According to the Chapel Hill Consensus Conference, large peripheral arteries are only affected by giant cell vasculitis and, in rare cases, by polyarteritis nodosa.^1,2 Vasculitis becomes apparent through involvement of typical organs (lung, kidney, skin) or raised C reactive protein (CRP) level or erythrocyte sedimentation rate (ESR). Thus, a specific diagnostic effort to exclude vasculitis as an underlying disease in patients with peripheral arterial occlusive disease (PAOD) may be unnecessary. On the other hand, there is increasing evidence that humoral immunity may have a role in the pathogenesis of atherosclerosis.^1,2,9 Antinuclear antibodies were reported in 70% of patients with severe coronary heart disease (CHD), compared with in only 17% in the control group.³ Thus, we prospectively studied the importance of autoantibody determination in patients with symptomatic PAOD.

METHODS AND RESULTS

Six hundred and ninety eight patients (mean (SD) age 68 (10) years) referred for treatment of PAOD between 1998 and 1999 were included. In 121 patients with PAOD (aged 61 (12) years) with a low atherosclerotic risk profile, or with rarefied distal arteries without media calcinosis, or with raised ESR or CRP not due to a local infection, the following autoantibodies were determined: antinuclear antibodies (ANA) by an indirect immunofluorescence technique; antibodies against extractable nuclear antigens (Scl-70, RNP, SSA, SSB, Jo-1, SM) by western blot; double stranded DNA antibodies, antineutrophil cytoplasmic antibodies (c- and pANCA), and antiphospholipid antibodies (cardiolipin, phosphatidylserine (APSA), and β₂-glycoprotein) by enzyme linked immunoassay. To stratify the importance of autoantibody determination all patients with increased autoantibody concentration were clinically and sonographically followed up for 24 (6) months for evidence of vasculitides or collagen disease. A multivariate logistic regression analysis was performed to evaluate the importance of CRP and ESR in patients with autoantibody concentrations above the appropriate reference value.

Thirty eight of the 121 patients had increased autoantibody concentrations (table 1). ANA were the most common autoantibodies detected in 14 patients followed by APSA in 11, and β₂-glycoprotein antibodies in 12. Patients with increased autoantibody concentration did not differ in their PAOD stages and affected segments, but in patients with increased autoantibody concentrations the ESR was higher (p = 0.0043). The ESR at 2 hours was associated with an odds ratio of 7.1 (95% confidence interval 1.5 to 33.8) in determination of increased autoantibody concentrations. During the follow up of 24 (6) months no vasculitides or collagen diseases could be detected by clinical examination or by nailfold capillary microscopy, pulmonary or gastrointestinal imaging in the 38 patients.

DISCUSSION

The group of 121 patients with PAOD analysed is a group selected individually from all the patients, but represents those patients in whom possible vasculitis may be present. Raised concentrations of autoantibodies were common in the patients investigated. Increased autoantibody concentrations significantly correlated with a raised ESR.

As far as we know, our data are the first to report the results of autoantibody determinations in a large group of patients with PAOD. In contrast with the high rate of ANA in patients with coronary atherosclerosis,^6–8 the prevalence of ANA in our patients with PAOD was much lower. Whether this difference in the prevalence of ANA was due to different forms of atherosclerosis, or due to specific differences in coronary and peripheral manifestations can only be speculated.

In agreement with the coronary studies, no association of the determined autoantibodies with classical risk factors was found. The higher ESR in the patients with increased autoantibody concentrations might be associated with a higher degree of inflammatory activity of the atherosclerosis. Antiphospholipid and β₂-glycoprotein antibodies, which are most relevant in association with atherosclerosis, did not seem to lead to a prognosis,^7–9 but antibody determination in larger groups of non-selected patients is desirable.