2011 American College of Rheumatology (ACR)/Association of Rheumatology Health Professionals (ARHP) Annual Meeting

November 5-9, 2011; Chicago, IL
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Balancing Intake of Omega 6 and Omega 3 Key to Health Benefits

Many people have heard about the health benefits of omega 3, but fewer are aware that consuming too much omega 6—another fatty acid—could compromise those benefits. Although the human diet has always included omega 3 and omega 6, Artemis P. Simopoulos, MD, founder and President, Center for Genetics, Washington, DC, and a renowned expert on the role of fatty acids on health and disease, says the level of omega 3 in the Western diet has dropped sharply over the past 150 years. She told an audience of medical professionals at the 2011 ACR/ARHP Annual Meeting that the ratio of omega 6 to omega 3 in today’s Western diet is approximately 20:1, whereas an optimal ratio is closer to 1-4:1.

High levels of omega 6 are largely found in refined vegetable oils, such as corn and soy. Omega 3 fatty acids occur naturally in fish, such as salmon and mackerel; flax, canola, and linseed oils; walnuts; and flaxseed. Disparate intake of omega 6 compromises the liver’s ability to process omega 3 into its bioavailable form. Many rodent species are fortunate in that they produce an enzyme that converts omega 6 to omega 3, allowing them to balance these nutrients. Simopoulos noted that rodents rarely develop cancer or coronary heart disease and have less severe inflammatory disease than humans, who lack this enzyme and are thus more susceptible to the prothrombotic and proinflammatory effects of too much omega 6.

“Having high amounts of omega 6 in your diet—having a proinflammatory diet—it’s not really consistent with good health,” she said, pointing out that inflammation has been associated with a host of chronic conditions, including neurological diseases such as Alzheimer’s and Parkinson’s. Omega 6 also increases oxidation of low-density lipoproteins (LDLs), a precursor to atherosclerosis. “As the omega 6/omega 3 ratio decreases, so does platelet aggregation,” she explained.

Joel M. Kremer, MD, Pfaff Family Professor of Medicine, Albany Medical College and The Center for Rheumatology, Albany, NY, also addressed the session. He and Simopoulos discussed decades of studies establishing the health benefits of omega 3 supplementation. Increasing intake of omega 3 modulates the immune system, lowers levels of triglycerides and LDL, and reduces cardiovascular mortality through its antiarrhythmic properties.

More than 20 peer-reviewed studies have demonstrated improvement in rheumatoid arthritis symptoms with omega 3 supplementation, particularly at higher doses. “The minimal effective dose which has been studied appears to be 3 to 5 g per day of omega 3,” said Kremer, adding that it typically takes at least 12 weeks to realize benefits. Most over-the-counter supplements contain approximately 300 mg of omega 3, requiring patients to take ten capsules per day to achieve a therapeutic dose. With newer high-potency capsules (500 to 950 mg of omega 3), as few as three capsules daily can be effective. He has also found this dose effective for Raynaud’s Syndrome, particularly in younger adults.

Fish is one of the best dietary sources of omega 3, with studies linking higher fish consumption to lower rates of coronary artery disease and nonfatal cardiac events. Simopoulos recommended eating fish two or three times weekly but cautioned against cooking it in corn or safflower oils to minimize the inhibitory effects of omega 6. “The importance of omega 3 essential fatty acids in the diet is now evident, as well as the need to return to a more physiological omega 6/omega 3 ratio of about 1-4:1, rather than the ratio of 20-16:1 provided by current Western diets,” Simopoulos concluded.—Christin Melton
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Methotrexate and TNF-α Inhibitors Reduce Cardiovascular Risks in Patients With Rheumatoid Arthritis

Long-term use of methotrexate or tumor necrosis factor (TNF)-ɑ was associated with a significant decrease in cardiovascular events in patients with rheumatoid arthritis (RA). Data from the study were presented in a plenary session at the 2011 ACR/ARHP Annual Meeting by Rasa Bozaite-Gluosniene, MD, Geisinger Medical Center, Danville, PA. Bozaite-Gluosniene said the findings were important because cardiovascular disease (CVD) is the leading cause of death in patients with RA. Although previous observational studies have shown that methotrexate and TNF-ɑ inhibitors decrease the risk of CVD in patients with RA, Bozaite-Gluosniene said they failed to control for inflammatory burden or lipid profile and their observational nature left them susceptible to biases.

Using electronic health records from Geisinger’s database, the researchers identified 1829 patients who received an RA diagnosis between 2001 and 2009. After they excluded individuals with preexisting coronary artery disease (CAD), the cohort comprised 1829 patients with a median age of 57 years at RA diagnosis. Nearly three-quarters of the patients were women, 95% were white, and 77% were rheumatoid factor–positive. The median follow-up was 3.4 years, during which 71% of patients used nonsteroidal anti-inflammatory drugs, 84% took steroids, 38% received hydroxychloroquine, 62% took methotrexate, and 33% used TNF-ɑ inhibitors. In total, 127 cases of incident CVD occurred, of which 48 were CAD (ie, myocardial infarction, unstable angina, cardiac revascularization); 45 were strokes or transient ischemic attacks, and 34 were peripheral artery disease or abdominal aortic aneurysm.

When patients were stratified according to methotrexate use, investigators identified 90 cases of incident CVD among the nonusers (n=710) compared with 37 cases among users (n=119), suggesting that patients treated with methotrexate were 46% less likely to experience a CAD event than those who were not. The median duration of methotrexate use was 22 months or more, which applied to 534 methotrexate users. Extended use was associated with a highly significant 72% reduction in incident risk of CAD events compared with nonuse (P<.0001).

Sorting patients by TNF-ɑ inhibitor use revealed 1241 nonusers and 588 users who had a median exposure to the TNF-ɑ agent of 17 months. The rate of CAD events was significantly higher among nonusers, who had 110 cases compared with 17 for users. The greater the exposure, the greater the decrease in risk, with a relative risk of .07 for patients who used a TNF-ɑ inhibitor for more than 35 months (P=.010). An analysis of patients who took a TNF-ɑ inhibitor longer than 17 months showed they had a 69% reduction in the rate of incident CAD events compared with those who did not use the drug and a hazard ratio (HR) of 0.31 for an instant cardiovascular event compared with an HR of 1.4 for those with 17 months or less of TNF-ɑ exposure.

Bozaite-Gluosniene said the study was limited by its status as an observational study; the broad primary end point, which included all cardiovascular events; and the lack of information on smoking history, family history of CVD, level of physical activity, and use of aspirin. Given the homogeneousness of the study population, she advised caution when applying results to other population groups. Despite these limitations, she said the study had several strengths. “These findings suggest these medications are protective against CVD in a group of patients who are at high risk of CVD,” she concluded.—Christin Melton
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Studies Suggest Gout Contributes to Risk of Common Comorbidities

From 1994 to 2007, the prevalence of gout increased 44%, and today gout affects an estimated 3.9% of the population and 12.6% of individuals older than 80 years. Gout is primarily a disease of the elderly, most of whom have comorbid conditions. At a presentation on gout and hyperuricemia at the 2011 ACR/ARHP Annual Meeting, Michael Pillinger, MD, Associate Professor of Medicine and Pharmacology, NYU Langone Medical Center, New York, NY, said a recent study at his institution determined that the average gout patient has three to four comorbidities, and some have seven or more. Of the 575 patients (median age, 72 years) enrolled in the study, nearly 90% had hypertension, approximately 60% had hyperlipidemia, 50% had chronic kidney disease, 40% had coronary artery disease, and 30% had diabetes.

Given the high rate of comorbidities in patients with gout, researchers are investigating whether gout or hyperuricemia play a causative role. “These diseases may just be fellow travelers. [Or] comorbidities may be promoting gout, in which case we have to deal with them, but if there’s any extent to which the gout is promoting the comorbidities, that’s important for a rheumatologist to know,” said Pillinger.

Treating gout is costly: patients experiencing six or more attacks per year accumulate nearly $20,000 annually in medical costs compared with less than $5000 annually for those without the condition. Gout also decreases longevity. Recent data show people with gout have a 10% to 15% increased risk of mortality compared with unaffected individuals. Patients’ deaths are typically attributable to one of their comorbid conditions, rather than to gout, further underscoring the importance of determining whether gout is causing or exacerbating these conditions.

Pillinger said animal and human studies show that high urate levels have several negative effects on the vasculature, possibly contributing to an increase in blood pressure. Treatment with allopurinol, a drug designed to lower serum urate levels, corresponds with declines in systolic and diastolic blood pressure, supporting the theory that hyperuricemia raises blood pressure. A meta-analysis of data from several large studies concluded that hyperuricemia was an independent risk factor for coronary artery disease (CAD), increasing risk by 10% to 15%, and a large retrospective study of Taiwanese patients found that those taking urate-lowering therapies had half the risk of cardiovascular mortality and stroke compared with those not taking them.

Other studies have linked high urate levels to kidney disease and osteoarthritis. In both cases, the relationship appears to be cyclical, with the disease precipitating an increase in urate levels. In patients with kidney disease, the elevated urate levels contribute to deterioration in renal function; in patients with osteoarthritis, high urate levels in the synovial fluid are followed by worsening osteoarthritic symptoms. Small or preliminary studies have reported that reducing uric acid levels in patients with these conditions improves symptoms, although Pillinger said more data are needed before applying the findings to practice.

According to Pillinger, the quality of gout care is suboptimal, largely because of poor adherence to therapy, physicians’ insufficient understanding of therapeutic objectives, and the dangers of treating gout aggressively due to comorbidities. He noted that many newer drugs are available or in the pipeline for gout-related inflammation and hyperuricemia, including anakinra, rilonacept (also known as “interleukin-1 Trap”), canakinumab, febuxostat, pegloticase, and lesinurad (RDEA594). Although early studies suggest the drugs are highly effective and well tolerated, Pillinger said he would like to see more data on how they work in the real-world setting.—Christin Melton