Identification of novel biomarkers for the prediction of subclinical coronary artery atherosclerosis in patients with rheumatoid arthritis: an exploratory analysis.

BACKGROUND: Cardiovascular (CV) risk estimation calculators for the general population underperform in patients with rheumatoid arthritis (RA). The purpose of this study was to identify relevant protein biomarkers that could be added to traditional CV risk calculators to improve the capacity of coronary artery calcification (CAC) prediction in individuals with RA. In a second step, we quantify the improvement of this prediction of CAC when these circulating biomarkers are added to standard risk scores. METHODS: A panel of 141 serum and plasma proteins, which represent a broad base of both CV and RA biology, were evaluated and prioritized as candidate biomarkers. Of these, 39 proteins were selected and measured by commercial ELISA or quantitative mass spectroscopy in 561 individuals with RA in whom a measure of CAC and frozen sera were available. The patients were randomly split 50:50 into a training/validation cohort. Discrimination (using area under the receiver operator characteristic curves) and re-classification (through net reclassification improvement and integrated discrimination improvement calculation) analyses were performed first in the training cohort and replicated in the validation cohort, to estimate the increase in prediction accuracy for CAC using the ACA/AHA (American College of Cardiology and the American Heart Association) score with, compared to without, addition of these circulating biomarkers. RESULTS: The model containing ACC/AHA score plus cytokines (osteopontin, cartilage glycoprotein-39, cystatin C, and chemokine (C-C motif) ligand 18) and plus quantitative mass spectroscopy biomarkers (serpin D1, paraoxonase, and clusterin) had a statistically significant positive net reclassifications index and integrated discrimination improvement for the prediction of CAC, using ACC/AHA score without any biomarkers as the reference category. These results were confirmed in the validation cohort. CONCLUSION: In this exploratory analysis, the addition of several circulating CV and RA biomarkers to a standard CV risk calculator yielded significant improvements in discrimination and reclassification for the presence of CAC in individuals with RA.

Significance of Crescentic Glomeruli in Acute Kidney Injury with Rheumatoid Arthritis.

Crescentic glomerulonephritis (GN) without immune reactants or deposits (referred to as pauci-immune) is typically characterized by the presence of anti-neutrophilic cytoplasmic antibodies (ANCA). While ANCA-negative patients might be expected to have a more benign course, they often have poor renal outcomes, especially without treatment with steroids and immune-modulating therapy. Pauci-immune crescentic GN can also co-exist with other autoimmune conditions, including rheumatoid arthritis (RA). Here, we describe an ANCA-negative patient with RA who developed dialysis-requiring acute kidney injury (AKI) with findings consistent with focal pauci-immune crescentic GN (i.e., no IgG or immune complex on kidney biopsy). Coexistent conditions included Klebsiella sepsis attributed to pneumonia, rhabdomyolysis, leukocytoclastic immune-mediated skin vasculitis, and positive ANA. He had spontaneous improvement in renal function without immunosuppressive therapy. This crescentic GN was not associated with poor renal outcome as AKI resolved with supportive care and treatment of his infection. The AKI was likely multifactorial with co-existing acute tubular necrosis in the setting of Kebsiella sepsis and rhabdomyolysis, and the crescentic GN was felt more likely to be related to the infection rather than having a primary role. This case highlights the importance of viewing crescentic GN in the context of the clinical picture, as it may not always lead to the need of aggressive immune suppression and is not a universally poor prognostic kidney finding. However, these cases do warrant close follow-up as our patient had recurrent RA disease manifestations over the next 2 years that eventually led to his death from severe pulmonary hypertension.

Exploring the Lipid Paradox Theory in Rheumatoid Arthritis: Associations of Low Circulating Low-Density Lipoprotein Concentration With Subclinical Coronary Atherosclerosis.

OBJECTIVE: Rheumatoid arthritis (RA) patients with the lowest circulating low-density lipoprotein (LDL) concentrations are at heightened risk of cardiovascular events. However, the atherosclerosis burden within this subgroup is unknown. METHODS: RA patients pooled from 4 cohort studies of cardiovascular disease (CVD; n = 546) were compared with non-RA controls from the Multi-Ethnic Study of Atherosclerosis (n = 5,279). Those taking lipid-lowering medications were excluded. Differences in cardiac computed tomography-derived Agatston coronary artery calcium (CAC) scores between the RA and control groups were compared across strata of LDL concentration. RESULTS: Among those with low LDL concentrations (<70 mg/dl), mean adjusted CAC scores were >4-fold higher for RA patients than for controls (18.6 versus 4.6 Agatston units, respectively; P < 0.001), a difference significantly greater than that in any other LDL concentration stratum except LDL concentration ≥160 mg/dl. Similarly, 32% of the RA patients with low LDL concentration had a CAC score of ≥100 Agatston units compared with only 7% of controls in the same LDL concentration stratum (odds ratio 5.97; P < 0.001), a difference significantly greater than that in all of the other LDL concentration strata. Low LDL concentration was most strongly associated with higher CAC score among RA patients who were white, had ever smoked, or were not obese. Other than a higher frequency of current smokers, RA patients with low LDL concentrations did not have more CVD risk factors or higher measures of RA disease activity or severity than RA patients with higher LDL concentrations. CONCLUSION: RA patients with low LDL concentration may represent a group for whom heightened screening and prevention of atherosclerotic CVD is appropriate.

Systemic Light Chain Amyloidosis Mimicking Rheumatic Disorders.

Secondary amyloidosis can complicate chronic inflammatory autoimmune diseases. However, the clinical findings of primary amyloidosis may mimic those of primary rheumatologic disorders. We present the case of a 53-year-old woman who presented with dystrophic nail changes, dry eyes, bilateral carpal tunnel syndrome, Raynaud's phenomenon, and high titer positive nucleolar pattern antinuclear antibody. She was initially misdiagnosed as having Undifferentiated Connective Tissue Disease (UCTD). On further workup, she was eventually diagnosed with lambda light chain systemic amyloidosis by abdominal fat pad biopsy. Her symptoms completely resolved after autologous stem cell transplantation. With this case, we would like to highlight the similarities in the clinical features between light chain amyloidosis and rheumatological disorders. We would also like to emphasize the importance of the prompt recognition of the clinical features of amyloidosis which are crucial to triggering appropriate diagnostic procedures, since early diagnosis is a key to improving outcomes in this disease with an otherwise poor prognosis.

Managing risks of TNF inhibitors: an update for the internist.

Tumor necrosis factor (TNF) inhibitors have many beneficial effects, but they also pose infrequent but significant risks, including serious infection and malignancy. These risks can be minimized by judicious patient selection, appropriate screening, careful monitoring during treatment, and close communication between primary care physicians and subspecialists.

Effects of golimumab, an anti-tumour necrosis factor-α human monoclonal antibody, on lipids and markers of inflammation.

OBJECTIVES: To assess the effect of golimumab, with or without methotrexate (MTX), on serum lipids and inflammatory markers of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) in two phase 3, randomised, placebo-controlled trials (GO-BEFORE and GO-FORWARD). METHODS: Patients in GO-BEFORE (n=637, MTX-naïve) and GO-FORWARD (n=444, MTX-inadequate response) were randomised to placebo+MTX, golimumab 100 mg+placebo, golimumab 50 mg+MTX, or golimumab 100 mg+MTX. Subcutaneous injections (placebo and golimumab) were given every 4 weeks. Patients with an insufficient response entered early escape at week 16 (GO-FORWARD) or 28 (GO-BEFORE). All placebo+MTX patients in GO-FORWARD crossed over to golimumab 50 mg+MTX at week 24. Changes from baseline to weeks 14 (GO-FORWARD) or 24 (GO-BEFORE), and 52 in serum lipid levels and inflammatory markers were assessed. RESULTS: At week 14 in the GO-FORWARD trial, total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) increased in golimumab+MTX patients versus MTX-only patients (16.00 vs 2.00 (p<0.001); 3.00 vs 0.00 (p<0.05); 8.00 vs 4.00 (p<0.001); respectively); favourable changes in LDL subfractions were only observed in golimumab-treated patients. At week 24 in GO-BEFORE, TC and LDL increased, and LDL subfractions improved in the MTX-only and golimumab+MTX groups. Inflammatory markers of CVD risk improved significantly with golimumab+MTX versus placebo+MTX in both studies and were generally maintained through week 52. Atherogenic indices were generally stable. CONCLUSIONS: While TC and LDL levels increased mildly in RA patients receiving golimumab+MTX, atherogenic indices generally remained stable, favourable changes in LDL subfractions were observed, and inflammatory markers improved.

Tumor necrosis factor α inhibitor use and decreased risk for incident coronary events in rheumatoid arthritis.

OBJECTIVE: To determine the association of tumor necrosis factor α (TNFα) inhibitors with risk for cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients. METHODS: A retrospective cohort of 2,101 incident RA patients was established. Medication exposure was categorized into the following groups: TNFα inhibitors alone or in combination with methotrexate (MTX; aTNF group); MTX alone or in combination with other nonbiologic disease-modifying antirheumatic drugs (DMARDs; MTX group); and no MTX, nonbiologic DMARDs (reference group). Primary outcome was adjudicated incident coronary artery disease (CAD), defined as myocardial infarction, unstable angina, or coronary revascularization procedure. Secondary outcome was adjudicated incident CVD, defined as a composite of CAD, stroke, transient ischemic attack, abdominal aortic aneurysm, peripheral arterial disease, or arterial revascularization procedure. Cox regression models were used to calculate the hazard ratio for CAD and CVD for the aTNF and MTX groups compared to the reference group. RESULTS: There were 46 incident CAD and 82 incident CVD events. Adjusting for covariates associated with CAD and CVD, the hazard ratio for incident CAD was 0.45 (95% confidence interval [95% CI] 0.21-0.96) for the aTNF group and 0.54 (95% CI 0.27-1.09) for the MTX group compared to the reference group. Use of TNFα inhibitors for >16.1 months was associated with a relative risk for CAD of 0.18 (95% CI 0.06-0.50) and for CVD of 0.31 (95% CI 0.15-0.65) compared to the reference group. A similar, although not significant, trend was seen with the MTX group. CONCLUSION: Use of TNFα inhibitors is associated with a decreased risk for CAD in RA; the risk decreases further with long-term use. This should be considered when weighing the risks versus benefits of these medications.

The effect of golimumab on haemoglobin levels in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis.

OBJECTIVE: To evaluate the effect of golimumab on haemoglobin levels in patients with RA, PsA or AS. METHODS: Secondary analysis was performed on integrated data from five randomized controlled studies: three RA, one PsA and one AS (2303 patients total). Golimumab 50 or 100 mg was injected s.c. every 4 weeks with or without MTX. Control groups received placebo injections plus MTX or background therapy. Patients with haemoglobin levels below the age- and sex-specific normal ranges were considered to have anaemia. Ferritin levels were used to distinguish anaemia of mixed aetiology (≥ 15 and <60 ng/ml) and anaemia of inflammation (≥ 60 ng/ml). Changes from baseline to weeks 14 and 24 in haemoglobin level were compared between treatment groups using an analysis of variance on the van der Waerden normal scores. RESULTS: At baseline, 21% of RA patients, 9% of PsA patients and 15% of AS patients had anaemia. Of these, 24%, 57% and 25%, respectively, had anaemia of inflammation. The median increase from baseline to week 14 in the haemoglobin level of anaemic patients was 0.3 g/dl in the control group and 0.9 g/dl in the golimumab group (P < 0.001). Haemoglobin levels improved within the subgroups of patients with anaemia of mixed aetiology (control, 0.4 g/dl vs golimumab, 0.7 g/dl) (P = 0.305) and with anaemia of inflammation (0.2 vs 1.4 g/dl, respectively) (P < 0.001). CONCLUSION: Compared with the control group, patients receiving golimumab treatment had significantly improved haemoglobin levels, particularly among patients with anaemia of inflammation.

Brief report: citrullination within the atherosclerotic plaque: a potential target for the anti-citrullinated protein antibody response in rheumatoid arthritis.

OBJECTIVE: To investigate whether citrullinated proteins within the atherosclerotic plaque can be targeted by anti-citrullinated protein antibodies (ACPAs), forming stimulatory immune complexes that propagate the progression of atherosclerosis. METHODS: Protein lysates prepared from atherosclerotic segments of human aorta were assessed for the presence of citrulline-modified proteins, and specifically citrullinated fibrinogen (Cit-fibrinogen), by immunoprecipitation and/or immunoblotting followed by mass spectrometry. Immunohistochemical analysis of coronary artery plaque was performed to determine the presence of citrullinated proteins and peptidylarginine deiminase type 4 (PAD-4). Serum levels of anti-cyclic citrullinated peptide (anti-CCP), anti-citrullinated vimentin (anti-Cit-vimentin), and anti-Cit-fibrinogen antibodies were measured in 134 women with seropositive rheumatoid arthritis; these subjects had previously been characterized for the presence of subclinical atherosclerosis, by electron beam computed tomography scanning. RESULTS: Western blot analysis of atherosclerotic plaque lysates demonstrated several citrullinated proteins, and the presence of Cit-fibrinogen was confirmed by immunoprecipitation and mass spectrometry. Immunohistochemical analysis showed colocalization of citrullinated proteins and PAD-4 within the coronary artery plaque. In age-adjusted regression models, antibodies targeting Cit-fibrinogen and Cit-vimentin, but not CCP-2, were associated with an increased aortic plaque burden. CONCLUSION: Citrullinated proteins are prevalent within atherosclerotic plaques, and certain ACPAs are associated with the atherosclerotic burden. These observations suggest that targeting of citrullinated epitopes, specifically Cit-fibrinogen, within atherosclerotic plaques could provide a mechanism for the accelerated atherosclerosis observed in patients with RA.

Tumor necrosis factor-α inhibitor use is not associated with lipid changes in rheumatoid arthritis.

OBJECTIVE: To determine the association of use of tumor necrosis factor-α (TNF-α) inhibitors with differences in lipid levels in patients with rheumatoid arthritis (RA). METHODS: We studied 807 patients with incident RA to compare differences in lipid levels in TNF-α inhibitor users versus nonusers, with adjustment for relevant covariables. RESULTS: TNF-α inhibitor use was not associated with differences in levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), triglycerides, LDL:HDL, or TC:HDL compared to nonusers. CONCLUSION: Use of TNF-α inhibitor was not associated with differences in lipid levels in patients with RA.

Perioperative all-cause mortality and cardiovascular events in patients with rheumatoid arthritis: comparison with unaffected controls and persons with diabetes mellitus.

OBJECTIVE: Rheumatoid arthritis (RA) is associated with an increased cardiovascular (CV) burden similar to that of diabetes mellitus (DM). This risk may warrant preoperative CV assessment as is performed for patients with DM. We aimed to determine whether the risks of perioperative death and CV events among patients with RA differed from those among unaffected controls and patients with DM. METHODS: We used 1998-2002 data from the Nationwide Inpatient Sample (NIS) database of the Healthcare Cost Utilization Project (HCUP) to identify hospitalizations of patients undergoing elective noncardiac surgery. Using established guidelines, surgical procedures were categorized as either low risk, intermediate risk, or high risk of having CV events. Logistic models provided the adjusted odds of study end points in patients with RA, DM, or both relative to patients with neither condition. RESULTS: Among 7,756,570 patients undergoing a low-risk, intermediate-risk, or high-risk noncardiac procedure, 2.34%, 0.51%, and 2.12%, respectively, had a composite CV event, and death occurred in 1.47%, 0.50%, and 2.59%, respectively. Among those undergoing an intermediate-risk procedure, death was less likely in RA patients than in DM patients (0.30% versus 0.65%; P < 0.001), but the difference in mortality rates among those undergoing low-risk versus high-risk procedures was not significant. Patients with RA were less likely to have a CV event than were patients with DM for procedures of low risk (3.38% versus 5.30%; P < 0.001) and intermediate risk (0.34% versus 1.07%; P < 0.001). In adjusted models, RA was not independently associated with an increased risk of perioperative death or a CV event. CONCLUSION: RA was not associated with adverse perioperative CV risk or mortality risk, which suggests that current perioperative clinical care does not need to be changed in this regard.

Diabetes mellitus risk in rheumatoid arthritis: reduced incidence with anti-tumor necrosis factor α therapy.

OBJECTIVE: To examine the association of tumor necrosis factor α (TNFα) inhibitor use and the risk of developing diabetes mellitus in a rheumatoid arthritis (RA) inception cohort. METHODS: Adults diagnosed with RA between January 1, 2001, and December 31, 2009, were identified (n = 1,881). Prevalent cases of diabetes mellitus (n = 294) were excluded. Information on sociodemographic data, medical history, body mass index (BMI), laboratory measures, and medications was collected from the electronic health record. Incident diabetes mellitus was defined using the 2010 American Diabetes Association criteria or physician-established diagnosis. Time-varying Cox proportional hazards regression models were used to adjust for age, sex, race, BMI, rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP), erythrocyte sedimentation rate (ESR), and use of nonsteroidal antiinflammatory drugs (NSAIDs), glucocorticoids, hydroxychloroquine, and methotrexate. RESULTS: A total of 1,587 incident RA patients without diabetes mellitus were included. The anti-TNFα users (n = 522) had a lower median age but greater baseline BMI; maximum ESR, RF, and anti-CCP positivity; and NSAID, glucocorticoid, or methotrexate use. The median followup time for the ever and never TNFα inhibitor users was 44.9 months (interquartile range [IQR] 23.7-73.0 months) and 37.1 months (IQR 16.3-65.1 months), respectively (P < 0.001). Of the 91 patients developing diabetes mellitus, 16 were ever and 75 were never TNFα inhibitor users, yielding incidence rates of 8.6 and 17.2 per 1,000 person-years (P = 0.048), respectively. Adjusting for covariates, the hazard ratio for incident diabetes mellitus in TNFα inhibitor users was 0.49 (95% confidence interval 0.24-0.99, P = 0.049) compared to the never users. CONCLUSION: In this inception RA cohort, anti-TNFα use was associated with a 51% reduction in risk of developing diabetes mellitus.

Diabetes mellitus and insulin resistance in patients with rheumatoid arthritis: risk reduction in a chronic inflammatory disease.

OBJECTIVE: To perform a systematic literature review of the potential association among molecular markers of inflammation, alterations in body composition, and insulin resistance (IR), a precursor to type 2 diabetes mellitus (DM), in rheumatoid arthritis (RA) patients. To determine the impact of tumor necrosis factor α (TNFα) as a pivotal proinflammatory cytokine in the pathophysiology of type 2 DM and RA, and the effect of antirheumatic drugs on glycemic control. METHODS: We performed a search of PubMed to identify articles on IR and body habitus in patients with RA. RESULTS: Patients with RA had characteristics placing them at high risk for IR and type 2 DM. The incidence and prevalence of type 2 DM in RA was not clearly increased compared with the general population; however, studies suggested that patients with RA are likely to have IR and have increased risk of cardiovascular disease (CVD). The prevalence of type 2 DM and IR could be estimated from reports of risk factors for CVD in RA patients. The TNFα antagonists provided rapid and effective control of RA-related inflammation. Evidence indicated that extended use of TNFα antagonists in RA may provide the additional benefit of improving insulin sensitivity. These treatment-related changes may contribute to an overall reduction in the risk of type 2 DM and CVD in RA patients. CONCLUSION: Controlling inflammation may improve insulin sensitivity and subsequently reduce the risk of developing type 2 DM in RA patients. This may also reduce the risk of CVD in this high-risk group. Future studies are required to elucidate the relationships between inflammation, body composition, IR, TNFα antagonist use, and the risk of developing type 2 DM in RA patients.

Hydroxychloroquine use and decreased risk of diabetes in rheumatoid arthritis patients.

BACKGROUND/OBJECTIVES: Several studies have associated hydroxychloroquine use with decreased risk of diabetes mellitus (diabetes) or improved glycemic control in rheumatoid arthritis patients, but the studies were small or used data from self-report. The present study sought to replicate this protective relationship in a health system using electronic health records with laboratory data and physician diagnoses. METHODS: This study is a retrospective cohort of 1127 adults with newly diagnosed rheumatoid arthritis and no diabetes within the Geisinger Health System between January 1, 2003, and March 31, 2008. Patients were classified as ever users (n = 333) or never users (n = 794) of hydroxychloroquine. Incident diabetes cases were defined using 2010 American Diabetes Association criteria. RESULTS: The median follow-up times for the ever and never hydroxychloroquine users were 26.0 and 23.0 months, respectively (P = 0.28). The median duration of hydroxychloroquine exposure was 14.0 months. Of the 48 cases developing diabetes during observation, 3 were exposed to hydroxychloroquine at time of development and 45 were nonexposed, yielding incidence rates of 6.2 and 22.0 per 1000 per year (P = 0.03), respectively. In time-varying Cox proportional hazards regression models adjusting for sex, age, body mass index, positive rheumatoid factor and anti-cyclic citrullinated peptide antibodies, erythrocyte sedimentation rate, and nonsteroidal anti-inflammatory drug, glucocorticoid, methotrexate, and tumor necrosis factor α inhibitor use, the hazard ratio for incident diabetes among hydroxychloroquine users was 0.29 (95% confidence interval, 0.09-0.95; P = 0.04) compared with nonusers. CONCLUSIONS: Our findings support the potential benefit of hydroxychloroquine in attenuating the risk of diabetes in rheumatoid arthritis patients. Further work is needed to determine its potential preventive role in other groups at high risk for diabetes.

Patterns of preventive health services in rheumatoid arthritis patients compared to a primary care patient population.

To determine the proportion of rheumatoid arthritis (RA) patients receiving preventive health care according to US Preventive Services Task Force recommendations compared with a community-based population sample, with emphasis on dyslipidemia testing, given the increased risk of cardiovascular disease (CVD) in RA patients. Patients with RA (ICD-9 code 714.0 at ≥2 office visits with a rheumatologist) and a primary care physician (PCP) at the Geisinger Health System (GHS) were identified through electronic health records. The records were searched back from 3/31/08 for the length of time required to satisfy each outcome measure. Percentages were compared with population testing rates using the Pearson Chi-square test. Eight hundred and thirty-one RA patients were compared to 169,476 subjects with a PCP at GHS, stratified by gender and age. Patients with RA were more likely to have had dyslipidemia and osteoporosis testing compared with the general population (86 vs. 75 and 75 vs. 55%, respectively, P < 0.0001 for both). The proportion of RA patients receiving breast and cervical cancer testing was similar to the general population. The majority (79%) of lipid testing was ordered by PCPs. Those RA patients with recommended lipid testing had more traditional CVD factors (hypertension, diabetes, coronary artery disease). RA patients are screened more than the general population for two RA-related co-morbidities, i.e. dyslipidemia and osteoporosis. The RA patients with traditional cardiovascular risk factors are more likely to be tested for dyslipidemia. Further work is warranted to improve testing for modifiable CVD risk factors in this group with multiple co-morbidities.

Treatment of postsurgical pyoderma gangrenosum with a high-potency topical steroid.

Pyoderma gangrenosum is a rare disease characterized by chronic, nonhealing, noninfectious ulcers that can become exacerbated by trauma or manipulation, including surgical treatment. We describe the case of a 30-year-old woman who presented with a large ulcer at the site of an excisional cervical lymph node biopsy; she also had a smaller ulcer at the site of an earlier biopsy that had been previously well healed. The ulcers persisted despite local care, and the larger ulcer was exacerbated by surgical debridement. Histopathology revealed the presence of intense neutrophilic infiltrates with sterile microabscesses-a finding consistent with pyoderma gangrenosum. With 9 weeks of treatment with a high-potency topical steroid, both ulcers gradually healed.

Problems experienced by people with arthritis when using a computer.

OBJECTIVE: To describe the prevalence of computer use problems experienced by a sample of people with arthritis, and to determine differences in the magnitude of these problems among people with rheumatoid arthritis (RA), osteoarthritis (OA), and fibromyalgia (FM). METHODS: Subjects were recruited from the Arthritis Network Disease Registry and asked to complete a survey, the Computer Problems Survey, which was developed for this study. Descriptive statistics were calculated for the total sample and the 3 diagnostic subgroups. Ordinal regressions were used to determine differences between the diagnostic subgroups with respect to each equipment item while controlling for confounding demographic variables. RESULTS: A total of 359 respondents completed a survey. Of the 315 respondents who reported using a computer, 84% reported a problem with computer use attributed to their underlying disorder, and approximately 77% reported some discomfort related to computer use. Equipment items most likely to account for problems and discomfort were the chair, keyboard, mouse, and monitor. Of the 3 subgroups, significantly more respondents with FM reported more severe discomfort, more problems, and greater limitations related to computer use than those with RA or OA for all 4 equipment items. CONCLUSION: Computer use is significantly affected by arthritis. This could limit the ability of a person with arthritis to participate in work and home activities. Further study is warranted to delineate disease-related limitations and develop interventions to reduce them.

C-reactive protein and coronary artery calcium in asymptomatic women with systemic lupus erythematosus or rheumatoid arthritis.

Patients with systemic lupus erythematosus (SLE) and those with rheumatoid arthritis (RA) have increased risk for atherosclerotic cardiovascular disease. The aims of this study were to compare the presence of coronary artery calcium (CAC) in age- and race-matched women with SLE, those with RA, and healthy controls without diabetes mellitus or history of myocardial infarction, angina pectoris, or stroke and to investigate its relation with traditional risk factors, inflammation, and endothelial activation. Study subjects completed cardiovascular risk factor assessment and electron-beam computed tomography that measured CAC. The 2 patient groups had similar prevalence and extent of CAC as well as significantly increased odds of having any CAC (odds ratio 1.87, 95% confidence interval 1.09 to 3.21) and more extensive CAC (odds ratio 4.04, 95% confidence interval 1.42 to 11.56 for CAC score >100) compared with healthy controls. After controlling for differences in cardiovascular risk factors, including insulin resistance and hypertension, the results remained statistically significant. After adjustment for differences in levels of C-reactive protein and/or soluble intercellular adhesion molecule-1, however, women with chronic inflammatory diseases no longer had significantly increased odds of having any CAC or more extensive CAC compared with controls. In conclusion, asymptomatic and nondiabetic women with chronic inflammatory diseases had significantly increased odds of having CAC and more extensive CAC compared with age- and race-matched healthy controls. The increased odds for CAC may in part result from higher levels of inflammation and endothelial activation in these patients.

Effects of postmenopausal hormone therapy on rheumatoid arthritis: the women's health initiative randomized controlled trials.

OBJECTIVE: To study the effects of postmenopausal hormone therapy (PHT) on the incidence and severity of rheumatoid arthritis (RA). METHODS: The Women's Health Initiative randomized controlled trials evaluated the effects of unopposed estrogen (E-alone) and estrogen plus progestin (E+P) compared with placebo on a diverse set of health outcomes over 7.1 and 5.6 years, respectively. RA cases were identified using historical and medication data. The hazard of developing RA was estimated using Cox proportional hazards regression models. Disease symptom severity was estimated using the Short Form 36 (SF-36) and self-reported joint pain scores at baseline and after 1 year. Mean changes in severity were compared using linear regression models. RESULTS: Of the 27,347 participants, 63 prevalent cases and 105 incident cases of RA were identified. A nonsignificant reduction in the risk of developing RA (hazard ratio 0.74; 95% confidence interval [95% CI] 0.51, 1.10) was noted with PHT use. PHT use led to improved SF-36 scores in unadjusted analyses (percent change 12.5%; 95% CI -24.45, -0.57) but not after adjustment for relevant covariates (P = 0.33). Nonsignificant improvements in joint pain scores were seen with PHT use (odds ratio [OR] 4.10; 95% CI 0.83, 20.20). PHT did not improve swelling (OR 1.27; 95% CI 0.08, 19.63) or prevent new joint pains (OR 0.72; 95% CI 0.11, 4.68) in RA participants. CONCLUSION: There were no statistically significant differences in the risk of developing RA or the severity of RA between the PHT and placebo groups.