Mortality risk associated with rheumatoid arthritis in a prospective cohort of older women: results from the Iowa Women's Health Study

OBJECTIVE: To determine whether rheumatoid arthritis (RA) is associated with excess mortality among older women. METHODS: RA associated mortality was examined in a prospective cohort study that was started in 1986, and included 31 336 women aged 55-69 years without a history of RA at baseline. Up to 1997, 158 cases of RA were identified and validated against medical records. The relative risk (RR) and 95% confidence interval (CI) were calculated as measures of association between RA onset and subsequent mortality (overall and cause-specific) using Cox proportional hazards regression. RESULTS: Compared with non-cases, women developing RA during follow up had a significantly increased mortality risk (RR=1.52; 95% CI 1.05 to 2.20). Mortality was higher among rheumatoid factor (RF) positive cases (RR=1.90; 95% CI 1.24 to 2.92) than among RF negative cases (RR=1.00; 95% CI 0.45 to 1.99). There were trends towards increased proportions of RA related deaths from infection (RR=3.61; 95% CI 0.89-14.69) and circulatory disease (RR=1.46; 95% CI 0.76 to 2.81) but not malignancy (RR=0.97; 95% CI 0.46 to 2.04). CONCLUSIONS: RA was associated with significantly increased mortality in a cohort of older women, and the association appeared to be restricted to those with RF positive disease.     

The widening mortality gap between rheumatoid arthritis patients and the general population

OBJECTIVE: Overall mortality rates in the general US population have declined substantially over the last 4-5 decades, but it is unclear whether patients with rheumatoid arthritis (RA) have experienced the same improvements in survival. The purpose of this study was to determine the mortality trends among RA patients compared with those in the general population. METHODS: A population-based incidence cohort of RA patients was assembled, comprising all residents of Rochester, Minnesota ages > or = 18 years in whom RA was first diagnosed (according to the American College of Rheumatology [formerly, the American Rheumatism Association] 1987 criteria) between 1955 and 1995 and all residents of Olmsted County, Minnesota in whom RA was first diagnosed between 1995 and 2000. The patients were followed up longitudinally through their complete (inpatient and outpatient) medical records until death or January 1, 2007. Expected mortality was estimated from the National Center for Health Statistics life tables on the white population in Minnesota, using person-year methods. Poisson regression was used to model the observed mortality rates, adjusting for age, sex, and disease duration. RESULTS: A cohort of 822 RA patients (72% women, mean age at RA incidence 58 years) was followed up for a median of 11.7 years, during which 445 of the RA patients died. Between 1965 and 2005, the mortality rates across the calendar years for female and male RA patients were relatively constant at 2.4 and 2.5 per 100 person-years, respectively. In contrast, the expected mortality rate in the Minnesota white population decreased substantially over the same time period in both sexes. Mortality in the female general population declined from 1.0 per 100 person-years in 1965 to 0.2 per 100 person-years in 2000. Mortality in the male general population decreased from 1.2 per 100 person-years in 1965 to 0.3 per 100 person-years in 2000. Therefore, the difference between the observed and expected mortality rates increased in more recent years, resulting in a widening of the mortality gap. CONCLUSION: Our findings show that RA patients have not experienced improvements in survival over the past 4 decades, despite dramatic improvements in the overall rates of mortality in the general US population. Further research into the causes of the widening gap in mortality between RA patients and the general population, and the influence of current therapeutic strategies on mortality, is needed in order to develop strategies to reduce the excess mortality observed in RA patients.     

Seronegative rheumatoid arthritis, rheumatoid factor cross reactive idiotype expression, and hidden rheumatoid factors.

The major rheumatoid factor cross reactive idiotype (RCRI), defined by prototypic monoclonal rheumatoid factors (RFs), is expressed as a dominant idiotype by pokeweed mitogen induced plasma cells obtained from seropositive (RF+) patients with rheumatoid arthritis (RA). Some patients who meet clinical diagnostic criteria for RA set by the American Rheumatism Association fail to express RFs at any time during their clinical course. To determine if seronegative (RF-) patients with RA, so designated by the latex fixation, Rose-Waaler classic binding assays, or a RF enzyme linked immunosorbent assay (ELISA), express the RCRI in the absence of detectable RFs we examined pokeweed mitogen plasma cells from these patients by indirect immunofluorescence. In addition, we used an inhibition ELISA to detect RCRI bearing molecules in the sera of RF- patients with RA. Five of 10 RF- patients with RA had a high prevalence of RCRI+ plasma cells (16-49% of total pokeweed mitogen plasma cells in culture). Six of 20 RF- patients with RA had high serum concentrations of molecules marked by the RCRI, equivalent to 21-110 micrograms/ml of RCRI+ reference monoclonal IgM RF. Four of five patients who expressed the RCRI in high prevalence in pokeweed mitogen plasma cells, also demonstrated high concentrations of RCRI in their sera detected by inhibition ELISA. There was significant concordance of RCRI expression determined by the two different assays. Four RF- patients with RA who expressed RCRI in their whole sera had hidden RFs detected in their 19S and, in one case, 7S serum fraction. Detection of RF related molecules in whole sera by the expression of RCRI in RF- patients with RA identifies a subgroup of RF- patients with RA who possess hidden RFs. Some RF- patients with RA can express the major RCRI in pokeweed mitogen plasma cells and in their sera and therefore are related to patients with prototypic Waldenstrom's macroglobulinaemia, who produce RCRI+ 19S IgM monoclonal RFs.     

Excess mortality emerges after 10 years in an inception cohort of early rheumatoid arthritis

Objective

To investigate mortality rates, causes of death, time trends in mortality, prognostic factors for mortality, and the relationship between disease activity and mortality over a 23‐year period in an inception cohort of rheumatoid arthritis (RA) patients.

Methods

A prospective inception cohort of RA patients diagnosed between January 1985 and October 2007 was followed for up to 23 years after diagnosis. Excess mortality was analyzed by comparing the observed mortality in the RA cohort with the expected mortality based on the general population of The Netherlands, matched for age, sex, and calendar year. Period analysis was used to examine time trends in survival across calendar time. Prognostic factors for mortality and the influence of the time‐varying Disease Activity Score in 28 joints (DAS28) on mortality were analyzed using multivariable Cox proportional hazards models. Causes of death were analyzed.

Results

Of the 1,049 patients in the cohort, 207 patients died. Differences in observed and expected mortality emerged after 10 years of followup. No improvement in survival was noted over calendar time. Significant baseline predictors of survival were sex, age, rheumatoid factor, disability, and comorbidity. Higher levels of DAS28 over time, adjusted for age, were associated with lower survival rates, more so in men (hazard ratio [HR] 1.58, 95% confidence interval [95% CI] 1.35–1.85) than in women (HR 1.21, 95% CI 1.04–1.42).

Conclusion

Excess mortality in RA emerged after 10 years of disease duration. Absolute survival rates have not improved in the last 23 years and a trend toward a widening mortality gap between RA patients and the general population was visible. Higher disease activity levels contribute to premature death in RA patients.     

Socioeconomic status and the risk of developing rheumatoid arthritis: results from the Swedish EIRA study

OBJECTIVE: To study whether formal education and occupational class are associated with incidence of rheumatoid arthritis overall and with the incidence of the two major subgroups of rheumatoid arthritis-seropositive (RF+) and seronegative (RF-) disease. METHODS: 930 cases and 1126 controls participated in a population based case-control study using incident cases of rheumatoid arthritis, carried out in Sweden during the period May 1996 to June 2001. The relative risk (RR) of developing rheumatoid arthritis with 95% confidence interval (CI) was calculated for different levels of formal education compared with university degree and for different occupational classes compared with higher non-manual employees. RESULTS: SUBJECTS: without a university degree had an increased risk of rheumatoid arthritis compared with those with a university degree (RR = 1.4 (95% CI, 1.2 to 1.8)). For manual employees, assistant and intermediate non-manual employees together, the risk of developing rheumatoid arthritis was about 20% more than for non-manual employees. These increased risks were more pronounced for RF+ than for RF- rheumatoid arthritis and were mainly confined to women. Smoking could not of its own explain the observed associations between risk of rheumatoid arthritis in different socioeconomic groups in Sweden. CONCLUSIONS: There was an association between high socioeconomic status and lower risk of rheumatoid arthritis in a population based investigation that was representative for the Swedish population. The study shows that as yet unexplained environmental or lifestyle factors, or both, influence the risk of rheumatoid arthritis, even in the relatively egalitarian Swedish society.     

Independent association of rheumatoid factor and the HLA-DRB1 shared epitope with radiographic outcome in rheumatoid arthritis

OBJECTIVE: Findings of a recent study suggested that HLA-DRB1 alleles encoding the rheumatoid arthritis (RA) "shared epitope" (SE) were not predictive of erosive damage at 2 years in patients with early inflammatory arthritis who were rheumatoid factor (RF) positive, but were predictive in those who were RF negative. The present study was undertaken to determine whether RF status was also important in the association between the SE and radiographic outcome in patients with longstanding RA. METHODS: The association between radiographic outcome, HLA-DRBI, and RF status was examined in 299 RA patients with established disease (5-30 years). Radiographic outcome was measured by scoring radiographs of the hands and feet using the standard radiographs of Larsen. HLA-DRB1 typing was performed using polymerase chain reaction methodology. Results were stratified by RF status and analyzed by multiple regression. RESULTS: An association between radiographic severity and the SE was found in RF-, but not RF+, patients. RF- patients carrying an SE allele had higher Larsen scores than RF- patients lacking the SE, although there was no association with SE dosage. The mean Larsen score was significantly higher in RF+ patients than in RF- patients, but there were no differences between RF+ patients with 0, 1, or 2 SE alleles. Multiple regression analysis confirmed independent associations of RF and SE positivity with radiographic outcome. No significant associations were found between RF and the SE, or RF and individual SE alleles. CONCLUSION: Our data indicate that RF and the SE are independently associated with radiographic outcome in RA. In RF+ patients with longstanding RA, there is no apparent association between the presence of the SE and radiographic damage. However, in RF-patients, although radiographic outcome is generally less severe, there is an association between severity and presence of the SE.     

Mortality in rheumatoid arthritis. Increased in the early course of disease, in ischaemic heart disease and in pulmonary fibrosis

OBJECTIVE: To examine the cause of death in a large UK inception cohort of rheumatoid arthritis (RA), and whether this was related to disease duration and severity, treatment effects or extra-articular features and complications of RA. METHODS: Standard clinical, laboratory, radiological and socio-economic measures were recorded at baseline and yearly in an inception cohort started in nine centres in 1986. Date and the cause of death were based on death certificates and the comparisons made with age and sex matched population figures. Risk factors for mortality were identified from baseline measures of disease. RESULTS: There were 459 deaths (32%) in 1429 patients followed for up to 18 yrs. Standard mortality ratio was 1.27. Survival was significantly lower in the first 7 yrs of RA. Excess mortality was seen in cardiovascular disease (31%), pulmonary fibrosis (4%) and lymphoma (2.3%). Baseline predictors for mortality were men, older age, poor function, lower socio-economic status, extra-articular features, comorbidity, rheumatoid factor, X-ray erosions, high-ESR and low-haemoglobin. CONCLUSION: There was a modest increase in mortality in RA, mainly in the first 7 yrs. Deaths from cardiovascular disease and pulmonary fibrosis were higher than expected, but treatment-related deaths were low. Risk factors included less favourable socio-economic status, markers of disease severity and diminished function within the first year.     

Regulation of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis: contrasting effects of HLA-DR3 and the shared epitope alleles

OBJECTIVE: To examine the association between HLA-DRB1 alleles and the production of anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) autoantibodies in patients with rheumatoid arthritis (RA). METHODS: We studied 1,723 Caucasian RA patients enrolled in the North American Rheumatoid Arthritis Consortium (NARAC) family cohort and the Study of New Onset Rheumatoid Arthritis (SONORA) cohort. All patients were tested for anti-CCP antibodies (by enzyme-linked immunosorbent assay), RF (by nephelometry), and HLA-DR genotype (by polymerase chain reaction and sequence-specific oligonucleotide hybridization). RESULTS: When controlled for the presence of RF, anti-CCP positivity was strongly associated with the HLA-DRB1 shared epitope (SE). In RF+ patients, the presence of the SE was very significantly associated with anti-CCP positivity, with an odds ratio (OR) of 5.8 and a 95% confidence interval (95% CI) of 4.1-8.3. This relationship was also seen in RF- patients (OR 3.1 [95% CI 1.8-5.3]). In contrast, RF positivity was not significantly associated with presence of the SE independently of anti-CCP antibodies. Strikingly, HLA-DRB1*03 was strongly associated with reduced anti-CCP titers, even after controlling for the presence of the SE and restricting the analysis to anti-CCP+ patients. HLA-DR3 was also associated with anti-CCP- RA in our population. CONCLUSION: The HLA-DRB1 SE is strongly associated with the production of anti-CCP antibodies, but not RF. In contrast, HLA-DR3 alleles are associated with anti-CCP- disease and with lower levels of anti-CCP antibodies, even when controlling for the SE. These data emphasize the complexity of the genetic effects of the major histocompatibility complex on the RA phenotype.     

Cardiovascular mortality in patients with rheumatoid arthritis

Patients with rheumatoid arthritis (RA), 500 men and 500 women, aged 40 years and over, together with a control population matched by age and sex were followed up with respect to cause-specific mortality over a 10-year period. The overall mortality was significantly higher in both men and women with RA than in the controls. A statistically significant increase in mortality from all cardiovascular diseases (p less than 0.001) and cardiac diseases (p = 0.004) was observed in men with RA but not in women with RA compared to corresponding controls. No difference in mortality from cerebrovascular diseases was observed between RA patients and controls.     

Rheumatoid factor by laser nephelometry and Waaler-Rose assay: prognostic value in patients with recent-onset rheumatoid arthritis

OBJECTIVE: To evaluate the prognostic value of rheumatoid factor (RF), detected in the Waaler-Rose agglutination assay and by nephelometry, in patients with recent-onset rheumatoid arthritis (RA). METHODS: Consecutive patients with new-onset RA between 1993 and 1997 were followed for a median period of 4.7 years. Clinical data at baseline and drug use during the disease course were recorded. Outcome parameters studied were disease process, damage (erosions, joint surgery, extra-articular manifestations, and new co-morbidity), and death. Cut-off levels for RF were >40 IU/mL (nephelometry) and titres 1:160 (Waaler-Rose haemagglutination). RESULTS: RF tests were negative by both methods in 22% of RA patients (RF- group), while 33% were RF positive by nephelometry only (RF+ group) and 45% were positive by Waaler-Rose and nephelometry (RF++ group). Baseline clinical and laboratory findings as well as the number of subsequently used disease-modifying anti-rheumatic drugs (DMARDs), the number of patients starting and the time spent on steroid therapy were similar in the three RF groups. Odd ratios for death (n = 23), erosions (n = 62), and serious extra-articular disease manifestations (EAMs) (n = 13) as well as patient survival, erosion-free or surgery-free survival rates did not differ between the RF groups. Only rheumatoid nodules were more frequent in RF++ patients. CONCLUSION: The baseline presence of RF by either Waaler-Rose or nephelometry was not associated with differences in drug therapy, morbidity other than rheumatoid nodules, or mortality in RA patients in the first 5 years of disease. Being immunoglobulin M (IgM) RF positive thus had little impact on RA patient outcome.     

The prognostic value of the antiperinuclear factor, anti-citrullinated peptide antibodies and rheumatoid factor in early rheumatoid arthritis

OBJECTIVE: To study the prognostic value of the antiperinuclear factor (APF), determined by an indirect immunofluorescence test (IIF) and a recently developed anti-citrullinated cyclic peptide (CCP) ELISA, in combination with rheumatoid factor (RF) status, in early RA (< 1 year). METHODS: A total of 249 participants in a randomized trial of treatment strategies were divided into 4 groups according to their APF (or CCP) and RF status at baseline. Differences in disability, joint involvement and radiological damage over a 3-year period were analysed. RESULTS: APF-IIF results differed from CCP-ELISA in 42 cases (17%); 38 of the 42 had a positive IIF and negative ELISA value. Disability after 3 years did not differ significantly between the RF and APF groups. APF- patients had significantly lower Thompson joint scores compared to APF+ patients (6 vs 24 for CCP-ELISA; 2 vs 24 for IIF). RF+APF+ patients exhibited more radiological damage compared to RF-APF- patients. RF+APF- and RF-APF+ patients had intermediate scores. Within the RF+ and RF- groups, APF+ was associated with more radiological damage and thus yielded prognostic information in addition to RF. In this respect, the results of ELISA and IIF were comparable. Thirty percent of the RF+APF+ patients had a radiological score higher than 45, compared to 13% of the RF+APF-, none of the RF-APF+, and 2% of RF-APF- patients (p < 0.001). In addition, more large joints were affected in APF+ than in APF- patients, while no difference was observed between RF+ and RF- patients. CONCLUSION: APF has prognostic value in addition to RF for joint involvement and radiological damage in early RA. The CCP-ELISA technique for APF assessment may facilitate its use in clinical practice. However, the prognostic value of the two tests lies in their ability to predict mild disease. Reliable identification at baseline of individual patients with progressive disease is still not possible.     

Mortality in rheumatoid arthritis patients with disease onset in the 1980s

OBJECTIVE: Several previous studies have shown increased mortality in rheumatoid arthritis (RA) patients. This study investigated if this was true also for patients with disease onset in the 1980s. PATIENTS AND METHODS: The study group comprised 183 patients (67 men and 116 women) with definite RA participating in an ongoing prospective study. Mean age at onset of disease was 51 years, and mean duration of joint symptoms at inclusion was 11 months. The patients were included between 1985-89. Seventy five per cent of the patients were rheumatoid factor (RF) positive, 85% carried the shared epitope, and 90% became erosive. By 1 September 1997 the number and causes of death, obtained from the death certificates, were recorded. Standardised mortality ratio (SMR) was calculated, comparing the observed number of deaths in the cohort with the expected number of deaths in the general population in the same area, age and sex matched. The predictive values of demographics, genotype, RF status, and clinical data at baseline were estimated using the Cox proportional hazards regression model. RESULTS: Eighteen patients (11 men and 7 women) had died compared with 20 expected deaths. SMR with 95% confidence intervals was 87 (53, 136). There was no significant increase in the number of deaths at any time during follow up for either sex. RA was not the main cause of death in any of the cases. By reading the patient charts two cases were found where RA or its treatment could have contributed to death. No RA related variable contributed significantly to an increased risk of death. CONCLUSION: There was no increased mortality during the first 8-13 years of disease in this group of patients who developed RA in the 1980s.     

Therapeutic strategies in rheumatoid arthritis over a 40-year period

OBJECTIVE: To examine trends in therapeutic strategies and to identify the determinants of starting disease modifying antirheumatic drug (DMARD) therapy over a 40-year period in a population based inception cohort of patients with rheumatoid arthritis (RA). METHODS: A population based inception cohort was assembled from among all Rochester, Minnesota, residents aged > or = 18 years who were first diagnosed with RA (1987 American College of Rheumatology criteria) between January 1, 1955, and January 1, 1995. All subjects were followed longitudinally through their complete medical records until death, migration from Olmsted County, or date of abstraction (January 1, 2001, to January 1, 2003). Drug exposure data were collected on all DMARD and corticosteroid regimens. Time to DMARD initiation was examined using the Kaplan-Meier method. The influence of calendar time and disease characteristics on time from incidence to first DMARD therapy and the number of DMARD regimens were analyzed using Cox regression and proportional odds models, respectively. RESULTS: The study population comprised 603 patients (73% female) with a mean age of 58 years and a mean followup of 15 years. At 2 years after RA onset, 26% of patients in the 1955-74 cohort, 40% in the 1975-84 cohort, and 70% in the 1985-94 cohort had received a DMARD (log-rank p < 0.001). Age, rheumatoid factor (RF) positivity, erythrocyte sedimentation rate, large joint swelling, rheumatoid nodules, and destructive changes on radiographs were significantly associated with time to first DMARD regimen after adjustment for calendar time and sex. Patients who were older and RF positive and who did not receive CS were more likely to have received more DMARD regimens. CONCLUSION: Time to initiation of DMARD therapy has shortened markedly over the past 3-4 decades. These changes in management of early RA provide evidence for the translation of scientific evidence into clinical practice in rheumatology. Age and various disease characteristics are significantly associated with initiation and the number of DMARD regimens used. These should be considered as confounders when examining the effect of early DMARD treatment on disease progression and mortality.     

Survival in rheumatoid arthritis: a population-based analysis of trends over 40 years

OBJECTIVE: To evaluate trends in and risk factors for mortality among patients with rheumatoid arthritis (RA) over a 40-year period. METHODS: A population-based inception cohort was assembled from among all Rochester, Minnesota residents ages > or =18 years who were first diagnosed with RA (fulfilling the 1987 American College of Rheumatology criteria for RA) between January 1, 1955 and December 31, 1994. Patients were followed up longitudinally through their entire medical records (including all inpatient and outpatient care by any provider) until death or migration from the county. Survival was described using the Kaplan-Meier method. Observed and expected survival were compared using the log-rank test, and standardized mortality ratios (SMRs) with expected survival were based on the sex and age of the study population and death rates from the Minnesota life tables. Cox proportional hazards models were used to estimate the influence of extraarticular manifestations and comorbidities, controlling for age, sex, body mass index (BMI), smoking, and rheumatoid factor positivity. RESULTS: Survival in this RA cohort was significantly lower than that expected in the population (P < 0.001) over the entire time period. Patients with RA were at significantly higher risk of death, with an SMR of 1.27 (95% confidence interval 1.13-1.41). Excess mortality among women was more pronounced than among men, with SMRs of 1.41 and 1.08, respectively. Presence of > or =1 extraarticular manifestation was the strongest predictor of mortality after adjusting for age, sex, BMI, smoking, and rheumatoid factor positivity. CONCLUSION: Survival in RA patients is significantly lower than expected. The strongest predictors of survival appear to be those related to RA disease complications, specifically, extraarticular manifestations of the disease and comorbidities. More attention should be paid to mortality as an outcome measure in RA.     

A prospective study on the incidence of rheumatoid arthritis among people with persistent increase of rheumatoid factor

OBJECTIVES: To study the stability of rheumatoid factor (RF) increases and to compare the incidence of rheumatoid arthritis (RA) in people with transient or persistent increase of one or more RF isotypes. METHODS: From an original cohort of nearly 14 000 participants in a population study, 135 previously RF positive persons were recruited in 1996 and evaluated according to the 1987 ACR criteria. The observation time ranged from 9-22 years (mean 16. 5). Blood samples were obtained from all participants at entry and again in 1996. RESULTS: About 40% of the participants who had only one raised RF isotype in the original sample had become RF negative in 1996 compared with only 15% of those with increase of two or three RF isotypes (p=0.002). The seven participants who developed RA during the study period all had persistently raised RF. Six of the 54 participants with more than one RF isotype raised in 1996 developed RA, corresponding to an annual incidence of 0.67%, which was 7.5 times higher than observed in the other participants (p=0. 045). CONCLUSION: Symptom free persons with persistently raised RF have greatly increased risk of developing RA. This suggests that dysregulation of RF production is a predisposing factor in RA.     

Genetic structure of the population with rheumatoid arthritis in north east England: a genetic approach to define different subtypes.

Clinically and immunologically rheumatoid arthritis (RA) is possibly a heterogeneous disorder. Despite numerous efforts clearer definition of this heterogeneity has been of limited success. Measurements of rheumatoid factor (RF) and antinuclear antibodies (ANA) by conventional methods define subpopulations of patients with RA and in a few recent studies an association of human leucocyte antigens (HLA) undoubtedly indicates the immunogenetic differences in the susceptibility of RA patients with different status of autoantibodies. The studies on a few isolated non-HLA genetic markers in RA are controversial. To understand the role of genetic factors in susceptibility 24 single gene characters other than HLA were investigated in 225 patients with RA classified by humoral status (presence or absence of RF and ANA) into three groups and in 104 healthy control individuals from the north east of England. Locus by locus comparison suggested associations of MN, Lewis, and Bf system with RF positive patients. Although the associations with MN and Lewis blood groups require further investigations, the involvement of the Bf locus is in agreement with the immunological component of the disease suggested by HLA associations and it could be due to the phenomenon of linkage disequilibrium. Measures of genetic distance applied to the subpopulations of patients with RA, divided according to the presence or absence of humoral factors, suggest that RF+ ANA+, RF- ANA-, and RF+ ANA- subgroups are distinct genetic diseases, each affecting a different subsection of the population which is genetically distinct. Such genetic heterogeneity may suggest a different pathogenetic mechanism for each of these subpopulations of rheumatoid arthritis.     

The predictive value of rheumatoid factor isotypes, anti-cyclic citrullinated peptide antibodies, and antineutrophil cytoplasmic antibodies for mortality in patients with rheumatoid arthritis

OBJECTIVE: To evaluate the significance of rheumatoid factor (RF) and its isotypes (IgA RF, IgG RF, and IgM RF), anti-cyclic citrullinated peptide antibodies (anti-CCP), and antineutrophil cytoplasmic antibodies (ANCA) in predicting mortality in patients with rheumatoid arthritis (RA). METHODS: The study population comprised 604 patients with RA participating in a cross-sectional study in 1987. Presence of RF (n = 604), RF isotypes (n = 206), anti-CCP (n = 184), and ANCA (n = 200) were determined in these patients from available baseline sera. Vital status was assessed in 1999 and multivariate Cox regression analysis used to compare mortality in RA patients with or without different antibodies. RESULTS: Of the 604 patients with RA, 55% were positive for RF, 66% for anti-CCP, and 14.5% for perinuclear ANCA. Twelve patients (19%) with RF were anti-CCP-negative and 34 (40%) without RF were anti-CCP-positive. Of the total 604 patients, 160 had died by 1999. Positive RF and high IgA and IgM RF levels predicted increased mortality, while positive anti-CCP or ANCA did not. However, high anti-CCP levels were related to an increased mortality risk. CONCLUSION: Patients with RA with positive RF, especially IgA and IgM isotypes, carry a risk of dying earlier than patients without these serological findings.     

Class-specific rheumatoid factors, DR antigens, and amyloidosis in patients with rheumatoid arthritis.

Class-specific rheumatoid factors (RFs) were measured by enzyme immunoassay in 59 patients with rheumatoid arthritis complicated by systemic amyloidosis (RA+A), 47 patients with rheumatoid arthritis without amyloid (RA), 106 patients with other rheumatic diseases (juvenile rheumatoid arthritis, systemic lupus erythematosus, Sjögren''s syndrome), and 55 blood donors. The patients with RA+A were characterised by a high prevalence of RF negativity; the IgM RF concentration was raised in only 18 of the 59 patients (31%, p less than 0.001 v RA), the IgG RF concentration in 20 of 59 (34%, p less than 0.001 v RA), and the IgA RF concentration in 24 of 59 (41%, p less than 0.001 v RA). A higher prevalence of HLA-DR4 (p less than 0.001) and a lower prevalence of DR2 (p less than 0.05) were found among 48 tested patients with RA+A when compared with a control panel consisting of 500 blood donors. No significant differences in the prevalence of DR1-DR7 or B27 antigens were observed, however, between patients with RA with or without amyloid.     

Psychological stress and rheumatoid arthritis in parents after death of a child: a national follow-up study

OBJECTIVE: To examine the risk of rheumatoid arthritis (RA) in parents after the death of a child. METHODS: All 21,062 parents whose child had died (younger than 18 years) between 1980 and 1996 in Denmark were included in the bereaved (exposed) cohort, and 293 745 parents matched on family structure were selected randomly from the general population for the unexposed cohort. RESULTS: We observed 600 incident RA cases during the follow-up (35 in the exposed cohort, 565 in the unexposed cohort). The relative risk (RR) of first hospitalisation for RA was 0.88 [95% confidence interval (CI) 0.63-1.24]. The RR was close to 1 throughout the 18 years of follow-up. CONCLUSION: Our findings do not support an association between severe psychological stress and RA.     

Coffee consumption, rheumatoid factor, and the risk of rheumatoid arthritis

BACKGROUND: Recent epidemiological studies have suggested that smoking is a risk factor for rheumatoid factor (RF) positive rheumatoid arthritis (RA). Being overweight, high serum cholesterol, and dietary factors have in some studies been found to be associated with the risk of RA. No attention, however, has been paid to coffee consumption as a risk determinant, though it is a shared covariate of the alleged risk factors. OBJECTIVES: This study aimed at examining coffee consumption for its associations with RF positivity and with the risk of RA. METHODS: Coffee consumption was studied, firstly, for its association with RF (sensitised sheep cell agglutination titre >/=128) in a cross sectional survey of 6809 subjects with no clinical arthritis, and secondly, for its prediction of RA in a cohort of 18 981 men and women who had neither arthritis nor a history of it at the baseline examination in 1973-76. Up to late 1989, 126 subjects of the cohort study had developed RA, of whom, 89 were positive for RF by the time of diagnosis. RESULTS: In the cross sectional survey the number of cups of coffee drunk daily was directly proportional to the prevalence of RF positivity. Adjusted for age and sex this association was significant (p value for linear trend, 0.008), but after further adjustment for smoking the linear trend declined below significance (p=0.06). In the cohort study there was an association between coffee consumption and the risk of RF positive RA that was not due to age, sex, level of education, smoking, alcohol intake, body mass index, or serum cholesterol. After adjustment for these potential confounders the users of four or more cups a day still had a relative risk of 2.20 (95% confidence interval 1.13 to 4.27) for developing RF positive RA compared with those drinking less. Coffee consumption did not predict the development of RF negative RA. CONCLUSION: Coffee consumption may be a risk factor for RA, possibly through mechanisms contributing to the production of RF. This hypothesis remains to be tested in further studies.