Diverse vascular lesions occur in about one third of patients with Behçet's disease (BD). Endothelial dysfunction is known to have an important role in the development of these lesions.1 Acute systemic inflammation and chronic systemic vasculitis are associated with endothelial dysfunction.2,3 Moreover, inflammation is an important risk factor for future cardiovascular events.4 These findings have led to the hypothesis that acute and chronic inflammatory processes associated with BD may cause endothelial dysfunction, which can then lead to a subsequent increase of arterial stiffness and vascular damage that are closely related to the clinical course of BD. Arterial stiffness is a reliable predictor of subsequent cardiovascular mortality and vascular damage. Pulse wave velocity (PWV) is an ideal indicator of arterial stiffness.5,6 Most investigators have studied PWV only in the aorta, although PWV should be measured along the entire arterial tree.6 Therefore we investigated PWV of different regions in patients with BD.
This study included 53 patients with BD who fulfilled the International Study Group criteria7 and 65 controls. Subjects with hypertension, diabetes mellitus, or a previous history of coronary artery disease or myocardial infarction were excluded. At the time of examination the presence of more than two of the following clinical features was considered to indicate active disease: oral ulceration, genital ulceration, skin lesions, ocular lesions, active major vessel disease, and active major organ involvement, including active gastrointestinal or neurological lesions. The presence of severe disease was defined as in the previous investigation.8 Information was obtained on corticosteroids and immunosuppressant drug use for the 3 months before the start of this study. PWV was measured with an automated device (VP‐2000, Colin Co Ltd, Japan) in the heart‐femoral, heart‐carotid, heart‐brachial, and femoral‐ankle segments.9,10
Table 1 summarises clinical features and cardiovascular variables of the study group. No differences between patients with BD and controls were found for age, sex ratio, other measures known to affect PWV, including height, blood pressure, heart rate, and total cholesterol levels. Patients with BD had significantly higher PWV values than controls in all the four arterial segments.
Table 1 Clinical characteristics and cardiovascular variables of the study group.
| Variables | Behçet's group | Controls | p Value | |
|---|---|---|---|---|
| (n = 53) | (n = 65) | |||
| Age (years) | 38.1 (8.1) | 38.2 (8.0) | NS | |
| Men, No (%) | 27 (51) | 32 (49) | NS | |
| Height (cm) | 164.7 (8.5) | 163.8 (8.2) | NS | |
| Body mass index | 22.1 (2.9) | 22.7 (2.7) | NS | |
| Systolic blood pressure (mm Hg) | 119.2 (11.1) | 117.2 (9.6) | NS | |
| Diastolic blood pressure (mm Hg) | 73.8 (8.3) | 72.5 (7.9) | NS | |
| Mean blood pressure (mm Hg) | 90.9 (9.0) | 88.4 (8.1) | NS | |
| Pulse pressure (mm Hg) | 45.4 (8.0) | 46.3 (6.1) | NS | |
| Heart rate (bpm) | 65.2 (7.8) | 65.5 (9.9) | NS | |
| Smokers, No (%) | 8 (15) | 9 (14) | NS | |
| Serum glucose (mmol/l) | 4.7 (0.5) | 4.8 (0.5) | NS | |
| Serum total cholesterol (mmol/l) | 4.25 (0.80) | 4.40 (0.55) | NS | |
| Serum triglyceride (mmol/l) | 1.16 (0.58) | 1.12 (0.54) | NS | |
| Clinical features, No (%) | ||||
| Oral ulcerations | 53 (100) | |||
| Genital ulcerations | 32 (60) | |||
| Erythema nodosum | 21 (40) | |||
| Papulopustular lesions | 44 (83) | |||
| Positive pathergy reaction | 28 (53) | |||
| Ocular lesions | 12 (23) | |||
| Intestinal lesions | 6 (11) | |||
| Peripheral arthritis | 14 (26) | |||
| Vascular lesions | 9 (17) | |||
| CNS lesions | 2 (4) | |||
| Positive HLA‐B51 | 22 (42) | |||
| Active disease | 16 (30) | |||
| Severe disease | 19 (36) | |||
| Immunosuppressive agents | 15 (28) | |||
| Azathioprine | 10 (19) | |||
| Ciclosporin | 5 (9) | |||
| Corticosteroids | 38 (72) | |||
| Pulse wave velocity (m/s) | ||||
| Heart‐femoral | 7.9 (1.1) | 7.2 (0.6) | <0.001 | |
| Heart‐carotid | 6.8 (1.5) | 6.2 (1.0) | 0.035 | |
| Heart‐brachial | 5.4 (0.7) | 5.1 (0.6) | 0.004 | |
| Femoral‐ankle | 10.4 (1.3) | 10.0 (0.9) | 0.034 |
Results are given as mean (SD) unless stated otherwise.
NS. non‐significant; CNS, central nervous system.
In the relationship between PWV values and clinical measures of BD in the different regions, it was found in univariate analysis that some clinical variables related to severe manifestations in BD, which included severe disease, male sex, vascular lesions, or immunosuppressant drug use, were partly associated with increased PWV. However, statistical significance for these clinical variables was lost in all the regional arterial segments in multivariate analysis (data not shown). In addition, the PWV levels did not differ significantly between patients with and without active disease. Patients treated with corticosteroids had PWV values similar to those of patients not receiving these drugs. In the Pearson correlation analyses, all the regional PWV levels, except for the femoral‐ankle segment, correlated well with increasing age. The PWV values in all the regional arterial segments correlated positively with mean blood pressure (MAP). After adjusting for any confounding factors through multivariate regression analysis, age and MAP remained statistically significant in most regional arterial segments (data not shown). However, none of the regional PWV values correlated with the disease duration.
Patients with BD had significantly higher PWV values in all the four regions than in controls, indicating the presence of increased arterial stiffness. Such increased arterial stiffness may be attributed to endothelial dysfunction and acute or chronic inflammatory processes associated with BD. On the other hand, similar to the well known effects of age and MAP on PWV,5,6,10 we found that age and MAP were independent significant factors associated with increased PWV in BD. Longitudinal studies in a large group are required to determine the pathophysiological and prognostic implications of increased arterial stiffness in BD.
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