RESEARCH - Endothelial dysfunction and atherosclerosis in RA: a multiparametric analysis using imaging techniques and lab markers of inflammation and autoimmunity

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J Rheumatol. 2008 Jan 15 [Epub ahead of print]

Endothelial Dysfunction and Atherosclerosis in Rheumatoid Arthritis: A

Multiparametric Analysis Using Imaging Techniques and Laboratory Markers of

Inflammation and Autoimmunity.

Kerekes G, Szekanecz Z, Dér H, Sándor Z, Lakos G, Muszbek L, Csipö I, Sipka

S, Seres I, Paragh G, Kappelmayer J, Szomják E, Veres K, Szegedi G,

Shoenfeld Y, Soltész P.

From the Cardiovascular Unit, Division of Rheumatology, and Laboratory of

Immunology, Third Department of Medicine; Department of Pathology; Center

for Clinical Research; Division of Metabolic Diseases, First Department of

Medicine; and Department of Clinical Biochemistry and Molecular Pathology,

University of Debrecen Medical and Health Science Center; Research Center

for Autoimmune Diseases, Hungarian Academy of Sciences, Debrecen, Hungary;

and the Department of Medicine B and Center for Autoimmune Diseases, Sheba

Medical Center, Tel-Hashomer, Israel.

OBJECTIVE: Cardiovascular disease is a leading cause of mortality in

rheumatoid arthritis (RA). Endothelial dysfunction often precedes manifest

atherosclerosis. We assessed endothelial dysfunction and atherosclerosis in

RA in context with laboratory markers. METHODS: Fifty-two patients with RA

and 40 matched healthy controls were studied. We assessed common carotid

intima-media thickness (ccIMT) and flow- (FMD) and nitroglycerine-mediated

vasodilation (NMD). We also assayed numerous immunological and metabolic

laboratory markers. RESULTS: FMD was significantly lower in RA (5.32% +/-

4.66%) compared to controls (8.30% +/- 3.96%) (p = 0.001). NMD was preserved

in RA. ccIMT was significantly greater in patients with RA (0.63 +/- 0.14

mm) versus controls (0.54 +/- 0.15 mm) (p = 0.012). In patients with RA,

ccIMT correlated with FMD% (R = -0.318, p = 0.022), age (R = 0.831, p <

0.001), and anti-dsDNA levels (R = 0.463, p = 0.006). FMD% correlated with

serum interferon-gamma (IFN-gamma) levels (R = 0.516, p = 0.014). NMD%

correlated inversely with the percentage of Th0 lymphocytes (R = -0.636, p =

0.006), serum immune complex (R = -0.692, p < 0.001), and IgM levels (R =

-0.606, p = 0.003). Patients with RA were divided as " low " (< 0.65 mm)

versus " high " (> 0.65 mm) ccIMT groups, and into " normal " (> 5%) versus

" impaired " (< 5%) FMD% subsets. Low and high ccIMT groups differed

significantly in age and serum interleukin 1 (IL-1) and anti-dsDNA levels.

RA patients with normal versus impaired FMD% differed significantly in age,

disease duration, and serum IFN-gamma levels. Lipoprotein(a) [Lp(a)] also

correlated with rheumatoid factor (RF) and C-reactive protein (CRP);

homocysteine (HCy) correlated with CRP and correlated inversely with folate

and vitamin B12 production. Paraoxonase-1 (PON-1) activity correlated with

serum tumor necrosis factor-alpha(TNF-alpha) and IL-6 levels. CONCLUSION:

This was a well characterized RA population, where FMD and ccIMT were

impaired, indicating early endothelial dysfunction and accelerated

atherosclerosis, respectively. RA-related autoimmune-inflammatory mechanisms

and metabolic factors including anti-CCP, RF, CRP, circulating immune

complexes, IgM, TNF-alpha, IL-6, Th0/Th1 ratio, HCy, folate, vitamin B12,

and PON-1 may all be involved in the development of vascular disease in RA.

Although ccIMT and FMD, as well as some laboratory factors, have been

assessed by other investigators in RA-associated atherosclerosis, our

results regarding the possible involvement of anti-CCP, anti-dsDNA, Lp(a),

some cytokines, and PON-1 activity are novel. Early determination of FMD%

and ccIMT may be useful to assess RA patients with high cardiovascular risk.

PMID: 18203326

http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve & db=PubMed & list_uids=18

203326

Not an MD