Pour savoir comment effectuer et gérer un dépôt de document, consultez le « Guide abrégé – Dépôt de documents » sur le site Web de la Bibliothèque. Pour toute question, écrivez à corpus@ulaval.ca.
 

Personne :
Couture, Christian

En cours de chargement...
Photo de profil

Adresse électronique

Date de naissance

Projets de recherche

Structures organisationnelles

Fonction

Nom de famille

Couture

Prénom

Christian

Affiliation

Université Laval. Département de biologie moléculaire, de biochimie médicale et de pathologie

ISNI

ORCID

Identifiant Canadiana

ncf11319393

person.page.name

Résultats de recherche

Voici les éléments 1 - 10 sur 18
  • PublicationAccès libre
    Transvalvular flow, sex, and survival after valve replacement surgery in patients with severe aortic stenosis
    (Elsevier, 2020-04-28) Bilodeau, Anthony; Guzzetti, Ezequiel; Kalavrouziotis, Dimitri; Zhang, Bin; Couture, Christian; Annabi, Mohamed Salah; Pibarot, Philippe; Clavel, Marie-Annick; Dagenais, François
    Background : The respective impacts of transvalvular flow, gradient, sex, and their interactions on mortality in patients with severe aortic stenosis undergoing surgical aortic valve replacement (AVR) are unknown. Objectives : This study sought to compare the impact of pre-operative flow-gradient patterns on mortality after AVR and to examine whether there are sex differences. Methods : This study analyzed clinical, echocardiographic, and outcome data prospectively collected in 1,490 patients (544 women [37%]), with severe aortic stenosis and preserved left ventricular ejection fraction who underwent AVR. Results : In this cohort, 601 patients (40%) had normal flow (NF) with high gradient (HG), 405 (27%) NF with low gradient (LG), 246 (17%) paradoxical low flow (LF)/HG, and 238 (16%) LF/LG. During a median follow-up of 2.42 years (interquartile range: 1.04 to 4.29 years), 167 patients died. Patients with LF/HG exhibited the highest mortality after AVR (hazard ratio [HR]: 2.01; 95% confidence interval [CI]: 1.33 to 3.03; p < 0.01), which remained significant after multivariate adjustment (HR: 1.96; 95% CI: 1.29 to 2.98; p < 0.01). Both LF/LG and NF/LG patients had comparable outcome to NF/HG (p ≥ 0.47). Optimal thresholds of stroke volume index were obtained for men (40 ml/m2) and women (32 ml/m2). Using these sex-specific cutpoints, paradoxical LF was independently associated with increased mortality in both women (adjusted HR: 2.05; 95% CI: 1.21 to 3.47; p < 0.01) and men (adjusted HR: 1.54; 95% CI: 1.02 to 2.32; p = 0.042), whereas guidelines’ threshold (35 ml/m2) does not. Conclusions : Paradoxical LF/HG was associated with higher mortality following AVR, suggesting that a reduced flow is a marker of disease severity even in patients with HG aortic stenosis. Early surgical AVR (i.e., before gradient attains 40 mm Hg) might be preferable in these patients. Furthermore, the use of sex-specific thresholds (<40 ml/m2 for men and <32 ml/m2 for women) to define low-flow outperforms the guidelines’ threshold of 35 ml/m2 in risk stratification after AVR.
  • PublicationRestreint
    Polygenic risk score for coronary artery disease improves the prediction of early-onset myocardial infarction and mortality in men
    (Lippincott Williams & Wilkins, 2021-10-21) Manikpurage, Hasanga D.; Eslami, Aida; Perrot, Nicolas; Li, Zhonglin; Couture, Christian; Mathieu, Patrick; Bossé, Yohan; Arsenault, Benoit; Thériault, Sébastien
    BACKGROUND: Several risk factors for coronary artery disease (CAD) have been described, some of which are genetically determined. The use of a polygenic risk score (PRS) could improve CAD risk assessment, but predictive accuracy according to age and sex is not well established. METHODS: A PRS$_\textup{CAD}$ including the weighted effects of >1.14 million single nucleotide polymorphisms associated with CAD was calculated in UK Biobank (n=408 422), using LDpred. Cox regressions were performed, stratified by age quartiles and sex, for incident myocardial infarction (MI) and mortality, with a median follow-up of 11.0 years. Improvement in risk prediction of MI was assessed by comparing PRS$_\textup{CAD}$ to the pooled cohort equation with categorical net reclassification index using a 2% threshold (NRI$^\textup{0.02}$) and continuous NRI (NRI$^\textup{>0}$). RESULTS: From 7746 incident MI cases and 393 725 controls, hazard ratio for MI reached 1.53 (95% CI, 1.49–1.56; P=2.69×10⁻²⁹⁶) per SD increase of PRS$_\textup{CAD}$. PRS$_\textup{CAD}$ was significantly associated with MI in both sexes, with a stronger association in men (interaction P=0.002), particularly in those aged between 40 and 51 years (hazard ratio, 2.00 [95% CI, 1.86–2.16], P=1.93×10⁻⁷²). This group showed the highest reclassification improvement, mainly driven by the up-classification of cases (NRI$^\textup{0.02}$, 0.199 [95% CI, 0.157–0.248] and NRI$^\textup{>0}$, 0.602 [95% CI, 0.525–0.683]). From 23 982 deaths, hazard ratio for mortality was 1.08 (95% CI, 1.06–1.09; P=5.46×10⁻³⁰) per SD increase of PRS$_\textup{CAD}$, with a stronger association in men (interaction P=1.60×10⁻⁶). CONCLUSIONS: Our PRS$_\textup{CAD}$ predicts MI incidence and all-cause mortality, especially in men aged between 40 and 51 years. PRS could optimize the identification and management of individuals at risk for CAD.
  • PublicationAccès libre
    Contrast-enhanced computed tomography assessment of aortic stenosis.
    (2021-01-29) Timothy Robert, Graham Cartlidge; Guzzetti, Ezequiel; Bing, Rong; Couture, Christian; Kwiecinski, Jacek; Pibarot, Philippe; Clavel, Marie-Annick; Pawade, Tania; Doris, Mhairi K; Adamson, Philip D; Massera, Daniele; Lembo, Maria; Peeters, Frederique E. C. M.; Berman, Daniel S; Dey, Damini; Slomka, Piotr; Newby, David E; Dweck, Marc R
    Abstract Objectives Non-contrast CT aortic valve calcium scoring ignores the contribution of valvular fibrosis in aortic stenosis. We assessed aortic valve calcific and non-calcific disease using contrast-enhanced CT. Methods This was a post hoc analysis of 164 patients (median age 71 (IQR 66–77) years, 78% male) with aortic stenosis (41 mild, 89 moderate, 34 severe; 7% bicuspid) who underwent echocardiography and contrast-enhanced CT as part of imaging studies. Calcific and non-calcific (fibrosis) valve tissue volumes were quantified and indexed to annulus area, using Hounsfield unit thresholds calibrated against blood pool radiodensity. The fibrocalcific ratio assessed the relative contributions of valve fibrosis and calcification. The fibrocalcific volume (sum of indexed non-calcific and calcific volumes) was compared with aortic valve peak velocity and, in a subgroup, histology and valve weight. Results Contrast-enhanced CT calcium volumes correlated with CT calcium score (r=0.80, p<0.001) and peak aortic jet velocity (r=0.55, p<0.001). The fibrocalcific ratio decreased with increasing aortic stenosis severity (mild: 1.29 (0.98–2.38), moderate: 0.87 (1.48–1.72), severe: 0.47 (0.33–0.78), p<0.001) while the fibrocalcific volume increased (mild: 109 (75–150), moderate: 191 (117–253), severe: 274 (213–344) mm3/cm2). Fibrocalcific volume correlated with ex vivo valve weight (r=0.72, p<0.001). Compared with the Agatston score, fibrocalcific volume demonstrated a better correlation with peak aortic jet velocity (r=0.59 and r=0.67, respectively), particularly in females (r=0.38 and r=0.72, respectively). Conclusions Contrast-enhanced CT assessment of aortic valve calcific and non-calcific volumes correlates with aortic stenosis severity and may be preferable to non-contrast CT when fibrosis is a significant contributor to valve obstruction.
  • PublicationRestreint
    Sex-specific associations of genetically predicted circulating Lp(a) (Lipoprotein(a)) and hepatic LPA gene expression levels with cardiovascular outcomes : mendelian randomization and observational analyses
    (Lippincott Williams & Wilkins, 2021-07-19) Guertin, Jakie; Kaiser, Yannick; Manikpurage, Hasanga D.; Perrot, Nicolas; Bourgeois, Raphaëlle; Couture, Christian; Wareham, Nicholas J.; Bossé, Yohan; Pibarot, Philippe; Stroes, Erik S.; Mathieu, Patrick; Clavel, Marie-Annick; Thériault, Sébastien; Boekholdt, Matthijs; Arsenault, Benoit
    Background: Elevated Lp(a) (Lipoprotein(a)) levels are associated with coronary artery disease (CAD), ischemic stroke (IS), and calcific aortic valve stenosis (CAVS). Studies investigating the association between Lp(a) levels and these diseases in women have yielded inconsistent results. Methods: To investigate the association of Lp(a) with sex-specific cardiovascular outcomes, we determined the association between genetically predicted Lp(a) levels (using 27 single nucleotide polymorphisms at the LPA locus) and hepatic LPA expression (using 80 single nucleotide polymorphisms at the LPA locus associated with LPA mRNA expression in liver samples from the Genotype-Tissue Expression dataset) on CAD, IS, and CAVS using individual participant data from the UK Biobank: 408 403 participants of European ancestry (37 102, 4283, and 2574 with prevalent CAD, IS, and CAVS, respectively). The long-term association between Lp(a) levels and incident CAD, IS, and CAVS was also investigated in European Prospective Investigation into Cancer and Nutrition-Norfolk: 18 721 participants (3964, 846, and 424 with incident CAD, IS, and CAVS, respectively). Results: Genetically predicted plasma Lp(a) levels were positively and similarly associated with prevalent and incident CAD and CAVS in men and women. Genetically predicted plasma Lp(a) levels were associated with prevalent and incident IS when we studied men and women pooled together, and in men only. Genetically predicted LPA expression levels were associated with prevalent CAD and CAVS in men and women but not with IS. Conclusions: Genetically predicted blood Lp(a) and hepatic LPA gene expression as well as serum Lp(a) levels predict the risk of CAD and CAVS in men and in women. Whether RNA interference therapies aiming at lowering Lp(a) levels could be useful in reducing cardiovascular disease risk in both men and women with high Lp(a) levels needs to be determined in large-scale cardiovascular outcomes trials.
  • PublicationRestreint
    Severe valvular regurgitation and late prosthesis embolization after percutaneous aortic valve implantation
    (Elsevier Science, 2009-01-19) Villeneuve, Jacques; Dumont, Éric; Rodés-Cabau, Josep; Couture, Christian; Doyle, Daniel; Bergeron, Sébastien; De Larochellière, Robert; Pibarot, Philippe; Clavel, Marie-Annick
    We report the case of a 79-year-old man with low-flow, low-gradient aortic stenosis who underwent transapical aortic valve implantation. The deployment of a 26-mm Edwards SAPIEN valve (Edwards Lifesciences Inc, Irvine, CA) was complicated with the occurrence of severe central aortic regurgitation that was successfully treated with the implantation of a second valve (“valve-in-valve”). Postoperative progress was satisfactory but 2 days after the procedure he suddenly developed cardiogenic shock secondary to the migration of the aortic bioprothesis into the left ventricular outflow tract. Open-heart surgery was undertaken to remove the valves and perform standard aortic valve replacement, but the patient died perioperatively.
  • PublicationRestreint
    Association between circulating oxidised low-density lipoprotein and fibrocalcific remodelling of the aortic valve in aortic stenosis
    (BMJ Publishing Group, 2008-09-01) Arsenault, Benoit; Mohty, Dania; Couture, Christian; Cartier, Amélie.; Côté, Claude; Pibarot, Philippe; Després, Jean-Pierre; Mathieu, Patrick
    Introduction : Aortic stenosis (AS) is the most common valvular heart disease in westernised societies. AS is a disease process akin to atherosclerosis in which calcification and tissue remodelling play a crucial role. In patients with moderate/severe AS, we sought to determine whether the remodelling process would be in relationship with transvalvular gradients and circulating oxidised low-density lipoprotein (ox-LDL) levels. Methods : In 105 patients with AS, the aortic valve and blood plasma were collected at the time of valve replacement surgery. The degree of valve tissue remodelling was assessed using a scoring system (Score: 1-4) and the amount of calcium within the valve cusps was determined. The standard plasma lipid profile, the size of LDL particles and the plasma level of circulating ox-LDL (4E6 antibody) were determined. Results : After adjustment for covariables, aortic remodelling score was significantly related to transvalvular gradients measured by Doppler echocardiography before surgery. Patients with higher valve remodelling score had higher circulating ox-LDL levels (score 2: 27.3 (SEM 2.6) U/l; score 3: 32.2 (SEM 2.3) U/l; score 4: 38.3 (SEM 2.3) U/l; p = 0.02). After correction for age, gender, hypertension and HDL-C, the plasma level of ox-LDL remained significantly associated with the aortic valve remodelling score (p<0.001). The plasma level of ox-LDL was significantly associated with LDL-C (r = 0.41; p<0.001), apoB (r = 0.59; p<0.001), triglyceride (r = 0.39; p<0.001), Apo A-I (r = 0.23; p = 0.01) and cholesterol in small (<255 Å) LDL particles (r = 0.22; p = 0.02). After correction for covariables, circulating ox-LDL levels remained significantly associated with apoB (p<0.001) and triglyceride (p = 0.01) levels. Conclusion : Increased level of circulating ox-LDL is associated with worse fibrocalcific remodelling of valvular tissue in AS. It remains to be determined whether circulating ox-LDL is a risk marker for a highly atherogenic profile and/or a circulating molecule which is actively involved in the pathogenesis of calcific aortic valve disease.
  • PublicationRestreint
    Association between plasma LDL particle size, valvular accumulation of oxidized LDL, and inflammation in patients with aortic stenosis
    (American Heart Association, 2007-11-01) Côté, Claude H.; Arsenault, Benoit; Mohty, Dania; Couture, Christian; Cartier, Amélie.; Pibarot, Philippe; Cosnay, Pierre; Després, Jean-Pierre; Mathieu, Patrick
    Objective— In patients with severe aortic stenosis (AS), we examine the association between: (1) the content of oxidized LDL (oxLDL) in the aortic valve and the degree of inflammation and remodeling; (2) The proportion of small dense LDL particles in the plasma and the presence of oxLDL in the valve along with hemodynamic progression of valve stenosis. Methods and Results— We have examined 102 explanted AS valves. Tissue remodeling, inflammation, and accumulation of oxLDL were determined. A complete plasma lipid profile including the measurement of the relative proportion of small low-density lipoprotein (%LDL<255Å) was obtained. Valves with higher oxLDL content had a significantly higher density of inflammatory cells, expression of tumor necrosis factor (TNF)-a, and increased tissue remodeling score. The %LDL<255Å was significantly associated with oxLDL score within the aortic valve. In a subset of 59 patients in whom stenosis progression was measured, the %LDL<255Å correlated with the annualized peak gradient (r=0.29; P=0.04). Conclusion— Increased proportion of circulating small dense LDL particles is associated with faster progression rate of stenosis and greater accumulation of oxLDL in the aortic valve. These findings suggest that therapeutic interventions aimed at lowering the production of small dense LDL particles in patients with AS might represent a potentially interesting therapeutic avenue.
  • PublicationRestreint
    Angiotensin receptor blockers are associated with reduced fibrosis and interleukin-6 expression in calcific aortic valve disease.
    (S. Karger, 2013-08-21) Trahan, Sylvain; Fournier, Dominique; Couture, Christian; Boulanger, Marie-Chloé; Côté, Nancy.; Bossé, Yohan; Mahmut, Ablajan; Pibarot, Philippe; Pagé, Sylvain; Després, Jean-Pierre; Mathieu, Patrick
    BACKGROUND: Calcific aortic valve disease (CAVD) is a chronic disorder characterized by the mineralization of the aortic valve and involving fibrosis. OBJECTIVES: In this work we sought to determine if the fibrotic component of the remodeling process of CAVD was related to the use of angiotensin-converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARBs). METHODS: In 477 patients with CAVD, the aortic valve was examined by histology. A semiquantitative score of fibrosis was generated and associations with clinical/cardiometabolic variables examined. In a subset of 103 patients the aortic valve was available to study the infiltration by inflammatory cells and expression of interleukin-6 (IL-6) by quantitative real-time PCR. RESULTS: The fibrosis score of the aortic valve was independently related to the hemodynamic severity of CAVD measured by echocardiography. The fibrotic score of the aortic valve was also related to the expression of IL-6. The use of ARBs but not of ACEi was associated with a lower fibrosis score of the aortic valve even after correction for covariates. In addition, patients under ARBs had lower aortic valve inflammation and expression of IL-6. CONCLUSIONS: These findings suggest that ARBs may alter the fibrotic process of the aortic valve in CAVD, possibly by lowering tissue inflammation.
  • PublicationRestreint
    Autotaxin Derived From Lipoprotein(a) and Valve Interstitial Cells Promotes Inflammation and Mineralization of the Aortic Valve
    (American Heart Association, etc., 2015-08-25) Dahou, Abdellaziz; Bouchareb, Rihab; Arsenault, Benoit; Trahan, Sylvain; Marette, André; Couture, Christian; Lépine, Jamie-Lee; Boulanger, Marie-Chloé; Bossé, Yohan; Mahmut, Ablajan; Pibarot, Philippe; Hadji, Fayez; Pagé, Sylvain; Scipione, Corey A.; Nsaibia, Mohamed Jalloul; Romagnuolo, Rocco; Laflamme, Marie-Hélène; Koschinsky, Marlys L.; Mathieu, Patrick
    Background—Mendelian randomization studies have highlighted that lipoprotein(a) [Lp(a)] was associated with calcific aortic valve disease (CAVD). Lp(a) transports oxidized phospholipids (OxPLs) with a high content in lysophosphatidylcholine (LPC). Autotaxin (ATX) transforms LPC into lysophosphatidic acid. We hypothesized that ATX-lysophosphatidic acid could promote inflammation/mineralization of the aortic valve. Methods and Results—We have documented the expression of ATX in control and mineralized aortic valves. By using different approaches we have also investigated the role of ATX- lysophosphatidic acid on the mineralization of isolated valves interstitial cells (VICs) and in a mouse model of CAVD. Enzyme specific ATX activity was elevated by 60% in mineralized aortic valves compared to control valves. Immunohistochemistry studies showed a high level of ATX in mineralized aortic valves, which co-localized with OxPL and apolipoprotein(a). We detected a high level of ATX activity in the Lp(a) fraction in circulation. Interaction between ATX and Lp(a) was confirmed by in situ proximity ligation assay. Moreover, we documented that VICs also expressed ATX in CAVD. We showed that ATX-lysophosphatidic acid promote the mineralization of the aortic valve through a NF-¿B/IL-6/BMP2 pathway. In LDLR-/-/ApoB100/100/IGFII mice, ATX is overexpressed and lysophosphatidic acid promotes a strong deposition of hydroxyapatite of calcium in aortic valve leaflets and accelerates the development of CAVD. Conclusions—ATX is transported in the aortic valve by Lp(a) and is also secreted by VICs. ATX-lysophosphatidic acid promotes inflammation and mineralization of the aortic valve and thus could represent novel therapeutic targets in CAVD.
  • PublicationRestreint
    Lipid-mediated inflammation and degeneration of bioprosthetic heart valves
    (Springer, 2009-06-01) Shetty, Rahul; Audet, Audrey; Couture, Christian; Voisine, Pierre; Perron, Jean; Pibarot, Philippe; Dagenais, François; Després, Jean-Pierre; Mathieu, Patrick; Janvier, R.
    BACKGROUND: The durability of bioprosthetic valves is limited by structural valve degeneration (SVD) leading to bioprostheses (BPs) stenosis or regurgitation. We hypothesized that a lipid-mediated inflammatory mechanism is involved in the SVD of BPs. MATERIAL AND METHODS: Eighteen Freestyle stentless BP valves were explanted for SVD at a mean time of 5.9 +/- 3 years after implantation and were analysed by immunohistochemistry and transmission electron microscopy (TEM). RESULTS: The mean age of the patients was 65 +/- 8 years and there were 11 male and seven female patients. Two of the 18 BPs had macroscopic calcification, whereas the other valves had minimal or no macroscopic calcification. Tears at the commissures leading to regurgitation was present in 16 BPs. Immunohistochemistry showed the presence of oxidized low-density lipoprotein (ox-LDL) and glycosaminoglycans in the fibrosa layer of 13 BPs. Areas with ox-LDL were infiltrated by macrophages (CD68(+)) co-expressing the scavenger receptor CD36 and metalloproteinase-9 (MMP-9). Zymogram showed the active form of MMP-9 within explanted BPs. EM studies revealed the presence of lipid-laden cells featuring foam cells and fragmented collagen. Nonimplanted control BPs obtained from the manufacturer (n = 4) had no evidence of lipid accumulation, inflammatory cell infiltration or expression of MMP9 within the leaflets. CONCLUSIONS: These results support the concept that lipid-mediated inflammatory mechanisms may contribute to the SVD of BPs. These findings suggest that modification of atherosclerotic risk factors with the use of behavioural or pharmacological interventions could help to reduce the incidence of SVD.