Endothelial dysfunction in young patients with rheumatoid arthritis and low disease activity.(Extended Report)

Background: Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease. Endothelial dysfunction represents the earliest stage of atherosclerosis.

Objective: To evaluate the influence of chronic inflammatory state on endothelial function in patients with RA by measuring endothelial reactivity in young patients with RA with low disease activity and without traditional cardiovascular risk factors.

Methods: Brachial flow mediated vasodilatation (FMV), assessed by non-invasive ultrasound, was evaluated in 32 young to middle aged patients with RA (age [less than or equal to] 59 years), with DAS28 [less than or equal to] 3.2 and without overt cardiovascular disease, and in 28 age and sex matched controls.

Results: Mean (SD) FMV was significantly lower in patients than in controls (3.2 (1.3)% v 5.7 (2.0)%; p<0.001), inversely related to low density lipoprotein cholesterol (r= -0.45, p<0.05) and C reactive protein (CRP), expressed as the value at the moment of ultrasound evaluation (r= -0.44, p<0.05), as the average of CRP levels evaluated at different times during the disease (r= -0.47, p<0.05), or as the average of [greater than or equal to] 4 determinations multiplied by the disease duration (r= -0.40, p<0.05). In a multivariate regression model, a lower brachial flow mediated vasodilatation was independently predicted by low density lipoprotein cholesterol ([beta] = -0.40, p<0.05), average CRP levels multiplied by the disease duration ([beta] = -0.44, p<0.05), and brachial artery diameter ([beta] =-0.28, p<0.05).

Conclusions: Young to middle aged patients with RA with low disease activity, free from cardiovascular risk factors and overt cardiovascular disease, have an altered endothelial reactivity that seems to be primarily related to the disease associated chronic inflammatory condition.

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Rheumatoid arthritis (RA) is characterised by a high cardiovascular mortality, which exceeds that of the general population. (1-4) About 50% of atherosclerotic coronary artery disease in the community occurs in the absence of "traditional" cardiovascular risk factors, including male sex, family history for cardiovascular disease, age, dyslipidaemia, arterial hypertension, diabetes mellitus, smoking, and obesity. (5) Increasing evidence suggests a key role of inflammation in the onset and progression of atherosclerosis. (6) Experimental studies have shown that several inflammatory mediators, including activated leucocytes, cytokines, and C reactive protein (CRP), have an active role within the atherosderotic plaques. (7 8) Moreover, some large scale prospective epidemiological studies have shown that high serum levels of inflammatory markers, such as CRP, are predictive of future cardiovascular events. (9-12)

Altered function of the arterial endothelium is currently considered the earliest stage of the development of the atheroma. Endothelial dysfunction is also recognised as a promoter of the disease progression and a trigger of cardiovascular events. It may be detected as an impaired ability of the artery to dilate in response to a variety of physical and chemical stimuli, as a consequence of a reduced nitric oxide bioavailability. (13) Ultrasonographic determination of arterial vasodilatation after post-occlusion reactive hyperaemia (flow mediated vasodilatation (FMV)) is an accurate and reproducible non-invasive method for evaluating endothelial function in humans. (14)

Endothelial dysfunction has been recently described in patients with RA with high inflammatory activity, (15-17) and an improvement in endothelial function has been observed after treatment with disease modifying antirheumatic drugs. (15 16) Similar findings were reported after treatment of patients affected by primary systemic necrotising vasculitis. (18) Although these findings support the notion that acute systemic inflammation favours altered endothelial reactivity, it is unknown whether a chronic inflammatory condition, such as RA, leads to the impairment of endothelial function, independently of disease flares.

This study aimed at evaluating the influence of chronic inflammatory state on endothelial function in patients with RA. For this purpose, brachial artery FMV was measured in young patients with RA with low disease activity and without conventional cardiovascular risk factors.

METHODS

Thirty two consecutive young patients (four men, 28 women; aged [less than or equal to] 59 years, mean age 50 (7) years, range 27-59) meeting the American College of Rheumatology criteria for classification of RA. (19) were enrolled from our outpatient clinic. The mean (SD) disease duration was 11 (8) years. Twenty eight subjects matched for age and sex acted as controls: 8 with fibromyalgia, 10 with knee osteoarthritis, and 10 with hand osteoarthritis.

All subjects underwent a detailed clinical global examination that also included measurement of height and weight. Disease activity was measured by…