• Cardiovascular

    Discovery’s Edge: The rheumatoid arthritis and heart disease connection

Physicians have long known that people with rheumatoid arthritis and other rheumatic conditions such as lupus are more likely to die at younger ages than are those without these conditions. Even with advances in treatment, the gap in life expectancy remains.

No one knew why until 15 years ago. That's when researchers at Mayo Clinic helped establish that people with rheumatoid arthritis have a greater chance of developing various types of cardiovascular disease.

"We now know that rheumatoid arthritis is associated with an increased risk of heart and vascular disease," says senior researcher Sherine E. Gabriel, M.D., a rheumatologist and epidemiologist in the Department of Health Sciences Research at Mayo Clinic's campus in Rochester, Minnesota. "What is less understood is why people with rheumatoid arthritis develop that increased risk."

Sharrine Gabriel, M.D., is now head of the medical school at Rutgers University.
Sherine Gabriel, M.D., is now head of the medical school at Rutgers University.

The evidence increasingly points to inflammation as a major contributor to that increased risk of cardiovascular disease.

In rheumatoid arthritis, the immune system attacks the synovium — the lining of the membranes around the joints. The resulting inflammation thickens the synovium, which can, in turn, eventually destroy cartilage and bone in the joint.

Inflammation can also cause the inner linings of arteries to swell. This narrows the arteries, raises blood pressure, and reduces blood flow to the heart and other organs.

Eric L. Matteson, M.D., chair of the Division of Rheumatology at Mayo Clinic in Rochester, notes that people with rheumatoid arthritis have a 50 percent higher risk of heart attack, twice the risk of heart failure and more peripheral vascular disease than people who don't have rheumatoid arthritis.

"Clearly, there's something about rheumatoid arthritis that affects the cardiovascular system, causes patients to suffer with more disease and even can affect their life expectancy," Dr. Matteson says.

The complexity of factors

Eric L. Matteson, M.D.
Eric L. Matteson, M.D.

Many factors associated with arthritis likely play a role in increasing heart disease risk. Some rheumatoid arthritis medicines such as steroids can promote high blood pressure, diabetes and hardening of the arteries. Anti-inflammatory drugs like naproxen and ibuprofen can affect kidney function and blood pressure.

In addition, because rheumatoid arthritis can limit mobility and make physical activity painful, patients tend to have higher rates of high blood pressure, elevated lipid levels and excess weight.

People with rheumatoid arthritis are less likely to have the typical signs and symptoms of heart disease. As a result, heart disease often goes unrecognized and untreated in its early stages, delaying treatment and increasing health risks.

"On top of that," Dr. Gabriel notes, "once people with rheumatoid arthritis develop heart disease, whether it's a heart attack or heart failure, their outcomes are poorer. They are more likely to die of it and more likely to have a second cardiovascular event."

Traditional cardiovascular risk factors seem to impact people with rheumatoid arthritis differently.

The standard physician-recommended treatment for patients at risk of cardiovascular disease is to lower lipid levels and control weight. For people with rheumatoid arthritis, however, the opposite may be recommended.

Lower lipid levels and weight loss in someone with rheumatoid arthritis can actually spur more severe systemic inflammation, in turn raising the risk of coronary artery disease.

"It's a complete paradox," Dr. Matteson acknowledges.

According to Dr. Gabriel, the challenge is to identify which patients with rheumatic conditions are most likely to develop cardiac disease, before symptoms appear.

Mayo Clinic is meeting this challenge on the research and clinical fronts. Research teams are exploring better imaging techniques, blood tests and risk assessments. And Mayo Clinic's Cardio-Rheumatology Clinic provides care tailored to people with rheumatic conditions.

Better imaging

Standard echocardiograms can show heart problems once they exist, but they aren't that helpful at detecting early disease at a time when physicians could potentially do something about it, Dr. Gabriel says.

A groundbreaking Mayo Clinic study found that a special kind of echocardiogram holds promise for early detection of heart disease in rheumatoid arthritis patients.

In the study, myocardial strain imaging using a type of ultrasound called speckle-tracking echocardiography identified a pattern of heart muscle damage unique to people with rheumatoid arthritis. Myocardial strain is a measure of how the heart muscle functions when it contracts and relaxes to pump blood.

The study used the resources of the Rochester Epidemiology Project. It was the largest study to evaluate myocardial strain characteristics of rheumatoid arthritis patients without known cardiovascular disease. In addition, it was the first study to look at right ventricle strain.

Speckle-tracking echocardiography holds great promise, and in the future could be used to show heart disease before patients have clinical signs, Dr. Gabriel says.

Specialized blood tests

In another recent study, Mayo Clinic immunologists exposed white blood cells from people with and without rheumatoid arthritis to various substances that stimulate inflammation. The results showed a unique immune response signature associated with advanced heart muscle dysfunction in people with rheumatoid arthritis.

Explains Dr. Gabriel: "Generally, if you measure inflammation markers in somebody's blood today, it reflects something that's already happened in the past. The novel thing about this particular test is that it looks at how the cells would respond should they be exposed to these stimulants (in the future). It's more a measure of immune potential."

Immunologists hope this information will help them create a blood test that predicts which people with rheumatoid arthritis are at highest risk of cardiovascular disease.

Targeted risk tools

Cardiovascular risk assessments use basic medical history and lifestyle information to predict a person's five-year risk of developing cardiovascular disease. Physicians use risk scores to guide preventive care and treatment recommendations.

Mayo Clinic research shows that standard cardiovascular risk assessments often underestimate the danger faced by rheumatoid arthritis patients.

Although inflammation plays a key role in the increased cardiovascular risk associated with rheumatoid arthritis, many risk assessment tools do not factor it in. Likewise, rheumatoid arthritis medication use is not part of a standard risk assessment.

As a result, traditional risk scores may give people with rheumatoid arthritis a false sense of security about their heart disease risks and result in missed opportunities for preventive measures.

"Our research emphasizes that patients with rheumatoid arthritis are at higher risk of heart disease and that conventional predictors of risk are not adequate," Dr. Matteson says. "Physicians caring for patients with rheumatoid arthritis should be aware of this heightened risk even when conventional risk factors seem to indicate no increased risk, and consider measures to assess and lower cardiovascular risk in these patients."

From the lab to the Cardio-Rheumatology Clinic

Translating research into clinical practice is paramount at Mayo Clinic. To that end, the divisions of cardiovascular diseases and rheumatology have joined forces to change the clinical approach to rheumatic conditions.

The Cardio-Rheumatology Clinic at Mayo Clinic opened in Rochester in the summer of 2013. The clinic provides specialized care focused on early detection, prevention and treatment of cardiovascular disease in patients with rheumatic conditions.

"We saw the need for a team of specialists that understand the unique risks and circumstances of people with rheumatoid arthritis, so we created this special clinic just for those patients," explains Mayo Clinic cardiologist Rekha Mankad, M.D., who directs the Cardio-Rheumatology Clinic in Rochester.

Dr. Gabriel concurs. "Because they don't necessarily show cardiovascular symptoms the same way as other people, and because they take medication that other people aren't on and have poorer outcomes when they develop heart disease, they need more specialized care," she says.

The Cardio-Rheumatology Clinic enables early referral of patients with rheumatic diseases to cardiology. Patients have both a traditional cardiovascular risk assessment and a vascular health assessment. The results help create an individualized plan to manage risks and symptoms.

Regular follow-up visits monitor the effect of different treatment and prevention strategies on patients' cardiovascular health. Dr. Mankad and her colleagues track this outcome information in a new database.

Dr. Mankad notes that cardiovascular treatment guidelines don't exist for rheumatic conditions. Other conditions that carry an increased cardiovascular risk, such as diabetes, do have guidelines for target lipid levels, blood pressure and weight.

"The hope is to get to that point for rheumatoid arthritis patients by having a database to track how we're treating these patients and seeing (whether) we have modulated the outcomes," Dr. Mankad says. "It's being very clinically driven."

The Cardio-Rheumatology Clinic's innovative practice gives physicians and patients the information they need to more accurately assess cardiovascular risk and to intervene much earlier. It paves the way for better management of heart disease and improved quality of life for people with rheumatic diseases.

"We've come full circle," Dr. Gabriel notes. "Careful clinical observation led to research that now informs and changes clinical practice, making things better for patients."

Dr. Mankad agrees. "This is an incredible niche," she says. "Right now, we don't know of any other place in the United States that has a specific cardio-rheumatology clinic. It's very exciting."