Rheumatology Advance Access originally published online on October 13, 2006
Rheumatology 2006 45(12):1580-1581; doi:10.1093/rheumatology/kel349
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Traditional cardiovascular risk factors in primary Sjögren's syndrome—role of dyslipidaemia
1Rheumatology Unit and 2Section of Internal Medicine, Angiology & Atherosclerosis Diseases, Department of Clinical & Experimental Medicine, University of Perugia, Italy, 3Department of Internal Medicine, VillaMarina Hospital, Piombino, Italy and 4Department of Medicine B and Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel Aviv University, Tel-Hashomer, Israel
Correspondence to: R. Gerli, MD, Rhematology Unit, Section of Internal Medicine and Oncological Sciences, Policlinico Monteluce, 1-06122 Perugia, Italy. E-mail: gerlir{at}unipg.it
SIR, The development of precocious atherosclerosis with its consequences on cardiovascular (CV) mortality in some rheumatic diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), is well established [1]. Although there is evidence that both the disorders represent an independent risk factor for CV disease, it is thought that traditional risk factors, including dyslipidaemia, also may contribute to accelerated atherosclerosis in these patients [1]. Primary Sjögren's syndrome (SS) is a systemic autoimmune disorder characterized by chronic inflammation of exocrine glands. Although it is not clear if an increase in CV death occurs in this disorder [2], SS may represent an interesting model to study the factors involved in early development of atherosclerosis. It shares, indeed, a number of clinical and serological features typical of both RA and SLE, but, unlike these disorders, it does not often need treatments, which may influence the CV risk profile of these subjects, because of a frequently indolent course of the disease.
Lodde et al. [3] recently described lower levels of total and high-density lipoprotein (HDL) cholesterol in patients with primary SS with respect to those of xerostomic control subjects. This datum confirms, at least in part, the results of our study showing reduced levels of HDL, but not total, cholesterol in 37 women with primary SS compared with 35 age-matched control females ([4] and Table 1). Similar to the Lodde's study, we failed to find differences in low-density lipoprotein (LDL) cholesterol, triglycerides, non-HDL cholesterol, total/HDL and LDL/HDL cholesterol ratio and high-risk HDL cholesterol levels between patient and control groups (data not shown). It is intriguing, however, that an association between anti-SSA/SSB antibodies and altered cholesterol levels was found in the Lodde's study. We performed, therefore, a post hoc analysis of lipid levels in our series by selecting the SS patient subset with evidence of circulating anti-SSA (71% also anti-SSB+). As shown in Table 1, the patients with anti-SSA/SSB antibodies had lower levels of total and HDL cholesterol and increased high-risk HDL cholesterol levels than control subjects, thereby confirming an association between dyslipidaemia and SS-specific autoantibodies.
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The finding of dyslipidaemia, and in particular low level of HDL cholesterol in SS, is of great interest, but raises some critical questions. As reminded by Lodde, similar findings have been found in both RA and SLE and it is conceivable that they may be the results of chronic inflammation. However, we do not believe that the presence of specific autoantibodies, such as anti-SSA/SSB, may reflect SS disease activity, as Lodde states. Unlike RA, where higher levels and frequent peaks of inflammation often occur, primary SS is usually characterized by chronic but milder inflammation than RA, as our study confirms [4]. This may justify the lack of correlation between HDL cholesterol and C-reactive protein [3], also confirmed in our series (data not shown). Although there are not yet established criteria of disease activity in SS, anti-SSA/SSB antibodies represent a disease marker useful to define the diagnosis, more than the activity of the disease. It has been shown, however, that these autoantibodies identify younger SS patients at the diagnosis with more evident T-cell dysregulation, lower number of circulating leukocytes, more extensive glandular infiltrate and more frequent extraglandular manifestations compared with SS subjects without circulating anti-SSA/SSB [5–7]. In other words, these antibodies appear to represent a marker of the autoimmune dysregulation which characterizes a subset of SS patients and it is not surprising, therefore, that altered lipid profile, similar to that seen in SLE and RA, has been found essentially in this SS patient subgroup. Increased serum levels of IgG, reflecting B-cell hyperactivity of these subjects, were predicted by HDL cholesterol in the Lodde's study. In our patients, mean levels of serum IgG in SS patients with high-risk HDL cholesterol levels were higher than the levels found in patients with normal HDL cholesterol (2077± 578 mg/dl vs 1690± 588 mg/dl, P< 0.05). Both observations suggest an association between hypergammaglobulinaemia and low HDL cholesterol levels and may be intriguing to test the hypothesis of the presence of circulating anti-HDL cholesterol antibodies in these patients.
The most critical question raised by Lodde's study, however, is the possible role exerted by this lipid alteration in favouring acceleration of atherosclerosis in SS. In fact, we showed that primary SS patients have subclinical atherosclerosis-related changes of the carotid arterial wall similar to RA and SLE subjects [4]. However, carotid intima-media thickening was associated with anti-SSA antibodies and leukopenia, but not with altered cholesterol levels [4].
In conclusion, there is evidence that primary SS patients have both early subclinical atherosclerosis and altered lipid profile with potential atherosclerotic risk. Both are associated with the presence of disease-specific autoantibodies, but the role of dyslipidaemia in favouring organic arterial wall damage in these patients appears to be marginal. In our opinion, it is conceivable that different, probably immune-mediated, mechanisms play a key role in determining the acceleration of atherosclerosis in SS.
The authors have declared no conflicts of interest.
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[Abstract/Free Full Text]
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