Atherosclerotic disease is increased in recent-onset rheumatoid arthritis: a critical role for inflammation

Abstract

Rheumatoid arthritis (RA) patients have increased mortality and morbidity as a result of cardiovascular and cerebrovascular disease. What is not clear, however, is either how early accelerated atherosclerosis begins in RA or how soon risk factors must be rigorously controlled. Furthermore, given the strong relationship of vascular disease to RA mortality and of inflammation to the accelerated atherosclerosis associated with RA, it is important to evaluate indices that could serially and noninvasively quantify atherosclerotic disease in RA patients. The carotid intima-media thickness (cIMT) and plaque, measured by ultrasound, correlate closely with direct measurement of the local and systemic atherosclerotic burden. To investigate the presence of subclinical atherosclerosis in the early stages of RA, the cIMT and plaque were measured using carotid duplex scanning in 40 RA patients with disease duration < 12 months and in 40 control subjects matched for age, sex and established cardiovascular risk factors. Patients with RA had significantly higher average cIMT values and more plaque than the control group (cIMT 0.64 +/- 0.13 mm versus 0.58 +/- 0.09 mm, respectively; P = 0.03). In RA patients, the cIMT was predicted by age and C-reactive protein level at first presentation to the clinic (R2 = 0.64). C-reactive protein was associated with age of disease onset and history of smoking. Since inflammation has been shown to predate onset of clinical RA, the accelerated atherogenic process related to inflammation may precede RA symptom onset.

Figure 1

Carotid intima media thickness in rheumatoid arthritis patients compared with matched healthy control individuals. The carotid intima media thickness (IMT) is increased in rheumatoid arthritis (RA) patients compared with healthy control individuals matched for age, sex and cardiovascular risk factors. Representative carotid ultrasound images from three matched RA patient and control individual pairs: (a) a 42-year-old male with RA and a 40-year-old control male, (b) a 58-year-old male with RA and a 58-year-old control male, and (c) a 31-year-old female with RA and a 31-year-old control female. The automated measurement lines over the region of interest are boxed (in blue).

Figure 2

Coassociation of carotid intima media thickness, age and rheumatoid arthritis inflammatory activity. The carotid intima media thickness (cIMT) was measured in 37 rheumatoid arthritis (RA) patients with disease duration <12 months and in 37 control subjects matched for age, sex and cardiovascular risk factors. The cIMT was plotted against (top left) age at RA diagnosis, (top right) age of controls, or (bottom left) the C-reactive protein (CRP) level at first presentation with RA. (Bottom right) CRP at first presentation plotted against history of smoking. Data presented as mean ± standard deviation. * p < 0.05