Recommendations. Systematic literature search A systematic search of literature published between January 1966 and May 2008 was undertaken using

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1 Additional tables are published online only at ard.bmj.om/ontent/vol69/ issue2 1 Department of Rheumatology, VU University Medial Centre, Amsterdam, The Netherlands; 2 University of Manhester, Manhester, UK; 3 Glasgow Royal Infirmary, Glasgow, UK; 4 Department of Rheumatology, Jan van Breemen Institute, Amsterdam, The Netherlands; 5 Department of Preventive Mediine, Faulty of Mediine of Lisbon, Lisbon, Portugal; 6 Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway; 7 Centre for Rheumati Diseases, University of Glasgow, UK; 8 Rheumazentrum am Universitätsklinikum Leipzig, Leipzig, Germany; 9 Rheumatology, Hospital Xeral- Calde, Lugo, Spain; 10 Department of Rheumatology, Clinial Immunology and Allergy, University of Crete Medial Shool, Heraklion, Greee; 11 Dudley Group of Hospitals NHS Trust Russells Hall Hospital, Dudley, UK; 12 Department of Internal Mediine, VU University Medial Centre, Amsterdam, The Netherlands; 13 Hôpital Gabriel Montpied, Servie de Rhumatologie, Clermont- Ferrand, Frane; 14 Department of Rheumatology University of Debreen, Debreen, Hungary; 15 BHF Glasgow Cardiovasular Researh Centre, University of Glasgow, Glasgow, UK Correspondene to: Dr M T Nurmohamed, VU University Medial Center, Departments of Internal Mediine and Rheumatology, PO Box 7057, 1007 MB Amsterdam, The Netherlands; mt.nurmohamed@vum.nl Aepted 3 September 2009 Published Online First 22 September 2009 EULAR evidene-based reommendations for ardiovasular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis M J L Peters, 1 D P M Symmons, 2 D MCarey, 3 B A C Dijkmans, 1,4 P Niola, 5 T K Kvien, 6 I B MInnes, 7 H Haentzshel, 8 M A Gonzalez-Gay, 9 S Provan, 6 A Semb, 6 P Sidiropoulos, 10 G Kitas, 11 Y M Smulders, 12 M Soubrier, 13 Z Szekanez, 14 N Sattar, 15 M T Nurmohamed 1,4,13 ABSTRACT Objetives: To develop evidene-based EULAR reommendations for ardiovasular (CV) risk management in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriati arthritis (PsA). Methods: A multidisiplinary expert ommittee was onvened as a task fore of the EULAR Standing Committee for Clinial Affairs (ESCCA), omprising 18 members inluding rheumatologists, ardiologists, internists and epidemiologists, representing nine European ountries. Problem areas and related keywords for systemati literature researh were identified. A systemati literature researh was performed using MedLine, Embase and the Cohrane library through to May Based on this literature review and in aordane with the EULAR s standardised operating proedures, the multidisiplinary steering ommittee formulated evidenebased and expert opinion-based reommendations for CV risk sreening and management in patients with inflammatory arthritis. Results: Annual CV risk assessment using national guidelines is reommended for all patients with RA and should be onsidered for all patients with AS and PsA. Any CV risk fators identified should be managed aording to loal guidelines. If no loal guidelines are available, CV risk management should be arried out aording to the SCORE funtion. In addition to appropriate CV risk management, aggressive suppression of the inflammatory proess is reommended to further lower the CV risk. Conlusions: Ten reommendations were made for CV risk management in patients with RA, AS and PsA. The strength of the reommendations differed between RA on the one hand, and AS and PsA, on the other, as evidene for an inreased CV risk is most ompelling for RA. Providing reommendations for monitoring and/or management and/or treatment of musuloskeletal disorders is one of the goals of the EULAR Standing Committee for Clinial Affairs (ESCCA). 1 Obviously, management of patients with inflammatory arthritis fouses not on ardiovasular (CV) morbidity and mortality. However, standardised mortality ratios (SMRs) are raised and the majority of premature deaths are attributable to CV disease. 2 4 CV morbidity is also enhaned and there is an inreased prevalene of all stages of Reommendations atherogenesis, from endothelial dysfuntion to inreased thikness and plaque in arotid arteries, to fatal and non-fatal myoardial infartion and stroke Moreover, the exess CV burden persists after adjustment for traditional CV risk fators. Evidene is best doumented for rheumatoid arthritis (RA), but patients with ankylosing spondylitis (AS) and psoriati arthritis (PsA) also appear to be at inreased CV risk. Aordingly, available evidene supports inflammatory arthritis as an independent CV risk fator, and CV risk sreening and management is therefore needed. CV risk sreening and management strategies have been developed for the general population and are based on CV risk sore alulators, suh as the Framingham sore (often used in the United States) and the Systemati Coronary Risk Evaluation (SCORE) model (often used in Europe). Traditional risk fators integrated in these models are age, gender, smoking, blood pressure and lipid (holesterol and high-density lipoprotein-holesterol (HDL-)) levels. Risk estimates are based on information from the general population but the auray of these models has not been adequately evaluated in inflammatory arthritis, suh as RA, AS and PsA. 15 Hene, we summarised and evaluated urrently available literature aording to the EULAR standardised operating proedures, to provide evidene-based EULAR reommendations for CV risk management in patients with inflammatory arthritis. Partiipants and objetives A multidisiplinary guideline development ommittee was ommissioned by ESCCA. The steering ommittee omprised 18 members inluding rheumatologists, ardiologists, internists and epidemiologists, representing nine European ountries. The objetives were (a) to identify and ritially appraise evidene for speifi CV interventions aimed at lowering the CV risk in RA; (b) to develop EULAR reommendations on the basis of the presented literature searh for CV risk assessment in patients with RA, AS and PsA; () to determine future researh goals. Systemati literature searh A systemati searh of literature published between January 1966 and May 2008 was undertaken using Ann Rheum Dis 2010;69: doi: /ard

2 Reommendations Medline, Embase and the Cohrane library databases (Appendix 1, supplementary online file). The searh onsisted of two or three omponents: (a) the rheumati disease in Medial Subjet Headings (MeSH) or title abstrat terms; (b) MeSH or title abstrat terms for eah CV traditional risk fator that is, age, gender, holesterol, blood pressure and smoking; () the MeSH or title abstrat term ardiovasular disease was added to the searh with age and gender in order to inrease speifiity. We only inluded key artiles supporting issued reommendations. Seleted artiles were sreened for eligibility by two investigators (MJLP and MTN). Experts onsensus When the literature searh was ompleted, 10 onept reommendations were formulated. These were disussed within the steering ommittee until onsensus was reahed. Categorising evidene The grading of the reommendations was based on the methodologial strength of the underlying literature, whih was ategorised aording to standard guidelines (supplementary online tables). Obviously, the level of evidene is far greater for RA than for AS and PsA and therefore, the strength of reommendations is higher for patients with RA. Hene, for AS and PsA our reommendations should be seen as points to onsider rather than definitive reommendations. RESULTS Reommendations Table 1 lists the reommendations for CV management in RA, PsA and AS. 1. RA should be regarded as a ondition assoiated with higher risk for CV disease. This may also apply to AS and PsA, although the evidene base is less. The inreased risk appears to be due to both an inreased prevalene of traditional risk fators and the inflammatory burden The overall SMR for RA is approximately two and numerous reports have demonstrated that the exess mortality is mostly due to CV disease. 12 It is unlear whether survival for patients with RA has improved over reent years as onfliting observations have been published The absolute risk of CV death is highest for elderly, male patients with RA, whereas the relative risk is highest for young female patients with RA CV morbidity is also enhaned and the magnitude of CV risk in RA may equal the CV risk in patients with type 2 diabetes. 22 Traditional CV risk fators that is, hypertension, dyslipidaemia and smoking, probably our more frequently, but the evidene is not uniform and adequate studies are laking Traditional CV risk fators, however, only aount partially for the exess CV risk. The key feature explaining the inreased CV risk seems to be inflammation, as it, on the one hand, has an important role in different stages of atherogenesis, and, on the other, aentuates established CV risk fators Moreover, there is strong evidene showing that hroni inflammatory markers are independently assoiated with CV mortality and morbidity in RA Information about mortality rates in AS or PsA ompared with the general population is limited, but reported SMRs are inreased and range from 1.5 to 1.9, and similar to RA, the exess mortality is predominantly due to CV disease. 4 Presently, evidene for an inreased CV risk in these patients is emerging and therefore AS and PsA should also be onsidered as CV risk fators. 2. Adequate ontrol of disease ativity is neessary to lower the CV risk (best evidene for anti-tumour nerosis fator treatment and methotrexate treatment) Studies investigating the assoiation between inflammation and atheroslerosis, using surrogate markers for CV disease, suh as Table 1 The 10 reommendations for ardiovasular (CV) risk management in rheumatoid arthritis (RA), psoriati arthritis (PsA) and ankylosing spondylitis (AS) Reommendations Level of evidene 1. RA should be regarded as a ondition assoiated with higher risk for 2b 3 B CV disease. This may also apply to AS and PsA, although the evidene base is less. The inreased risk appears to be due to both an inreased prevalene of traditional risk fators and the inflammatory burden 2. Adequate ontrol of disease ativity is neessary to lower the CV risk 2b 3 B 3. CV risk assessment using national guidelines is reommended for all patients 3 4 C with RA and should be onsidered annually for all patients with AS and PsA. Risk assessments should be repeated when antirheumati treatment has been hanged 4. Risk sore models should be adapted for patients with RA by introduing a 1.5 multipliation fator. This multipliation fator should be used when the patient with RA meets two of the following three riteria: 3 4 C Disease duration of more than 10 years RF or anti-ccp positivity Presene of ertain extra-artiular manifestations 5. TC/HDL holesterol ratio should be used when the SCORE model is used 3 C 6. Intervention should be arried out aording to national guidelines 3 C 7. Statins, ACE inhibitors and/or AT-II blokers are preferred treatment options 2a 3 C-D 8. The role of oxibs and most NSAIDs in CV risk is not well established 2a 3 C and needs further investigation. Hene, we should be very autious about presribing them, espeially for patients with a doumented CV disease or in the presene of CV risk fators 9. Cortiosteroids: use the lowest dose possible 3 C 10. Reommend smoking essation 3 C Strength of reommendation ACE, angiotensin-onverting enzyme; anti-ccp, anti-yli itrullinated peptide; AT-II, angiotensin II; oxibs, ylo-oxygenase-2 inhibitors; HDL, high-density lipoprotein; NSAIDs, non-steroidal anti-inflammatory drugs; RF, rheumatoid fator; SCORE, Systemati Coronary Risk Evaluation; TC, total holesterol. 326 Ann Rheum Dis 2010;69: doi: /ard

3 Reommendations intima medial thikness, onfirm the important role of inflammation in aelerating atheroslerosis These results illustrate the interplay between inflammation and atheroslerosis in inflammatory arthritis and underline the importane of a more aggressive approah for treatment of inflammatory arthritis. Early and effetive antirheumati treatment, suh as tumour nerosis fator blokers and methotrexate (MTX), has been shown to be independently assoiated with a lower CV risk Effetive treatment may also result in improved physial ativity, subsequently leading to a dereased risk of hypertension, obesity and diabetes, all important determinants of CV disease. Moreover, MTX may indue hyperhomoysteinaemia through a depletion of foli aid levels. 46 Hyperhomoysteinaemia has toxi effets on the endothelium, is prooagulant and therefore a CV risk fator Hene, foli aid is advised as it prevents MTX-indued hyperhomoysteinaemia, albeit the ultimate effet on CV risk in RA is unknown. 3. CV risk assessment using national guidelines is reommended for all patients with RA and should be onsidered annually for all patients with AS and PsA. Risk assessments should be repeated when antirheumati treatment has been hanged (in absene of national guidelines the SCORE funtion model is reommended) As notied earlier, CV risk assessment is reommended for all patients with RA and should be onsidered for all patients with AS and PsA. In this regard, to ensure suffiient take up of CV risk assessment, we have reommended that all patients reeive an annual CV risk assessment but we reognise that in patients with low CV risk and inative disease a lower frequeny of assessment for example, every 2 or 3 years, ould be adopted. Additionally, CV risk assessment should be reonsidered during the disease ourse, as inflammation as well as antirheumati treatment may alter CV risk fators, but again this is only neessary in patients already at inreased CV risk. Hene, the treatment and follow-up plan should be determined on an individual basis and with regard to risk profile, morbidity, omorbidity and the patient s preferenes. It should also be noted that CV risk assessment an be easily inorporated into a routine visit to monitor RA by addition of the determination of non-fasting lipids (holesterol and HDL-) to routine laboratory tests and by measurement of blood pressure. 4. Risk sore models should be adapted for patients with RA by introduing a 1.5 multipliation fator. This multipliation fator should be used when the patient with RA meets two of the following three riteria: Disease duration of more than 10 years RF or anti-ccp positivity Presene of ertain extra-artiular manifestations Sine traditional CV risk fators are already inluded in existing CV risk sore models, it is important to identify other fators assoiated with an inreased CV risk in RA. One important preditor is disease duration, whih is illustrated by numerous reports observing that exess mortality inreases with a longer disease duration A meta-analysis showed a mean SMR of 1.2 for ineption ohorts (,2 years disease duration) ompared with a mean SMR of 1.9 for established disease. 53 Other prognosti CV disease markers are rheumatoid fator (RF) or anti-yli itrullinated peptide (anti-ccp) positivity. Finally, patients with severe disease (eg, those with extraartiular manifestations) have an inreased risk for CV disease. Therefore, it is reommended that the derived CV risk estimate should be multiplied by 1.5 if at least two of the following riteria are present: disease duration of more than 10 years, RF and/or anti-ccp positivity, presene of severe extra-artiular manifestations. 61 Sine available omparative studies did not adequately adjust for important onfounders (soial lass, physial ativity and others), and in addition, few, if any, adjusted for all established CV risk fators using ontinuous data, it is possible that the exess CV risk in inflammatory arthritis, over and above traditional risk fators, has been overestimated. Hene, a onservative approah that is, a multipliation fator of 1.5 (rather than 2.0), has been hosen on the basis of the evidene from observational SMR reporting studies as well as expert opinion. At present, this multipliation fator should only be used for patients with RA. 5. Total holesterol/hdl holesterol ratio should be used when the SCORE model is used Dyslipidaemia, partiularly low levels of HDL-, and high levels of total holesterol (TC), low-density lipoprotein holesterol (LDL-) and triglyerides are assoiated with an inreased CV risk in the general population Partiularly, the TC/HDL- ratio is an important prognosti indiator for future CV disease. 64 Patients with inflammatory arthritis, partiularly those with ative disease, have low HDL- levels resulting in a higher that is, unfavourable, TC/HDL- ratio, and high triglyeride levels Moreover, it appears that these unfavourable lipid hanges may already be present at least 10 years before the onset of RA. 68 Hene, an unfavourable lipid profile may ontribute to the inreased CV risk in patients with inflammatory arthritis. By ontrast, disease-modifying antirheumati drugs (inluding initial ortiosteroids) appear to have benefiial effets on the lipid profile in patients with early ative RA that is, an inrease of TC but a more pronouned inrease of HDL- resulting in a lower (more favourable) TC/HDL- ratio Tumour nerosis fator blokers are also assoiated with a transient inrease of TC and HDL-, mostly aompanied with improvement of the TC/HDL- ratio, during the first few months of the treatment Thereafter the results beome divergent and this might be due to differenes in disease ativity, (hanges of) o-mediation, partiularly ortiosteroids, dietary intake and physial ativity Hene, future studies should appropriately examine these potential onfounders to reah valid onlusions. In the meantime, it appears that the ratio of TC to HDL- is the most stable marker of lipidassoiated risk in RA. 6. Intervention should be arried out aording to national guidelines. CV risk assessment differs from ountry to ountry. The SCORE model is used in some ountries, whereas in other ountries the Framingham or no model is used. In addition, risk fators inluded in the models as well as treatment thresholds for initiation of ardioprotetive agents or treatment goals may differ. As there is no evidene to indiate preferene of one model above the other (and likewise treatment thresholds), risk assessment and management should be arried out aording to national guidelines. If there are no loal guidelines on the risk model to use then, the use of SCORE (see Example below) is advised. Commonly used treatment thresholds are a systoli blood pressure of 140 mm Hg and an LDL- level of 2.5 mmol/l. As evidene desribing the effet of ardioprotetive agents on CV end points in inflammatory arthritis is laking, we have to extrapolate evidene from the general population in order to guide liniians in their deision on the use of ardioprotetive Ann Rheum Dis 2010;69: doi: /ard

4 Reommendations agents in inflammatory arthritis. This means that modifiation and or speifi intervention, suh as antihypertensive agents or statins, should be the same as in the general population and should be initiated aording to national guidelines. This statement is supported by a great number of observational studies as well as expert onsensus. 7. Statins, ACE-inhibitors and/or angiotensin II blokers are preferred treatment options due to their potential anti-inflammatory effets Intervention trials with statins and/or antihypertensive agents and CV end points in RA have not been published thus far. However, it is very unlikely that the effet of statins and/or antihypertensive agents would be attenuated. The effet might be more pronouned as statins and ACE inhibitors possess potential anti-inflammatory properties, whih may be linially signifiant in the ontext of inflammatory disorders. A randomised ontrolled trial of atorvastatin in RA demonstrated, 78 in addition to a moderate derease in disease ativity, a signifiant redution in TC and LDL- in statin-treated patients with RA. The observed hanges were at least equivalent to expeted redutions in TC and LDL- in non-ra subjets given atorvastatin. 79 Sine redution in LDL- is the best simple preditor of relative CV risk redution, it is oneivable that at least an equivalent risk redution will be ahieved Similarly to statins, ACE inhibitors and angiotensin II (AT-II) blokers may also have a favourable effet on inflammatory markers and endothelial funtion in RA. Hene, these agents are preferred, when antihypertensive agents are indiated. Nevertheless, future researh with CV end points is needed to examine these questions more profoundly. 8. The role of ylo-oxygenase-2 inhibitors and most non-steroidal anti-inflammatory drugs in CV risk is not well established and needs further investigation. Hene, we should be very autious about presribing them, espeially for patients with a doumented CV disease or in the presene of CV risk fators Non-steroidal anti-inflammatory drugs (NSAIDs), and ylooxygenase-2 inhibitors (oxibs) are assoiated with an inreased CV risk The overall effets of NSAIDs and oxibs on CV risk are diffiult to asertain, as on the one hand, most of them, but not all, have prothromboti effets due ylo-oxygenase 2 inhibition, and on the other hand, these agents improve mobility of patients with RA, whih might ounterbalane the prothromboti effets Moreover, a possible interation between some NSAIDs and aspirin has been reported as some NSAIDs may impair aspirin s antiplatelet funtion Conlusive evidene is not yet available and therefore the potential atherothromboti risk of any NSAID or COXIB must be taken into aount when presribing these drugs aording to reommendations from the European Mediines Ageny, espeially in patients with doumented CV disease or in the presene of CV risk fators. 9. Cortiosteroids: use the lowest dose possible Cortiosteroids are ommonly used in rheumati patients and may influene the CV risk in two ompeting ways. On the one hand, ortiosteroids ould enhane CV risk owing to their potentially deleterious effets on lipids, gluose tolerane, insulin prodution and resistane, blood pressure and obesity On the other hand, ortiosteroids may atually derease the risk of atheroslerosis and CV disease by suppressing inflammation, whih paradoxially may improve gluose intolerane and dyslipidaemia. Owing to these opposing Box 1 Researh agenda Information about the effets of lipid-lowering and antihypertensive agents on ardiovasular (CV) risk in inflammatory arthritis is laking. Randomised ontrolled trials are needed to examine this question and some long-term trials are urrently being onduted. Additional information is needed about the number needed to harm and the number needed to treat with respet to interation between lipidlowering agents and/or antihypertensive agents and antirheumati treatment in inflammatory arthritis. The searh strategy did not inlude information about lifestyle modifiation for example, weight ontrol and physial ativity. Lifestyle should be onsidered as a major CV risk fator. Modest redution in weight or improvement in physial ativity may signifiantly redue the CV risk. Hene, lifestyle modifiation should be given to all patients. Briefly, smoking essation, weight redution and exerise are pivotal (evaluating the effet of lifestyle modifiation on the CV risk in inflammatory arthritis was added to the future researh agenda). The ontribution of other CV risk fators like stress, eduational and soial bakground towards exess CV disease in inflammatory rheumati onditions is presently unknown and needs to be established. Aurate CV risk assessment may be more diffiult in inflammatory arthritis as the relative role of traditional risk fators ontributing to the inreased CV risk is unlear. Therefore, studies evaluating the effiay and appliability of different CV risk sores are needed in inflammatory arthritis. Probably, existing risk sore models underestimate risk in women. This may be important partiularly in rheumatoid arthritis, where there is a female sex preponderane, and warrants further investigation. As evidene for ankylosing spondylitis and psoriati arthritis is emerging we will revise the guidelines aordingly within 3 years. Our reommendation for the multipliation fator of 1.5 is derived mainly from relevant standardised mortality ratios and, beause information from large-sale prospetive ohort studies is laking. Obviously, this value should be re-examined in due ourse when better evidene emerges. effets of ortiosteroids on CV risk, it is important to take into aount rheumati disease features as well as traditional CV risk fators when onsidering the net effets of ortiosteroids on CV risk. 100 Furthermore, CV risk is higher in patients treated with long-term high doses ompared with low doses of ortiosteroids. 101 Altogether, there is no lear evidene that low-dose ortiosteroids ontribute signifiantly to the enhaned CV risk in inflammatory arthritis, in ontrast to high-dose ortiosteroids. Cortiosteroids rapidly and effetively suppress inflammation in RA and their use might be justified for short-term treatment for example, for bridging therapy in the period between initiation and response to disease-modifying antirheumati drug treatment, although the debate appears not to be settled yet. Therefore, a onservative approah was hosen, reommending the use of the lowest dose for the shortest period possible. 10. Reommend smoking essation At present, although there is no strong evidene that smoking has a key role in the exess CV risk in RA, it learly ontributes to a higher absolute risk in individual patients. Hene, 328 Ann Rheum Dis 2010;69: doi: /ard

5 Reommendations Figure 1 Ten-year risk of fatal ardiovasular disease (CVD) in patients at high CVD risk. Chart based on total holesterol:high-density lipoprotein (HDL) holesterol. Reprodued from Conroy RM, Pyorala K, Fitzgerald AP, et al. Estimation of ten-year risk of fatal ardiovasular disease in Europe: the SCORE projet. Eur Heart J 2003;24(11): , by permission of Oxford University Press. rheumatologists are strongly reommended to advise and help their patients to stop smoking, wherever possible, using best evidene-based methods. RESEARCH AGENDA The ommittee omposed a researh agenda to further optimise CV risk management (box 1). As evidene for AS and PsA is emerging, we will re-evaluate the evidene for AS and PsA and aim to revise the guidelines within 3 years. We aknowledge that our reommendations for the multipliation fator of 1.5 are derived mainly from relevant SMRs, whih stritly speaking is not ideal. However, there is a sarity of prospetive ohorts to enable the more usual approah in defining multipliation fators. Therefore, the arbitrary but onservative threshold of 1.5 has been hosen. Interestingly, data from a reent UK general pratitioner study provides additional support for a multipliation fator of around Obviously, this value an be re-examined in due ourse when better evidene emerges. CLINICAL IMPLICATIONS AND IMPLEMENTATION OF RECOMMENDATIONS This guideline is aimed primarily at rheumatologists but also at a broad spetrum of other healthare providers and reflet best pratie for patients with inflammatory arthritis. Although the greater CV risk is inreasingly aknowledged, limited attention is paid to deteting and managing CV omorbid onditions suh as hypertension and dyslipidaemia. Early identifiation, adequate CV risk management and ongoing monitoring of risk fators are mandatory to redue the (exess) CV risk. The first priniple of management is to assess and ontrol all omponents of total CV risk. This inludes appropriate evidened-based advie with regard to smoking, physial ativity, nutrition, weight and blood pressure. Cardioprotetive treatment should be initiated when the estimated 10-year CV risk is above the risk threshold for eah ountry, whether 10% or 20%. Finally, the lear relationship between disease ativity and CV disease underlines the importane of tight disease ontrol. Overall, this doument provides evidene-based and expert opinion-based reommendations on the steps that should be followed to lower the CV risk in patients with inflammatory arthritis. EXAMPLE Figure 1 shows the 10-year risk of fatal ardiovasular disease in patients at high risk. Consider a 63-year-old female patient with RA with total holesterol of 7.5 mmol/l and HDL- of 1.5 mmol/l, a systoli blood pressure of 165 mm Hg, who smokes. In this instane, aording to the SCORE model, the 10- year CV risk is 7% risk of fatal CV disease within 10 years. If this patient is IgM-RF positive and has disease duration of more than 10 years, we need to multiply this risk by 1.5, resulting in a 10.5% hane of fatal CV disease within 10 years. Aording to urrent Duth guidelines, treatment with statins and/or hypertensive agents will be started when the CV risk sore is above 10%, provided that the systoli blood pressure is >140 mm Hg and/or the LDL- is >2.5 mmol/l. Hene, treatment with a statin and an antihypertensive agent will be started. Ann Rheum Dis 2010;69: doi: /ard

6 Reommendations Aknowledgements: We thank Hans Ket, medial information speialist (VU University Medial Center) for his ontribution to the systemati literature searh. Funding: This projet was finanially supported by the European League Against Rheumatism (EULAR). Competing interests: Hans Bijlsma was the Handling Editor for this artile. Provenane and peer review: Not ommissioned; externally peer reviewed. REFERENCES 1. Dougados M, Betteridge N, Burmester GR, et al. EULAR standardised operating proedures for the elaboration, evaluation, dissemination, and implementation of reommendations endorsed by the EULAR standing ommittees. Ann Rheum Dis 2004;63: Avina-Zubieta JA, Choi HK, Sadatsafavi M, et al. Risk of ardiovasular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum 2008;59: Van Doornum S, MColl G, Wiks IP. Aelerated atheroslerosis: an extraartiular feature of rheumatoid arthritis? 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