Homocysteine and vascular disease in the autoimmune connective tissue diseases

Premature, or accelerated, atherosclerosis has become recognized as a major determinant of both morbidity and mortality in chronic autoimmune diseases, especially systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). The pathogenesis of accelerated atherosclerosis is almost certainly multifactorial. The initial insult is likely a direct attack on the endothelial surface of blood vessels, due to immune complex deposition, cytokines, or other immune-derived factors. The chronic phase, however, is more complicated, and is less likely to involve factors related to active autoimmune disease, and more likely to involve so-called “traditional” cardiovascular risk factors (Figure 6.1). It is now recognized that the levels of some “traditional” risk factors can be increased by common treatments of autoimmune disease, including prednisone and methotrexate, and by organ system involvement in specific autoimmune diseases, such as renal involvement in SLE leading to hypertension and hyperlipidemia. This chapter will review the role of homocysteine, a newly recognized, but important “traditional” cardiovascular risk factor, and its importance in both systemic lupus erythematosus and rheumatoid arthritis.