Guide patient: Risques cardio-vasculaires et rhumatismes inflammatoires chroniques

Polyarthrite rhumatoïde PR et risque CV Polyarthrite rhumatoïde Une pathologie à haut risque CV = facteur de risque CV indépendant prise en charge des co-morbidités souvent négligée dans les maladies chroniques mortalité cardiovasculaire augmenté 1/ Pham T JBS 2006 Abstract: OBJECTIVE: To develop clinical practice guidelines for the evaluation and management of cardiovascular risk in patients with rheumatoid arthritis (RA), using the evidence-based approach and expert opinion. METHODS: Recommendations were developed using the evidence-based approach and expert opinion: A scientific committee used a Delphi procedure to select five questions, which formed the basis for developing the recommendations; Evidence providing answers to the five questions was sought in the literature; Based on this evidence, recommendations were developed by a panel of experts. RESULTS: The recommendations were as follows: 1) In patients with RA, attention should be given to the risk of cardiovascular disease, which is responsible for an excess burden of morbidity and mortality; 2) It must be recognized that RA may be an independent cardiovascular risk factor. Persistent inflammation is an additional risk factor; 3) The cardiovascular risk should be evaluated, and modifiable risk factors should be corrected; 4) In patients with RA requiring glucocorticoid therapy, the need for cardiovascular risk minimization is among the reasons that mandate the use of the minimal effective dose; 5) It should be recognized that methotrexate may protect against cardiovascular mortality in patients with RA; 6) It should be recognized that TNFalpha antagonists remain contraindicated in patients with RA and severe heart failure. TNFalpha antagonists do not seem to worsen moderate heart failure and may protect against cardiovascular mortality; 7) AFSSAPS recommendations about LDL-cholesterol objectives should be followed, with active RA being counted as a cardiovascular risk factor; 8) In patients with RA, statin therapy should be considered only when cholesterol levels are elevated despite appropriate dietary treatment; 9) RA per se does not indicate aspirin for primary prevention. When aspirin is used for secondary prevention, it should be recognized that concomitant treatment with nonsteroidal antiinflammatory drugs (NSAIDs) may decrease the antiplatelet effects and increase the gastrointestinal side effects of aspirin therapy. Une prise en charge de la PR + des facteurs de risque CV Pham T Joint Bone Spine 2006;73:379-387.

Recommandations EULAR de prise en charge du risque CV dans la PR La PR est une maladie à risque CV plus élevé, ceci étant lié à : Augmentation de la prévalence des facteurs de risque traditionnels Et état inflammatoire Un contrôle adapté de l’activité de la maladie est nécessaire pour réduire le risque CV L’évaluation du risque CV est recommandée pour tous les patients PR, 1 fois par an, et répétés en cas de changement de traitement de fond (on peut utiliser l’équation SCORE) On adapte le modèle d’évaluation du risque pour les patients PR en multipliant le résultat obtenu par un facteur 1,5 lorsque le patient présente 2 des 3 critères suivants : Ancienneté de la PR > 10 ans FR ou anti-CCP positif Présence de certaines manifestations extra-articulaires Quand on utilise le modèle SCORE, utiliser le rapport cholestérol total / cholestérol HDL Prise en charge des dyslipidémies en accord avec les recommandations locales Statines, IEC et/ou antagonistes de l’angiotensines II sont les options thérapeutiques de choix en raison de leur effets anti-inflammatoires potentiels Rôle des Coxibs et de la plupart des AINS sur le risque CV : pas encore très bien établi, doit être exploré Corticoïdes : utiliser la dose la plus faible possible Il est recommandé d’arrêter de fumer Peters MJL et al. 2010 Abstract: Objectives: To develop evidence-based EULAR recom- mendations for cardiovascular (CV) risk management in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Methods: A multidisciplinary expert committee was convened as a task force of the EULAR Standing Committee for Clinical Affairs (ESCCA), comprising 18 members including rheumatologists, cardiologists, inter- nists and epidemiologists, representing nine European countries. Problem areas and related keywords for systematic literature research were identified. A sys- tematic literature research was performed using MedLine, Embase and the Cochrane library through to May 2008. Based on this literature review and in accordance with the EULAR’standardised operating procedures, the multi-disciplinary steering committee formulated evidence- based and expert opinion-based recommendations for CV risk screening and management in patients with inflammatory arthritis. Results: Annual CV risk assessment using national guidelines is recommended for all patients with RA and should be considered for all patients with AS and PsA. Any CV risk factors identified should be managed according to local guidelines. If no local guidelines are available, CV risk management should be carried out according to the SCORE function. In addition to appropriate CV risk management, aggressive suppression of the inflammatory process is recommended to further lower the CV risk. Conclusions: Ten recommendations were made for CV risk management in patients with RA, AS and PsA. The strength of the recommendations differed between RA on the one hand, and AS and PsA, on the other, as evidence for an increased CV risk is most compelling for RA. CV = Cardiovasculaire Peters Ann Rheum Dis 2010

Place de l’ETP dans ce contexte ? Répondre aux objectifs ETP: sensibilisation, correction des FDR cardio-vasculaires, rôle délétère de certains traitements Convergence des acteurs: diététicienne, cardiologue, éducateur sportif, pneumologue (anti-tabac) Conception et édition d’un guide

Guide patient Introduction Questionnaire FDR cardio-vasculaires Domaines de prévention: J’ai quelques kilos en trop Je suis suivi pour HTA Je suis diabétique J’ai trop de cholestérol Je suis accro au tabc Je dois bouger mais comment ? Mes traitements peuvent-ils aggraver le risque CV? Ce que je dois retenir Lexique et signes d’alerte

Je suis accro au tabac ! Que faire ? Pour vous aider Le tabac accentue incontestablement le risque cardio-vasculaire en : ¤ augmentant le rythme cardiaque ¤ augmentant la pression artérielle ¤ détériorant les artères ¤ augmentant le risque de déclencher une Polyarthrite Rhumatoïde Le risque Homme/Femme est quasi-égal. Que faire ? La baisse ou l'arrêt total du tabac donne le résultat le + spectaculaire sur le risque Cardio-vasculaire Des solutions existent : substituants nicotiniques, acupuncture, patch… Ne pas hésiter à vous faire aider et demander une consultation anti-tabac  rôle majeur du tabacologue (Dr Delecluse Philippe Saint Philibert) Pour vous aider A tout âge, l’arrêt du tabac est bénéfique Modifier vos habitudes de vie Utiliser le temps de la cigarette à autre chose = bénéfice, regain de l’odorat, goût, diminution de la toux, régulation du rythme de votre cœur, meilleur souffle, tension artérielle normalisée … Méfiez vous des cigarettes « light » : le risque est identique! A partir de 50-60 ans : tabac + pillule ne font pas bon ménage les femmes ont autant de risques que les hommes  Parlez en à votre gynécologue

Guide patient Introduction Questionnaire FDR cardio-vasculaires Domaines de prévention: J’ai quelques kilos en trop Je suis suivi pour HTA Je suis diabétique J’ai trop de cholestérol Je suis accro au tabc Je dois bouger mais comment ? Mes traitements peuvent-ils aggraver le risque CV? Ce que je dois retenir Lexique et signes d’alerte

PR et mortalité coronarienne et cérébrale PR : un risque de mortalité cardiovasculaire augmenté PR et mortalité coronarienne et cérébrale 0,5 1 1,5 2 4 3,5 3 2,5 1,50 (1,39 -1,61) 1,59 (1,46 – 1,73) 1,52 (1,40 -1,67) Total Femmes Hommes Ischémie myocardique Ischémie cérébrale Avina-Zubieta Arthritis Rheum 2008 Abtsract: OBJECTIVE: To determine the magnitude of risk of cardiovascular mortality in patients with rheumatoid arthritis (RA) compared with the general population through a meta-analysis of observational studies. METHODS: We searched Medline, EMBase, and Lilacs databases from their inception to July 2005. Observational studies that met the following criteria were assessed by 2 researchers: 1) prespecified RA definition, 2) clearly defined cardiovascular disease (CVD) outcome, including ischemic heart disease (IHD) and cerebrovascular accidents (CVAs), and 3) reported standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs). We calculated weighted-pooled summary estimates of SMRs (meta-SMRs) for CVD, IHD, and CVAs using the random-effects model, and tested for heterogeneity using the I(2) statistic. RESULTS: Twenty-four studies met the inclusion criteria, comprising 111,758 patients with 22,927 cardiovascular events. Overall, there was a 50% increased risk of CVD death in patients with RA (meta-SMR 1.50, 95% CI 1.39-1.61). Mortality risks for IHD and CVA were increased by 59% and 52%, respectively (meta-SMR 1.59, 95% CI 1.46-1.73 and meta-SMR 1.52, 95% CI 1.40-1.67, respectively). We identified asymmetry in the funnel plot (Egger's test P = 0.002), as well as significant heterogeneity in all main analyses (P < 0.0001). Subgroup analyses showed that inception cohort studies (n = 4, comprising 2,175 RA cases) were the only group that did not show a significantly increased risk for CVD (meta-SMR 1.19, 95% CI 0.86-1.68). CONCLUSION: Published data indicate that CVD mortality is increased by approximately 50% in RA patients compared with the general population. However, we found that study characteristics may influence the estimate. 24 études : 111758 patients; 22927 évènements CV Avina-Zubieta A Arthritis Rheum, 2008;59:16690-7

En pratique : quels grands principes de prise en charge du risque CV dans la PR ? Contrôle adéquat de la PR et suppression de l’inflammation pour diminuer le risque CV (1) En pratique (1) : Les statines, les IEC ou les ARA II sont les options de choix. Le rôle des AINS et des coxibs dans le risque cardio-vasculaire est certain mais leur prescription doit être très prudente en cas de maladie CV ou de facteurs de risque CV. Les corticoïdes doivent être utilisés à la dose la plus faible possible. L’arrêt du tabac est recommandé. Peters MJL et al. 2010 Abstract: Objectives: To develop evidence-based EULAR recom- mendations for cardiovascular (CV) risk management in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Methods: A multidisciplinary expert committee was convened as a task force of the EULAR Standing Committee for Clinical Affairs (ESCCA), comprising 18 members including rheumatologists, cardiologists, inter- nists and epidemiologists, representing nine European countries. Problem areas and related keywords for systematic literature research were identified. A sys- tematic literature research was performed using MedLine, Embase and the Cochrane library through to May 2008. Based on this literature review and in accordance with the EULAR’standardised operating procedures, the multi-disciplinary steering committee formulated evidence- based and expert opinion-based recommendations for CV risk screening and management in patients with inflammatory arthritis. Results: Annual CV risk assessment using national guidelines is recommended for all patients with RA and should be considered for all patients with AS and PsA. Any CV risk factors identified should be managed according to local guidelines. If no local guidelines are available, CV risk management should be carried out according to the SCORE function. In addition to appropriate CV risk management, aggressive suppression of the inflammatory process is recommended to further lower the CV risk. Conclusions: Ten recommendations were made for CV risk management in patients with RA, AS and PsA. The strength of the recommendations differed between RA on the one hand, and AS and PsA, on the other, as evidence for an increased CV risk is most compelling for RA. Peters MJ Ann Rheum Dis. 2010;69:325-31.

PR : une augmentation des facteurs de risque classiques ? ➌ Une sédentarité plus fréquente avec un impact négatif sur le risque CV Inactivité physique = complication fréquente des rhumatismes inflammatoires (1) Moins d’activité physique pratiquée par les patients atteints de PR vs contrôles (2) BPCO (n = 526) PR (n = 1120) DT2 (n = 2149) Contrôles sains Niveau d’activité physique élevé* 15,8 25,6 27,5 39,8 Faible niveau activité physique** 84,2 74,4 75,5 60,2 OR (IC 95 %)*** 1 1,8 (1,33-2,45) 2,7 (1,63 – 2,9) 2,49 (1,88 – 3,28) * Activité régulière modérée (activité élevée > 30 min, 1-2 fois/sem) ou activité régulière et entrainement (activité élevée > 30 min ≥ 3 fois/sem) ** Sédentarité (principalement assis ou faible activité < 2 h/sem.) ou activité modérée (faible activité > 2 h/sem) *** OR ajusté de la probabilité d’un niveau d’activité élevé dans les groupes non BPCO vs BPCO. 1/ Turesson Curr Opin Rheumatol 2007 Abstract: PURPOSE OF REVIEW: There is increased recognition of an excess risk of cardiovascular disease in patients with rheumatic disorders. Physical inactivity is a frequent complication of arthritis, and also common in the general population. In this review, we highlight recent findings on risk factors for cardiovascular disease in patients with rheumatic diseases, and explore the role of physical activity for the prevention of cardiovascular disease. RECENT FINDINGS: Inflammatory mechanisms are clearly involved in cardiovascular disease in patients with systemic lupus erythematosus and rheumatoid arthritis. In rheumatoid arthritis, disability is also a major predictor of cardiovascular disease. A sedentary lifestyle increases the risk of cardiovascular disease in the general population, and high physical activity prevents cardiovascular disease mortality and morbidity. Successful treatment of rheumatic disease with control of inflammation and improved functional capacity may also reduce the risk of cardiovascular disease. SUMMARY: As part of the effort to prevent vascular comorbidity, regular exercise should be encouraged in patients with rheumatic diseases, and structured interventions to reduce adverse lifestyle factors scientifically evaluated. 2/ Arne et al. Scand J Prim Health Care 2009 Abstract: OBJECTIVE: Chronic diseases interfere with the life situation of the affected person in different ways. The aim was to compare the burden of disease in three chronic diseases - chronic obstructive pulmonary disease (COPD), rheumatoid arthritis (RA), diabetes mellitus (DM) - and in healthy subjects, with a particular interest in physical activity, quality of life, and psychological health. DESIGN: Cross-sectional, observational study. SETTING AND SUBJECTS: Postal survey questionnaire to a stratified, random population of 68 460 subjects aged 18-84 years in Sweden. The subjects included were 40-84 years old (n = 43 589) and data were analysed for COPD (n = 526), RA (n = 1120), DM (n = 2149) and healthy subjects (n = 6960). RESULT: Some 84% of subjects with COPD, 74% (RA), 72% (DM), and 60% in healthy subjects (p < 0.001, COPD versus RA, DM, and healthy subjects) had a physical activity level considered too low to maintain good health according to guidelines. Quality of life (EuroQol five-dimension questionnaire, EQ-5D) was lower in COPD and RA than in DM. Anxiety/depression was more common in subjects with COPD (53%) than in those with RA (48%) and DM (35%) (p < 0.001, COPD versus RA and DM), whereas mobility problems were more common in RA (55%) than COPD (48%) and DM (36%) (p < 0.001, RA versus COPD and DM). All differences between groups remained significant after adjusting for age, sex, and socioeconomic background factors. CONCLUSION: Subjects with chronic diseases had a low level of physical activity, most evident in subjects with COPD. COPD and RA had a higher negative impact on quality of life than DM. Our results indicate that increased attention regarding physical inactivity in subjects with chronic diseases is needed to minimize the burden of disease. 3/ Metsios GS et al. Eur J cardiovasc Prev Rehabil 2009 Abstract: OBJECTIVE: Patients with rheumatoid arthritis (RA) are characterized by reduced physical activity and increased morbidity and mortality from cardiovascular disease (CVD). The aim of this study was to investigate associations between levels of physical activity and CVD risk profile in RA patients. METHODS: Levels of physical activity were assessed in 65 RA patients (43 females). Using the International Physical Activity Questionnaire, patients were allocated into three groups: active, moderately active and inactive. Anthropometric characteristics, RA activity/severity, multiple classical and novel CVD risk factors and 10-year CVD event probability were assessed and compared among the three groups. RESULTS: Significant differences were detected among groups in systolic blood pressure (P=0.006), cholesterol (P<0.001), low-density lipoprotein (P=0.01), homeostasis model assessment (P=0.001), type-I plasminogen activator inhibitor antigen (P<0.001), tissue-type plasminogen activator antigen (P=0.019), homocysteine (P=0.027), fibrinogen (P=0.001), apolipoprotein B (P=0.002) and von Willebrand Factor (P=0.001), with a consistent deterioration from the physically active to the physically inactive group. Multivariate analysis of variance revealed that levels of physical activity were significantly associated with the differences in all of the above variables (P<0.05) after adjustment for age, weight, sex, smoking status, as well as RA disease activity and severity. CONCLUSION: This cross-sectional study suggests that physically inactive RA patients have significantly worse CVD risk profile compared with physically active patients. The possible beneficial impact of increased physical activity, including structured exercise, to the CVD risk of RA patients needs to be accurately assessed in prospective studies. Un manque d’activité associé à un risque CV dans la PR (3) - Association entre de nombreux facteurs de risque CV (PA, cholestérol, C-LDL, PAI-1, ApoB, fibrinogène…) et la sédentarité chez les patients atteints de PR . (1) Turesson C, Matteson EL. Curr Opin Rheumatol. 2007;19:190-6. (2) Arne M et al. Scand J Prim Health Care. 2009;27:141-7. (3) Metsios GS, et al. Eur J Cardiovasc Prev Rehabil. 2009;16:188-94.

Conclusions (1/3) La polyarthrite rhumatoïde (PR) est un facteur de risque cardiovasculaire (CV) indépendant, dont l’impact est d’autant plus péjoratif que la durée et la sévérité de la maladie augmentent. Elle est responsable d’un excès de mortalité cardiovasculaire et d’un profil de coronaropathie plus sévère. L’inflammation chronique et persistance est l’acteur clé du risque CV de la PR, via l’augmentation des protéines/cytokines inflammatoires : CRP, TNF-a, IL-6 et récepteurs aux cytokines (OPG). Ainsi, le contrôle de la PR et la prise en charge des facteurs de risque, encore insuffisante (sédentarité++, statines--, anti-hypertenseurs--…), constituent la pierre angulaire du traitement.

C’est aussi le cas pour la PR (2): PR : une moins bonne prise en charge des facteurs de risque associés La prise en charge des co-morbidités est souvent négligée dans les maladies chroniques (1). C’est aussi le cas pour la PR (2): Étude de Panoulas : 400 patients PR consécutifs 71% hypertendus et parmi eux seulement 61% sous traitement anti-hypertenseur (3) 1/ Redelmeier NEJM 1998 Abstract: BACKGROUND: Patients can have several illnesses concurrently, yet some of these diseases may be neglected if one problem consumes attention. We conducted a population-based analysis in Ontario, Canada - where universal health insurance is provided - to determine whether unrelated disorders are less likely to be treated in patients with chronic diseases. METHODS: We studied the 1,344,145 residents of Ontario in 1995 who were 65 or older and eligible to receive prescription medications free of charge as part of the Ontario Drug Benefit program. Patients with diabetes mellitus were identified by prescriptions for insulin, pulmonary emphysema by prescriptions for ipratropium bromide, and psychotic syndromes by prescriptions for haloperidol. For each chronic disease, we selected an unrelated treatment: estrogen-replacement therapy for patients with diabetes mellitus, lipid-lowering medications for those with pulmonary emphysema, and medical treatment of arthritis for those with psychotic syndromes. RESULTS: The 30,669 patients with diabetes mellitus were less likely to receive estrogen-replacement therapy than the other subjects in the study (2.4 percent vs. 5.9 percent, P<0.001). The disease was associated with a 60 percent reduction in the odds of estrogen treatment (odds ratio, 0.40; 95 percent confidence interval, 0.37 to 0.43). Findings were similar for the 56,779 patients with pulmonary emphysema, who were less likely to receive lipid-lowering medications (odds ratio, 0.69; 95 percent confidence interval, 0.67 to 0.72; P<0.001), and the 17,336 patients with psychotic syndromes, who were less likely to receive medical treatments for arthritis (odds ratio, 0.59; 95 percent confidence interval, 0.57 to 0.62; P<0.001). CONCLUSIONS: In patients 65 or older who have chronic medical diseases and who receive prescription medications free of charge, unrelated disorders are undertreated. Clinicians caring for patients with chronic diseases should remain alert to other disorders and minimize the number of missed opportunities for treating them. 2/ Nurmohamed Autoimmunity Res 2009 Abstarct: The increased mortality in rheumatoid arthritis (RA) is mainly due to (atherosclerotic) cardiovascular disease. The cardiovascular morbidity is also increased in comparison with the general population. This increased cardiovascular burden could be caused by 1) an enhanced prevalence of cardiovascular risk factors 2) under treatment of cardiovascular risk factors or 3) RA itself, particularly due to its chronic inflammatory component. Cardiovascular risk factors only partially explain the increased cardiovascular risk and it is becoming increasingly acknowledged that the underlying inflammation in RA plays an essential role. This is probably related to the fact that atherosclerosis also has an inflammatory etiology that is accelerated by RA. Similarly, it can be expected that effective suppression of this inflammatory process by disease modifying antirheumatic drugs and/or biologicals lowers the cardiovascular risk. Altogether, there is accumulating evidence that the increased cardiovascular risk in RA is comparable to that of type 2 diabetes and actually RA should be seen as a new, independent, cardiovascular risk factor for which cardiovascular risk management is essential. 3/ Panoulas VF Rheumatology 2007 Abstract: OBJECTIVES: Rheumatoid arthritis (RA) associates with excessive cardiovascular morbidity and mortality. Hypertension (HT) contributes significantly to the development of cardiovascular disease (CVD). Little is known about the factors that influence blood pressure (BP) in patients with RA. In this study, we assessed the prevalence of HT in a secondary care cohort of RA patients, and aimed to identify factors associated with its presence and inadequate control. METHODS: A total of 400 consecutive RA patients were studied. HT was defined as systolic BP >/=140 mmHg and/or diastolic BP >/=90 mmHg or current use of antihypertensive drugs. The association of HT with several demographic and RA-related factors, comorbidities and drugs was evaluated using logistic regression. RESULTS: HT was present in 282 (70.5%) patients. Of those, 171 (60.6%) received anti-hypertensive therapy, but 111 (39.4%) remained undiagnosed. Of those treated, only 37/171 (21.8%) were optimally controlled. Multivariable logistic regression revealed age (OR = 1.054, CI: 1.02 to 1.07, P = 0.001), body mass index [BMI (OR = 1.06, CI: 1.003-1.121, P = 0.038)] and prednisolone use (OR = 2.39, CI: 1.02-5.6, P = 0.045) to be independently associated with the presence of HT. BMI (OR = 1.11, CI: 1.02-1.21, P = 0.002) and the presence of CVD (OR = 4.01, CI: 1.27-12.69, P = 0.018) associated with uncontrolled HT. CONCLUSIONS: HT is highly prevalent in RA, under-diagnosed particularly in the young, and under-treated particularly in old RA patients with CVD. RA patients receiving steroids should be specifically targeted for screening and treatment; those with any cardiovascular comorbidity may require particularly aggressive monitoring and treatment strategies. (1) Redelmeier DA NEJM 1998;338:1516-20 ; (2) Nurmohamed MT Autoimmunity Rev 2009;8:663-7 ; (3) Panoulas VF Rheumatology 2007;46:1477-82.