The multiple facets of premature aging in rheumatoid arthritis.

Abstract

Among the processes that characterize aging in normal individuals, the best documented include atherosclerosis, osteoporosis, sleep disturbance, and muscle wasting, as well as others (Table 1). Over the course of 30 years, premature atherosclerosis has been recognized as an important factor in the morbidity and mortality of patients with systemic lupus erythematosus (1). This has been attributed to vasculitis and corticosteroid use in these patients. Today, the phenomenon of premature atherosclerosis is observed in many different chronic inflammatory diseases with an increased proinflammatory load independent of glucocorticoid therapy (ref. 2; see refs. at URL in Table 1 footnote). A recent study in female patients with rheumatoid arthritis (RA) demonstrated adjusted relative risks of myocardial infarction of 2.0 (for all women with RA) and 3.1 (for women with a disease duration of at least 10 years) (3). Overall, patients with RA were at significantly higher risk of death, with an adjusted relative risk of 1.27 (4). With respect to osteoporosis, a similar premature aging process is now being recognized in a variety of chronic inflammatory diseases independent of administered glucocorticoids (see refs. at URL in Table 1 footnote). As the result of our understanding of anti–tumor necrosis factor (anti-TNF) strategies, we observe that this particular molecule and TNF-inducible proinflammatory downstream molecules contribute strikingly to accelerated aging phenomena (e.g., see ref. 5). In chronic inflammatory diseases, it seems that the initial proinflammatory load has a general impact on premature aging, which affects organ systems such as the endocrine system and the neuromuscular system. In this review, with the main focus on RA, we want to demonstrate the following: