Improving joint disease in patients with rheumatoid arthritis: is this enough to treat the accompanying dyslipidemias?

In the past few years it has become apparent that atherosclerosis is in part caused by inflammation in the arteries. Inflammation around lipid deposits in arterial walls has been reported in some patients, as has a correlation between atherosclerosis and elevated C-reactive protein levels in peripheral blood (1). Furthermore, there has been increasing interest in reports that patients with diseases associated with chronic inflammation, including systemic lupus erythematosus (2,3), chronic bacterial infections (4), and rheumatoid arthritis, may have accelerated atherosclerosis. However, the results of recent studies of rheumatoid arthritis and atherosclerosis are conflicting (5-7), with approximately half reporting increased atherosclerotic events in patients with rheumatoid arthritis compared with controls, and other studies observing no increase in the number of events. Comparison of these studies is difficult because control groups and methodologies vary. In this issue of The American Journal of Medicine, Park and colleagues (8) present evidence that dyslipidemia in patients with rheumatoid arthritis who have not been treated with disease-modifying anti-inflammatory medications or glucocorticoids improves in those in whom rheumatoid arthritis‐specific therapy is effective. Hence, instead of adding therapy for dyslipidemias, the physician might focus initially on controlling the systemic and arthritic manifestations of the disease. There are many features of systemic rheumatoid arthritis that may be associated with initiation or acceleration of atherosclerosis. These include systemic inflammation (which may target blood vessels as well as the synovium) marked by elevations in erythrocyte sedimentation rates and C-reactive protein levels, elevated tissue expression of monocyte chemoattractant protein 1, elevated systemic levels of interleukin 6 and tumor necrosis factor , dyslipidemia, and endothelial dysfunction (particularly in patients with vasculitis). In a prior cross-sectional study (9), the authors observed dyslipidemia characterized by decreased levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I and increased ratios of low-density lipoprotein (LDL) cholesterol to HDL cholesterol in newly diagnosed patients with rheumatoid arthritis. In the 42 patients with rheumatoid arthritis described in the Journal, there were significant increases at 12 months after initiation of therapy in HDL cholesterol and apolipoprotein A-I levels. These changes were most dramatic in the 64% of patients who achieved at least 20% improvement (by American College of Rheumatology criteria): HDL cholesterol level increased by 21%, apolipoprotein A-I level increased by 23%, and the ratio of LDL cholesterol to HDL cholesterol decreased by 13%. Differences were statistically significant and were in the range that could be achieved with use of statins. In the remaining patients, there was a significant change only in apolipoprotein A-I levels. Because use of glucocorticoids has been associated with some of the accelerated atherosclerosis seen in autoimmune chronic inflammatory diseases, the authors’ observations that prednisolone use (in 50% to 60% of patients) was not associated with significant changes in lipid levels are interesting. No doubt the numbers of patients were relatively small, but the elevations in total cholesterol and LDL cholesterol levels generally associated with glucocorticoid therapy (10) were not sufficient at the doses used (10 mg/d) to inhibit disease-suppressing activity. Methotrexate was administered to 93% of both responders and nonresponders, so the effects on lipid levels were more likely to be attributable to improvement related to the medication than to the medication itself. There is considerable enthusiasm for the use of statins in dyslipidemia (10), particularly because heart disease and stroke cause approximately 47% of all deaths in the