Common atherosclerosis genetic risk factors and subclinical atherosclerosis in rheumatoid arthritis: the relevance of disease duration.

Rheumatoid arthritis (RA) is a common systemic autoimmune disease characterized by increased cardiovascular morbidity. Several previous studies assessed associations between common atherosclerotic genetic risk factors and subclinical atherosclerosis (SA) in RA patients, yet most of them gave negative results. We undertook a cross-sectional study to evaluate the association between previously reported SNPs and subclinical atherosclerosis in a cohort of Polish RA patients. 29 SNPs associated with atherosclerosis in general population were genotyped in 289 RA patients: 116 patients with SA (increased carotid intima-media thickness and/or presence of carotid plaque) and 173 patients without SA. To assess the cumulative effect of SNPs we calculated 3 weighted genetic risk scores: GRSIMT, GRSCP and GRSCAD, comprising intima-media thickness-associated SNPs, carotid plaque-associated SNPs and coronary artery disease-associated SNPs, respectively. None of the SNPs showed a significant association with SA. However, we found an association between SA and GRSIMT. Interestingly, this association was limited to patients with short disease duration (P = 0.00004 vs. P > 0.5, for comparison of GRSIMT among patients within the 1st quartile of disease duration vs. others, respectively). Patients within the 1st quartile of disease duration were more frequently disease modifying anti-rheumatic drugs (DMARDs)-naïve and less frequently treated with biologics. Our study suggests that in patients with early RA subclinical atherosclerosis may be driven by similar genetic factors as in general population, while in long-lasting disease, the role common genetic risk factors may decrease. Possibly, this effect may be due to the influence of DMARDs.

Prevalence of Atherosclerosis in diabetic and non-diabetic patients with rheumatoid arthritis.

OBJECTIVES: (1) To compare the prevalence of preclinical atherosclerosis in diabetic vs. non-diabetic rheumatoid arthritis (RA) patients; (2) to determine the influence of classical and RA-related factors on atherosclerosis; (3) to assess the usefulness of combined carotid and femoral ultrasonography in detecting atherosclerosis. METHODS: The study comprised 42 non-diabetic RA patients, 42 diabetic RA patients and 42 controls. Intima media thickness (IMT) was measured in the common carotid and superficial femoral arteries. These vessels were screened for atherosclerotic plaque. RESULTS: Plaque was more prevalent in diabetic RA patients than in non-diabetic RA patients or controls. Carotid IMT and femoral IMT were higher in diabetic RA patients compared to controls. So was femoral IMT in diabetic compared to non-diabetic RA patients. The prevalence of increased IMT and plaque was comparable in carotid ultrasonography and combined carotid and femoral ultrasonography in all groups. CONCLUSIONS: Subclinical atherosclerosis was found to be higher in diabetic RA patients than in non-diabetic RA patients. The combination of carotid and femoral artery ultrasonography did not improve the detection of atherosclerosis in RA.

Systemic lupus erythematosus: the influence of disease-related and classical risk factors on intima media thickness and prevalence of atherosclerotic plaques--a preliminary report. Beneficial effect of immunosuppressive treatment on carotid intima media thickness.

OBJECTIVE: The risk of cardiovascular disease is increased in systemic lupus erythematosus (SLE). A meta-analysis showed increased carotid intima media thickness (IMT) in SLE. The aim of this study was to assess the influence of different SLE characteristics and treatment regimens on IMT and atherosclerotic plaques. METHODS AND RESULTS: One hundred and three SLE patients and 95 age- and sex-matched control subjects were included in the study. MT was measured in the common carotid arteries bilaterally. Common carotid arteries, internal carotid arteries and superficial femoral arteries were also screened for the presence of plaques. The presence of plaques was correlated with age (P = 0.00002), male sex (P = 0.034), Framingham 10-year risk score (P < 1 x 10(-6)), SLE duration (P = 0.00006), lack of immunologic disorder (P = 0.0014) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (P = 0.049). IMT was associated with SLE duration (P = 0.002), body mass index (P = 0.026), Framingham 10-year risk score (P < 0.001), total cholesterol concentration (P = 0.002), LDL cholesterol concentration (P = 0.007), SLICC/ACR (P = 0.035), hypertension (P = 0.002), immunologic disorder (P = 0.00008) and discontinuous treatment with immunosuppressive drugs (P = 0.043). CONCLUSIONS: We found a correlation between atherosclerosis and several classical cardiovascular risk factors and disease-related factors. A beneficial effect of continuous immunosuppressive treatment on IMT suggests that appropriate disease control with steroid-sparing agents may protect against atherosclerosis in SLE patients.

Methotrexate, Cyclosporine A, and Biologics Protect against Atherosclerosis in Rheumatoid Arthritis.

INTRODUCTION: The risk of cardiovascular disease is increased in rheumatoid arthritis (RA). A meta-analysis showed increased intima media thickness (IMT) in RA. It has been shown that disease modifying antirheumatic drugs (DMARDs) may influence the progression of atherosclerosis. However, it was suggested that biologics may be more efficient than other DMARDs (including methotrexate--MTX) in protecting against atherosclerosis. OBJECTIVES: The aim of this study was to assess the influence of different RA characteristics and treatment regimens on IMT and atherosclerotic plaques. PATIENTS AND METHODS: 317 RA patients and 111 controls were included in the study. IMT was measured in carotid (CIMT) and femoral (FIMT) arteries. Arteries were screened for the presence of plaques. RESULTS: CIMT, FIMT, and prevalence of plaques were lower in patients treated with methotrexate (MTX) ≥ 20 mg/wk, cyclosporine (CsA), or biologics than in patients treated with lower doses of MTX and other disease modifying antirheumatic drugs. No differences in IMT between patients treated with MTX ≥ 20 mg/wk, biologics, or CsA were found. CONCLUSIONS: We found a beneficial effect of MTX ≥ 20 mg/wk, biologics, and CsA on atherosclerosis. We do not confirm a stronger influence of biologics on IMT compared with therapeutic doses of MTX.

Idiopathic retroperitoneal fibrosis: case report.

A 45-year-old woman was admitted to the hospital because of abdominal pain, fever, and weight loss. Laboratory tests performed on admission revealed raised inflammatory markers. Ultrasonography of the abdomen showed dilatation of the pyelocalyceal system of the left kidney, while computed tomography showed retroperitoneal concentric periaortic mass extending to common iliac arteries and entrapping the left ureter. We established the diagnosis of idiopathic retroperitoneal fibrosis (RPF). JJ catheter was placed in the left ureter, and treatment with corticosteroids and azathioprine was started. Follow-up examinations showed a gradual improvement, namely a progressive remission of the retroperitoneal mass and normalization of both erythrocyte sedimentation rate and C-reactive protein concentration. Case reports, including our paper, and small case series showed azathioprine to be particularly effective in the treatment of RPF.

[The effect of 5-days of cetirizine, desloratadine, fexofenadine 120 and 180 mg, levocetirizine, loratadine treatment on the histamine-induced skin reaction and skin blood flow--a randomized, double-blind, placebo controlled trial]. / Wplyw 5-dniowego stosowania zalecanych dawek cetyryzyny, desloratadyny, feksofenadyny 120 i 180 mg, lewocetyryzyny i loratadyny na pohistaminowa reaktwnosc skóry i przeplyw wltsniczkowy - badanie randomizowane, kontrolowane placebo.

THE AIM: of this study was to compare the effect of the following antihistamines: cetirizine 10mg, desloratadine 5mg, fexofenadine 120 and 180mg, levocetirizine 5mg, loratadine 10mg, and placebo, administered in the recommended doses over the period of 5 days, on the visually assessed histamine-induced skin reaction, using the Laser Doppler flowmetry (LDF). MATERIAL AND METHODS: Forty two volunteers (aged 18-22) who gave a written consent before entering the study, were randomized in seven groups of six subjects each. The skin prick test with histamine solution of 10mg/ml was performed on the ventral forearm, 10 cm from the elbow, before and at 2, 4, 6, 8, 10, 12, 18, and 24 hours after drug administration, as well as once daily for the next 4 days of antihistamine drug or placebo intake, and 9 days following the treatment. Diameters of wheal and flare as well as the LDF index measured with Periflux PF3 flowmeter and skin probe, 5mm from the histamine-provoked area, were assessed 10 minutes after performing the above-mentioned skin prick test. RESULTS: The current study revealed that during the 5-day treatment with recommended doses of cetirizine, desloratadine, fexofenadine, levocetirizine, and loratadine, a significant reduction of histamine-induced wheal, flare and the LDF index was observed as compared to the initial values and placebo intake, reaching the maximum value within the first 24 hours, weakening on the next day, and then gradually increasing during the following days. After the 5-day treatment drugs used for the study were lined up according to the volume of reduction in histamine-induced skin reaction (largest>smallest): levocetirizine > cetirizine > fexofenadine 180mg = fexofenadine 120mg > loratadine = desloratadine. CONCLUSIONS: Following the end of the treatment, the effect of the antihistamines on skin reaction was subsiding in such an order: after 24 hours in case of loratadine and desloratadine, after two days for both doses of fexofenadine, and 3-4 days for cetirizine and levocetirizine.