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Cardiovascular risk factors in immune thrombocytopenia adults: Results from the CARMEN registry

2018; Wiley; Volume: 93; Issue: 7 Linguagem: Inglês

10.1002/ajh.25127

1096-8652

Guillaume Moulis, Johanne Germain, Thibault Comont, A. Arrouy, Maryse Lapeyre‐Mestre, D. Adoué,

Heparin-Induced Thrombocytopenia and Thrombosis

American Journal of HematologyVolume 93, Issue 7 p. E181-E184 CORRESPONDENCEFree Access Cardiovascular risk factors in immune thrombocytopenia adults: Results from the CARMEN registry Guillaume Moulis, Corresponding Author Guillaume Moulis moulis.g@chu-toulouse.fr orcid.org/0000-0001-9953-4640 UMR 1027, Inserm, Université de Toulouse, France Service de Médecine Interne, Centre Hospitalier Universitaire de Toulouse, France Centre d'Investigation Clinique 1436, axe pharmacoépidémiologie, Centre Hospitalier Universitaire de Toulouse, FranceCorrespondence Guillaume Moulis, UMR 1027 INSERM-UPS, Pharmacoepidemiology unit, Faculté de Médecine, 37 allées Jules Guesde, 31000 Toulouse, France. Email: moulis.g@chu-toulouse.frSearch for more papers by this authorJohanne Germain, Johanne Germain Centre d'Investigation Clinique 1436, axe pharmacoépidémiologie, Centre Hospitalier Universitaire de Toulouse, FranceSearch for more papers by this authorThibault Comont, Thibault Comont orcid.org/0000-0002-6891-9238 Service de Médecine Interne, Institut Universitaire du Cancer de Toulouse-Oncopôle, Toulouse, FranceSearch for more papers by this authorAmélie Arrouy, Amélie Arrouy Centre d'Investigation Clinique 1436, axe pharmacoépidémiologie, Centre Hospitalier Universitaire de Toulouse, FranceSearch for more papers by this authorMaryse Lapeyre-Mestre, Maryse Lapeyre-Mestre UMR 1027, Inserm, Université de Toulouse, France Centre d'Investigation Clinique 1436, axe pharmacoépidémiologie, Centre Hospitalier Universitaire de Toulouse, France Service de Pharmacologie Médicale et Clinique, Centre Hospitalier Universitaire de Toulouse, FranceSearch for more papers by this authorDaniel Adoue, Daniel Adoue Service de Médecine Interne, Institut Universitaire du Cancer de Toulouse-Oncopôle, Toulouse, FranceSearch for more papers by this authorthe CARMEN investigators group, the CARMEN investigators groupSearch for more papers by this author Guillaume Moulis, Corresponding Author Guillaume Moulis moulis.g@chu-toulouse.fr orcid.org/0000-0001-9953-4640 UMR 1027, Inserm, Université de Toulouse, France Service de Médecine Interne, Centre Hospitalier Universitaire de Toulouse, France Centre d'Investigation Clinique 1436, axe pharmacoépidémiologie, Centre Hospitalier Universitaire de Toulouse, FranceCorrespondence Guillaume Moulis, UMR 1027 INSERM-UPS, Pharmacoepidemiology unit, Faculté de Médecine, 37 allées Jules Guesde, 31000 Toulouse, France. Email: moulis.g@chu-toulouse.frSearch for more papers by this authorJohanne Germain, Johanne Germain Centre d'Investigation Clinique 1436, axe pharmacoépidémiologie, Centre Hospitalier Universitaire de Toulouse, FranceSearch for more papers by this authorThibault Comont, Thibault Comont orcid.org/0000-0002-6891-9238 Service de Médecine Interne, Institut Universitaire du Cancer de Toulouse-Oncopôle, Toulouse, FranceSearch for more papers by this authorAmélie Arrouy, Amélie Arrouy Centre d'Investigation Clinique 1436, axe pharmacoépidémiologie, Centre Hospitalier Universitaire de Toulouse, FranceSearch for more papers by this authorMaryse Lapeyre-Mestre, Maryse Lapeyre-Mestre UMR 1027, Inserm, Université de Toulouse, France Centre d'Investigation Clinique 1436, axe pharmacoépidémiologie, Centre Hospitalier Universitaire de Toulouse, France Service de Pharmacologie Médicale et Clinique, Centre Hospitalier Universitaire de Toulouse, FranceSearch for more papers by this authorDaniel Adoue, Daniel Adoue Service de Médecine Interne, Institut Universitaire du Cancer de Toulouse-Oncopôle, Toulouse, FranceSearch for more papers by this authorthe CARMEN investigators group, the CARMEN investigators groupSearch for more papers by this author First published: 26 April 2018 https://doi.org/10.1002/ajh.25127Citations: 1 Collaborators (CARMEN investigators group): Laurent Alric, Sophie Arista, Leonardo Astudillo, Laurent Balardy, Sarah Betrian, Odile Beyne-Rauzy, Delphine Bonnet, Cécile Borel, Delphine Brechemier, Natacha Brun, Miguel Carreiro, Brice Castel, Leo Caudrelier, Pierre Cougoul, Alina Danu, Karen Delavigne, Claire Dingremont, Thomas Faurie, Francis Gaches, Marie-Hélène Gaspard, Clément Gaudin, Aurélie Godel-Labouret, Patrick Giraud, Sondess Hadj-Khelifa, Benjamin Hebraud, Sarah Khatibi, Lorraine Leplay, Yann Leveneur, Nicolas Limal, Sylvie Ollier, Serge Madaule, Bruno Marchou, Clothilde Martel, Guillaume Martin-Blondel, Philippe Montane De La Roque, Martin Michaud, Julia Moeglin, Fanny Nuccio, Marie-Léa Piel-Julian, Laurent Prudhomme, Grégory Pugnet, Christian Recher, Véronique Remy, Laurent Sailler, Stéphane Sire, Agnès Sommet, Suzanne Tavitian, Marie-Françoise Thiercelin-Legrand, Willy Vaillant. AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Immune thrombocytopenia (ITP) is associated to an increased risk of thrombotic events in adults as compared with the general population. If the risk of venous events is demonstrated, the risk of arterial events is still debated.1 Thanks to a new population-based study conducted in the THIN database in UK, Chandan et al. provided recently new evidence for an increased risk of myocardial infarction and stroke in ITP adults as compared with the general population.2 Causal studies are still needed to determine the risk factors of thrombosis in ITP, including the exposure to drugs used for ITP treatment. Among these potential risk factors, a retrospective multicenter Italian study raised the impact of cardiovascular risk factors.3 The study by Chandan et al. presents the high interest of providing original data regarding the prevalence of cardiovascular risk factors in ITP patients, found as frequent as in the general population controls. However, the patients with previous cardiovascular diseases at index date were excluded.2 Consequently, the prevalence of cardiovascular risk factors might be lower in this study as compared with the whole population of ITP patients. Moreover, like every study based on electronic medical records, it presents a risk of missing data,4 miscoding, and incomplete clinical data leading to the use of proxies to identify some covariables (e.g., lipid-lowering drugs to address dyslipidemia). Consequently, we aimed at assessing the prevalence of cardiovascular risk factors at ITP diagnosis in a prospective clinical cohort of ITP adults. The source of data was the CARMEN (Cytopénies Auto-immunes Registre Midi-PyrénéEN) registry. It is a multicenter prospective registry aimed at following all newly diagnosed ITP adults in the Midi-Pyrénées region, southwest of France (3 million inhabitants) since June 2013. Inclusion criteria in the registry are: (1) age ≥18 years, (2) incident ITP (diagnosis < 3 months) defined according to 2009 French guidelines as a platelet count < 150 x 109/L and the exclusion of other causes of thrombocytopenia, (3) and follow-up in the region.5 Known cardiovascular risk factors (except the body mass index) are recorded at ITP diagnosis. They are defined according to international standards: arterial hypertension, ≥140/90 mmHg; diabetes mellitus, glycemia ≥126 mg/dL; hypercholesterolemia, LDL-cholesterol ≥160 mg/dL; hypertriglyceridemia, ≥150 mg/dL; chronic kidney disease, estimated glomerular filtration rate using the CKD-EPI formula 3 8 (2.6) Exposure to cardiovascular and metabolic drugs at the time of ITP diagnosisb 151 (47.8) Antiplatelet drugs 57 (18.0) Aspirin 48 (15.2) Clopidogrel 14 (4.4) Ticagrelor 1 (0.3) Anticoagulant drugs 29 (9.2) Vitamin K antagonists 18 (5.7) Direct oral anticoagulants 10 (3.2) Heparin 4 (1.3) Antihypertensive/heart insufficiency drugs 124 (39.2) Beta blockers 58 (18.2) Converting enzyme inhibitors 36 (11.3) Angiotensin receptor antagonists 32 (10.1) Calcium channel blockers 27 (8.5) Diuretics 57 (18.0) Urapidil 3 (0.9) Anti-arrhythmic drugsg 18 (5.7) Symptomatic treatment of angina pectorish 12 (3.8) Lipid-lowering drugs 59 (18.7) Statins 53 (16.8) Fibrates 4 (1.3) Ezetimibe 2 (0.6) Antidiabetic drugs 34 (10.8) Oral antidiabetic drugs 23 (7.3) Insulin 18 (5.7) a 4 missing values. b 2 missing values. c 3 missing values. d 4 missing values. e 11 missing values. f Includes being a man aged ≥50 years or a woman aged ≥60 years, history of at least one cardiovascular disease, arterial hypertension, diabetes mellitus, dyslipidemia, tobacco use in the previous 3 years and chronic kidney disease stage; 14 missing values. g Includes amiodarone, digitalic treatments, flecaine, diltiazem, verapamil. h Includes nitric oxide, nicorandil, ivabradine. Sensitivity analysis restricted to primary ITP patients and to patients with at least one hospital stay due to ITP (i.e., those captured in most medico-administrative databases) led do similar results (data not shown). The most detailed and recent data regarding the prevalence cardiovascular risk factors in the French general population are from the MONA-LISA cross-sectional study. The population of this study is younger than in the CARMEN registry, explaining an overall higher prevalence of cardiovascular risk factors in our ITP population (Supporting Information Table S1).7 Regarding previous ITP cohorts, we found a higher prevalence of cardiovascular risk factors than in the study by Chandan et al.2 Our population was older than in this study (66 vs 48 years old) and with a balanced men/women repartition, with no female predominance (males: 50.9% vs. 41.3%).2 This may be due, at least in part, by the exclusion of the patients with a previous cardiovascular disease in the study by Chandan et al. In contrast, our results are close to those of the multicenter Italian study by Ruggeri et al.3 and to those of the study conducted in the Clinical Practice Research Database by Sarpatwari et al., that also found a higher prevalence of diabetes and of chronic kidney disease in ITP patients in comparison with the general population.8 The prevalence of chronic kidney disease was lower in our study (1.6% vs. 2.8%), but might be underreported. In conclusion, cardiovascular risk factors are frequent in ITP patients and the use of drug exposures as proxies reflects the underlying conditions. ACKNOWLEDGMENTS The CARMEN registry setting up has been supported by a grant from the Délégation Régionale à la Recherche Clinique des Hôpitaux de Toulouse 2012 and was also granted by the French National Society of Internal Medicine (Société Nationale Française de Médecine Interne). It is supported by the French referral center for autoimmune cytopenia and the French national center for rare diseases in immunohematology (MaRIH). CSL Behring and Novartis also support the CARMEN registry since 2016. The sponsors had no role in the study (see Conflict of interest section). CONFLICT OF INTERESTS GM received meeting attendance grants from Novartis and Amgen, as well as research grants from CSL Behring and Novartis for the CARMEN registry. These sponsors have no role in data collection and have not the property of data; they have no role in the conception, the methodology, the analyses, the interpretation of the studies conducted in the registry; manuscripts of research studies conducted in the CARMEN registry are not submitted to the sponsors before publication. Daniel Adoue participated to boards for Novartis and Amgen. All other authors declare having no conflict of interest. Supporting Information Additional Supporting Information may be found online in the supporting information tab for this article. Filename Description ajh25127-sup-0001-suppinfo01.docx127.8 KB Supporting Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. REFERENCES 1 Rodeghiero F. Is ITP a thrombophilic disorder?. Am J Hematol. 2016; 91(1): 39– 45. 2 Chandan JS, Thomas T, Lee S, et al. The association between idiopathic thrombocytopenic purpura and cardiovascular disease: a retrospective cohort study. J Thromb Haemost. 2018; 16(3): 474– 480. 3 Ruggeri M, Tosetto A, Palandri F, Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) Anemia and Thrombocytopenias Working Party. GIMEMA Study ITP0311, et al. Thrombotic risk in patients with primary immune thrombocytopenia is only mildly increased and explained by personal and treatment-related risk factors. J Thromb Haemost. 2014; 12(8): 1266– 1273. 4 Marston L, Carpenter JR, Walters KR, et al. Smoker, ex-smoker or non-smoker? The validity of routinely recorded smoking status in UK primary care: a cross-sectional study. BMJ Open. 2014; 4(4): e004958. 5 Moulis G, Germain J, Comont T, CARMEN Investigators Group, et al. Newly diagnosed immune thrombocytopenia adults: Clinical epidemiology, exposure to treatments, and evolution. Results of the CARMEN multicenter prospective cohort. Am J Hematol. 2017; 92(6): 493– 500. 6 Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009; 113(11): 2386– 2393. 7 Bongard V, Dallongeville J, Arveiler D, et al. Assessment and characteristics of chronic renal insufficiency in France. Ann Cardiol Angeiol (Paris). 2012; 61: 239– 244. 8 Sarpatwari A, Bennett D, Logie JW, et al. Thromboembolic events among adult patients with primary immune thrombocytopenia in the United Kingdom General Practice Research Database. Haematologica. 2010; 95(7): 1167– 1175. Citing Literature Volume93, Issue7July 2018Pages E181-E184 ReferencesRelatedInformation