Abstract & Commentary
Synopsis: Antirheumatic therapy lowers lipid levels in patients with rheumatoid arthritis.
Source: Park YB, et al. Am J Med. 2002;113:188-193.
Park and colleagues have previously noted adverse lipid profiles in patients with rheumatoid arthritis (RA). Since inflammation may be associated with atherosclerosis, Park et al sought to determine the effects of treating RA with antirheumatic drugs on the abnormal lipid levels.
They selected 42 patients with newly diagnosed RA who had not been treated with corticosteroids or disease modifying antirheumatic drugs. Serum lipid levels were measured at baseline and at one year. They then determined whether there were differences in the changes in lipid levels between patients who met the American College of Rheumatology criteria for a 20% improvement in RA and those who did not.
Of the 42 patients, 27 (64%) met the criteria for a 20% improvement in RA activity criteria during the 12-month study. In these patients, mean high-density lipoprotein (HDL) cholesterol levels increased by 21% (P < 0.001), and apolipoprotein A-1 levels increased by 23%, (P < 0.001). Among the 13 nonresponders, mean HDL levels and mean LDL to HDL ratio did not change significantly. The mean apolipoprotein A-1 level increased by 10%; P = 0.02. Among the responders, the number of HDL levels < 35 mg/dL decreased significantly (from 9 to 2 patients; P = 0.04). Prednisone and methotrexate were not associated with significant differences in any of the lipid levels. The benefits were achieved without using lipid-lowering agents.
Park et al concluded that active RA is associated with an adverse lipid profile that improves substantially following effective treatment of the RA. This improvement may reduce the risk of cardiovascular disease in this group of patients.
Comment by Ralph R. Hall, MD, FACP
These studies are important not only because there is an increase in cardiovascular morbidity and mortality in RA but because there is increasing evidence supporting the hypothesis that atherosclerotic vascular disease shares many similarities with other inflammatory/autoimmune diseases.1
It is interesting to note that the C-reactive protein in the patients in this study was 10 times higher than in patients without inflammatory disease. Park et al have previously reported that there was a strong correlation between lipid levels and C-reactive protein and that as lipid levels improved in RA patients the C-reactive protein levels decrease.2
Park et al point out in their discussion that HDL and apolipoprotein A-1 are negatively correlated with disease activity in several rheumatic disorders, including Kawasaki’s disease, systemic lupus erythematosus, Behcet’s disease, and gout. In animal models, inflammation decreases the levels of HDL and apolipoprotein A-1 during the acute stage response.
It is interesting to note that the improvement in HDL and apolipoprotein A-1 in this study is greater than one would expect from statins and equal to the response to nicotinic acid.3,4
Since there are animal models for RA and tissue is readily available for study there may be avenues for understanding the inflammatory and immunologic responses of atherosclerosis. There are no such tools to investigate and follow the inflammatory response in arteriosclerotic plaques at the present time. As Pasceri and Yeh have stated "the study of the molecular mechanisms of RA may give valuable hints for research on the inflammatory/immunological mechanisms for atherosclerosis and acute coronary syndromes."1
Dr. Hall, Emeritus Professor of Medicine, University of Missouri-Kansas City School of Medicine, is Associate Editor of Internal Medicine Alert.
1. Pasceri V, Yeh E. Circulation. 1999;100:2124-2126.
2. Park YB, et al. J Rheumatol. 1999;26:1701-1704.
3. Blumenthal R S. Am Heart J. 2000;139:377-383.
4. Martin-Iadraque R, et al. Arch Intern Med. 1996;156: 1081-1088.