A Moving Target: Cardiovascular Risk & Rheumatic Disease

With little research and no clear guidelines, physicians have to rely on expert opinions and their own experience when treating patients with both rheumatic and cardiovascular conditions. It’s a significant patient population, treatment is more dynamic and the risk stratification is a moving target, according to rheumatologist and clinical investigator Katherine Liao, MD, of Brigham and Women’s Hospital in Boston.

“The relationship between cholesterol, cardiovascular risk and inflammation is different in patients with rheumatic disease. In the general population, higher cholesterol means higher cardiovascular risk. That is not necessarily the case with [our] patients,” says Dr. Liao. “With rheumatic diseases, such as RA [rheumatoid arthritis], we know that treating to general population guidelines is suboptimal. However, we do not yet have data that definitively tell us, ‘yes, if you reduce inflammation, you will reduce cardiovascular risk by X%.’”

Dr. Liao says the general population guidelines typically underestimate cardiovascular risk in RA patients by 1.5 to two times. However, the math isn’t that simple.

“The problem is always confounded by the patients’ level of disease activity or inflammation. That can modify what the patients’ risk is,” she notes. “We want to be able to better estimate risk, but we don’t really have a way to do that yet. That is what a lot of studies are looking at.”

Dr. Liao points out that patients with rheumatic conditions routinely incur inflammation changes, and as a result, changes to lipid levels. Although no validated formula exists, understanding the variance is key, as is knowing when your patient is an outlier due to “flares, length of time the patient has had a rheumatic disease or how much steroid treatment the patient has had.”

When evaluating patients with a C-reactive protein (CRP) test, clinicians should be wary of the results for patients with active rheumatic conditions. In the general population, a CRP result of 3 mg/L is considered elevated and a patient with that result is considered at high risk of heart disease.

“But in RA, you are dealing with a completely different scale,” she says. “The mean CRP in a well-treated RA cohort is about 9 mg/L. If patients are flaring, the CRP easily could be in the 20s or 50s, and it is not unusual to see a level of 100 mg/L. It is a completely different scale of inflammation, and again, we don’t have data on how we should be integrating this information about how we assess [cardiovascular] risk.

“The treatment for these patients may not be more statins,” she adds. “It may actually mean we should be more aggressive with controlling inflammation.”

Considering the lack of guidelines, Dr. Liao understands why disease activity isn’t factored into cardiovascular risk stratification. Her clinical research includes serving as a co-investigator in a randomized controlled trial known as TARGET, which is investigating if the tight control of inflammation means lower cardiovascular risk in RA.¹ She also is a principal investigator for an ongoing study designed to more closely examine the relationship between cholesterol, inflammation and cardiovascular risk in RA.²

For now, Dr. Liao suggests considering two groups of rheumatology patients.

“For the RA patient who is flaring, where we have a plan—for example, they are on a TNFi, but not responding—we still have a lot of agents we can switch to. For these patients, I wouldn’t necessarily start a statin that day, based on concern for elevated [cardiovascular] risk, unless their cholesterol is clearly elevated,” she says. “I would recommend reassessing their risk after their disease activity is controlled.

“For patients who are already maxed out on RA therapies and their inflammation remains uncontrolled, … I would say let’s get as aggressive as possible with all their risk factors, potentially beyond general population guidelines, particularly with regard to statin use.”

Work with Cardiologists & Others
Dr. Liao, who is co-chair of the ACR’s Health Services Research Abstract Selection Subcommittee, encourages discussions between primary care physicians, rheumatologists and cardiologists. Her institution and others—including the Mayo Clinic, the Cleveland Clinic and Johns Hopkins—have created cardiology-rheumatology clinics that foster communication about patients’ disease history and activity.

And while a formal construct between cardiology and rheumatology may not be feasible in smaller institutions or rural settings, Dr. Liao says having a dedicated cardiology point person “who understands rheumatology patients, knows the drugs we use” can be a good first step to facilitating communication and improved patient care.

“[Access] is a system-wide issue, but it is helpful to get someone into the clinic in a timely manner. The point person doesn’t have to know everything about rheumatic diseases, but should have a sense of our drugs and treatment strategies. That is very helpful,” she says. “I consider that part of access because some people need to get into the clinic right away and some don’t. Having a point person see a young lupus patient with new onset exertional chest pain and history of heavy steroid use right away is important.”

Richard Quinn is a freelance writer in New Jersey

References

1. U.S. National Institutes of Health. Treatments against RA and effect on FDG-PET/CT (TARGET). ClinicalTrials.gov. 2017 Jan 24.
2. U.S. National Institutes of Health. Lipids, inflammation and CV risk in RA. ClinicalTrials.gov. 2016 Oct 3.