Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Christian Agard is active.

Publication


Featured researches published by Christian Agard.


Annals of the Rheumatic Diseases | 2008

Mortality and risk factors of scleroderma renal crisis: a French retrospective study of 50 patients

Luis Teixeira; Luc Mouthon; Alfred Mahr; Alice Bérezné; Christian Agard; Marion Mehrenberger; Laure-Hélène Noël; Pierre Trolliet; C. Francès; Jean Cabane; Loïc Guillevin

Objectives: To describe presentation and outcome of patients with scleroderma renal crisis (SRC). Methods: SRC was defined as rapidly progressive oliguric renal insufficiency and/or rapidly progressive arterial hypertension occurring during the course of systemic sclerosis (SSc). Chronic dialysis-free survival was analysed using multivariate Cox proportional hazards regression models. The risk for developing SRC associated with corticosteroid (CS) exposure during the preceding 1- or 3-month periods was analysed according to a case–crossover design. Results: A total of 50 SSc patients aged 53.3 (14.5) (mean (SD)) years were included in the study. SRC occurred between 1979 and 2003, after a mean (SD) disease duration of 27.7 (49.1) months. A total of 43 (86%) patients had diffuse SSc, 5 (10%) had limited cutaneous SSc and 2 (4%) had SSc sine scleroderma. At the time of SRC, 10 (20%) patients were taking angiotensin converting enzyme inhibitors, and mean creatininaemia was 468 (293) μmol/l. A total of 28 (56%) patients required haemodialysis. In all, 11 patients underwent a renal biopsy, all of them had specific vascular lesions of SRC. Multivariate analyses retained age >53 years and normal blood pressure as independent predictors of decreased dialysis-free survival. Exposure to CS prior to SRC was identified in 30 (60%) patients. The odds ratios for developing SRC associated with CS exposure during the preceding 1- or 3-month periods were 24.1 (95% CI 3.0–193.8) and 17.4 (95% CI 2.1–144.0), respectively. Conclusion: SRC remains associated with severe morbidity and mortality. CS might increase the risk of developing SRC. Further studies are needed to confirm these results.


Arthritis & Rheumatism | 2009

The three-year incidence of pulmonary arterial hypertension associated with systemic sclerosis in a multicenter nationwide longitudinal study in France.

E. Hachulla; Pascal de Groote; Virginie Gressin; Jean Sibilia; Elisabeth Diot; Patrick H. Carpentier; Luc Mouthon; Pierre-Yves Hatron; Patrick Jego; Yannick Allanore; K. Tiev; Christian Agard; Anne Cosnes; Daniéla Cirstéa; J. Constans; Dominique Farge; Jean-François Viallard; J.-R. Harle; F. Patat; B. Imbert; André Kahan; Jean Cabane; Pierre Clerson; Loïc Guillevin; Marc Humbert

OBJECTIVE An algorithm for the detection of pulmonary arterial hypertension (PAH), based on the presence of dyspnea and the findings of Doppler echocardiographic evaluation of the velocity of tricuspid regurgitation (VTR) and right-sided heart catheterization (RHC), which was applied in a large multicenter systemic sclerosis (SSc) population, estimated the prevalence of PAH to be 7.85%. The aim of this observational study was to investigate the incidence of PAH and pulmonary hypertension (PH) during a 3-year followup of patients from the same cohort (the ItinérAIR-Sclérodermie Study). METHODS Patients with SSc and without evidence of PAH underwent evaluation for dyspnea and VTR at study entry and during subsequent visits. Patients in whom PAH was suspected because of a VTR of 2.8-3.0 meters/second and unexplained dyspnea or a VTR of >3.0 meters/second underwent RHC to confirm the diagnosis. RESULTS A total of 384 patients were followed up for a mean+/-SD of 41.03+/-5.66 months (median 40.92 months). At baseline, 86.7% of the patients were women, and the mean+/-SD age of the patients was 53.1+/-12.0 years. The mean+/-SD duration of SSc at study entry was 8.7+/-7.6 years. After RHC, PAH was diagnosed in 8 patients, postcapillary PH in 8 patients, and PH associated with severe pulmonary fibrosis in 2 patients. The incidence of PAH was estimated to be 0.61 cases per 100 patient-years. Two patients who exhibited a mean pulmonary artery pressure of 20-25 mm Hg at baseline subsequently developed PAH. CONCLUSION The estimated incidence of PAH among patients with SSc was 0.61 cases per 100 patient-years. The high incidence of postcapillary PH highlights the value of RHC in investigating suspected PAH.


American Journal of Respiratory and Critical Care Medicine | 2009

RhoA and Rho kinase activation in human pulmonary hypertension: role of 5-HT signaling.

Christophe Guilluy; Saadia Eddahibi; Christian Agard; Christophe Guignabert; Mohamed Izikki; Ly Tu; Laurent Savale; Marc Humbert; Elie Fadel; Serge Adnot; Gervaise Loirand; Pierre Pacaud

RATIONALE The complex and multifactorial pathogenesis of pulmonary hypertension (PH) involves constriction, remodeling, and in situ thrombosis of pulmonary vessels. Both serotonin (5-HT) and Rho kinase signaling may contribute to these alterations. OBJECTIVES To investigate possible links between the 5-HT transporter (5-HTT) and RhoA/Rho kinase pathways, as well as their involvement in the progression of human and experimental PH. METHODS Biochemical and functional analyses of lungs, platelets, and pulmonary artery smooth muscle cells (PA-SMCs) from patients with idiopathic PH (iPH) and 5-HTT overexpressing mice. MEASUREMENTS AND MAIN RESULTS Lungs, platelets, and PA-SMCs from patients with iPH were characterized by marked elevation in RhoA and Rho kinase activities and a strong increase in 5-HT binding to RhoA indicating RhoA serotonylation. The 5-HTT inhibitor fluoxetine and the type 2 transglutaminase inhibitor monodansylcadaverin prevented 5-HT-induced RhoA serotonylation and RhoA/Rho kinase activation, as well as 5-HT-induced proliferation of PA-SMCs from iPH patients that was also inhibited by the Rho kinase inhibitor fasudil. Increased Rho kinase activity, RhoA activation, and RhoA serotonylation were also observed in lungs from SM22-5-HTT(+)mice, which overexpress 5-HTT in smooth muscle and spontaneously develop PH. Treatment of SM22-5-HTT(+) mice with either fasudil or fluoxetine limited PH progression and RhoA/Rho kinase activation. CONCLUSIONS RhoA and Rho kinase activities are increased in iPH, in association with enhanced RhoA serotonylation. Direct involvement of the 5-HTT/RhoA/Rho kinase signaling pathway in 5-HT-mediated PA-SMC proliferation and platelet activation during PH progression identify RhoA/Rho kinase signaling as a promising target for new treatments against PH.


Arthritis Care and Research | 2008

Aortic involvement in recent‐onset giant cell (temporal) arteritis: A case–control prospective study using helical aortic computed tomodensitometric scan

Christian Agard; Jacques-H. Barrier; B. Dupas; T. Ponge; Alfred Mahr; Gérard Fradet; Pascal Chevalet; A. Masseau; Eric Batard; P. Pottier; Bernard Planchon; Jean-Marie Brisseau; Mohamed-A. Hamidou

OBJECTIVE The prevalence of the involvement of large vessels in giant cell arteritis (GCA) is 3-13%. Aortitis is the most serious complication of GCA. Computed tomodensitometric (CT) scan allows analysis of both the aortic wall and endoluminal part of the aorta. Therefore, we conducted a study using CT scan to analyze aortic abnormalities in patients with recent-onset GCA. METHODS This prospective controlled study compared patients with biopsy-proven GCA with a matched control group based on sex, age, and cardiovascular risk factors. During the 4-week period following diagnosis of GCA, patients underwent an aortic CT scan. The aortic imaging results were blindly compared between both groups. RESULTS From January 5, 1998 to January 11, 1999, 22 patients and 22 controls were screened by CT scan for aortic involvement. Thickening of the aortic wall was more frequent among patients than controls (45.4% versus 13.6%; P = 0.02). Aortic thickening (mean 3.3 mm) was located on the ascending part of the thoracic aorta in 22.7% of the patients, with no evidence of thickening in the controls (P = 0.05). Thickening of the abdominal aortic wall was noted in 27.3% of the patients and none of the controls (P = 0.02). CONCLUSION This study suggests that inflammatory aortic thickening, detected by CT scan, occurs frequently at the time of diagnosis of GCA, and that this condition predominantly occurs on the ascending part of the aorta.


Rheumatology | 2012

Scleroderma renal crisis: a retrospective multicentre study on 91 patients and 427 controls

L. Guillevin; Alice Bérezné; Raphaèle Seror; Luis Teixeira; Jacques Pourrat; Alfred Mahr; E. Hachulla; Christian Agard; Jean Cabane; Philippe Vanhille; Jean-Robert Harlé; Isabelle Deleveaux; Luc Mouthon

OBJECTIVE Scleroderma renal crisis (SRC) is a severe manifestation of SSc, whose prognosis remains severe, despite treatment with angiotensin-converting-enzyme inhibitor and dialysis. This study was undertaken to describe SRC characteristics, prognosis and outcome, and evaluate the responsibility of CSs in its occurrence. METHODS Analysis concerned 91 SSc patients with SRC who were compared with 427 non-SRC-SSc patients taken as controls. RESULTS Among the 91 SRC patients, 71 (78.0%) had high blood pressure, 53 (58.2%) hypertensive encephalopathy and 51 (56.0%) thrombotic microangiopathy; 64 (70.3%) had received CSs before or concomitantly with SRC vs 156 (36.5%) non-SRC-SSc patients (P < 0.001). Treated SRC patients also received more prednisone 29.3 (28.4) vs 3.6 (9.9) mg than controls (P < 0.001). SRC clinical outcomes were poor: 49 (53.8%) patients required dialysis, which was definitive for 38. Thirty-seven (40.7%) SRC patients died vs 10.8% of the controls (P < 0.001). Death was most frequent among dialysed patients who never recovered renal function (22 vs 2) and 13 never-dialysed SRC patients died. CONCLUSIONS Although SRC prognosis has improved markedly, SRC remains a severe manifestation of SSc, despite treatment with angiotensin-converting enzyme inhibitor and dialysis. CSs contributed significantly to SRC occurrence.


Annals of the Rheumatic Diseases | 2009

Pulmonary fibrosis associated with ANCA-positive vasculitides. Retrospective study of 12 cases and review of the literature

B. Hervier; Christian Pagnoux; Christian Agard; Julien Haroche; Zahir Amoura; L. Guillevin; M. Hamidou

Objective: To describe the clinical presentation of the association between pulmonary fibrosis (PF) and systemic vasculitis related to antineutrophil cytoplasmic antibodies (ANCA-V). Methods: 12 patients (three female, mean age 70.7 years) with ANCA-V associated with “idiopathic” PF were studied retrospectively. Results: ANCA-V and PF were diagnosed simultaneously in eight cases; PF occurred earlier in three cases and during ANCA-V follow-up in one. No patient had intra-alveolar haemorrhage (IAH). ANCA were myeloperoxidase (MPO)-ANCA in all cases. Seven patients had blood eosinophilia at diagnosis. Two patients died during ANCA-V induction therapy. The respiratory status of five patients worsened and three of them died from exacerbation of end-stage respiratory failure. The five remaining patients had a stable respiratory status. Conclusion: The association of PF and ANCA-V does not seem to be fortuitous, even though their clinical evolutions are clearly not related. PF was the major cause of death.


European Respiratory Journal | 2013

Pulmonary hypertension in antisynthetase syndrome: prevalence, aetiology and survival.

B. Hervier; Alain Meyer; C. Dieval; Yurdagul Uzunhan; Hervé Devilliers; David Launay; Matthieu Canuet; Laurent Tetu; Christian Agard; Jean Sibilia; Mohamed Hamidou; Zahir Amoura; Hilario Nunes; Olivier Benveniste; P. Grenier; David Montani; E. Hachulla

Antisynthetase syndrome is characterised by the association of interstitial lung disease and myositis with different anti-tRNA-synthetase antibodies. The occurrence, aetiology and prognosis of pulmonary hypertension have not yet been evaluated. Among 203 consecutive patients, transthoracic echocardiogram and right heart catheterisation results were retrospectively analysed in the light of clinico-biological, morphological and functional parameters. Definitions of pulmonary hypertension were based on the European Society of Cardiology/European Respiratory Society 2009 guidelines, with severe pulmonary hypertension being defined by a mean pulmonary arterial pressure >35 mmHg. Pulmonary hypertension was suspected by transthoracic echocardiogram in 47 (23.2%) cases, corresponding to pulmonary hypertension “possible” (n=27, 13.3%) or “likely” (n=20, 9.9%). Right heart catheterisation was performed in 21 patients, excluding pulmonary hypertension in five and confirming pre-capillary pulmonary hypertension in 16 (7.9%). Although related to interstitial lung disease in all cases, pre-capillary pulmonary hypertension was severe in 13 (81.3%) patients (mean±sd pulmonary arterial pressure 46±9 mmHg), frequently associated with low cardiac index (mean±sd 2.3±0.8 L·min−1·m−2) and high forced vital capacity/diffusing capacity of the lung for carbon monoxide ratio (2.5±0.6). Pulmonary hypertension was significantly associated with a lower survival rate (p<0.001), with a 3-year survival rate of 58%. The occurrence of pulmonary hypertension in antisynthetase syndrome is significant and dramatically worsens the prognosis. Although systematically associated with interstitial lung disease, pulmonary hypertension was usually severe, suggesting a specific pulmonary vascular involvement. PH in antisynthetase syndrome significantly worsens the prognosis, suggesting a specific pulmonary vascular involvement http://ow.ly/okXyG


Presse Medicale | 2006

Physiopathologie de la sclérodermie systémique: état des lieux sur une affection aux multiples facettes

Amélie Servettaz; Christian Agard; Mathieu C. Tamby; P. Guilpain; Loïc Guillevin; Luc Mouthon

Points essentiels La sclerodermie systemique est une affection rare qui se traduit par des lesions de fibrose et une hyperreactivite vasculaire. Des dysfonctionnements des cellules endotheliales, des fibroblastes et des lymphocytes ont ete identifies. Le dysfonctionnement des fibroblastes se caracterise par une activation incontrolee de la voie du Transforming Growth Factor-s (TGF-s), une synthese inadaptee de Connective Tissue Growth Factor (CTGF) et de radicaux libres, favorisant la synthese de matrice extracellulaire en exces. Les cellules endotheliales synthetisent en exces de l’endotheline 1, vasoconstricteur puissant, produisent de grandes quantites de NO-synthase inductible et subissent une apoptose precoce. Le stress oxydatif semble jouer un role majeur dans la progression de la sclerodermie systemique. Des taux eleves d’interleukine 4, cytokine profibrosante, sont trouves dans le plasma et le derme de malades atteints de sclerodermie systemique. Des autoanticorps sont detectables dans le serum de la majorite des patients sclerodermiques. Certains sont diriges contre des proteines nucleaires ubiquitaires bien identifiees mais n’ont pas de role pathogenique demontre. D’autres autoanticorps reconnaissent les cellules endotheliales et/ou les fibroblastes et pourraient avoir un role pathogene.


The Journal of Rheumatology | 2014

Prevalence, correlates and outcomes of gastric antral vascular ectasia in systemic sclerosis: A eustar case-control study

E. Ghrenassia; Jérôme Avouac; Dinesh Khanna; Chris T. Derk; Oliver Distler; Yossra A. Suliman; Paolo Airò; Patricia Carreira; Brigitte Granel; Alice Bérezné; Jean Cabane; Francesca Ingegnoli; Edoardo Rosato; Paola Caramaschi; Roger Hesselstrand; Ulrich A. Walker; Juan J. Alegre-Sancho; Virginie Zarrouk; Christian Agard; Valeria Riccieri; Elena Schiopu; Heather Gladue; Virginia D. Steen; Yannick Allanore

Objective. To estimate the prevalence, determine the subgroups at risk, and the outcomes of patients with systemic sclerosis (SSc) and gastric antral vascular ectasia (GAVE). Methods. We queried the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) network for the recruitment of patients with SSc-GAVE. Each case was matched for cutaneous subset and disease duration with 2 controls with SSc recruited from the same center, evaluated at the time the index case made the diagnosis of GAVE. SSc characteristics were recorded at the time GAVE occurred and the last observation was collected to define the outcomes. Results. Forty-nine patients with SSc and GAVE were included (24 with diffuse cutaneous SSc) and compared to 93 controls with SSc. The prevalence of GAVE was estimated at about 1% of patients with SSc. By multivariate analysis, patients with SSc-GAVE more frequently exhibited a diminished (< 75%) DLCO value (OR 12.8; 95% CI 1.9–82.8) despite less frequent pulmonary fibrosis (OR 0.2; 95% CI 0.1–0.6). GAVE was also associated with the presence of anti-RNA-polymerase III antibodies (OR 4.6; 95% CI 1.2–21.1). SSc-GAVE was associated with anemia (82%) requiring blood transfusion (45%). Therapeutic endoscopic procedures were performed in 45% of patients with GAVE. After a median followup of 30 months (range 1–113 months), survival was similar in patients with SSc-GAVE compared to controls, but a higher number of scleroderma renal crisis cases occurred (12% vs 2%; p = 0.01). Conclusion. GAVE is rare and associated with a vascular phenotype, including anti-RNA-polymerase III antibodies, and a high risk of renal crisis. Anemia, usually requiring blood transfusions, is a common complication.


Annals of the Rheumatic Diseases | 2015

Efficacy of sildenafil on ischaemic digital ulcer healing in systemic sclerosis: the placebo-controlled SEDUCE study

Eric Hachulla; P.-Y. Hatron; Patrick H. Carpentier; Christian Agard; Emmanuel Chatelus; Patrick Jego; Luc Mouthon; V. Queyrel; Anne-Laure Fauchais; U. Michon-Pasturel; Roland Jaussaud; Alexis Mathian; Brigitte Granel; Elisabeth Diot; Dominique Farge-Bancel; A. Mekinian; Jérôme Avouac; H. Desmurs-Clavel; Pierre Clerson

Objective To assess the effect of sildenafil, a phosphodiesterase type 5 inhibitor, on digital ulcer (DU) healing in systemic sclerosis (SSc). Methods Randomised, placebo-controlled study in patients with SSc to assess the effect of sildenafil 20 mg or placebo, three times daily for 12 weeks, on ischaemic DU healing. The primary end point was the time to healing for each DU. Time to healing was compared between groups using Cox models for clustered data (two-sided tests, p=0.05). Results Intention-to-treat analysis involved 83 patients with a total of 192 DUs (89 in the sildenafil group and 103 in the placebo group). The HR for DU healing was 1.33 (0.88 to 2.00) (p=0.18) and 1.27 (0.85 to 1.89) (p=0.25) when adjusted for the number of DUs at entry, in favour of sildenafil. In the per protocol population, the HRs were 1.49 (0.98 to 2.28) (p=0.06) and 1.43 (0.93 to 2.19) p=0.10. The mean number of DUs per patient was lower in the sildenafil group compared with the placebo group at week (W) 8 (1.23±1.61 vs 1.79±2.40 p=0.04) and W12 (0.86±1.62 vs 1.51±2.68, p=0.01) resulting from a greater healing rate (p=0.01 at W8 and p=0.03 at W12). Conclusions The primary end point was not reached in intention-to-treat, partly because of an unexpectedly high healing rate in the placebo group. We found a significant decrease in the number of DUs in favour of sildenafil compared with placebo at W8 and W12, confirming a sildenafil benefit. Trial registration number NCT01295736.

Collaboration


Dive into the Christian Agard's collaboration.

Top Co-Authors

Avatar
Top Co-Authors

Avatar

Luc Mouthon

Paris Descartes University

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Loïc Guillevin

Paris Descartes University

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Elisabeth Diot

François Rabelais University

View shared research outputs
Top Co-Authors

Avatar

Alice Bérezné

Paris Descartes University

View shared research outputs
Researchain Logo
Decentralizing Knowledge