Matters of the Heart

by Paul Wynn

Matters of the Heart

First, the bad news: If you have arthritis or inflammatory conditions, you’re at increased risk of experiencing heart disease. This means you have a greater chance of living with high blood pressure and elevated cholesterol and of experiencing a heart attack or stroke.

Don’t despair, though—there’s good news. With new research and awareness, doctors better understand that arthritis and inflammatory conditions are major risk factors for heart disease, and this new understanding is helping them treat both conditions more effectively without ignoring one of them. In addition, people can take several actions—avoiding smoking, losing weight, doing joint-friendly exercises—that will help prevent the onset of heart disease.

“Virtually every rheumatologist confronts the issue of caring for patients with both arthritis and cardiovascular disease,” says rheumatologist Michael Pillinger, MD, professor of medicine at NYU Langone Medical Center in Manhattan. “But it wasn’t that many years ago that we didn’t have a clue about the connection.”

Those living with rheumatoid arthritis (RA) tend to be at highest risk of heart complications. According to a review of 24 studies, more than half of premature deaths in people with RA stem from heart disease. Boston researchers found that women with RA are twice as likely to have a heart attack than those without the condition.

Vicky Besley was diagnosed with RA in her early 20s. Fortunately, she has not suffered any heart events and has low blood pressure, but “it’s always a concern,” she says. “That’s why I’m always aware of my cholesterol and blood pressure.”

Besley’s primary care doctor monitors her for any signs of heart disease and would manage any treatment. That’s typical for most people with arthritis: Their internist or family physician will care for their heart disease and their rheumatologist will manage the inflammatory condition and symptoms. Open communication between your primary care doctor and your rheumatologist is key to managing both conditions well. Newly trained rheumatologists are also better educated about heart disease risks than in years before. Says Pillinger, who oversees the rheumatology training program at NYU’s Hospital for Joint Diseases: “We recognize this as a new frontier.”

Not just RA patients
People who have other rheumatic inflammatory conditions such as gout, lupus, and psoriatic arthritis are also at increased risk. Pillinger notes a significant increase in heart events among lupus patients. “Lupus has a higher mortality rate in general,” he says, “but when they die prematurely, it’s usually because of heart disease.”

One study estimates that people with lupus had at least a two- to three-fold increased chance of heart disease and stroke compared to people without the autoimmune disease. Research also shows that people who have gout have a higher risk of heart attack and death from cardiovascular and coronary heart disease. High uric acid levels found in people with gout have resulted in a 44% increased risk of high blood pressure, according to a review of 18 studies. That puts uric acid on the potential culprit list of causing heart disease.

Despite a vast amount of research pointing to a correlation between rheumatic conditions and risk of heart disease, experts are still unsure of which exact mechanisms underlie the cause and effect. Questions remain about the biologic basis for increased heart disease; some researchers theorize that the molecules that cause RA (called cytokines) also contribute to blood vessel damage, but this relationship has not been fully explained.

Mounting evidence shows that inflammation itself is the main cause of greater risk of heart disease among people with inflammatory conditions. “Inflammation is a risk factor for heart disease, so it’s not that unexpected that people with inflammatory arthritis like RA, lupus, and psoriatic arthritis have more heart events,” says Pillinger.

Allison Reiss, MD, head of the Inflammation Section of the Winthrop Research Institute in Mineola, N.Y., points out that chronic inflammation due to RA causes changes in the lining of the blood vessels and increases the likelihood that cholesterol will deposit in the vessel wall. “There’s also increasing evidence that when patients have higher levels of inflammation and RA, the severity of cholesterol deposits is unpredictable, leading to difficulty in assessing the risk of heart attack,” she says.

Identifying patients at high risk for heart disease is a challenge, as is knowing which prevention strategies can positively affect heart disease outcomes. The risk factors identified through the famous Framingham Heart Study, which has tracked heart disease and outcomes among three generations of families, underestimate the risk for heart disease in patients with RA. The same is true with the SCORE method, a heart disease risk assessment model developed in Europe.

“Right now, we don’t know which RA patient is going to need more aggressive therapy,” says Reiss. “Additionally, it’s uncertain what therapy is going to be effective because the standard therapies that target the lipid profile may not be warranted. It’s not known if statins are helpful in RA patients.” Reiss adds that new risk scores that are more specific for the RA population are being developed to identify those at greater risk: “It’s more of a personalized medicine approach for testing patients.”

Research horizons
Within the past decade, doctors have gained new insights into the effects of common anti-inflammatory medicines on heart disease risk. NSAIDs like ibuprofen (Advil, Motrin), naproxen (Naprosyn, Anaprox, Aleve), and celecoxib (Celebrex) have been shown to increase the chance of heart attack or stroke. “Some of the drugs that we use to manage inflammatory conditions may actually raise the risk of heart disease,” says Pillinger. “So it’s important to weigh the benefit-risk of each medication.” For instance, the steroid prednisone promotes the risk of heart events, so long-term use is not advised for most patients.”

The widely used drug methotrexate has been the focus of several research studies to confirm its potential role as a cardio-protective agent. Methotrexate, which has been around for more than six decades, is a mainstay in the treatment of RA and other inflammatory conditions. The government is funding a large study to investigate the role of inflammation and whether methotrexate may reduce heart attacks, strokes, and deaths due to heart disease in people at high risk.

The study, led by the National Heart, Lung, and Blood Institute, is called the Cardiovascular Inflammation Reduction Trial (CIRT). While CIRT will not specifically enroll patients with RA, it will study about 7,000 patients from the United States and Canada who have had a heart attack within the past five years and who also have Type 2 diabetes or metabolic syndrome. The study started in early 2013 and will follow patients for two to four years. Says Paul Ridker, MD, principal investigator for CIRT and professor of medicine at Harvard Medical School, “If this generic drug, which is already on the market at low cost, proves effective for reducing risk of heart attacks, stroke, or death, it has the potential for broad public health impact in saving lives and reducing disease.”

However, methotrexate may not be the magic bullet for everyone. Even at lower doses, it is associated with side effects such as hair loss, nausea, headaches, and skin pigmentation. “It acts like a machine gun,” says Reiss, “but we need a pistol, with fewer side effects.”

Vicky tried methotrexate to treat her RA, but she experienced harsh side effects. “It was not a good experience for me and led me to become medication free,” she says. “The drug made me feel poorly—I stayed in bed for a week and felt sick at even the smell of food. I lost weight and had hallucinations after one week. I decided my body couldn’t cope with the medication.”

There were high expectations that other disease modifying anti-rheumatic drugs (DMARDs) would reduce the risk of heart disease. However, one recent study among psoriatic arthritis patients showed only mixed results.

“Our results seem to indicate that DMARD treatment was beneficial in patients with psoriatic arthritis for stroke and a total of major adverse cardiac events, but not heart attack specifically, and the results were not substantially different,” says lead author Alexis Ogdie, MD, assistant professor of medicine and epidemiology at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia. Ogdie notes that the study was done based on patient records and that new research should address whether DMARDs may reduce heart disease risk.

Alternative research path
At the Winthrop Research Institute, a new study is underway led by Reiss, who has dedicated much of her career to researching RA, pain management, and the increased risks for heart disease and heart attack. “The goal of my research program is to predict which RA patients are most vulnerable to developing heart disease so we can target appropriate preventative and treatment measures to improve the quality of life for these individuals,” she says.

One aspect of her work that holds particular promise is the finding that a naturally occurring substance in the blood called adenosine has the ability to restore normal cholesterol metabolism even in the presence of inflammatory conditions. Adenosine works through a path similar to methotrexate, but in a more targeted way that generates fewer side effects. Several adenosine-based agents are being studied for future evaluation in patients.

Current research is investigating adenosine and related compounds to understand how they accomplish this beneficial effect. “Our ultimate goal,” Reiss says, “is to see how these agents could improve medical treatment of heart disease in patients with RA.”

Much remains to be learned. However, the increased awareness and study of the issue combined with positive steps people with rheumatic conditions can take for themselves means that good reasons exist for people with RA to take heart.

Heart Wisdom
If you’re living with arthritis or another rheumatic condition, don’t gamble with the potential threat of heart disease. Here are some ways to take charge and lower your risk.

• Understand your risk factors. Get screened for high blood pressure, cholesterol, obesity, and diabetes, particularly if these conditions run in your family. It’s important to monitor these risks and talk to your doctor about how to lower them and avoid complications.

• Don’t ignore heart disease symptoms. People with arthritis can become so focused on their painful joints and inflammation that they may ignore other problematic signs that may be red flags for heart disease: shortness of breath; chest pain; pain, numbness, weakness, or coldness in the legs or arms; or pain in the neck, jaw, throat, upper abdomen, or back.

• Stop smoking now. Research shows that smoking cigarettes triggers heart disease. The chemicals in tobacco smoke can damage the heart and the structure and function of blood vessels. This damage increases the risk of atherosclerosis, in which a waxy substance called plaque builds up in and narrows the arteries, leading to heart attacks, heart failure, arrhythmias, and sometimes death.

• Talk about medication options. Some arthritis medications can increase heart risk. Commonly used NSAIDs like ibuprofen, naproxen, and celecoxib can increase the chance of heart attack and stroke. The steroid prednisone may also have detrimental effects on the heart over the long run. However, growing evidence suggests that methotrexate, aside from its effectiveness for relieving arthritis symptoms, may have cardio-protective properties.

• Adopt heart-healthy routines. Lifestyle modifications including a balanced diet and regular exercise can make a big difference in managing some heart disease risk factors, and improving physical function can lower blood pressure and cholesterol levels. Walking, swimming, and biking are generally joint-friendly exercises. Several exercise programs, some developed by the Arthritis Foundation, are available in many communities and are appropriate for people with arthritis and heart disease.

Last Reviewed On May 27, 2015

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Paul Wynn, based in Garrison, N.Y., has covered health-care trends for the past 20 years.

Statements and opinions expressed on this Web site are those of the authors and not necessarily those of the publishers or advertisers. The information provided on this Web site should not be construed as medical instruction. Consult appropriate health-care professionals before taking action based on this information.

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