The objective of this study was to investigate the relationship between insulin resistance (IR) and subclinical atherosclerosis in patients with rheumatoid arthritis (RA). Carotid artery intima media thickness (IMT), using ultrasound evaluation, and other clinical and laboratory variables were investigated in 45 RA outpatients and in 48 controls with soft tissue disorders. IR was assayed by homeostasis model assessment (HOMA2) and metabolic syndrome by National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III) criteria. Insulin resistance, as defined by HOMA2-IR>1, was seen in 40 (88.9%) RA patients and in three (6.2%) controls (p<0.001). No significant difference was detected in the prevalence of metabolic syndrome. The median IMT was greater in RA patients (0.76 mm; interquartile range [IQR] 0.65, 0.85) than in the controls (0.66 mm; IQR 0.60, 0.72) (p<0.001). Dividing the RA patients according to the cut-off IMT value (0.72 mm), a difference was detected in both systolic (p=0.04) and diastolic blood pressure (p=0.02), disease activity score (DAS28) (p=0.008), HOMA2-IR (p<0.001) and cumulative oral steroid dose (p=0.001). Moreover, the frequency of cases with increased IMT was higher in glucocorticoid users than in non-users (21/23 vs. 9/22, respectively) (p<0.001). Spearman's rho correlation showed a significant positive relationship between IMT and HOMA2-IR (p<0.001). Multivariate stepwise analysis selected HOMA2-IR plus diastolic BP plus glucocorticoid exposure as the best predictive model for subclinical atherosclerosis (R2c=0.577, F=21, p<0.001). In conclusion, this study showed a significantly higher prevalence of IR in RA patients and pointed out a significant association between IR and subclinical atherosclerosis. This relationship may be driven primarily by exposure to steroid therapy.

The objective of this work is to investigate the occurrence of atherosclerosis and metabolic syndrome (MetS) in ankylosing spondylitis (AS) patients (pts). Twenty-four consecutive AS pts (men, 87.5%; median age, 50.5 years; median disease duration, 16.5 years), fulfilling the modified 1984 New York criteria for AS criteria, and 19 age- and sex-matched controls were investigated. Clinical atherosclerosis was evaluated by physical examination for cardiovascular (CV) diseases and history or drug use for CV events. Subclinical atherosclerosis was detected by mean intima media thickness (a-IMT) and maximum IMT (max-IMT) of carotid arteries using ultrasonography. Laboratory investigations including fasting plasma glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides were assessed by standard methods, while homocysteine was assessed by chemiluminescence. MetS was assessed using the updated NCEP-ATP III criteria. Disease activity was defined according to the International Ankylosing Spondylitis Assessment Study criteria. The 10-year CV risk (%) profile was evaluated in agreement to the Progetto Cuore criteria. No major CV event was detected in the study population. No significant differences were found when AS pts and controls were compared according to the mean a-IMT (0.52+/-0.26 vs 0.51+/-0.13 mm), max-IMT (0.92+/-0.20 vs 0.85+/-0.39 mm), prevalence of abnormal max-IMT >1 mm (27.2 vs 5.3%), and 10-year CV risk (9.9+/-9.6 vs 3.6+/-1.8%). Systolic blood pressure (p=0.04), triglyceride to HDL cholesterol ratio (p=0.002), and LDL cholesterol (p=0.03) were found significantly higher in AS pts than in controls; on the contrary, HDL cholesterol was pointed out as significantly lower (p<0.001). MetS was found in 11/24 (45.8%) AS pts and in 2/19 (10.5%) controls (p=0.019). No significant relationship emerged in MetS prevalence among AS pts regarding the mean value of age, disease duration, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Disease Activity Index, and the Italian version of Health Assessment Questionnaire. This preliminary report points out a higher prevalence of MetS in AS pts than in controls. Further studies are needed to confirm this finding.

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Objective. To evaluate the treatment duration with MTX monotherapy or in association with DMARDs or anti TNFa inhibitors and the incidence and typology of adverse events (AE) occurred in rheumatoid arthritis (RA) patients. Methods. A retrospective large cohort study of RA outpatients, consecutively seen from January 2000 to June 2005 was performed. Study group were RA patients classified according to the 1984 ACR criteria for the classification of rheumatoid arthritis. The patients were divided in 3 groups according to the treatment regimen: MTX monotherapy, MTX in combination with DMARD or with anti TNFa agents. We analyzed 348 therapeutic cycles, 177 of whom using MTX monotherapy. Results. The 224 RA patients accumulated 800 person-years of follow up. Follow up for each of the groups was: MTX monotherapy 479.4 person-years, MTX in combination with DMARDs 244.5, or with anti TNFa inhibitors, 75.7 person- years. From the Kaplan-Meier analysis, the probability of patients remaining on treatment 5 years was 58.5 after starting MTX. The incidence of any AE was 8.87 per 100 person-years. From all, 69 (97.2%) AE were no severe. Among those, more frequently were observed at gastrointestinal tract (31%), liver (19.7%), skin (15.5%). Incidence of severe AE (lung adenocarcinoma, 1 case; pancreatitis, 1 case) was 0.25 per 100 person-years, occurring in patients taking MTX monotherapy or MTX in combination with DMARDs, respectively. Conclusions. These data confirm that methotrexate is well tolerated in clinical practice in the medium-long term. Nevertheless, the occurrence of severe AE require an accurate vigilance for methotrexate toxicity