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Q&A: Two experts discuss proposals for formal CVD risk calculators in RA and the need for long-term research to validate them.
It's well-known that patients with rheumatoid arthritis are at higher risk than people without the disease for cardiovascular complications - both because of traditional risk factors like smoking or hypertension, and because of additional risk bestowed by rheumatoid arthritis itself.
Despite this common knowledge, there's no agreed-upon way to quantify the risk of cardiovascular disease in a rheumatoid arthritis patient. A review published in the July 18 issue of the journal Reumatologia, rheumatologists Krzysztof Bonek and Piotr Gluszko, of the National Institute of Geriatrics, Rheumatology and Rehabilitation in Poland, discuss proposals for formal risk calculators and the need for long-term research to validate them. Bonek and Gluszko spoke with Rheumatology Network via email to discuss the issues raised in that paper.
Rheumatology Network: What are the challenges to developing a useful cardiovascular screening tool for RA, and why don't we have one already?
To create such tool, we need a huge group of patients in primary prevention (without cardiovascular disease) and a set of factors that are associated with cardiovascular end points (such as stroke or acute ischemia or simply development of atherosclerotic plaques). On one side, rheumatoid arthritis is associated with the occurrence of "traditional" cardiovascular risk factors (like hypertension or dyslipidemia). On the other side, rheumatoid arthritis itself promotes the development of atherosclerosis. Considering aforementioned conditions and following literature there are a number of factors associated with cardiovascular risk in patients with rheumatoid arthritis. Therefore, the creation of a homogenous group of patients, separating "most important" factors and eventually reaching a mathematical formula, proves to be an extremely difficult task.
Rheumatology Network: What are the pros and cons of the most common approaches currently in use?
There are three main approaches: The first approach is a calculated risk with EULAR modification of SCORE algorithm by multiplying by 1.5 after matching certain requirements. It is in use and widely available. The main problem with EULAR mSCORE is the underestimation of cardiovascular risk in low and medium risk groups of patients.
The second approach is a creation of cardiovascular risk calculators based on assessed population risk factors considering rheumatoid arthritis (RA) as one of risk factors. Such calculator is QRISK-2. The main drawback to this approach is lack of certain RA-specific factors, like disease activity or seropositivity and treatment. Moreover, UK QRISK-2 is dedicated for designated population and is not validated for other populations.
The third concept is to create RA-specific tools, such as ERS-RA, which combines "traditional" and "RA-specific" risk factors. The main hindrances are lack of strong proofs of its superiority and so far ERS-RA is not recommended by any rheumatological society.
Rheumatology Network: Tell me a bit about the debate over an RA-specific tool like ERS-RA and a general tool adjusted for RA like the QRISK-2. What are the potential pros and cons of each approach?
Two main concepts can be identified. The first one is to focus on risk calculators developed for the general population taking account of rheumatoid arthritis as one of cardiovascular risk factors. This is a position represented by Deborah Symmons, M.D., of the University of Manchester. The main concept following this approach is to minimalize disease activity and simultaneous assessment of traditional risk factors using well established protocols such as QRISK-2 equation.
The second concept is to create RA-specific risk calculators. This position is taken by D.H. Solomon et al., who developed a new cardiovascular risk calculator for RA patients called Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis (ERS-RA).This calculator takes into account several “general” and “RA-specific” factors, such as occurrence of RA-nodules , erosions or seropositivity. It is very complex and assessment using this calculator requires more experience in the field of rheumatology and additional test such as X-ray imagining, ultrasonography and patient’s serological status.
As both calculators are quite new, further studies are needed to establish which concept will prove superior. Yet, during EULAR 2016 congress C. Crowson presented results of a trial on behalf of ATACC-RA consortium that none of those calculators (QRISK-2, ERS-RA, mSCORE) performed better then calculators developed for general population. In these conditions, in countries using SCORE, the preferred method of cardiovascular risk assessment is EULAR’s multiplier of 1.5.
Rheumatology Network: You mention in your review that you and others think carotid ultrasound is effective. What is the argument against this tool, and why do you think it is in fact useful?
Carotid ultrasonography is cheap and non-invasive test that allows to visualize atherosclerotic plaques if present. There are two major drawbacks. The first is required experience in carotid ultrasound, which is rare in everyday practice. Second, EULAR has not stated exact guidelines regarding time of the first test nor intervals for follow-up tests during disease progression. In addition, ultrasonographic criteria (like IMT) for a proper and accurate diagnosis of atherosclerosis are not commonly accepted.
Rheumatology Network: What kind of studies are needed to clarify the best approach?
To be exact, we need prospective cohort observational studies dedicated for patients in primary prevention of cardiovascular disease, followed by active scanning for subclinical atherosclerosis.
Rheumatology Network: What is the best advice for practicing rheumatologists who want to know the best way to screen in the meantime?
Only three pieces of advice: First, always follow current guidelines of your local cardiological and rheumatological societies.
Second, assess cardiovascular risk in every patient and try to eliminate traditional risk factors (such as tobacco smoking or obesity). Strive towards lowest possible disease activity. Apply statins, aspirin and antihypertensive treatment if needed.
Third, actively search for subclinical vascular disease. Carotid ultrasonography is a useful tool. Follow experts when RA-patient is classified in high CV risk group with extra-articular manifestations and RF or anti CCP antibodies positivity or 10 years disease progression.
Bonek K, GÅuszko P. “Cardiovascular risk assessment in rheumatoid arthritis – controversies and the new approach.” Reumatologia/Rheumatology r. 2016;3:128-135. DOI:10.5114/reum.2016.61214.
Nurmohamed M. “SP0033â Eular Recommendation Update on Cardiovascular Disease in RA.” Ann Rheum Dis 2015;74:9. DOI:10.1136/annrheumdis-2015-eular.6614.
Symmons D.P.M. “Do We Need a Disease-Specific Cardiovascular Risk Calculator for Patients With Rheumatoid Arthritis?” Arthritis Rheumatol 2015 Jul 2;8(67): 1990–1994. doi:10.1002/art.3919.
Solomon D. H, Greenberg J, Curtis J R et.al. “Derivation and Internal Validation of an Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis: A Consortium of Rheumatology Researchers of North America Registry Study Arthritis.” Rheumatol. 2015 May;67(8):1995-2003. doi: 10.1002/art.39195.
Crowson C.S. “Rheumatoid Arthritis-specific cardiovascular risk calculators are not superior to risk calculators established for the general population : a validation analysis in a cohort of RA patients from 7 countries.” Ann Rheum Dis 2016;75(suppl2): 155. doi: 10.1136/annrheumdis-2016-eular.1457.
Sattar N. “How to assess the CVD risk in the individual patient?” Ann Rheum Dis. 2016:SP0012. doi: 10.1136/annrheumdis-2016-eular.6435.
GÅuszko P, Bonek K. “Statins in rheumatology: revisited.” Reumatologia 2014; 52: 351 353.
Gonzalez-Gay M A, Gonzalez-Juanatey C, Llorca J. “Carotid ultrasound in the cardiovascular risk stratification of patients with rheumatoid arthritis: When and for whom?” Ann rheum Dis. 2012; 71: 796-798. doi: 10.1136/annrheumdis-2011-201209.