Cardiovascular risk management in arthritis: Why still a bridge too far?
Cardiovascular disease (CVD) is the main cause of death in patients with rheumatoid arthritis (RA) . Compared with the general population, patients with RA have a doubled risk for incident CVD, comparable to that of diabetes patients [2,3]. Both systemic inflammation and increased prevalence of traditional CVD risk factors (including age, male gender, hypercholesterolemia, hypertension, smoking, obesity, and diabetes) contribute to this increased CVD risk.
Both these aspects should be addressed to lower the CVD risk for our patients, and appropriate risk assessment and management strategies are mandatory in order to lower healthcare costs and improve survival and, more importantly, quality of life.
The increasing impact of traditional cardiovascular risk factors
It is important to realize that the relative role of traditional CVD risk factors may have increased during the last decade, due to more effective antirheumatic treatment, and its effect on systemic inflammation. For instance, Crowson et al demonstrated, in a large, international cohort of 5600 RA patients, that 49% of CVD events were attributable to traditional CVD risk factors, versus 30% that were attributable to RA characteristics .
EULAR recommendations for cardiovascular risk management: An explicit role for rheumatologists
The role of the rheumatologist
Recently, EULAR issued updated guidelines for the management of CVD risk factors in patients with RA and other forms of inflammatory joint disorders such as ankylosing spondylitis and psoriatic arthritis . An important overarching principle is that the rheumatologist is responsible for CVD risk management in these inflammatory arthritis patients. This does not mean that rheumatologists should themselves carry out CVD risk management, but that the rheumatologist should ensure that CVD risk management takes place, as in daily practice it is often not known if this is taking place and who is responsible for this.
Risk prediction algorithms
All inflammatory arthritis patients should receive CVD risk management, and optimal disease control will lower their CVD risk. In general, algorithms such as Framingham and SCORE may be used to predict 10-year CVD risk. However, these tools are based on the general population, and are thus inadequate for use in RA patients, in view of their increased CVD risk. Therefore, EULAR has advised that these risk charts should be adapted by a 1.5 multiplication factor, provided that this is not already included in the model (e.g. QRISK2) .
Guidance on diet and smoking cessation are similar to the general population. Exercise has been shown to have beneficial effects on CVD risk in patients with RA , as well as improvements in pain, physical function and disease activity . Therefore, EULAR has very recently issued evidence-based guidelines for physical activity in patients with arthritis .
Treatment thresholds for statins and antihypertensive agents are the same as for the general population . A recent Dutch study investigating CVD management in 720 consecutive RA patients demonstrated that while almost 70% of the patients had an indication for preventive treatment (with either cholesterol-lowering and/or antihypertensive drugs), 42% received inadequate treatment and 40% received no treatment at all; thus only 18% were optimally treated . Possible reasons for undertreatment include concerns regarding the efficacy of statins, and muscle-related adverse effects. However, Kitas et al convincingly demonstrated the efficacy of statins in RA in their TRACE-RA study , and a large randomized placebo-controlled trial by Gupta et al found an excess rate of muscle-related adverse event reports only when patients and their doctors were aware that statin therapy was being used, indicating that musculoskeletal complaints might be nocebo effects .
Cautious use of nonsteroidal anti-inflammatory drugs/cyclooxygenase-2 selective inhibitors is also advocated, as well as the restricted use of corticosteroids .
Implementation of cardiovascular risk management
While many studies have indicated poor performance of CVD risk management in RA, successful implementation of CVD risk management has taken place in a Dutch general practitioner (GP) -led CVD care program . This program included strong collaboration between primary and secondary care professionals, with strict definitions of their tasks and responsibilities. The program included a shared laboratory system for rheumatologists and GPs, and GPs received reimbursement for the additional costs from healthcare insurance companies. Past lipid screening was used as a proxy for CVD risk management, and this was performed in 72% of the 628 screened RA patients, increasing to 88% after reminder letters were sent to GPs. Hopefully, this will ultimately translate to a decreased cardiovascular burden, provided that the additional funding continues.
Multimorbidity is defined as the presence of two or more chronic diseases in the same person, and accounts for all potential interactions of coexisting diseases and their impact on the patient’s overall wellbeing. Nowadays, the need for a more holistic approach to multimorbidity in patients is increasingly acknowledged. From a pathogenic point of view, this appears wise as the underlying mechanisms of common comorbidities in RA, such as CVD, osteoporosis, fatigue and depression, overlap.
As the poor identification and treatment of unrelated disorders or comorbidities in patients with chronic disease such as RA has hardly improved during the past 20 years, a more intense screening program and regular active counselling of patients as well as treating physicians is urgently needed. The INCLUDE study, a nurse-led general practice feasibility study for screening, assessment and initial management of common comorbid conditions in rheumatic diseases, is an important initiative in this respect . It would be wise to start similar studies in secondary care, in close collaboration with primary care.
Do not wait, but act
Nowadays, the major challenge in treatment of RA is no longer the disease itself, but the associated comorbidities that have a negative effect on the quality of life of our patients. I feel it is our responsibility to make this a top priority and to obtain the necessary funding. Implementation of an extensive screening programme for all common comorbidities may presently be a bridge too far. But as we frequently see our patients, carry out disease activity assessments, and obtain blood from them, it should not be too difficult to also measure blood pressure, determine the lipid profile, and carry out CVD risk assessment. We should start with this today, and this would be a major first step towards reaching the ultimate goal of eliminating the comorbidity burden of our patients.
- Nurmohamed MT, Heslinga M, Kitas GD. Cardiovascular comorbidity in rheumatic diseases. Nat Rev Rheumatol 2015; 11: 693–704.
- van Halm VP, Peters MJ, Voskuyl AE et al. Rheumatoid arthritis versus diabetes as a risk factor for cardiovascular disease: a cross-sectional study, the CARRE Investigation. Ann Rheum Dis 2009; 68: 1395–1400.
- Lindhardsen J, Ahlehoff O, Gislason GH et al. The risk of myocardial infarction in rheumatoid arthritis and diabetes mellitus: a Danish nationwide cohort study. Ann Rheum Dis 2011; 70: 929–934.
- Crowson CS, Rollefstad S, Ikdahl E et al. Impact of risk factors associated with cardiovascular outcomes in patients with rheumatoid arthritis. Ann Rheum Dis 2018; 77: 48–54.
- Agca R, Heslinga SC, Rollefstad S et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis 2017; 76: 17–28.
- Stavropoulos-Kalinoglou A, Metsios GS, Veldhuijzen van Zanten JJ et al. Individualised aerobic and resistance exercise training improves cardiorespiratory fitness and reduces cardiovascular risk in patients with rheumatoid arthritis. Ann Rheum Dis 2013; 72: 1819–1825.
- Verhoeven F, Tordi N, Prati C et al. Physical activity in patients with rheumatoid arthritis. Joint Bone Spine 2016; 83: 265–270.
- Rausch Osthoff AK, Niedermann K, Braun J et al. 2018 EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis. Ann Rheum Dis 2018; 77: 1251–1260.
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- Kitas GD, Nightingale P, Armitage J et al. SAT0105 Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients with Rheumatoid Arthritis (TRACE RA). Ann Rheum Dis 2015; 74: 688.
- Gupta A, Thompson D, Whitehouse A et al. Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase. Lancet 2017; 389: 2473–2481.
- Weijers JM, Rongen-van Dartel SAA, Hoevenaars DMGMF et al. Implementation of the EULAR cardiovascular risk management guideline in patients with rheumatoid arthritis: results of a successful collaboration between primary and secondary care. Rheum Ann Dis 2018; 77: 480–483.
- Hider SL, Bucknall M, Cooke K et al. The INCLUDE study: INtegrating and improving Care for patients with infLammatory rheUmatological DisordErs in the community; identifying multimorbidity: Protocol for a pilot randomized controlled trial. J Comorb 2018; 8: 2235042X18792373.