Rheumatoid Arthritis: Galarraga B

Galarraga B, Khan F, Kumar P, Pullar T, Belch JJ. · Institute of Cardiovascular Research, Vascular and Inflammatory Diseases Research Unit, University Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. · Rheumatology (Oxford). · Pubmed #18854346 No free full text.

Abstract: OBJECTIVE: RA is a chronic autoimmune inflammatory condition associated with increased cardiovascular morbidity and mortality. Endothelial dysfunction, a marker of early atherosclerotic disease, occurs in some inflammatory diseases but this relationship has not been previously explored within the microvasculature of patients with RA. We therefore assessed forearm microvascular endothelial function in patients with RA and determined its relationship to RA disease activity and inflammation. METHODS: A total of 128 RA patients with no previous history of cardiovascular disease were evaluated. Endothelium-dependent and -independent forearm skin microvascular function was measured using laser Doppler imaging after iontophoretic delivery of acetylcholine (ACh) and sodium nitroprusside (SNP), respectively. Parameters of RA disease activity and inflammation were also checked. RESULTS: There was a significant negative correlation between the level of inflammation measured by log(10)CRP and maximum vasodilatation measured by peak ACh response (r(2) = -0.209, P = 0.018, Pearson correlation test). In a multiple regression model, age (beta = -0.449, P < 0.0001) and log(10)CRP (beta = -0.193, P = 0.026) were independently negatively associated with ACh responses. When RA patients were sub-divided according to their systemic inflammatory status (CRP > 10 mg/l vs CRP </= 10 mg/l), the high CRP group showed lower vasodilator responses to ACh [P = 0.018, analysis of variance (ANOVA)] and SNP (P = 0.05, ANOVA) than the low CRP group. CONCLUSIONS: In this large cross-sectional study, we found for the first time systemic inflammation (CRP) to be independently associated with microvascular dysfunction in patients with RA. This strong correlation was independent of other conventional vascular risk factors.

Galarraga B, Ho M, Youssef HM, Hill A, McMahon H, Hall C, Ogston S, Nuki G, Belch JJ. · Vascular and Inflammatory Diseases Research Unit, University Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. · Rheumatology (Oxford). · Pubmed #18362100 links to  free full text

Abstract: OBJECTIVES: Dose-dependant gastrointestinal and cardiovascular side-effects limit the use of NSAIDs in the management of RA. The n-3 essential fatty acids (EFAs) have previously demonstrated some anti-inflammatory and NSAID-sparing properties. The objective of this study was to determine whether cod liver oil supplementation helps reduce daily NSAID requirement of patients with RA. METHODS: Dual-centre, double-blind placebo-controlled randomized study of 9 months' duration. Ninety-seven patients with RA were randomized to take either 10 g of cod liver oil containing 2.2 g of n-3 EFAs or air-filled identical placebo capsules. Documentation of NSAID daily requirement, clinical and laboratory parameters of RA disease activity and safety checks were done at 0, 4, 12, 24 and 36 weeks. At 12 weeks, patients were instructed to gradually reduce, and if possible, stop their NSAID intake. Relative reduction of daily NSAID requirement by >30% after 9 months was the primary outcome measure. RESULTS: Fifty-eight patients (60%) completed the study. Out of 49 patients 19 (39%) in the cod liver oil group and out of 48 patients 5 (10%) in the placebo group were able to reduce their daily NSAID requirement by >30% (P = 0.002, chi-squared test). No differences between the groups were observed in the clinical parameters of RA disease activity or in the side-effects observed. CONCLUSIONS: This study suggests that cod liver oil supplements containing n-3 fatty acids can be used as NSAID-sparing agents in RA patients.

McLaren M, Waring A, Galarraga B, Rudd A, Morley K, Belch JJ. · Vascular Diseases Research Unit, The Institute of Cardiovascular Research, Department of Medicine, Ninewells Hospital and Medical School, Dundee, Scotland, UK. · Scand J Rheumatol. · Pubmed #16393764 No free full text.

Abstract: OBJECTIVES: Previous work has shown that the human platelet antigen (HPA) 1b polymorphism of platelet glycoprotein IIIa (GPIIIa) is implicated in the development of ischaemic vascular disease. HPA1b positive platelets have a lower threshold for activation and may exert a greater thrombotic tendency than those without the 1b allele. However, platelets heterozygous for the polymorphism are also more sensitive to aspirin than those homozygous for the 1b allele, which have a similar sensitivity to those without the 1b allele. A flow cytometric method has become available to identify this polymorphism. The aim of our study was to evaluate the use of this assay in patients with rheumatoid arthritis (RA) and to determine the incidence of the 1b allele in these patients. We also compared platelet aggregation and platelet/white blood cell interaction in patients with or without this polymorphism. METHODS: We enrolled 99 patients and measured platelet aggregation in whole blood and platelet-rich plasma (prp), platelet/white blood cell interaction and C-reactive protein (CRP). RESULTS: Thirty-four of the 99 patients were unsuitable for analysis because their baseline expression of GPIIIa was outwith the normal range, making the results outwith the limits of the flow cytometric method. The incidence of the 1b allele in the patients was 29%, with incidence being higher in females, although this failed to reach statistical significance. The number of circulating platelet aggregates and adenosine diphosphate (ADP)-induced aggregation in prp was significantly higher in those patients with the 1b allele. CONCLUSIONS: This method may be of use as an initial screening test.