Though numerous approaches have been proposed to calculate risk scores for cardiovascular disease (CVD) in rheumatoid arthritis (RA), each may have shortcomings limiting their utility. For example, the Systematic COronary Risk Evaluation (SCORE) calculator created by the European Society of Cardiology and the European Society of Hypertension does not account for nonfatal cardiovascular (CV) events, is unreliable for many patient groups, and “may cause various difficulties in evaluation of RA patients because it does not recognize validated risk factors for CVD, such as RA disease progression, high disease clinical activity, higher C-reactive protein (CRP) levels and seropositivity,” according to a recent paper.1
Similarly, the Framingham Risk Score (FRS) — the most common algorithmic tool used to estimate CV risk in the US — does not consider inflammatory disease activity or abnormal lipid levels that often characterize active RA. The FRS has also been linked with lower accuracy in young patients and women, and some findings suggest that it may underestimate CVD risk for patients with RA.
“Unfortunately, there really is a dearth of validated calculators for assessing risk of CVD in patients with RA, and none are used in routine practice,” said Eric Matteson, MD, a rheumatologist at Mayo Clinic in Rochester, Minnesota, who works with Mayo’s Cardio-Rheumatology Clinic. The specialized team there is currently evaluating an approach for assessing and managing CVD risk in patients with RA. “And importantly, it has not been shown that using these calculators in this subset of patients actually reduces long-term CVD risk,” he told Rheumatology Advisor.
Still, CVD risk must be adequately assessed and addressed in the RA population, and that is not happening for many patients. “Overall, probably less than 40% of patients have CV risk assessment done by their primary care MDs or their rheumatologists,” said Dr Matteson.
To get in in-depth view of the best current practices for evaluating and managing CVD risk in RA, Rheumatology Advisor interviewed Erin D. Michos, MD, FACC, FAHA, an associate professor of medicine and epidemiology, and associate director of preventive cardiology at Johns Hopkins School of Medicine in Baltimore, Maryland.
Rheumatology Advisor (RA): What are some of the most common ways in which CV risk in RA is calculated and interpreted?
Erin D. Michos, MD, FACC, FAHA: Patients with RA are indeed at increased risk of developing CVD. A prior meta-analysis of more than 24 studies involving over 111,000 patients found that patients with RA have a 50% greater risk of mortality attributed to CVD as compared to the general population.2
Of note, patients with other inflammatory and autoimmune disease such systemic lupus erythematosus (SLE) and psoriasis also have increased CVD risk. This excess risk is beyond what might be anticipated based on their profile of traditional cardiovascular risk factors — for example, blood pressure, blood cholesterol, and diabetes — alone. As a result, the need to improve CV risk assessment and treatment in patients with rheumatologic disorders is paramount.
For all adults, prevention guidelines recommend starting with a global risk assessment to estimate one’s risk for CVD. There are several validated calculators to help doctors estimate one’s risk of stroke, heart attack, or death using these traditionally-established risk factors.
The most recent one recommended for adults in the United States was published by the American Heart Association (AHA)/American College of Cardiology (ACC) in 2013 (http://www.cvriskcalculator.com). It estimates the 10-year risk of heart attack and stroke among people ages 40 to 79 and can gauge the 30-year risk for those 20 to 59 years old.
RA: What are the shortcomings of currently available risk calculation methods?
Dr Michos: One’s CV risk estimated by these calculators is determined by a combination of traditional risk factors, including age, gender, blood pressure, cholesterol, diabetes, and smoking. These calculators do not factor in a history of auto-immune or inflammatory disorders. Therefore, patients with RA may be underestimated by these risk calculators aimed at the general population.
At this time, there are no risk calculators specifically designed for patients with RA and thus recommendations are extrapolated from recommendations targeted at the general population.
RA: In your opinion, what are the best such methods?
Dr Michos: To account for the excess CV risk associated with RA disease, some experts have proposed taking one’s 10-year risk score estimated by one of these validated calculators and multiplying that by a factor of 1.5, because RA patients have a relative 50% greater CV risk. This new calculation would then revise one’s risk estimation upward when making treatment decisions about whether to initiate preventive pharmacotherapies such as aspirin and statins — decisions based on published guidelines that use 10-year risk to make treatment recommendations.
However, there is a lot of heterogeneity of RA disease between individuals, meaning some patients have greater or lower disease burden, and there is also heterogeneity of CV risk — not everyone with RA will go on to experience a CV event. Furthermore, there are established limitations of these risk calculators. Therefore, estimating one’s CV risk still may indeed be uncertain, and there is a need to better personalize risk estimation for an individual patient.
In our practice, we certainly recommend starting with these established calculators. For those patients with RA that already have a history of CVD or those already calculated to be high risk (≥15% 10-year risk) by these risk calculators, they should be treated aggressively with preventive therapy.
And everyone should be recommended to follow healthy lifestyles, including a healthy diet and recommended amounts of physical activity to reduce CV risk. But in cases of uncertainty of whether aspirin or statin pharmacotherapy drugs should be also started, we feel an additional test called a coronary artery calcium (CAC) measured by a non-contrast CT scan could provide much-needed clarity and move the needle in terms of treatment choice.
CAC score is a well-established marker of the burden of subclinical coronary atherosclerosis.
RA: Can you tell us more about the value of the CAC?
Dr. Michos: In large studies conducted in the general population, CAC scores have been shown to predict future risk of heart attacks better than age and other traditional risk factors like cholesterol and blood pressure. Studies have shown that people with a CAC score of zero have a very low risk of heart attack over the next 5 to 10 years. These patients might not need any drug treatment now and can focus on maintaining a healthy lifestyle. But patients with scores greater than 100 may be at higher risk and may benefit from targeted prevention with medications.
Therefore, for RA patients, CAC scoring may offer additional prognostic information when CV risk is uncertain after traditional risk factor evaluation. Of note, in one study, patients with RA of more than 10 years’ of duration were 3 times more likely to have severe CAC compared to a control group.3
There also have been some studies about measuring ankle-brachial index (ABI) or carotid intimal medial thickness (cIMT) as alternate measures of subclinical atherosclerosis, or C-reactive protein as a marker of inflammation, in patients with RA.
However, among the available options for additional tests suggested by the ACC/AHA for refining risk prediction, the test that appears to have superior discrimination and risk reclassification compared to the other markers is CAC. Therefore, based on these studies, CAC is the preferred testing by our preventive cardiology group in RA patients older than 40 years who might benefit from further refinement of their CV risk
RA: In closing, how would you sum up the ways in which CVD risk can be mitigated in RA?
Dr Michos: As mentioned above, everyone is strongly encouraged to follow a healthy lifestyle and participate in adequate physical activity. It is important to screen for and control the well-established traditional factors of CV risk, such as blood pressure, blood glucose, blood lipids, per established guidelines.
If additional testing with CAC — or ABI or carotid ultrasound — revealed evidence of subclinical atherosclerosis, [I] would strongly consider initiating statin medications for preventive therapy if not already statin-eligible by the guidelines, after having a risk discussion with the patient.
Limitations & Disclosures
Erin D. Michos, MD, and Eric Matteson, MD, have no conflicts of interest to disclose.
1. Bonek K, Głuszko P. Cardiovascular risk assessment in rheumatoid arthritis – controversies and the new approach. Reumatologia. 2016; 54(3): 128–135.
2. Aviña-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum. 2008; 59(12):1690-7.
3. Chung CP, Oeser A, Raggi P, et al. Increased coronary-artery atherosclerosis in rheumatoid arthritis: relationship to disease duration and cardiovascular risk factors. Arthritis Rheum. 2005; 52(10):3045-53.