These results suggest that LRP8 gene polymorphisms influence plasma cholesterol levels as well as size and composition of LDL particles.
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- 2020
10. A sequence variation in the mitochondrial glycerol-3-phosphate dehydrogenase gene is associated with increased plasma glycerol and free fatty acid concentrations among French Canadians
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St-Pierre, Julie, Perron, Patrice, Gaudet, Daniel, Brisson, Diane, Vohl, Marie-Claude, Després, Jean-Pierre, Hudson, Thomas J., St-Pierre, Julie, Perron, Patrice, Gaudet, Daniel, Brisson, Diane, Vohl, Marie-Claude, Després, Jean-Pierre, and Hudson, Thomas J.
- Abstract
FAD-dependent glycerol-3-phosphate dehydrogenase (mGPD) enzyme is located in the mitochondrial inner membrane where it catalyzes irreversible oxidation reactions. Type 2 diabetes mellitus (DM) is a multifactorial disorder associated with physiological abnormalities in the glycerol and free fatty acids (FFA) metabolic pathways. In the present study, we have evaluated the association among the mGPD H264R sequence variation and postabsorptive plasma FFA and glycerol concentrations in a sample of French Canadians with and without type 2 DM. A sample of 81 recently diagnosed type 2 DM and 318 nondiabetic, nonobese, normotriglyceridemic French Canadians were screened for the presence of the mGPD H264R genetic variant using a PCR-RFLPbased method. The 318 nondiabetic subjects were free of known type 2 DM covariates (fasting glucose <7.0 mmol/L, body mass index <29 kg/m2, fasting glycerol <2.0 mmol/L and absence of the N288D sequence variation in the glycerol kinase gene, fasting triglyceride <2.5 mmol/L). The association of mGPD H264R sequence variation with plasma FFA and glycerol concentrations was assessed in different regression models. Among non-DM individuals, the R allele (HR and RR genotypes) was associated with increased plasma FFA and glycerol concentrations (P < 0.05). However, the mean plasma FFA and glycerol concentrations were not affected by the H264R genotype in the type 2 DM sample. Overall, mean plasma FFA concentrations in non-DM RR homozygotes reached values that were similar to those achieved in patients with type 2 diabetes (0.87 6 0.63 vs 0.90 6 0.48 mmol/L). After controlling for age, gender, body mass index, fasting glucose, and fasting triglyceride concentrations, the relative odds of having fasting plasma FFA levels above the 90th percentile (0.9 mmol/L) in the absence of DM was increased by twofold in H264R heterozygotes (P 5 0.04) and fourfold among R264 homozygotes (P 5 0.009) compared to noncarriers. In the absence of DM, the mGPD R allele wa
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- 2020
11. Fine mapping of low-density lipoprotein receptor gene by genetic linkage on chromosome 19p13.1-p13.3 and study of the founder effect of four French Canadian low-density lipoprotein receptor gene mutations
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Simard, Jacques, Morissette, Jean, Gaudet, Daniel, Vohl, Marie-Claude, Gagné, Claude, Després, Jean-Pierre, Couture, Patrick, Bergeron, Jean, Simard, Jacques, Morissette, Jean, Gaudet, Daniel, Vohl, Marie-Claude, Gagné, Claude, Després, Jean-Pierre, Couture, Patrick, and Bergeron, Jean
- Abstract
Familial hypercholesterolemia (FH) is one of the most common autosomal codominant diseases. FH is caused by mutations in the low-density lipoprotein receptor (LDLR) gene and is characterized by raised plasma LDL-cholesterol, tendon xanthomas, and premature coronary heart disease. The frequency of FH among French Canadians in northeastern Québec is higher than in most other populations, 1:154 vs. 1:500 due to high prevalence of few recurrent mutations in the LDLR gene. In the French Canadian population, 11 mutations in the LDLR gene have been found to occur in geographically diverse areas and account for >90% of cases. We have first constructed a high-resolution genetic map to locate several highly polymorphic markers close to LDLR locus, thus providing the necessary tools to study the origin of the four most common mutations which account for ≈80% of our FH patients. We have then genotyped five markers (D19S413, D19S865, D19S221, D19S914, D19S586) in 102 heterozygotes (38 del>15kb; 36 W66G; 16 C646Y; 12 E207K), two compound heterozygotes (del>15kb/W66G; del>15kb/C646Y) and seven homozygotes (three del>15 kb; three W66G; one E207K) with FH unrelated to the first and second degree. We have found that patients bearing the same LDLR gene mutation carry a common haplotype at the LDLR locus although there is evidence for the early occurrence of a recombinational event between the LDLR and the D19S221 locus in the French Canadian patients bearing the W66G mutation. The fine mapping of LDLR gene close to several highly informative microsatellite markers provide fine mapping details of the LDLR region and additional tools for studies of association between plasma lipoprotein levels and LDLR gene.
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- 2020
12. Heterozygous familial hypercholesterolemia in children : low-density lipoprotein receptor mutational analysis and variation in the expression of plasma lipoprotein-lipid concentrations
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Torres, Ana Lucia, Lupien, Paul-J., Moorjani, Sital, Lamarche, Benoît, Vohl, Marie-Claude, Gagné, Claude, Després, Jean-Pierre, Brun, Louis-Daniel, Torres, Ana Lucia, Lupien, Paul-J., Moorjani, Sital, Lamarche, Benoît, Vohl, Marie-Claude, Gagné, Claude, Després, Jean-Pierre, and Brun, Louis-Daniel
- Abstract
The phenotypic expression 01‘ heterozygous familial hypercholesterolemia (FH) is variable from biochemical and clinical standpoints and several genetic and environmental factors could contribute to explain this variability. We have compared, in a cohort of 266 heterozygous FH children and adolescents (l-19 years), the variation in plasma lipoprotein-lipid levels among patients defined by three mutations in the low density lipoprotein receptor (LDLR) gene. Comparison of the plasma total and LDL-cholesterol (LDL-C) levels among the three mutation groups revealed significant differences. Plasma total and LDL-C levels were significantly higher (P < 0.05) in the group bearing the French-Canadian A > 15 kb null allele mutation (8.17 rt 1.45 and 6.58 + 1.42 mmol/l) and in the group with the defective allele Ch46Y missense mutation (8.18 + 1.53 and 6.65 + 1.50 mmol/l) compared to the group with the defective allele W66G missense mutation (7.19 f 1.23 and 5.62 f 1.16 mmol/l). Comparisons of other lipoprotein-lipid parameters between FH heterozygotes and normolipemic (n = 120) children indicated that all mutation groups had significantly (P= 0.0001) lower plasma HDL-cholesterol (HDL-C) levels and a higher total cholesterol (TC) to HDL-C ratio (P <: 0.05). Among FH heterozygote groups, the W66G group had the lowest TC to HDL-C ratio. Multivariate analyses revealed that in FH heterozygotes as well as in controls, HDL-C levels contributed to a greater proportion of the variation in TC to HDL-C ratio than TC. In order to examine the age effect, control and FH heterozygote A > 15 kb groups were then subdivided into four groups (l-4; 5-8; 9-13, and 14-19 years). The variation in HDL-C and triglycerides with age in heterozygous FH children showed a pattern which was similar to the one noted in the control group. In conclusion, the present study demonstrated that the overall contribution of age to variation in the lipoprotein profile of heterozygous FH children is similar to the effe
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- 2020
13. Visceral obesity and hyperinsulinemia modulate the impact of the microsomal triglyceride transfer protein −493G/T polymorphism on plasma lipoprotein levels in men
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St-Pierre, Julie, Nadeau, André, Gaudet, Daniel, Miller-Felix, Isabelle, Prud'homme, Denis, Vohl, Marie-Claude, Després, Jean-Pierre, Lemieux, Isabelle., Bergeron, Jean, St-Pierre, Julie, Nadeau, André, Gaudet, Daniel, Miller-Felix, Isabelle, Prud'homme, Denis, Vohl, Marie-Claude, Després, Jean-Pierre, Lemieux, Isabelle., and Bergeron, Jean
- Abstract
The dyslipidemic state of visceral obesity is characterized by increased plasma triglyceride levels, low high-density lipoprotein-cholesterol concentration and alterations in low-density lipoprotein (LDL) composition and concentration. A functional, non-coding microsomal triglyceride transfer protein (MTP) −493G/T polymorphism of the microsomal triglyceride transfer protein gene has been related to variations in LDL-cholesterol levels. To study the effect of the MTP −493G/T polymorphism on lipoprotein levels in visceral obesity and hyperinsulinemia, a total of 227 men were assigned into two groups on the basis of their MTP −493G/T polymorphism, including 121 GG homozygotes and 105 carriers of the T allele (92 GT and 13 TT). The two genotypic groups did not differ for their physiological characteristics nor for lipoprotein–lipid profiles, before and after adjustment for age. However, GG homozygotes were characterized by higher fasting insulin levels than carriers of the T allele (P<0.05). When the two genotypic groups were further divided on the basis of their visceral adipose tissue (AT) accumulation, assessed by computed tomography, we observed that T allele carriers with low levels of visceral AT (<130 cm2) had decreased plasma total cholesterol and LDL-apolipoprotein B (LDL-apoB) levels compared to viscerally obese men (P=0.035 and P=0.0001, respectively). Among GG homozygotes, no significant difference were observed. Although not significant, T allele carriers characterized by visceral obesity tended to have smaller, denser LDL particles than T allele carriers characterized by a low accumulation of visceral AT. When subjects were divided on the basis of their fasting insulin levels, it appears that hyperinsulinemic men were characterized by a deteriorated lipoprotein–lipid profile when they were carriers of the T allele compared to normoinsulinemic men. In summary, visceral obesity and hyperinsulinemia modulate the impact of the MTP −493G/T polymorphism on plasm
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- 2020
14. Influences of the phosphatidylcholine transfer protein gene variants on the LDL peak particle size
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Bouchard, Claude, Berthier, Marie-Thérèse, Pérusse, Louis, Dolley, Guillaume, Lamarche, Benoît, Vohl, Marie-Claude, Després, Jean-Pierre, Bouchard, Claude, Berthier, Marie-Thérèse, Pérusse, Louis, Dolley, Guillaume, Lamarche, Benoît, Vohl, Marie-Claude, and Després, Jean-Pierre
- Abstract
Background: The small, dense LDL phenotype is associated with an increased cardiovascular disease risk. A genome-wide scan performed on 236 nuclear families of the Quebec Family Study (QFS) revealed a quantitative trait locus (QTL) affecting LDL peak particle size (LDL-PPD) and density on the 17q21 region. This region contains the phosphatidylcholine transfer protein gene (PCTP). In the liver, phosphatidylcholine transfer protein binds specifically phosphatidylcholine suggesting a role for this protein in the formation of HDL and possibly VLDL phospholipid membranes. Objectives: To test the association between two coding polymorphisms (c.29A>C (Glu10Ala) and c.188G>A (Cys63Tyr)) in PCTP gene and the LDL-PPD. Methods: LDL-PPD was measured by non-denaturating 2–16% polyacrylamide gradient gel electrophoresis on 623 QFS subjects. Results: After adjustment for age and sex, carriers of the c.29C allele showed larger LDL-PPD than A/A homozygotes (p < 0.05). These results remained significant when LDL-PPD was further adjusted for the effects of BMI and triglyceride levels (p < 0.04). We also observed a three-fold lower risk of having the small (LDL-PPD <256 Å), dense LDL phenotype in subjects carrying the c.29C allele, when compared to A/A homozygotes (OR = 0.35 (95% CI: 0.14–0.91; p = 0.03)). Conclusion: PCTP gene variants are associated with LDL-PPD.
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- 2020
15. Endocannabinoid Receptor Blockers
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Després, Jean-Pierre, primary
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- 2009
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16. Contributing Authors
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Assmann, Gerd, primary, Bagshaw, Deborah, additional, Balasubramanyam, Ashok, additional, Ballantyne, Christie M., additional, Barter, Philip, additional, Bays, Harold, additional, Blumenthal, Roger S., additional, Brewer, H. Bryan, additional, Brown, B. Greg, additional, Brunzell, John D., additional, Campbell, Catherine Y., additional, Canner, Paul L., additional, Carlson, Lars A., additional, Catapano, A.L., additional, Chahil, Tina J., additional, Church, Timothy S., additional, Cohen, David E., additional, Davidson, Michael H., additional, Deedwania, Prakash C., additional, Després, Jean-Pierre, additional, Devaraj, Sridevi, additional, Devine, Patrick J., additional, Fayad, Zahi A., additional, Fazio, Sergio, additional, Fellstrøm, Bengt, additional, Ganz, Peter, additional, Ginsberg, Henry N., additional, Goldberg, Anne Carol, additional, Gotto, Antonio M., additional, Guyton, John R., additional, Harris, William S., additional, Holdaas, Hallvard, additional, Hoogeveen, Ron C., additional, Jacobson, Terry A., additional, Jardine, Alan G., additional, Jenkins, David J.A., additional, Jialal, Ishwarlal, additional, Jones, Peter H., additional, Josse, Andrea R., additional, Kendall, Cyril W.C., additional, Kobashigawa, Jon A., additional, Koschinsky, Marlys L., additional, Kris-Etherton, Penny M., additional, Kurra, Salila, additional, Lavie, Carl J., additional, Le, Ngoc-Anh, additional, Libby, Peter, additional, Linton, MacRae F., additional, Marcovina, Santica M., additional, Mark, Patrick B., additional, McGovern, Mark E., additional, McKenney, James M., additional, Merz, C. Noel Bairey, additional, Miller, Michael, additional, Miller, Yury I., additional, Mora, Samia, additional, Moriarty, Patrick M., additional, Musunuru, Kiran, additional, Myers, Kelly S., additional, Nambi, Vijay, additional, Nguyen, Tri H., additional, Nicholls, Stephen J., additional, Nissen, Steven E., additional, Norata, G.D., additional, Ohlson, Melissa, additional, Packard, Chris J., additional, Pi-Sunyer, F. Xavier, additional, Polk, Donna, additional, Pownall, Henry J., additional, Rader, Daniel J., additional, Rosenson, Robert S., additional, Rudd, James H.F., additional, Saseen, Joseph S., additional, Schwartz, Gregory G., additional, Seedorf, Udo, additional, Sekhar, Rajagopal V., additional, Stone., Neil J., additional, Taylor, Allen J., additional, Tsimikas, Sotirios, additional, Vijayaraghavan, Krishnaswami, additional, Wang, David Q.-H., additional, Wenger, Nanette K., additional, Wiggins, Barbara S., additional, Wilson, Peter W.F., additional, and Wong, Julia M.W., additional
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- 2009
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17. Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies
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Wood, Angela M, Kaptoge, Stephen, Butterworth, Adam S, Willeit, Peter, Warnakula, Samantha, Bolton, Thomas, Paige, Ellie, Paul, Dirk S, Sweeting, Michael, Burgess, Stephen, Bell, Steven, Tjønneland, Anne, Brenner, Hermann, Palmieri, Luigi, Dallongeville, Jean, Brunner, Eric J, Assmann, Gerd, Trevisan, Maurizio, Gillum, Richard F, Ford, Ian, Sattar, Naveed, Astle, William, Lazo, Mariana, Thompson, Simon G, Ferrari, Pietro, Leon, David A, Smith, George Davey, Peto, Richard, Jackson, Rod, Banks, Emily, Di Angelantonio, Emanuele, Danesh, John, Stevens, David, Butterworth, Adam, Koulman, Albert, Selmer, Randi M, Verschuren, Monique, Sato, Shinichi, Njølstad, Inger, Woodward, Mark, Veikko, Salomaa, Nordestgaard, Børge G, Yeap, Bu B, Flecther, Astrid, Melander, Olle, Kuller, Lewis H, Balkau, Beverley, Marmot, Michael, Koenig, Wolfgang, Casiglia, Edoardo, Cooper, Cyrus, Verschuren, W M Monique, Arndt, Volker, Franco, Oscar H, Wennberg, Patrik, Gallacher, John, Gómez de la Cámara, Agustín, Völzke, Henry, Dahm, Christina C, Dale, Caroline E, Bergmann, Manuela, Crespo, Carlos, van der Schouw, Yvonne T, Kaaks, Rudolf, Simons, Leon A, Lagiou, Pagona, Schoufour, Josje D, Boer, Jolanda M.A, Key, Timothy J, Rodriguez, Beatriz, Moreno-Iribas, Conchi, Davidson, Karina W, Taylor, James O, Sacerdote, Carlotta, Wallace, Robert B, Quiros, J. Ramon, Rimm, Eric B, Tumino, Rosario, Blazer III, Dan G, Linneberg, Allan, Daimon, Makoto, Panico, Salvatore, Howard, Barbara, Skeie, Guri, Salomaa, Veikko, Strandberg, Timo, Weiderpass, Elisabete, Nietert, Paul J, Psaty, Bruce M, Kromhout, Daan, Salamanca-Fernandez, Elena, Kiechl, Stefan, Krumholz, Harlan M, Grioni, Sara, Palli, Domenico, Huerta, José M, Price, Jackie, Sundström, Johan, Arriola, Larraitz, Arima, Hisatomi, Travis, Ruth C, Panagiotakos, Demosthenes B, Karakatsani, Anna, Trichopoulou, Antonia, Kühn, Tilman, Grobbee, Diederick E, Barrett-Connor, Elizabeth, van Schoor, Natasja, Boeing, Heiner, Overvad, Kim, Kauhanen, Jussi, Wareham, Nick, Langenberg, Claudia, Forouhi, Nita, Wennberg, Maria, Després, Jean-Pierre, Cushman, Mary, Cooper, Jackie A, Rodriguez, Carlos J, Sakurai, Masaru, Shaw, Jonathan E, Knuiman, Matthew, Fletcher, Astrid, Voortman, Trudy, Meisinger, Christa, Dallongeville, Jean-Pierre, Gillumn, Richard F, Ford, Ian Ford, Thompson, Simon, Davey Smith, George, de la Cámara, Agustín Gómez, Bergmann, Manuela M, Crespo, Carlos J, Boer, Jolanda M A, Quiros, J Ramon, Blazer, Dan G, Wood, Angela M, Kaptoge, Stephen, Butterworth, Adam S, Willeit, Peter, Warnakula, Samantha, Bolton, Thomas, Paige, Ellie, Paul, Dirk S, Sweeting, Michael, Burgess, Stephen, Bell, Steven, Tjønneland, Anne, Brenner, Hermann, Palmieri, Luigi, Dallongeville, Jean, Brunner, Eric J, Assmann, Gerd, Trevisan, Maurizio, Gillum, Richard F, Ford, Ian, Sattar, Naveed, Astle, William, Lazo, Mariana, Thompson, Simon G, Ferrari, Pietro, Leon, David A, Smith, George Davey, Peto, Richard, Jackson, Rod, Banks, Emily, Di Angelantonio, Emanuele, Danesh, John, Stevens, David, Butterworth, Adam, Koulman, Albert, Selmer, Randi M, Verschuren, Monique, Sato, Shinichi, Njølstad, Inger, Woodward, Mark, Veikko, Salomaa, Nordestgaard, Børge G, Yeap, Bu B, Flecther, Astrid, Melander, Olle, Kuller, Lewis H, Balkau, Beverley, Marmot, Michael, Koenig, Wolfgang, Casiglia, Edoardo, Cooper, Cyrus, Verschuren, W M Monique, Arndt, Volker, Franco, Oscar H, Wennberg, Patrik, Gallacher, John, Gómez de la Cámara, Agustín, Völzke, Henry, Dahm, Christina C, Dale, Caroline E, Bergmann, Manuela, Crespo, Carlos, van der Schouw, Yvonne T, Kaaks, Rudolf, Simons, Leon A, Lagiou, Pagona, Schoufour, Josje D, Boer, Jolanda M.A, Key, Timothy J, Rodriguez, Beatriz, Moreno-Iribas, Conchi, Davidson, Karina W, Taylor, James O, Sacerdote, Carlotta, Wallace, Robert B, Quiros, J. Ramon, Rimm, Eric B, Tumino, Rosario, Blazer III, Dan G, Linneberg, Allan, Daimon, Makoto, Panico, Salvatore, Howard, Barbara, Skeie, Guri, Salomaa, Veikko, Strandberg, Timo, Weiderpass, Elisabete, Nietert, Paul J, Psaty, Bruce M, Kromhout, Daan, Salamanca-Fernandez, Elena, Kiechl, Stefan, Krumholz, Harlan M, Grioni, Sara, Palli, Domenico, Huerta, José M, Price, Jackie, Sundström, Johan, Arriola, Larraitz, Arima, Hisatomi, Travis, Ruth C, Panagiotakos, Demosthenes B, Karakatsani, Anna, Trichopoulou, Antonia, Kühn, Tilman, Grobbee, Diederick E, Barrett-Connor, Elizabeth, van Schoor, Natasja, Boeing, Heiner, Overvad, Kim, Kauhanen, Jussi, Wareham, Nick, Langenberg, Claudia, Forouhi, Nita, Wennberg, Maria, Després, Jean-Pierre, Cushman, Mary, Cooper, Jackie A, Rodriguez, Carlos J, Sakurai, Masaru, Shaw, Jonathan E, Knuiman, Matthew, Fletcher, Astrid, Voortman, Trudy, Meisinger, Christa, Dallongeville, Jean-Pierre, Gillumn, Richard F, Ford, Ian Ford, Thompson, Simon, Davey Smith, George, de la Cámara, Agustín Gómez, Bergmann, Manuela M, Crespo, Carlos J, Boer, Jolanda M A, Quiros, J Ramon, and Blazer, Dan G
- Abstract
BACKGROUND: Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease. METHODS:We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose–response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years [5th–95th percentile 1·04–13·5]) from 71 011 participants from 37 studies. FINDINGS: In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around o
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- 2018
18. Visceral obesity and the heart
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Larose, Éric, Marette, André, Poirier, Paul, Pibarot, Philippe, Després, Jean-Pierre, Mathieu, Patrick, Larose, Éric, Marette, André, Poirier, Paul, Pibarot, Philippe, Després, Jean-Pierre, and Mathieu, Patrick
- Abstract
Obesity and particularly its deleterious form, visceral adiposity, has reached a high prevalence in the industrialized world owing to the lack of exercise and the widely available energy-dense diet. As a consequence, cardiovascular diseases and metabolic disorders are afflicting an unprecedented number of individuals at a world-wide scale. Over the last decades, investigations have established firm links between visceral obesity and the development of cardiovascular diseases. Moreover, studies in the field of lipid partitioning have demonstrated that inadequacy of homeostatic mechanism ensuring adequate handling of energy surplus is associated with accumulation of visceral fat and lipid overload of internal organs, which are participating to the development of heart diseases. Visceral obesity and its metabolic consequences often referred to as the metabolic syndrome is associated with the production of an atherosclerosis prone milieu. In this review, clinical implications of visceral obesity on the development of cardiovascular disorders are reviewed along with important mechanisms participating to the development of these disorders. Implications and failure of lipid partitioning and some of the potential pathways mediating development of heart diseases are also covered in view of recent development of therapeutic options.
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- 2016
19. Oxidized low-density lipoprotein, angiotensin II and increased waist cirumference are associated with valve inflammation in prehypertensive patients with aortic stenosis
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Arsenault, Benoit, Fournier, Dominique, Audet, Audrey, Couture, Christian, Côté, Nancy, Poirier, Paul, Pépin, Andrée, Pibarot, Philippe, Després, Jean-Pierre, Mathieu, Patrick, Arsenault, Benoit, Fournier, Dominique, Audet, Audrey, Couture, Christian, Côté, Nancy, Poirier, Paul, Pépin, Andrée, Pibarot, Philippe, Després, Jean-Pierre, and Mathieu, Patrick
- Abstract
Introduction: The progression of aortic stenosis (AS) has been shown to be faster in patients with the metabolic syndrome. We sought to determine the relationships between blood pressure, inflammation, oxidative stress and valvular inflammation in a population of normotensive and prehypertensive patients with AS. Methods: In this study, 36 male patients (age: 61.5 ± 2 years) with AS undergoing an aortic valve replacement were investigated. Plasma levels of adiponectin, oxidized-LDL (ox-LDL), angiotensinogen (AGN) and angiotensin I-II (Ang I-II) were measured. On explanted aortic valves, immunohistochemistry studies and quantitative PCR (q-PCR) analyses were performed to document the expression of inflammatory cytokines. Results: Systolic blood pressure (SBP) was positively correlated with plasma level of ox-LDL ( r = 0.4; p = 0.02), AGN ( r = 0.41; p = 0.01), and white blood cells count ( r = 0.33; p = 0.04), whereas it was inversely related to plasma level of adiponectin ( r = - .35; p = 0.04). After adjustment for covariates, plasma level of ox-LDL ( p = 0.01) remained significantly associated with SBP ( p = 0.01). Within the aortic valve, expression of TNF-a was significantly associated with plasma levels of ox-LDL ( r = 0.58; p = 0.03), Ang II ( r = 0.69; p = 0.013), and waist circumference ( r = 0.60; p = 0.02), whereas valvular expression of IL-6 was associated with plasma level of Ang II ( r = 0.51; p = 0.03). In explanted AS valves, ox-LDL was documented near calcified areas and colocalized with Ang II, IL-6, and TNF-a. Conclusion: Conditions associated with a higher oxidative stress and activation of the renin angiotensin system, such as encountered in viscerally obese and prehypertensive patients, contribute to higher valvular inflammation in AS.
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- 2016
20. Transient myocardial tissue and function changes during a marathon in less fit marathon runners
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Bertrand, Olivier, Gaudreault, Valérie, Tizón-Marcos, Helena, Larose, Éric, Rodés-Cabau, Josep, Gilbert, Philippe, Amyot, Marc, Poirier, Paul, Pibarot, Philippe, Després, Jean-Pierre, Bertrand, Olivier, Gaudreault, Valérie, Tizón-Marcos, Helena, Larose, Éric, Rodés-Cabau, Josep, Gilbert, Philippe, Amyot, Marc, Poirier, Paul, Pibarot, Philippe, and Després, Jean-Pierre
- Abstract
Background : Although regular physical activity improves health, strenuous exercise might transiently increase cardiac risk. Training and fitness might provide protection. Methods : We prospectively studied 20 recreational marathon runners without known cardiovascular disease or symptoms: at peak training before, immediately after, and 3 months after a 42.2-km marathon. Changes in global/segmental myocardial function, edema, resting perfusion, and fibrosis were measured. Results : At peak training, runners exercised 8.1 ± 2.3 hours and 62 ± 18 km per week with mean maximal oxygen consumption (VO2max) of 53.2 ± 8.3 mL/kg/min. In response to the marathon, global left ventricular and right ventricular ejection fraction decreased in half of the runners; these runners had poorer peak training distance, training time, and fitness level. Change in global left ventricular ejection fraction was associated with VO2max. Overall, 36% of segments developed edema, 53% decreased function, and 59% decreased perfusion. Significant agreement was observed between segment decreasing function, decreasing perfusion, and developing edema. Myocardial changes were reversible at 3 months. Conclusions : Completing a marathon leads to localized myocardial edema, diminished perfusion, and decreased function occurring more extensively in less trained and fit runners. Although reversible, these changes might contribute to the transient increase in cardiac risk reported during sustained vigorous exercise., Introduction : Bien que l’activité physique régulière améliore la santé, l’exercice intense pourrait augmenter de façon passagère le risque de maladies du cœur. L’entraînement et la bonne forme physique pourraient apporter une protection contre ce risque. Méthodes : Nous avons étudié de façon prospective les coureurs récréatifs de marathon n’ayant pas de maladies ou de symptômes cardiovasculaires connus : au sommet de leur entraînement, avant, immédiatement après et 3 mois après un marathon de 42,2 km. Les changements dans le fonctionnement myocardique global et segmentaire, l’œdème, la perfusion au repos et la fibrose ont été mesurés. Résultats : Au sommet de leur entraînement, les coureurs ont accompli 8,1 ± 2,3 heures et 62 ± 18 km par semaine selon une consommation d'oxygène maximal (VO2 max) moyenne de 53,2 ± 8,3ml/kg/min. En réponse au marathon, la fraction d’éjection globale du ventricule gauche et du ventricule droit a diminué chez la moitié des coureurs; ces coureurs ont obtenu au sommet de leur entraînement une distance, une durée et un niveau de forme physique médiocres. La modification de la fraction d’éjection globale du ventricule gauche a été associée à la VO2 max. Dans l’ensemble, 36 % des segments ont développé un œdème, 53 % ont diminué le fonctionnement et 59 % ont diminué la perfusion. Une concordance significative a été observée entre le segment diminuant le fonctionnement, le segment diminuant la perfusion et le segment développant l’œdème. Les modifications du myocarde ont été réversibles à 3 mois. Conclusions : La réalisation d’un marathon mène à un œdème localisé du myocarde, à une perfusion réduite et à un fonctionnement diminué apparaissant davantage chez les coureurs moins entraînés et moins en forme. Bien que ces modifications soient réversibles, ils pourraient contribuer à l’augmentation passagère du risque de problèmes cardiaques signalés durant l’exercice intense soutenu.
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- 2016
21. Age-related differences in the pathogenesis of calcific aortic stenosis : the potential role of resistin
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Arsenault, Benoit, Picard, Frédéric, Mohty, Dania, Cartier, Amélie., Pibarot, Philippe, Després, Jean-Pierre, Mathieu, Patrick, Arsenault, Benoit, Picard, Frédéric, Mohty, Dania, Cartier, Amélie., Pibarot, Philippe, Després, Jean-Pierre, and Mathieu, Patrick
- Abstract
Background: Aortic stenosis (AS) is considered as an atherosclerotic related process. However, there are uncertainties whether AS in the elderly is associated with the same pathophysiological processes as in younger patients. We hypothesized that the metabolic determinants of the valvular inflammatory and calcifying processes occurring in elderly patients are different from those observed earlier in life. Methods: Among 114 patients operated for a severe AS, a complete plasma lipid blood profile and plasma levels of adipokines (resistin, leptin) were determined. The calcium content of the aortic valve was measured and valvular inflammation was quantified. Results Elderly patients (= 70 years) had significantly lower LDL-C ( p = 0.02), lower LDL-C associated with small size particles (LDL-C < 255 Å) ( p = 0.003), and higher HDL peak particle size than younger patients ( p = 0.03). In addition, elderly patients had increased plasma leptin ( p = 0.04) and resistin ( p = 0.0004) levels compared to the middle-aged group (< 70 years). In the elderly patients, higher plasma resistin blood levels were associated with increased valve calcium content and inflammation. Conclusion: The lipid profile of elderly patients was found less atherogenic than that of middle-aged patients. On the other hand, older patients with AS had higher plasma level of resistin which was associated with the degree of valvular calcification and inflammation. These results suggest that, beyond lipid model of atherosclerosis, age-related processes affecting resistin blood levels may also be involved in the late development of AS.
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- 2016
22. Insulin resistance and LVH progression in patients with calcific aortic stenosis : a substudy of the ASTRONOMER trial.
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Capoulade, Romain, Côté, Nancy., Pibarot, Philippe, Chan, Kwan-Leung, Dumesnil, Jean G., Teo, Koon Kang, Clavel, Marie-Annick, Tam, James W., Després, Jean-Pierre, Mathieu, Patrick, Capoulade, Romain, Côté, Nancy., Pibarot, Philippe, Chan, Kwan-Leung, Dumesnil, Jean G., Teo, Koon Kang, Clavel, Marie-Annick, Tam, James W., Després, Jean-Pierre, and Mathieu, Patrick
- Abstract
Background : In a recent cross-sectional study, the authors reported that the metabolic syndrome was associated with an increased prevalence of concentric LVH in patients with AS. As a central feature of the metabolic syndrome, insulin resistance could be an important mediator of this association. Methods : This substudy included 250 of 269 patients enrolled in ASTRONOMER. Follow-up was 3.4 ± 1.3 years. Insulin resistance was evaluated using the homeostatic assessment model (HOMA) index, and patients were dichotomized using the median HOMA index value (1.24). The rate of LVH progression was estimated by calculating the annualized change in LV mass index (LVMi), measured on echocardiography. The presence of LVH was defined as an LVMi >47 g/m2.7 in women and >49 g/m2.7 in men. Results : There was a significant progression of LVH among the patients without LVH at baseline (n = 134; p < 0.0001) but not in those with it (n = 116; p = NS). In those without LVH at baseline, the annualized progression rate of LVMi was significantly faster in the subset with HOMA >1.24 compared to that in the subset with HOMA <1.24 (2.49 ± 4.38 g/m2.7/year vs. -0.03 ± 3.90 g/m2.7/year; p = 0.001). During follow-up, LVH developed in 46% of patients with HOMA >1.24 compared to 11% of those with HOMA <1.24 (p = 0.0005). Independent predictors of faster LVH progression identified on multivariate analysis were history of hypertension (p = 0.048), degree of aortic valve calcification (p = 0.035), and HOMA index (p = 0.02). Conclusions : In this ASTRONOMER substudy, insulin resistance was a powerful independent predictor of progression to LVH in patients with AS. Visceral obesity and ensuing insulin resistance may thus present novel therapeutic targets in AS patients.
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- 2016
23. Visceral / epicardial adiposity in nonobese and apparently healthy young adults : association with the cardiometabolic profile
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De Larochellière, Élianne, Ross, Marie-Kristelle, Larose, Éric, Bibeau, Karine, Latzko-Toth, Guillaume, Côté, Julie, Pibarot, Philippe, Roy, Véronique, Després, Jean-Pierre, De Larochellière, Élianne, Ross, Marie-Kristelle, Larose, Éric, Bibeau, Karine, Latzko-Toth, Guillaume, Côté, Julie, Pibarot, Philippe, Roy, Véronique, and Després, Jean-Pierre
- Abstract
Objective: We investigate associations of regional adipose tissues with cardiometabolic profile of nonobese and apparently healthy young adults. Methods: Four hundred twenty-five nonobese and apparently healthy individuals were assessed for blood pressure and fasting lipid profile, blood glucose and adiponectin. Subcutaneous abdominal adipose tissue (SAT) and ectopic fat depots (visceral abdominal adipose tissue [VAT], epicardial adipose tissue [EAT] and hepatic fat fraction [HFF]) were quantified by magnetic resonance imaging. Results: According to anthropometric measurements, blood pressure and blood markers, the population (18–35 years, 54% women) had a low cardiometabolic risk. Compared to women, men had more VAT, EAT and HFF, but less SAT. Regional adipose tissues were positively correlated with each other. VAT and EAT carried significant correlations with all markers of cardiometabolic risk, while SAT and HFF correlated variably with these markers. While taking into account age and gender, SAT, VAT and EAT were associated with most cardiometabolic markers, while HFF was only associated with total cholesterol/high-density lipoprotein ratio (TC/HDL-C) and triglycerides (TG). When comparing SAT, VAT and EAT head-to-head, VAT was the only adipose tissue location maintaining significant association with most markers of cardiometabolic risk. Greater VAT (=50th percentile) was associated with a worse cardiometabolic profile, whether individuals were overweight or normal weight. Conclusion: Even in nonobese and apparently healthy young women and men, accumulation of ectopic visceral adiposity in general, and of VAT in particular, is associated with a worse cardiometabolic profile whether individuals were overweight or normal weight.
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- 2016
24. Increased biglycan in aortic valve stenosis leads to the overexpression of phospholipid transfer protein via toll-like receptor 2
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Arsenault, Benoit, Bosse, Yohan, Audet, Audrey, Couture, Christian, Côté, Nancy, Pépin, Andrée, Pibarot, Philippe, Derbali, Habib, Després, Jean-Pierre, Mathieu, Patrick, Arsenault, Benoit, Bosse, Yohan, Audet, Audrey, Couture, Christian, Côté, Nancy, Pépin, Andrée, Pibarot, Philippe, Derbali, Habib, Després, Jean-Pierre, and Mathieu, Patrick
- Abstract
Aortic stenosis (AS) is the most common valvular heart disease, and it is suspected that atherosclerotic mechanisms are involved in the development of this disorder. Therefore, the retention of lipids within the aortic valve may play a role in the pathobiology of AS. In this study, a gene expression microarray experiment was conducted on human aortic valves with and without AS. The expression levels of transcripts encoding proteoglycans and enzymes involved in lipid retention were compared between the two groups. The microarray results were subsequently replicated in a cohort of 87 AS valves and 36 control valves. In addition, the interaction between proteoglycan and lipid-modifying enzyme was documented in isolated valve interstitial cells (VICs). The microarray results indicated that only biglycan (BGN) and phospholipid transfer protein (PLTP) were overexpressed in the AS valves. These results were then confirmed by quantitative PCR. The immunohistochemical analysis revealed a colocalization of BGN, PLTP, and Toll-like receptor-2 (TLR 2) in AS valves. In vitro, we showed that BGN induces the production of PLTP in VICs via the stimulation of TLR 2. Thus, increased accumulation of BGN in AS valves contributes to the production of PLTP via TLR 2. These results suggest that intricate links between valve matrix proteins, inflammation, and lipid retention are involved in the pathobiology of AS.
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- 2016
25. Metabolic syndrome negatively influences disease progression and prognosis in aortic stenosis
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Briand, Martin., Couët, Jacques, Cartier, Amélie., Pibarot, Philippe, Dumesnil, Jean G., Després, Jean-Pierre, Mathieu, Patrick, Lemieux, Isabelle., Arsenault, Marie, Briand, Martin., Couët, Jacques, Cartier, Amélie., Pibarot, Philippe, Dumesnil, Jean G., Després, Jean-Pierre, Mathieu, Patrick, Lemieux, Isabelle., and Arsenault, Marie
- Abstract
Objectives: This study sought to examine the association between the metabolic syndrome (MS) and the progression of aortic stenosis (AS). Background: It has been suggested that aortic valve sclerosis and its progression to AS are caused by an atherosclerotic process. Metabolic syndrome is associated with a higher risk of vascular atherosclerosis. Thus, we hypothesized that the atherogenic features of MS could negatively influence disease progression and prognosis in patients with AS. Methods: We retrospectively analyzed the data of 105 consecutive patients (age 69 ± 12 years, 64 men) with at least moderate AS. Of these patients, 40 (38%) had MS identified according to the modified clinical criteria proposed by the National Cholesterol Education Program-Adult Treatment Panel III. The hemodynamic progression of AS was assessed by the measurement of the annualized decrease in valve area during the follow-up period of the study, which averaged 28 ± 13 months. Event-free survival was defined as the absence of death or aortic valve replacement during follow-up. Results: The hemodynamic progression of the stenosis was twice as fast (-0.14 ± 0.13 cm2/year vs. -0.08 ± 0.08 cm2/year, p = 0.008) and the three-year event-free survival was markedly lower (44 ± 8% vs. 69 ± 6%, p = 0.002) among patients with MS. In multivariate analysis, MS was found to be a strong independent predictor of both stenosis progression (p = 0.006) and event-free survival (odds ratio 3.85, 95% CI 1.96 to 7.58, p < 0.001). Conclusions: The present study is the first to report that MS is associated with a faster disease progression and worse outcome in patients with AS. Such findings open new avenues of research and provide a strong impetus for the elaboration of additional prospective studies focusing on this association.
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- 2016
26. Does milk consumption contribute to cardiometabolic health and overall diet quality?
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Lamarche, Benoît, Givens, D Ian, Soedamah-Muthu, Sabita, Krauss, Ronald M, Jakobsen, Marianne Uhre, Bischoff-Ferrari, Heike A, Pan, An, Després, Jean-Pierre, Lamarche, Benoît, Givens, D Ian, Soedamah-Muthu, Sabita, Krauss, Ronald M, Jakobsen, Marianne Uhre, Bischoff-Ferrari, Heike A, Pan, An, and Després, Jean-Pierre
- Abstract
Although milk consumption is recommended in most dietary guidelines around the world, its contribution to overall diet quality remains a matter of debate in the scientific community as well as in the public domain. This article summarizes the discussion among experts in the field on the place of milk in a balanced healthy diet. The evidence to date suggests at least a neutral effect of milk intake on health outcomes. The possibility that milk intake is simply a marker of diets higher in nutritional quality cannot be ruled out. This review also identifies a number of key research gaps pertaining to the impact of milk consumption on health. These need to be addressed to better inform future dietary guidelines.
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- 2016
27. Visceral / epicardial adiposity in nonobese and apparently healthy young adults : association with the cardiometabolic profile
- Author
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De Larochellière, Élianne, Côté, Julie, Gilbert, Guillaume, Bibeau, Karine, Ross, Marie-Kristelle, Dion Roy, Véronique, Pibarot, Philippe, Després, Jean-Pierre, Larose, Éric, De Larochellière, Élianne, Côté, Julie, Gilbert, Guillaume, Bibeau, Karine, Ross, Marie-Kristelle, Dion Roy, Véronique, Pibarot, Philippe, Després, Jean-Pierre, and Larose, Éric
- Abstract
Objective: We investigate associations of regional adipose tissues with cardiometabolic profile of nonobese and apparently healthy young adults. Methods: Four hundred twenty-five nonobese and apparently healthy individuals were assessed for blood pressure and fasting lipid profile, blood glucose and adiponectin. Subcutaneous abdominal adipose tissue (SAT) and ectopic fat depots (visceral abdominal adipose tissue [VAT], epicardial adipose tissue [EAT] and hepatic fat fraction [HFF]) were quantified by magnetic resonance imaging. Results: According to anthropometric measurements, blood pressure and blood markers, the population (18–35 years, 54% women) had a low cardiometabolic risk. Compared to women, men had more VAT, EAT and HFF, but less SAT. Regional adipose tissues were positively correlated with each other. VAT and EAT carried significant correlations with all markers of cardiometabolic risk, while SAT and HFF correlated variably with these markers. While taking into account age and gender, SAT, VAT and EAT were associated with most cardiometabolic markers, while HFF was only associated with total cholesterol/high-density lipoprotein ratio (TC/HDL-C) and triglycerides (TG). When comparing SAT, VAT and EAT head-to-head, VAT was the only adipose tissue location maintaining significant association with most markers of cardiometabolic risk. Greater VAT (=50th percentile) was associated with a worse cardiometabolic profile, whether individuals were overweight or normal weight. Conclusion: Even in nonobese and apparently healthy young women and men, accumulation of ectopic visceral adiposity in general, and of VAT in particular, is associated with a worse cardiometabolic profile whether individuals were overweight or normal weight.
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- 2014
28. Transient myocardial tissue and function changes during a marathon in less fit marathon runners
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Gaudreault, Valérie, Tizón-Marcos, Helena, Poirier, Paul, Pibarot, Philippe, Gilbert, Philippe, Amyot, Marc, Rodés-Cabau, Josep, Després, Jean-Pierre, Bertrand, Olivier, Larose, Éric, Gaudreault, Valérie, Tizón-Marcos, Helena, Poirier, Paul, Pibarot, Philippe, Gilbert, Philippe, Amyot, Marc, Rodés-Cabau, Josep, Després, Jean-Pierre, Bertrand, Olivier, and Larose, Éric
- Abstract
Background : Although regular physical activity improves health, strenuous exercise might transiently increase cardiac risk. Training and fitness might provide protection. Methods : We prospectively studied 20 recreational marathon runners without known cardiovascular disease or symptoms: at peak training before, immediately after, and 3 months after a 42.2-km marathon. Changes in global/segmental myocardial function, edema, resting perfusion, and fibrosis were measured. Results : At peak training, runners exercised 8.1 ± 2.3 hours and 62 ± 18 km per week with mean maximal oxygen consumption (VO2max) of 53.2 ± 8.3 mL/kg/min. In response to the marathon, global left ventricular and right ventricular ejection fraction decreased in half of the runners; these runners had poorer peak training distance, training time, and fitness level. Change in global left ventricular ejection fraction was associated with VO2max. Overall, 36% of segments developed edema, 53% decreased function, and 59% decreased perfusion. Significant agreement was observed between segment decreasing function, decreasing perfusion, and developing edema. Myocardial changes were reversible at 3 months. Conclusions : Completing a marathon leads to localized myocardial edema, diminished perfusion, and decreased function occurring more extensively in less trained and fit runners. Although reversible, these changes might contribute to the transient increase in cardiac risk reported during sustained vigorous exercise., Introduction : Bien que l’activité physique régulière améliore la santé, l’exercice intense pourrait augmenter de façon passagère le risque de maladies du cœur. L’entraînement et la bonne forme physique pourraient apporter une protection contre ce risque. Méthodes : Nous avons étudié de façon prospective les coureurs récréatifs de marathon n’ayant pas de maladies ou de symptômes cardiovasculaires connus : au sommet de leur entraînement, avant, immédiatement après et 3 mois après un marathon de 42,2 km. Les changements dans le fonctionnement myocardique global et segmentaire, l’œdème, la perfusion au repos et la fibrose ont été mesurés. Résultats : Au sommet de leur entraînement, les coureurs ont accompli 8,1 ± 2,3 heures et 62 ± 18 km par semaine selon une consommation d'oxygène maximal (VO2 max) moyenne de 53,2 ± 8,3ml/kg/min. En réponse au marathon, la fraction d’éjection globale du ventricule gauche et du ventricule droit a diminué chez la moitié des coureurs; ces coureurs ont obtenu au sommet de leur entraînement une distance, une durée et un niveau de forme physique médiocres. La modification de la fraction d’éjection globale du ventricule gauche a été associée à la VO2 max. Dans l’ensemble, 36 % des segments ont développé un œdème, 53 % ont diminué le fonctionnement et 59 % ont diminué la perfusion. Une concordance significative a été observée entre le segment diminuant le fonctionnement, le segment diminuant la perfusion et le segment développant l’œdème. Les modifications du myocarde ont été réversibles à 3 mois. Conclusions : La réalisation d’un marathon mène à un œdème localisé du myocarde, à une perfusion réduite et à un fonctionnement diminué apparaissant davantage chez les coureurs moins entraînés et moins en forme. Bien que ces modifications soient réversibles, ils pourraient contribuer à l’augmentation passagère du risque de problèmes cardiaques signalés durant l’exercice intense soutenu.
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- 2013
29. Insulin resistance and LVH progression in patients with calcific aortic stenosis : a substudy of the ASTRONOMER trial.
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Capoulade, Romain, Clavel, Marie-Annick, Dumesnil, Jean G., Chan, Kwan-Leung, Teo, Koon Kang, Tam, James W., Côté, Nancy, Mathieu, Patrick, Després, Jean-Pierre, Pibarot, Philippe, Capoulade, Romain, Clavel, Marie-Annick, Dumesnil, Jean G., Chan, Kwan-Leung, Teo, Koon Kang, Tam, James W., Côté, Nancy, Mathieu, Patrick, Després, Jean-Pierre, and Pibarot, Philippe
- Abstract
Background : In a recent cross-sectional study, the authors reported that the metabolic syndrome was associated with an increased prevalence of concentric LVH in patients with AS. As a central feature of the metabolic syndrome, insulin resistance could be an important mediator of this association. Methods : This substudy included 250 of 269 patients enrolled in ASTRONOMER. Follow-up was 3.4 ± 1.3 years. Insulin resistance was evaluated using the homeostatic assessment model (HOMA) index, and patients were dichotomized using the median HOMA index value (1.24). The rate of LVH progression was estimated by calculating the annualized change in LV mass index (LVMi), measured on echocardiography. The presence of LVH was defined as an LVMi >47 g/m2.7 in women and >49 g/m2.7 in men. Results : There was a significant progression of LVH among the patients without LVH at baseline (n = 134; p < 0.0001) but not in those with it (n = 116; p = NS). In those without LVH at baseline, the annualized progression rate of LVMi was significantly faster in the subset with HOMA >1.24 compared to that in the subset with HOMA <1.24 (2.49 ± 4.38 g/m2.7/year vs. -0.03 ± 3.90 g/m2.7/year; p = 0.001). During follow-up, LVH developed in 46% of patients with HOMA >1.24 compared to 11% of those with HOMA <1.24 (p = 0.0005). Independent predictors of faster LVH progression identified on multivariate analysis were history of hypertension (p = 0.048), degree of aortic valve calcification (p = 0.035), and HOMA index (p = 0.02). Conclusions : In this ASTRONOMER substudy, insulin resistance was a powerful independent predictor of progression to LVH in patients with AS. Visceral obesity and ensuing insulin resistance may thus present novel therapeutic targets in AS patients.
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- 2013
30. Investigation of LRP8 gene in 1p31 QTL linked to LDL peak particle diameter in the Quebec family study
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Dolley, Guillaume, Lamarche, Benoît, Després, Jean-Pierre, Bouchard, Claude, Pérusse, Louis, Vohl, Marie-Claude, Dolley, Guillaume, Lamarche, Benoît, Després, Jean-Pierre, Bouchard, Claude, Pérusse, Louis, and Vohl, Marie-Claude
- Abstract
The small, dense LDL phenotype is associated with an increased cardiovascular disease risk. A genome-wide scan performed on 236 nuclear families of the Quebec Family Study (QFS) revealed a quantitative trait locus affecting LDL peak particle diameter (LDL-PPD) and density on the 1p31 region. This region contains the low-density lipoprotein receptor-related protein 8 (LRP8) gene. LRP8, a receptor for apolipoprotein (apo) E, modulates apoE levels, thus contributing to plasma cholesterol and triglyceride (TG) concentrations. We investigate the effects of LRP8 polymorphisms on LDL-PPD, on the relative proportion of small LDL (< 255 Å) and the absolute concentration of cholesterol among the small LDL particles. LRP8 rs5174 was associated with LDL-PPD and estimated cholesterol concentrations in the small LDL particles adjusted for the effects of age and sex (p = 0.008, p = 0.04, respectively). LRP8 rs3820198 was associated with total and LDL-cholesterol levels as well as with apoB concentrations adjusted for the effects of age and sex (p = 0.005, p = 0.004 and p = 0.01, respectively) but not with LDL size-related variables. These results suggest that LRP8 gene polymorphisms influence plasma cholesterol levels as well as size and composition of LDL particles.
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- 2010
31. Increased biglycan in aortic valve stenosis leads to the overexpression of phospholipid transfer protein via toll-like receptor 2
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Derbali, Habib, Bosse, Yohan, Côté, Nancy, Pibarot, Philippe, Audet, Audrey, Pépin, Andrée, Arsenault, Benoit, Couture, Christian, Després, Jean-Pierre, Mathieu, Patrick, Derbali, Habib, Bosse, Yohan, Côté, Nancy, Pibarot, Philippe, Audet, Audrey, Pépin, Andrée, Arsenault, Benoit, Couture, Christian, Després, Jean-Pierre, and Mathieu, Patrick
- Abstract
Aortic stenosis (AS) is the most common valvular heart disease, and it is suspected that atherosclerotic mechanisms are involved in the development of this disorder. Therefore, the retention of lipids within the aortic valve may play a role in the pathobiology of AS. In this study, a gene expression microarray experiment was conducted on human aortic valves with and without AS. The expression levels of transcripts encoding proteoglycans and enzymes involved in lipid retention were compared between the two groups. The microarray results were subsequently replicated in a cohort of 87 AS valves and 36 control valves. In addition, the interaction between proteoglycan and lipid-modifying enzyme was documented in isolated valve interstitial cells (VICs). The microarray results indicated that only biglycan (BGN) and phospholipid transfer protein (PLTP) were overexpressed in the AS valves. These results were then confirmed by quantitative PCR. The immunohistochemical analysis revealed a colocalization of BGN, PLTP, and Toll-like receptor-2 (TLR 2) in AS valves. In vitro, we showed that BGN induces the production of PLTP in VICs via the stimulation of TLR 2. Thus, increased accumulation of BGN in AS valves contributes to the production of PLTP via TLR 2. These results suggest that intricate links between valve matrix proteins, inflammation, and lipid retention are involved in the pathobiology of AS.
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- 2010
32. Age-related differences in the pathogenesis of calcific aortic stenosis : the potential role of resistin
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Mohty, Dania, Pibarot, Philippe, Després, Jean-Pierre, Cartier, Amélie, Arsenault, Benoit, Picard, Frédéric, Mathieu, Patrick, Mohty, Dania, Pibarot, Philippe, Després, Jean-Pierre, Cartier, Amélie, Arsenault, Benoit, Picard, Frédéric, and Mathieu, Patrick
- Abstract
Background: Aortic stenosis (AS) is considered as an atherosclerotic related process. However, there are uncertainties whether AS in the elderly is associated with the same pathophysiological processes as in younger patients. We hypothesized that the metabolic determinants of the valvular inflammatory and calcifying processes occurring in elderly patients are different from those observed earlier in life. Methods: Among 114 patients operated for a severe AS, a complete plasma lipid blood profile and plasma levels of adipokines (resistin, leptin) were determined. The calcium content of the aortic valve was measured and valvular inflammation was quantified. Results Elderly patients (= 70 years) had significantly lower LDL-C ( p = 0.02), lower LDL-C associated with small size particles (LDL-C < 255 Å) ( p = 0.003), and higher HDL peak particle size than younger patients ( p = 0.03). In addition, elderly patients had increased plasma leptin ( p = 0.04) and resistin ( p = 0.0004) levels compared to the middle-aged group (< 70 years). In the elderly patients, higher plasma resistin blood levels were associated with increased valve calcium content and inflammation. Conclusion: The lipid profile of elderly patients was found less atherogenic than that of middle-aged patients. On the other hand, older patients with AS had higher plasma level of resistin which was associated with the degree of valvular calcification and inflammation. These results suggest that, beyond lipid model of atherosclerosis, age-related processes affecting resistin blood levels may also be involved in the late development of AS.
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- 2009
33. Oxidized low-density lipoprotein, angiotensin II and increased waist cirumference are associated with valve inflammation in prehypertensive patients with aortic stenosis
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Côté, Nancy, Pibarot, Philippe, Pépin, Andrée, Fournier, Dominique, Audet, Audrey, Arsenault, Benoit, Couture, Christian, Poirier, Paul, Després, Jean-Pierre, Mathieu, Patrick, Côté, Nancy, Pibarot, Philippe, Pépin, Andrée, Fournier, Dominique, Audet, Audrey, Arsenault, Benoit, Couture, Christian, Poirier, Paul, Després, Jean-Pierre, and Mathieu, Patrick
- Abstract
Introduction: The progression of aortic stenosis (AS) has been shown to be faster in patients with the metabolic syndrome. We sought to determine the relationships between blood pressure, inflammation, oxidative stress and valvular inflammation in a population of normotensive and prehypertensive patients with AS. Methods: In this study, 36 male patients (age: 61.5 ± 2 years) with AS undergoing an aortic valve replacement were investigated. Plasma levels of adiponectin, oxidized-LDL (ox-LDL), angiotensinogen (AGN) and angiotensin I-II (Ang I-II) were measured. On explanted aortic valves, immunohistochemistry studies and quantitative PCR (q-PCR) analyses were performed to document the expression of inflammatory cytokines. Results: Systolic blood pressure (SBP) was positively correlated with plasma level of ox-LDL ( r = 0.4; p = 0.02), AGN ( r = 0.41; p = 0.01), and white blood cells count ( r = 0.33; p = 0.04), whereas it was inversely related to plasma level of adiponectin ( r = - .35; p = 0.04). After adjustment for covariates, plasma level of ox-LDL ( p = 0.01) remained significantly associated with SBP ( p = 0.01). Within the aortic valve, expression of TNF-a was significantly associated with plasma levels of ox-LDL ( r = 0.58; p = 0.03), Ang II ( r = 0.69; p = 0.013), and waist circumference ( r = 0.60; p = 0.02), whereas valvular expression of IL-6 was associated with plasma level of Ang II ( r = 0.51; p = 0.03). In explanted AS valves, ox-LDL was documented near calcified areas and colocalized with Ang II, IL-6, and TNF-a. Conclusion: Conditions associated with a higher oxidative stress and activation of the renin angiotensin system, such as encountered in viscerally obese and prehypertensive patients, contribute to higher valvular inflammation in AS.
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- 2009
34. Visceral obesity and the heart
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Mathieu, Patrick, Pibarot, Philippe, Larose, Éric, Poirier, Paul, Marette, André, Després, Jean-Pierre, Mathieu, Patrick, Pibarot, Philippe, Larose, Éric, Poirier, Paul, Marette, André, and Després, Jean-Pierre
- Abstract
Obesity and particularly its deleterious form, visceral adiposity, has reached a high prevalence in the industrialized world owing to the lack of exercise and the widely available energy-dense diet. As a consequence, cardiovascular diseases and metabolic disorders are afflicting an unprecedented number of individuals at a world-wide scale. Over the last decades, investigations have established firm links between visceral obesity and the development of cardiovascular diseases. Moreover, studies in the field of lipid partitioning have demonstrated that inadequacy of homeostatic mechanism ensuring adequate handling of energy surplus is associated with accumulation of visceral fat and lipid overload of internal organs, which are participating to the development of heart diseases. Visceral obesity and its metabolic consequences often referred to as the metabolic syndrome is associated with the production of an atherosclerosis prone milieu. In this review, clinical implications of visceral obesity on the development of cardiovascular disorders are reviewed along with important mechanisms participating to the development of these disorders. Implications and failure of lipid partitioning and some of the potential pathways mediating development of heart diseases are also covered in view of recent development of therapeutic options.
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- 2008
35. Relation of the “Hypertriglyceridemic Waist” phenotype to earlier manifestations of coronary artery disease in patients with glucose intolerance and type 2 diabetes mellitus
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St-Pierre, Julie, Perron, Patrice, Brisson, Diane, Santuré, Marta, Vohl, Marie-Claude, Després, Jean-Pierre, Gaudet, Daniel, St-Pierre, Julie, Perron, Patrice, Brisson, Diane, Santuré, Marta, Vohl, Marie-Claude, Després, Jean-Pierre, and Gaudet, Daniel
- Abstract
This study tested the hypothesis that the “hypertriglyceridemic waist” phenotype (waist girth >90 cm [35.4 inches] in men and >85 cm [33.5 inches] in women, along with a plasma triglyceride concentration of ≥2.0 mmol/L [177 mg/dl]) as a covariate of metabolic syndrome features (hyperinsulinemia, hyperapolipoprotein B, and small low-density lipoprotein particles), is predictive of premature coronary artery disease (CAD) among patients with glucose intolerance or type 2 diabetes. Glucose intolerance and type 2 diabetes were assessed after an oral glucose tolerance test among 1,190 men and women using the American Diabetes Association criteria. Glycemic control was evaluated using hemoglobin A1c levels. CAD was considered present on the basis of a clinical history of retrosternal pains on exertion, electrophysiologically and clinically documented myocardial infarction, or angiographic evidence of coronary lesions. More than 53% of men (n = 103) with a waist circumference ≥90 cm (35.4 inches) and nearly 80% of women (n = 122) with a waist circumference ≥85 cm (33.5 in.) with triglyceride levels ≥2 mmol/L (177 mg/dl) were diagnosed with glucose intolerance or type 2 diabetes. Survival models revealed that those with glucose intolerance or type 2 diabetes with the “hypertriglyceridemic waist” phenotype experienced their first CAD symptoms 5 years earlier than those without this phenotype. This elevated and earlier risk of CAD was statistically significant (hazard ratio 2.0, 95% confidence interval 1.2 to 3.7, p = 0.02). In conclusion, the “hypertriglyceridemic waist” phenotype, an inexpensive and simple tool identifying subjects with metabolic syndrome features, is a significant marker of CAD manifestations occurring at an earlier age in those with glucose intolerance or type 2 diabetes.
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- 2006
36. Metabolic syndrome negatively influences disease progression and prognosis in aortic stenosis
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Briand, Martin, Lemieux, Isabelle, Dumesnil, Jean G., Mathieu, Patrick, Cartier, Amélie, Després, Jean-Pierre, Arsenault, Marie, Couët, Jacques, Pibarot, Philippe, Briand, Martin, Lemieux, Isabelle, Dumesnil, Jean G., Mathieu, Patrick, Cartier, Amélie, Després, Jean-Pierre, Arsenault, Marie, Couët, Jacques, and Pibarot, Philippe
- Abstract
Objectives: This study sought to examine the association between the metabolic syndrome (MS) and the progression of aortic stenosis (AS). Background It has been suggested that aortic valve sclerosis and its progression to AS are caused by an atherosclerotic process. Metabolic syndrome is associated with a higher risk of vascular atherosclerosis. Thus, we hypothesized that the atherogenic features of MS could negatively influence disease progression and prognosis in patients with AS. Methods: We retrospectively analyzed the data of 105 consecutive patients (age 69 ± 12 years, 64 men) with at least moderate AS. Of these patients, 40 (38%) had MS identified according to the modified clinical criteria proposed by the National Cholesterol Education Program-Adult Treatment Panel III. The hemodynamic progression of AS was assessed by the measurement of the annualized decrease in valve area during the follow-up period of the study, which averaged 28 ± 13 months. Event-free survival was defined as the absence of death or aortic valve replacement during follow-up. Results: The hemodynamic progression of the stenosis was twice as fast (-0.14 ± 0.13 cm2/year vs. -0.08 ± 0.08 cm2/year, p = 0.008) and the three-year event-free survival was markedly lower (44 ± 8% vs. 69 ± 6%, p = 0.002) among patients with MS. In multivariate analysis, MS was found to be a strong independent predictor of both stenosis progression (p = 0.006) and event-free survival (odds ratio 3.85, 95% CI 1.96 to 7.58, p < 0.001). Conclusions: The present study is the first to report that MS is associated with a faster disease progression and worse outcome in patients with AS. Such findings open new avenues of research and provide a strong impetus for the elaboration of additional prospective studies focusing on this association.
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- 2006
37. Detection of a major gene effect for LDL peak particle diameter and association with apolipoprotein H gene haplotype
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Bossé, Yohan, Feitosa, Mary F., Després, Jean-Pierre, Lamarche, Benoît, Rice, Treva, Rao, D. C. (Dabeeru C.), Bouchard, Claude, Pérusse, Louis, Vohl, Marie-Claude, Bossé, Yohan, Feitosa, Mary F., Després, Jean-Pierre, Lamarche, Benoît, Rice, Treva, Rao, D. C. (Dabeeru C.), Bouchard, Claude, Pérusse, Louis, and Vohl, Marie-Claude
- Abstract
Low-density lipoprotein (LDL) size, a coronary heart disease risk factor, is influenced by both genetic and environmental factors. Results from the Quebec Family Study (QFS) revealed that the LDL peak particle diameter (LDL-PPD) aggregates in families with a heritability coefficient above 50% and is affected by a major quantitative trait locus on chromosome 17q (LOD = 6.8). Complex segregation analyses have consistently demonstrated a major gene effect influencing LDL size. In the present study, we report a similar analysis in the QFS cohort, which suggests that a major gene explains 23% of the variance in age–body mass index and triglyceride-adjusted LDL-PPD. The most intuitive positional candidate gene on chromosome 17q is the apolipoprotein H gene. Direct sequencing of the promoter, coding regions, and exon–intron splicing boundaries of this gene revealed the presence of three missense mutations and two polymorphisms in the untranslated regions. Using family-based association tests, none of these variants was individually associated with LDL-PPD. However, analysis of the haplotypes constructed from the three missense mutations, suggested that one particular haplotype (frequency = 20.9%) was associated with a significant increase in LDL-PPD trait values (p = 0.046). Taken together, these results suggest the presence of a major gene effect influencing LDL-PPD and a positive association with a positional candidate gene located on chromosome 17q. Replication of the association between apolipoprotein H gene haplotype and LDL-PPD is required before reaching firm conclusion.
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- 2005
38. Fine mapping of low-density lipoprotein receptor gene by genetic linkage on chromosome 19p13.1-p13.3 and study of the founder effect of four French Canadian low-density lipoprotein receptor gene mutations
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Couture, Patrick, Morissette, Jean, Gaudet, Daniel, Vohl, Marie-Claude, Gagné, Claude, Bergeron, Jean, Després, Jean-Pierre, Simard, Jacques, Couture, Patrick, Morissette, Jean, Gaudet, Daniel, Vohl, Marie-Claude, Gagné, Claude, Bergeron, Jean, Després, Jean-Pierre, and Simard, Jacques
- Abstract
Familial hypercholesterolemia (FH) is one of the most common autosomal codominant diseases. FH is caused by mutations in the low-density lipoprotein receptor (LDLR) gene and is characterized by raised plasma LDL-cholesterol, tendon xanthomas, and premature coronary heart disease. The frequency of FH among French Canadians in northeastern Québec is higher than in most other populations, 1:154 vs. 1:500 due to high prevalence of few recurrent mutations in the LDLR gene. In the French Canadian population, 11 mutations in the LDLR gene have been found to occur in geographically diverse areas and account for >90% of cases. We have first constructed a high-resolution genetic map to locate several highly polymorphic markers close to LDLR locus, thus providing the necessary tools to study the origin of the four most common mutations which account for ≈80% of our FH patients. We have then genotyped five markers (D19S413, D19S865, D19S221, D19S914, D19S586) in 102 heterozygotes (38 del>15kb; 36 W66G; 16 C646Y; 12 E207K), two compound heterozygotes (del>15kb/W66G; del>15kb/C646Y) and seven homozygotes (three del>15 kb; three W66G; one E207K) with FH unrelated to the first and second degree. We have found that patients bearing the same LDLR gene mutation carry a common haplotype at the LDLR locus although there is evidence for the early occurrence of a recombinational event between the LDLR and the D19S221 locus in the French Canadian patients bearing the W66G mutation. The fine mapping of LDLR gene close to several highly informative microsatellite markers provide fine mapping details of the LDLR region and additional tools for studies of association between plasma lipoprotein levels and LDLR gene.
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- 2004
39. Contribution of receptor negative versus receptor defective mutations in the LDL-receptor gene to angiographically assessed coronary artery disease among young (25–49 years) versus middle-aged (50–64 years) men
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Gaudet, Daniel, Vohl, Marie-Claude, Couture, Patrick, Moorjani, Sital, Tremblay, Gérald, Perron, Patrice, Gagné, Claude, Després, Jean-Pierre, Gaudet, Daniel, Vohl, Marie-Claude, Couture, Patrick, Moorjani, Sital, Tremblay, Gérald, Perron, Patrice, Gagné, Claude, and Després, Jean-Pierre
- Abstract
Elevated plasma LDL-cholesterol (LDL-C) levels are associated with an increased risk of coronary artery disease (CAD). Familial hypercholesterolemia (FH), a monogenic trait due to mutations in the LDL-receptor (R) gene is characterized by raised plasma LDL-C levels and premature CAD. The aim of the present investigation, derived from the study of a population of 1465 unrelated men aged 25 to 64 years, was to compare the expression of CAD assessed by coronary angiography in young (aged 25–49 years) versus middle-aged (50–64 years) heterozygous FH patients of French Canadian descent. Furthermore, the relationship of binding-defective versus receptor negative mutations in the LDL-R to premature CAD (B50 years) was examined and compared with men displaying a normal plasma lipoprotein-lipid profile. From the original study sample, a total of 100 men met the clinical criteria of heterozygous FH. Among them, 30 were carriers of a receptor negative mutation (deletion \15 kb or point mutations Y468X or R329X) whereas 64 were carriers of a receptor defective mutation (W66G, E207K or C646Y). As expected, in both age groups (25–49 years vs. 50–64 years), carriers of a receptor negative mutation had higher plasma cholesterol and LDL-C levels than carriers of a defective allele or men with a normal plasma lipoprotein-lipid profile. In addition, the mean number of diseased vessels (with\50% stenosis) was higher in men aged 50–64 years compared to those aged 25–49 years. In the two age groups, FH patients were characterized by a higher number of stenosed coronary vessels than the normal phenotype group. Within each group (either receptor negative, receptor defective or normal phenotype) plasma cholesterol, LDL-C, HDL-C, triglyceride and apolipoprotein B levels were similar irrespective of age (25–49 years vs. 50–64 years). Finally, multiple logistic regression analyses revealed that compared to non-FH men, the relative odds of being affected by CAD before the age of 50 years was 7.
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- 2004
40. Visceral obesity attenuates the effect of the hepatic lipase −514C > T polymorphism on plasma HDL-cholesterol levels in French-Canadian men
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St-Pierre, Julie, Miller-Felix, Isabelle, Paradis, Marie-Eve, Bergeron, Jean, Lamarche, Benoît, Després, Jean-Pierre, Gaudet, Daniel, Vohl, Marie-Claude, St-Pierre, Julie, Miller-Felix, Isabelle, Paradis, Marie-Eve, Bergeron, Jean, Lamarche, Benoît, Després, Jean-Pierre, Gaudet, Daniel, and Vohl, Marie-Claude
- Abstract
The dyslipidemic state of visceral obesity is characterized by increased plasma triglyceride (TG) levels, low HDL-cholesterol concentrations and alterations in LDL composition and concentration. A functional, non-coding −514C>T single nucleotide polymorphism (SNP) of the hepatic lipase gene (LIPC) has been related to variation in HDL-cholesterol concentrations. Objectives: To investigate the hypotheses that the LIPC −514C>T polymorphism may be associated with a deteriorated lipoprotein-lipid profile and that environmental factor, such as abdominal obesity, alters this association. Methods: A total of 235 French-Canadian men from the greater Quebec City area were assigned into three groups on the basis of their LIPC −514C>T SNP, including 149 CC homozygotes, 75 CT heterozygotes, and 11 TT homozygotes. Results: In the present study, the highest values of BMI, waist circumference, and accumulation of visceral adipose tissue (VAT) were observed among TT homozygotes (p < 0:05). After adjustment for age and BMI, TT homozygotes still showed higher plasma apolipoprotein (apo) AI and HDL-TG concentrations than the two other groups (p < 0:05). When the two genotype groups (CC vs CT/TT) were further divided on the basis of VAT accumulation using a cut-off point of 130 cm2 (high vs low) it appears that irrespective of the genotype subjects with low VAT had higher HDL2-cholesterol concentrations (p < 0:0001). However, lean carriers of the T allele had higher plasma HDL2-cholesterol levels than lean CC homozygotes. The beneficial effect of the T allele on plasma HDL2-cholesterol levels was abolished in the presence of visceral obesity (VAT > 130 cm2). Conclusion: In summary, the presence of visceral obesity attenuates the impact of the LIPC −514C>T polymorphism on plasma HDL2-cholesterol levels.
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- 2003
41. A sequence variation in the mitochondrial glycerol-3-phosphate dehydrogenase gene is associated with increased plasma glycerol and free fatty acid concentrations among French Canadians
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St-Pierre, Julie, Vohl, Marie-Claude, Brisson, Diane, Perron, Patrice, Després, Jean-Pierre, Hudson, Thomas J., Gaudet, Daniel, St-Pierre, Julie, Vohl, Marie-Claude, Brisson, Diane, Perron, Patrice, Després, Jean-Pierre, Hudson, Thomas J., and Gaudet, Daniel
- Abstract
FAD-dependent glycerol-3-phosphate dehydrogenase (mGPD) enzyme is located in the mitochondrial inner membrane where it catalyzes irreversible oxidation reactions. Type 2 diabetes mellitus (DM) is a multifactorial disorder associated with physiological abnormalities in the glycerol and free fatty acids (FFA) metabolic pathways. In the present study, we have evaluated the association among the mGPD H264R sequence variation and postabsorptive plasma FFA and glycerol concentrations in a sample of French Canadians with and without type 2 DM. A sample of 81 recently diagnosed type 2 DM and 318 nondiabetic, nonobese, normotriglyceridemic French Canadians were screened for the presence of the mGPD H264R genetic variant using a PCR-RFLPbased method. The 318 nondiabetic subjects were free of known type 2 DM covariates (fasting glucose <7.0 mmol/L, body mass index <29 kg/m2 , fasting glycerol <2.0 mmol/L and absence of the N288D sequence variation in the glycerol kinase gene, fasting triglyceride <2.5 mmol/L). The association of mGPD H264R sequence variation with plasma FFA and glycerol concentrations was assessed in different regression models. Among non-DM individuals, the R allele (HR and RR genotypes) was associated with increased plasma FFA and glycerol concentrations (P < 0.05). However, the mean plasma FFA and glycerol concentrations were not affected by the H264R genotype in the type 2 DM sample. Overall, mean plasma FFA concentrations in non-DM RR homozygotes reached values that were similar to those achieved in patients with type 2 diabetes (0.87 6 0.63 vs 0.90 6 0.48 mmol/L). After controlling for age, gender, body mass index, fasting glucose, and fasting triglyceride concentrations, the relative odds of having fasting plasma FFA levels above the 90th percentile (0.9 mmol/L) in the absence of DM was increased by twofold in H264R heterozygotes (P 5 0.04) and fourfold among R264 homozygotes (P 5 0.009) compared to noncarriers. In the absence of DM, the mGPD R allele w
- Published
- 2002
42. Visceral obesity and hyperinsulinemia modulate the impact of the microsomal triglyceride transfer protein −493G/T polymorphism on plasma lipoprotein levels in men
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St-Pierre, Julie, Lemieux, Isabelle, Miller-Felix, Isabelle, Prud'homme, Denis, Bergeron, Jean, Gaudet, Daniel, Nadeau, André, Després, Jean-Pierre, Vohl, Marie-Claude, St-Pierre, Julie, Lemieux, Isabelle, Miller-Felix, Isabelle, Prud'homme, Denis, Bergeron, Jean, Gaudet, Daniel, Nadeau, André, Després, Jean-Pierre, and Vohl, Marie-Claude
- Abstract
The dyslipidemic state of visceral obesity is characterized by increased plasma triglyceride levels, low high-density lipoproteincholesterol concentration and alterations in low-density lipoprotein (LDL) composition and concentration. A functional, non-coding microsomal triglyceride transfer protein (MTP) −493G/T polymorphism of the microsomal triglyceride transfer protein gene has been related to variations in LDL-cholesterol levels. To study the effect of the MTP −493G/T polymorphism on lipoprotein levels in visceral obesity and hyperinsulinemia, a total of 227 men were assigned into two groups on the basis of their MTP −493G/T polymorphism, including 121 GG homozygotes and 105 carriers of the T allele (92 GT and 13 TT). The two genotypic groups did not differ for their physiological characteristics nor for lipoprotein–lipid profiles, before and after adjustment for age. However, GG homozygotes were characterized by higher fasting insulin levels than carriers of the T allele (P 0.05). When the two genotypic groups were further divided on the basis of their visceral adipose tissue (AT) accumulation, assessed by computed tomography, we observed that T allele carriers with low levels of visceral AT ( 130 cm2 ) had decreased plasma total cholesterol and LDL-apolipoprotein B (LDL-apoB) levels compared to viscerally obese men (P=0.035 and P=0.0001, respectively). Among GG homozygotes, no significant difference were observed. Although not significant, T allele carriers characterized by visceral obesity tended to have smaller, denser LDL particles than T allele carriers characterized by a low accumulation of visceral AT. When subjects were divided on the basis of their fasting insulin levels, it appears that hyperinsulinemic men were characterized by a deteriorated lipoprotein–lipid profile when they were carriers of the T allele compared to normoinsulinemic men. In summary, visceral obesity and hyperinsulinemia modulate the impact of the MTP −493G/T polymorphism on plasm
- Published
- 2002
43. Relative contribution of low-density lipoprotein receptor and lipoprotein lipase gene mutations to angiographically assessed coronary artery disease among French Canadians
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Gaudet, Daniel, Vohl, Marie-Claude, Julien, Pierre, Tremblay, Gérald, Perron, Patrice, Gagné, Claude, Bergeron, Jean, Moorjani, Sital, Després, Jean-Pierre, Gaudet, Daniel, Vohl, Marie-Claude, Julien, Pierre, Tremblay, Gérald, Perron, Patrice, Gagné, Claude, Bergeron, Jean, Moorjani, Sital, and Després, Jean-Pierre
- Abstract
Men with low-density lipoprotein receptor gene mutations causing familial hypercholesterolemia (FH) are at high risk of premature coronary artery disease (CAD). The dyslipidemic state found among patients who are heterozygous for mutations in the lipoprotein lipase (LPL) gene may also increase the risk of CAD. In the present study, the association of the heterozygous forms of low-density lipoprotein receptor gene mutations causing FH as well as of LPL gene mutations causing (P207L and G188E) or not causing (D9N and N291S) complete loss of LPL activity with angiographically assessed CAD was estimated in a cohort of 412 French Canadian men aged <60 years who consecutively underwent coronary angiography for the investigation of retrosternal pain. The frequency of FH as well as of LPL gene mutations tended to increase with the number of narrowed coronary arteries. However, CAD occurred earlier in FH patients than in partly LPL-deficient patients. Indeed, the proportion of men affected by FH was of 16.4% in those <45 years of age, and solely 4.3% among those between 56 and 60 years of age (p <0.0001). In contrast, the LPL gene defect was found in only 4.0% of men aged <45 years, whereas this prevalence reached 8.3% among those aged 56 to 60 years. In multivariate analyses, the association of LPL with CAD was not independent of age, high-density lipoprotein cholesterol concentrations, and other covariates included at baseline, and was not affected by the type of mutation in the LPL gene. In contrast, FH was associated with CAD with minimal contribution of other cardiovascular risk factors. However, the relation between FH and CAD was at least partly dependent on plasma apolipoprotein B concentrations. In the different regression models, fasting insulin and plasma high-density lipoprotein cholesterol concentrations were important covariates of CAD, whether or not patients were affected by FH or LPL deficiency. In conclusion, the association of LPL gene mutations with CAD w
- Published
- 1998
44. Heterozygous familial hypercholesterolemia in children : low-density lipoprotein receptor mutational analysis and variation in the expression of plasma lipoprotein-lipid concentrations
- Author
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Torres, Ana Lucia, Moorjani, Sital, Vohl, Marie-Claude, Gagné, Claude, Lamarche, Benoît, Brun, Louis-Daniel, Lupien, Paul-J., Després, Jean-Pierre, Torres, Ana Lucia, Moorjani, Sital, Vohl, Marie-Claude, Gagné, Claude, Lamarche, Benoît, Brun, Louis-Daniel, Lupien, Paul-J., and Després, Jean-Pierre
- Abstract
The phenotypic expression 01‘ heterozygous familial hypercholesterolemia (FH) is variable from biochemical and clinical standpoints and several genetic and environmental factors could contribute to explain this variability. We have compared, in a cohort of 266 heterozygous FH children and adolescents (l-19 years), the variation in plasma lipoprotein-lipid levels among patients defined by three mutations in the low density lipoprotein receptor (LDLR) gene. Comparison of the plasma total and LDL-cholesterol (LDL-C) levels among the three mutation groups revealed significant differences. Plasma total and LDL-C levels were significantly higher (P < 0.05) in the group bearing the French-Canadian A > 15 kb null allele mutation (8.17 rt 1.45 and 6.58 + 1.42 mmol/l) and in the group with the defective allele Ch46Y missense mutation (8.18 + 1.53 and 6.65 + 1.50 mmol/l) compared to the group with the defective allele W66G missense mutation (7.19 f 1.23 and 5.62 f 1.16 mmol/l). Comparisons of other lipoprotein-lipid parameters between FH heterozygotes and normolipemic (n = 120) children indicated that all mutation groups had significantly (P= 0.0001) lower plasma HDL-cholesterol (HDL-C) levels and a higher total cholesterol (TC) to HDL-C ratio (P <: 0.05). Among FH heterozygote groups, the W66G group had the lowest TC to HDL-C ratio. Multivariate analyses revealed that in FH heterozygotes as well as in controls, HDL-C levels contributed to a greater proportion of the variation in TC to HDL-C ratio than TC. In order to examine the age effect, control and FH heterozygote A > 15 kb groups were then subdivided into four groups (l-4; 5-8; 9-13, and 14-19 years). The variation in HDL-C and triglycerides with age in heterozygous FH children showed a pattern which was similar to the one noted in the control group. In conclusion, the present study demonstrated that the overall contribution of age to variation in the lipoprotein profile of heterozygous FH children is similar to the effe
- Published
- 1996
45. Substituting Refined Sugars With Maple Syrup Decreases Key Cardiometabolic Risk Factors in Individuals With Mild Metabolic Alterations: A Randomized, Double-Blind, Controlled Crossover Trial.
- Author
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Morissette A, Agrinier AL, Gignac T, Ramadan L, Diop K, Marois J, Varin TV, Pilon G, Simard S, Larose É, Gagnon C, Arsenault BJ, Després JP, Carreau AM, Vohl MC, and Marette A
- Subjects
- Humans, Double-Blind Method, Male, Female, Adult, Middle Aged, Blood Glucose metabolism, Sweetening Agents pharmacology, Sweetening Agents administration & dosage, Blood Pressure drug effects, Gastrointestinal Microbiome drug effects, Overweight, Dietary Sugars administration & dosage, Cross-Over Studies, Acer chemistry, Cardiometabolic Risk Factors
- Abstract
Background: Maple syrup, a minimally transformed sweetener rich in polyphenols, can exert a action and improve metabolic parameters in animal models. However, no randomized clinical trial has investigated this., Objectives: This study aims to determine whether replacing refined sugars with an equivalent quantity of maple syrup could decrease key cardiometabolic risk factors in individuals with mild metabolic alterations., Methods: In a randomized, double-blind, controlled crossover trial with 42 overweight adults with mild cardiometabolic alterations, participants were instructed to substitute 5% of their total caloric intake from added sugars with either maple syrup or an artificially flavored sucrose syrup for 8 wk. The primary outcome included changes in glucose homeostasis, whereas secondary outcomes were changes in other cardiometabolic risk factors such as blood pressure, anthropometric indices, and blood lipid profiles. Exploratory outcomes involved analyzing changes in gut microbiota composition., Results: Replacing refined sugars with maple syrup over 8 wk decreased the glucose area under the curve when compared with substituting refined sugars with sucrose syrup, as determined during the oral glucose tolerance test, leading to a significant difference between the intervention arms (-50.59 ± 201.92 compared with 29.93 ± 154.90; P < 0.047). Substituting refined sugar with maple syrup also significantly decreased android fat mass (-7.83 ± 175.05 g compared with 67.61 ± 206.71 g; P = 0.02) and systolic blood pressure (-2.72 ± 8.73 mm Hg compared with 0.87 ± 8.99 mm Hg; P = 0.03). No changes in the blood lipid profile were observed. As an exploratory outcome, we further observed that substituting refined sugars with maple syrup promoted selective taxonomic changes in the gut microbiota such as a significant reduction in the abundance of Klebsiella species and decreased microbial functions associated with bacterial-induced cytokine response, when compared with substitution with sucrose syrup., Conclusions: Substituting refined sugars with maple syrup in individuals with mild metabolic alterations result in a significantly greater reduction of key cardiometabolic risk factors compared with substitution with sucrose syrup, in association with specific changes in gut microbiota. The role of the gut microbiota in these effects remains to be further explored. This trial was registered at clinicaltrials.gov as NCT04117802., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
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46. Visceral adiposity: A major mediator of the relationship between epicardial adiposity and cardiorespiratory fitness in adults.
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Chartrand DJ, Larose E, Poirier P, Mathieu P, Alméras N, Pibarot P, Lamarche B, Rhéaume C, Lemieux I, Després JP, and Piché ME
- Abstract
Background and Aims: Epicardial adiposity has been positively associated with visceral adipose tissue (VAT). Few studies have examined the association between cardiorespiratory fitness (CRF) and epicardial adiposity. Furthermore, whether this relationship was independent of VAT remains unexplored. Our purpose was to investigate the contribution of VAT in the relationships between CRF, physical activity (PA) and epicardial adipose tissue (EAT) in asymptomatic women and men., Methods and Results: We examined the associations between EAT and VAT measured by magnetic resonance imaging, CRF measured by cardiopulmonary exercise testing, and PA assessed using pedometers and a 3-day PA journal in 239 apparently healthy adults (43 % women). Participants were compared according to EAT tertiles and CRF level in both sexes. Participants with the highest EAT level presented more VAT (p < 0.001), lower CRF (p < 0.01), and a more deteriorated cardiometabolic health score (p < 0.01) than those with the lowest EAT level. CRF was negatively associated with EAT in both sexes (p < 0.01). No significant relationship was found with PA (p = NS). Stepwise multivariable regression analyses showed that VAT explained most of the variance in EAT in women and men. Mediation analyses confirmed that VAT was a mediator of the association between CRF and EAT in both sexes., Conclusion: In women and men, VAT appears as a major mediator of the association between CRF and EAT thereby suggesting that managing VAT by improving CRF could help in the prevention of cardiometabolic disorders related to excess EAT., Competing Interests: Declaration of competing interest Philippe Pibarot has received institutional funding from Edwards Lifesciences, Novartis, Medtronic and Pi-Cardia outside the submitted work and for which he has received no personal compensation. The other authors declared no conflict of interest., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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47. Adiposity, type 2 diabetes and atherosclerotic cardiovascular disease risk: Use and abuse of the body mass index.
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Arsenault BJ, Carpentier AC, Poirier P, and Després JP
- Subjects
- Humans, Risk Assessment, Risk Factors, Risk Reduction Behavior, Heart Disease Risk Factors, Body Mass Index, Diabetes Mellitus, Type 2 epidemiology, Diabetes Mellitus, Type 2 diagnosis, Adiposity, Obesity epidemiology, Obesity physiopathology, Atherosclerosis epidemiology
- Abstract
The worldwide prevalence of individuals with an elevated body weight has increased steadily over the past five decades. Billions of research dollars have been invested to improve our understanding of the causes and consequences of having an elevated body weight. All this knowledge has, however, failed to influence populational body weight trajectories of most countries around the world. Research on the definition of "obesity" has also evolved. Body mass index (BMI), the most commonly used tool to make its diagnosis, has major limitations. In this review article, we will highlight evidence from observational studies, genetic association studies and randomized clinical trials that have shown the remarkable inter-individual differences in the way humans store energy as body fat. Increasing evidence also suggests that, as opposed to weight inclusive, lifestyle-based approaches, weight-centric approaches advising people to simply eat less and move more are not sustainable for most people for long-term weight loss and maintenance. It is time to recognize that this outdated approach may have produced more harm than good. On the basis of pathophysiological, genetic and clinical evidence presented in this review, we propose that it may be time to shift away from the traditional clinical approach, which is BMI-centric. Rather, emphasis should be placed on actionable lifestyle-related risk factors aiming at improving overall diet quality and increasing physical activity level in the general population., Competing Interests: Declaration of competing interests BJA is a consultant for Novartis, Eli Lilly, Editas Medicine and Silence Therapeutics and has received research contracts from Pfizer, Eli Lilly, Ionis Pharmaceuticals and Silence Therapeutics. ACC received research funding by Eli Lilly (2019 - ongoing) and NovoNordisk (2021 - ongoing) and consultation fees by Eli Lilly, HLS Therapeutics, Janssen Inc., Novartis Pharmaceuticals Canada Inc., and Novo Nordisk Canada Inc. PP received continuous medical education/consultation fees from Abbott, Amgen, Astrazeneca, Bayer, Bausch Health, Boehringer Ingelheim, Eli Lilly, GSK, HLS Therapeutics Inc, Janssen Inc, Novartis Pharmaceuticals Canada Inc, Mantra Pharma, Novo Nordisk Canada Inc, Sanofi, Servier. JPD discloses having received consulting fees from Inversago., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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48. Weight gain with age and coronary atherosclerosis: Only the tip of a deadly iceberg.
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Lemieux I and Després JP
- Subjects
- Humans, Weight Gain, Adipose Tissue, Coronary Artery Disease, Atherosclerosis
- Abstract
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
- Published
- 2023
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49. Should we target increased physical activity or less sedentary behavior in the battle against cardiovascular disease risk development?
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Katzmarzyk PT, Ross R, Blair SN, and Després JP
- Subjects
- Exercise, Humans, Risk Factors, Sitting Position, Cardiovascular Diseases diagnosis, Cardiovascular Diseases epidemiology, Cardiovascular Diseases prevention & control, Sedentary Behavior
- Abstract
Physical inactivity is a well-established risk factor for cardiovascular disease (CVD) incidence and mortality. In the last decade, there is also emerging evidence of the role of sedentary behaviors (sitting) as a risk factor for CVD. Therefore, there is increasing interest in understanding the independent and joint effects of physical activity and sedentary behavior on CVD risk. Higher levels of moderate-to-vigorous physical activity and less time spent in sedentary behavior are associated with a decreased risk of CVD. There is also preliminary evidence that higher levels of light-intensity physical activity are associated with lower all-cause mortality rates; however, the cardio-protective effects of light-intensity physical activity are yet to be determined. The results from several studies have demonstrated that the effects of sedentary behavior on CVD risk is more pronounced among individuals who are physically inactive, compared to those who are more active. Further, high levels (60-75 min per day) of moderate-to-vigorous physical activity appear to eliminate the increased risk of CVD associated with excessive sedentary behavior. Replacing sedentary behavior with any intensity of physical activity will produce health benefits; however, the greatest benefits occur when replacing sedentary behavior with moderate-to-vigorous intensity physical activity., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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50. Changes in IGFBP-2 levels following a one-year lifestyle modification program are independently related to improvements in plasma apo B and LDL apo B levels.
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Carter S, Lemieux I, Li Z, Alméras N, Tremblay A, Bergeron J, Poirier P, Després JP, and Picard F
- Subjects
- Adiposity, Adult, Aged, Biomarkers blood, Caloric Restriction, Diet, Healthy, Exercise, Humans, Insulin Resistance, Longitudinal Studies, Male, Middle Aged, Obesity, Abdominal blood, Obesity, Abdominal diagnosis, Time Factors, Up-Regulation, Apolipoprotein B-100 blood, Healthy Lifestyle, Insulin-Like Growth Factor Binding Protein 2 blood, Lipoproteins, LDL blood, Obesity, Abdominal therapy, Risk Reduction Behavior
- Abstract
Background and Aims: Recent transversal studies have associated insulin-like growth factor binding protein (IGFBP)-2 levels with glucose tolerance and parameters of the lipoprotein-lipid profile. Here, we aimed at determining the longitudinal effects of a one-year lifestyle modification program on IGFBP-2 levels and to identify specific metabolic improvements impacted by the changes in IGFBP-2., Methods: 99 middle-aged Caucasian men were involved in a lifestyle modification program consisting in personalized healthy eating and physical activity counseling, combined to elicit a daily 500 kcal deficit. Anthropometric and metabolic parameters as well as circulating IGFBP-2 levels were measured before and after one year of the lifestyle modification program., Results: The intervention triggered positive changes in many metabolic parameters and a 43% (p < 0.0001) increase of IGFBP-2 levels. Subjects with the most substantial increases in IGFBP-2 also experienced the most important metabolic improvements. Changes in IGFBP-2 levels (both absolute and relative) were correlated with markers of body fat distribution and lipoprotein-lipid profile, and independently associated with changes in LDL apolipoprotein (apo) B but not VLDL apo B concentrations. Further analyses showed that for similar changes in BMI, waist circumference and visceral adipose tissue volume, large changes in IGFBP-2 levels were required to observe improvements in LDL apo B levels., Conclusions: The 1-year lifestyle modification program was associated with increased IGFBP-2 concentrations. Increases in IGFBP-2 levels were closely associated with reduced LDL apo B concentrations and independently of the modifications in fat mass and insulin sensitivity. Further mechanistic studies are required to assess the effects of IGFBP-2 levels on LDL metabolism., (Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
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