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 ≥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 ≥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.

     

Occurrence of extraarticular disease manifestations is associated with excess mortality in a community based cohort of patients with rheumatoid arthritis

OBJECTIVE: To investigate the occurrence of extraarticular manifestations (ExRA) in a well defined community based cohort of patients with rheumatoid arthritis (RA), and to examine their effect on mortality. METHODS: Using the resources of the Rochester Epidemiology Project, a retrospective medical record review was conducted of a cohort of 424 cases of RA in Olmsted County, MN, USA, diagnosed during the period 1955-1985. These cases had been classified using the American College of Rheumatology 1987 criteria for RA. Patients were followed 1955-1998 (median followup 14.8 yrs; range 0.2-42.8 yrs), and incident ExRA manifestations were recorded according to predefined criteria. Data on comorbidities were extracted using the definitions of the Charlson comorbidity index. Survival was compared to the general population using Kaplan-Meier estimates. RESULTS: ExRA occurred in 169 patients, corresponding to an incidence rate of 3.67/100 person-yrs. Compared to the general population, survival among patients with RA was decreased. Survival among patients with ExRA was markedly decreased compared to the general population and to patients without ExRA (p < 0.001). A particularly poor prognosis was noted in a subgroup of 63 patients (incidence rate 1.04/100 person-yrs) who fulfilled predefined criteria for severe ExRA (i.e., vasculitis, pericarditis, pleuritis, and/or Felty's syndrome). For RA patients who did not fulfill these criteria, there was no significant increase of mortality (p = 0.09). In a multivariate model of mortality, including age, sex, and the presence of known comorbidities, the presence of one or more of these ExRA was the strongest predictor of mortality. CONCLUSION: In this first community based study of extraarticular manifestations in RA, virtually all the excess mortality occurred in a subgroup of patients with severe extraarticular disease, suggesting that extraarticular disease is the major predictor of mortality in patients with RA.     

Mortality in rheumatoid arthritis: have we made an impact in 4 decades?

OBJECTIVE: To evaluate trends in survival among patients with rheumatoid arthritis (RA) over the past 4 decades. METHODS: Three population based prevalence cohorts of all Rochester, Minnesota, residents age > or =35 years with RA (1987 American College of Rheumatology criteria) on January 1, 1965, January 1, 1975, and January 1, 1985; and an incidence cohort of all new cases of RA occurring in the same population between January 1, 1955 and January 1, 1985, were followed longitudinally through their entire medical records (including all inpatient and outpatient care by any provider) until death or migration from the county. Mortality was described using the Kaplan-Meier method and the influence of age, sex, rheumatoid factor (RF) positivity, and comorbidity (using the Charlson Comorbidity Index) on mortality was analyzed using Cox proportional hazards models. RESULTS: Mortality was statistically significantly worse than expected for each of the cohorts (overall p<0.0001). A trend toward increased mortality in the 1975 and 1985 prevalence cohorts compared to the 1965 prevalence cohort was present, even after adjusting for significant predictors of mortality (age, RF positivity, and comorbidity). Survival for the general population of Rochester residents of similar age and sex improved in 1975 compared to 1965, and in 1985 compared to 1975. CONCLUSION: The excess mortality associated with RA has not changed in 4 decades. Moreover, people with RA have not enjoyed the same improvements in survival experienced by their non-RA peers. More attention should be paid to mortality as an outcome measure in RA.     

Mortality trends in rheumatoid arthritis: the role of rheumatoid factor

OBJECTIVE: We previously demonstrated a widening in the mortality gap between subjects with rheumatoid arthritis (RA) and the general population. We examined the contribution of rheumatoid factor (RF) positivity on overall mortality trends and cause-specific mortality. METHODS: A population-based RA incidence cohort (1955-1995, and aged >or= 18 yrs) was followed longitudinally until death or January 1, 2006. The underlying cause of death as coded from national mortality statistics and grouped according to ICD-9/10 chapters was used to define cause-specific mortality. Expected cause-specific mortality rates were estimated by applying the age-, sex-, and calendar-year-specific mortality rates from the general population to the RA cohort. Poisson regression was used to model the observed overall and cause-specific mortality rates according to RF status, accounting for age, sex, disease duration, and calendar year. RESULTS: A cohort of 603 subjects (73% female; mean age 58 yrs) with RA was followed for a mean of 16 years, during which 398 died. Estimated survival at 30 years after RA incidence was 26.0% in RF+ RA subjects compared to 36.0% expected (p < 0.001), while in RF- RA subjects, estimated survival was 29.1% compared to 28.3% expected (p = 0.9). The difference between the observed and the expected mortality in the RF+ RA subjects increased over time, resulting in a widening of the mortality gap, while among RF- RA subjects, observed mortality was very similar to the expected mortality over the entire time period. Among RF+ RA subjects, cause-specific mortality was higher than expected for cardiovascular [relative risk (RR) 1.50; 95% confidence interval (CI) 1.22, 1.83] and respiratory diseases [RR 3.49; 95% CI 2.51, 4.72]. Among RF- RA subjects, no significant differences were found between observed and expected cause-specific mortality. CONCLUSION: The widening in the mortality gap between RA subjects and the general population is confined to RF+ RA subjects and largely driven by cardiovascular and respiratory deaths.     

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.     

Cardiovascular death in rheumatoid arthritis: a population-based study

OBJECTIVE: To determine whether systemic inflammation confers any additional risk for cardiovascular death among patients with rheumatoid arthritis (RA), after adjusting for traditional cardiovascular risk factors and comorbidities. METHODS: Using the population-based data resources of the Rochester Epidemiology Project, we assembled an incidence cohort of all Rochester, Minnesota residents ages >or=18 years who first fulfilled the American College of Rheumatology 1987 criteria for RA between January 1, 1955 and January 1, 1995. All subjects were followed up longitudinally through their complete (inpatient, outpatient) medical records, beginning at age 18 years and continuing until death, migration, or January 1, 2001. Detailed information on the occurrence of various cardiovascular risk factors (personal history of coronary heart disease [CHD], congestive heart failure, smoking, hypertension, dyslipidemia, body mass index [BMI], diabetes mellitus, menopausal status) as well as indicators of systemic inflammation and RA disease severity (rheumatoid factor [RF] seropositivity, erythrocyte sedimentation rate [ESR], joint swelling, radiographic changes, RA nodules, RA complications, RA treatments, disease duration) and comorbidities were collected on all subjects. Causes of death were ascertained from death certificates and medical records. Cox regression models were used to estimate the independent predictors of cardiovascular death. RESULTS: This inception cohort comprised a total of 603 RA patients whose mean age was 58 years, of whom 73% were women. During a mean followup of 15 years, 354 patients died and cardiovascular disease was the primary cause of death in 176 patients. Personal history of CHD, smoking, hypertension, low BMI, and diabetes mellitus, as well as comorbidities, including peripheral vascular disease, cerebrovascular disease, chronic pulmonary disease, dementia, ulcers, malignancies, renal disease, liver disease, and history of alcoholism, were all significant risk factors for cardiovascular death (P < 0.01 for each). Multivariable Cox regression analyses, controlled for cardiovascular risk factors and comorbidities, revealed that the risk of cardiovascular death was significantly higher among RA patients with at least 3 ESR values of >or=60 mm/hour (hazard ratio [HR] 2.03, 95% confidence interval [95% CI] 1.45-2.83), RA vasculitis (HR 2.41, 95% CI 1.00-5.81), and RA lung disease (HR 2.32, 95% CI 1.11-4.84). CONCLUSION: These results indicate that markers of systemic inflammation confer a statistically significant additional risk for cardiovascular death among patients with RA, even after controlling for traditional cardiovascular risk factors and comorbidities.     

Predictors of infection in rheumatoid arthritis

OBJECTIVE: Patients with rheumatoid arthritis (RA) have been shown to have an increased susceptibility to the development of infections. The exact causes of this increased risk are unknown, but may relate to immunologic disturbances associated with the disease or to the immunosuppressive effects of agents used in its treatment. This study was undertaken to identify predictors of serious infections among patients with RA. Identification of such factors is the necessary first step in reducing the excess risk of infection in RA. METHODS: Members of a population-based incidence cohort of Rochester, Minnesota residents ages >or=18 years, who had been diagnosed with RA between 1955 and 1994, were followed up longitudinally through their complete medical records until January 1, 2000. We examined potential risk factors for the development of all objectively confirmed (by microbiology or radiology) infections and for infections requiring hospitalization. Potential risk factors included RA severity measures (rheumatoid factor positivity, elevated erythrocyte sedimentation rate, extraarticular manifestations of RA, and functional status), comorbidities (diabetes mellitus, alcoholism, and chronic lung disease), and other risk factors for infection (presence of leukopenia, smoking). Predictors were identified using multivariate time-dependent Cox proportional hazards modeling. RESULTS: The 609 RA patients in the cohort had a total followup time of 7,729.7 person-years (mean 12.7 years per patient). A total of 389 patients (64%) had at least 1 infection with objective confirmation, and 290 (48%) had at least 1 infection requiring hospitalization. Increasing age, presence of extraarticular manifestations of RA, leukopenia, and comorbidities (chronic lung disease, alcoholism, organic brain disease, and diabetes mellitus), as well as use of corticosteroids, were strong predictors of infection (P < 0.004) in both univariate and multivariate analyses. Notably, use of disease-modifying antirheumatic drugs was not associated with increased risk of infection in multivariate analyses, after adjustment for demographic characteristics, comorbidities, and disease-related variables. CONCLUSION: We identified a number of strong predictors of infections in a population-based cohort of patients with RA. These results can be used to prospectively identify high-risk patients, who may benefit from closer followup and implementation of preventive strategies.     

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.     

Paradoxical effect of body mass index on survival in rheumatoid arthritis: role of comorbidity and systemic inflammation

BACKGROUND: Despite high cardiovascular mortality in rheumatoid arthritis (RA), few studies of body mass index (BMI) and obesity as risk factors for death in RA have been published. METHODS: We estimated the effect of BMI on survival in a cohort of 779 patients with RA adjusting for comorbidity, RA disease severity, erythrocyte sedimentation rate (ESR), and other potential confounders. RESULTS: The cohort accrued 123 deaths in 3460 person-years (3.6 deaths per 100 person-years; 95% confidence interval [CI], 3.0-4.2). The BMI was inversely associated with mortality. Patients with BMIs of 30 or higher had the lowest mortality, 1.7 deaths per 100 person-years (95% CI, 1.1-2.5). Mortality was higher in each lower BMI category, reaching its highest rate among patients with BMIs lower than 20 with 15.0 deaths per 100 person-years (95% CI, 9.9-23.0). The survival advantage of high BMI was independent of RA onset age, RA duration, sex, ethnic group, socioeconomic status, smoking status, and use of methotrexate but was lost on adjusting for comorbidity and RA severity. We observed an interaction between BMI and ESR, where the BMI protective influence occurred only if the ESR was low. The BMI x ESR interaction was independent of all covariates, including comorbidity and RA severity. CONCLUSIONS: Body mass has a paradoxical effect on mortality in RA. Patients with high BMI have lower mortality than thinner patients. This effect is mediated in part by comorbidity. The effect of body mass on survival seems to be modified by the level of systemic inflammation.     

Rheumatoid arthritis and mortality. A longitudinal study in pima indians

Objective. To determine the effect of rheumatoid arthritis (RA) on mortality rates. Methods. Longitudinal analyses of data from a cohort of Pima Indians from the Gila River Indian Community in Arizona, who were followed up during the period February 1965 through December 1989. Results. Among 2,979 study subjects aged ≤25 years, there were 858 deaths, 79 of which occurred in subjects with RA (36 men, 43 women). Age and sex-adjusted mortality rates were slightly higher in subjects with RA than in those without (mortality rate ratio 1.28, 95% confidence interval [95% CI] 1.01–1.62). Among those with RA, mortality rates were higher in older subjects (mortality rate ratio 1.51 per 10-year increase in age, 95% CI 1.22–1.88), in male subjects (mortality rate ratio 2.23, 95% CI 1.44–3.45, adjusted for age), and in subjects with proteinuria (mortality rate ratio 1.88, 95% CI 1.02–3.46, adjusted for age and sex). Mortality rate ratios for these risk factors were similar in subjects without RA. In addition, among subjects with RA, rheumatoid factor (RF) positivity was predictive of death (mortality rate ratio 1.94, 95% CI 1.10–3.43), and the excess mortality was found primarily among subjects who were seropositive. The death rate from cardiovascular disease (mortality rate ratio 1.77, 95% CI 1.10–2.84) and from liver cirrhosis or other alcohol-related disease (mortality rate ratio 2.52, 95% CI 1.06–6.01) was increased in persons with RA. Conclusion. The results of this population-based study suggest that although the risk of mortality in subjects with RA is significantly higher than in those without RA, the risk ratio is in the lower range of that described previously in studies of clinic-based cohorts. RF positivity as a predictor of early death among subjects with RA indicates that the immunologic processes in seropositive RA may contribute to the events that eventually lead to early death.     

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.     

Incidence of noncardiac vascular disease in rheumatoid arthritis and relationship to extraarticular disease manifestations

OBJECTIVE: To investigate the incidence of noncardiac vascular disease in patients with rheumatoid arthritis (RA) and its relationship to systemic extraarticular disease in a community-based cohort. METHODS: A retrospective medical record review of 609 patients with incident RA diagnosed during 1955-1994 was carried out in Olmsted County, Minnesota. Patients were followed up from 1955 to 2000 (median followup 11.8 years). Incident noncardiac vascular disease and severe extraarticular RA manifestations (including pericarditis, pleuritis, and vasculitis) were recorded according to predefined criteria, and incidence rates were estimated. Using Cox proportional hazards models, the risk (hazard ratio [HR]) of developing vascular events was assessed in patients with and without severe extraarticular RA. RESULTS: Cerebrovascular and peripheral arterial events occurred in 139 patients (22.8%). The 30-year cumulative incidence rates of peripheral arterial events, cerebrovascular events, and venous thromboembolic events were estimated to be 19.6%, 21.6%, and 7.2%, respectively. The presence of severe extraarticular RA manifestations was found to be associated with all subgroups of noncardiac vascular disease except cerebrovascular disease alone (HR 2.3, 95% confidence interval [95% CI] 1.2-4.3 for peripheral arterial events; HR 3.7, 95% CI 1.3-10.3 for venous thromboembolic events; HR 1.5, 95% CI 0.7-3.2 for cerebrovascular events) after adjusting for age, sex, body mass index, smoking, and rheumatoid factor status. CONCLUSION: This is the first study to assess the incidence of noncardiac vascular disease in RA. Severe extraarticular RA was associated with all forms of noncardiac vascular disease except cerebrovascular disease alone. Similar to cardiac disease, the excess risk of noncardiac vascular disease in RA is likely to be related, in part, to the systemic inflammation associated with the extraarticular manifestations of RA.     

Cardiovascular death in rheumatoid arthritis: A population‐based study

Objective

To determine whether systemic inflammation confers any additional risk for cardiovascular death among patients with rheumatoid arthritis (RA), after adjusting for traditional cardiovascular risk factors and comorbidities.

Methods

Using the population‐based data resources of the Rochester Epidemiology Project, we assembled an incidence cohort of all Rochester, Minnesota residents ages ≥18 years who first fulfilled the American College of Rheumatology 1987 criteria for RA between January 1, 1955 and January 1, 1995. All subjects were followed up longitudinally through their complete (inpatient, outpatient) medical records, beginning at age 18 years and continuing until death, migration, or January 1, 2001. Detailed information on the occurrence of various cardiovascular risk factors (personal history of coronary heart disease [CHD], congestive heart failure, smoking, hypertension, dyslipidemia, body mass index [BMI], diabetes mellitus, menopausal status) as well as indicators of systemic inflammation and RA disease severity (rheumatoid factor [RF] seropositivity, erythrocyte sedimentation rate [ESR], joint swelling, radiographic changes, RA nodules, RA complications, RA treatments, disease duration) and comorbidities were collected on all subjects. Causes of death were ascertained from death certificates and medical records. Cox regression models were used to estimate the independent predictors of cardiovascular death.

Results

This inception cohort comprised a total of 603 RA patients whose mean age was 58 years, of whom 73% were women. During a mean followup of 15 years, 354 patients died and cardiovascular disease was the primary cause of death in 176 patients. Personal history of CHD, smoking, hypertension, low BMI, and diabetes mellitus, as well as comorbidities, including peripheral vascular disease, cerebrovascular disease, chronic pulmonary disease, dementia, ulcers, malignancies, renal disease, liver disease, and history of alcoholism, were all significant risk factors for cardiovascular death (P < 0.01 for each). Multivariable Cox regression analyses, controlled for cardiovascular risk factors and comorbidities, revealed that the risk of cardiovascular death was significantly higher among RA patients with at least 3 ESR values of ≥60 mm/hour (hazard ratio [HR] 2.03, 95% confidence interval [95% CI] 1.45–2.83), RA vasculitis (HR 2.41, 95% CI 1.00–5.81), and RA lung disease (HR 2.32, 95% CI 1.11–4.84).

Conclusion

These results indicate that markers of systemic inflammation confer a statistically significant additional risk for cardiovascular death among patients with RA, even after controlling for traditional cardiovascular risk factors and comorbidities.

     

Obesity and mortality in advanced chronic renal failure patients

A protective effect of obesity on the mortality of end-stage renal failure patients has been observed in several studies. Most of these studies have been based on prevalent dialysis population. The aim of the present study was to evaluate if obesity has beneficial effects on the survival of advanced chronic renal failure patients. The study group consisted of 376 patients (mean age 63 +/- 15 years) with advanced chronic renal failure not yet on dialysis. Obesity was defined as a body mass index (BMI) > or = 30 kg/m2. Grade of comorbidity was quantified by the method devised by Davies. Survival was analyzed as time from the referral to the predialysis outpatient clinic to patient death, censoring from contributing additional survival data to the analysis following transplantation. Kaplan-Meier analysis was used to test survival differences according to quartiles of BMI, and between obese and nonobese patients. Further analysis were performed, stratifying survival curves by comorbid scores, lean body mass, age, and sex. Cox proportional hazard regression models were used to investigate the best determinants of mortality, and the role of obesity adjusted for other covariates. Median survival time was 1,453 days. During the follow-up time, 158 patients (42%) died. Survival differences among quartiles of BMI were statistically significant (Breslow = 10.7, p = 0.017). Patients within the lowest and the highest quartiles of BMI had higher mortality than the rest of patients. Survival curves between obese and non-obese patients did not differ significantly. However, when patients without comorbidity were studied apart, those with obesity showed worse survival than the rest of patients (log-rank = 7.42, p = 0.0064). Since the effect of obesity on mortality did not follow a proportional hazard pattern throughout the study period, multivariable analysis for mortality was stratified by 18 months intervals. The variables which fitted the best model were: age (Hazard Ratio: 1.04), comorbid score (HR: 2.17), serum albumin (HR: 0.62), GFR at the study entry (HR: 0.91), male gender (HR: 1.48), and obesity (HR: 1.51). In conclusion, obesity had no survival benefit in patients with advanced chronic renal failure. Obesity had a noteworthy impact on early mortality of advanced chronic kidney disease patients without comorbidities.     

The natural history of nonalcoholic fatty liver disease: a population-based cohort study

BACKGROUND & AIMS: The natural history of nonalcoholic fatty liver disease (NAFLD) in the community remains unknown. We sought to determine survival and liver-related morbidity among community-based NAFLD patients. METHODS: Four hundred twenty patients diagnosed with NAFLD in Olmsted County, Minnesota, between 1980 and 2000 were identified using the resources of the Rochester Epidemiology Project. Medical records were reviewed to confirm diagnosis and determine outcomes up to 2003. Overall survival was compared with the general Minnesota population of the same age and sex. RESULTS: Mean (SD) age at diagnosis was 49 (15) years; 231 (49%) were male. Mean follow-up was 7.6 (4.0) years (range, 0.1-23.5) culminating in 3192 person-years follow-up. Overall, 53 of 420 (12.6%) patients died. Survival was lower than the expected survival for the general population (standardized mortality ratio, 1.34; 95% CI, 1.003-1.76; P = .03). Higher mortality was associated with age (hazard ratio per decade, 2.2; 95% CI, 1.7-2.7), impaired fasting glucose (hazard ratio, 2.6; 95% CI, 1.3-5.2), and cirrhosis (hazard ratio, 3.1, 95% CI, 1.2-7.8). Liver disease was the third leading cause of death (as compared with the thirteenth leading cause of death in the general Minnesota population), occurring in 7 (1.7%) subjects. Twenty-one (5%) patients were diagnosed with cirrhosis, and 13 (3.1%) developed liver-related complications, including 1 requiring transplantation and 2 developing hepatocellular carcinoma. CONCLUSIONS: Mortality among community-diagnosed NAFLD patients is higher than the general population and is associated with older age, impaired fasting glucose, and cirrhosis. Liver-related death is a leading cause of mortality, although the absolute risk is low.     

Prognostic importance of low body mass index in relation to cardiovascular mortality in rheumatoid arthritis

OBJECTIVE: Various etiologic mechanisms have been implicated in the observed increase in cardiovascular mortality in rheumatoid arthritis (RA). Body mass index (BMI) is associated with cardiovascular mortality in the general population. This study compared the effect of BMI on cardiovascular mortality in a population-based cohort of subjects with RA with that in a cohort of individuals without RA from the same population. METHODS: The RA cohort comprised all members of an incidence cohort of Rochester, Minnesota residents ages > or =18 years who were first diagnosed with RA (by the American College of Rheumatology 1987 criteria) from 1955 through 1994. An age- and sex-matched comparison cohort of subjects without RA was assembled. Both cohorts were followed up longitudinally through their complete (inpatient, outpatient) medical records beginning at age 18 years and continuing until death, migration, or January 1, 2001, and the details of weight and height changes during this period were recorded. High BMI was defined as a BMI >30 kg/m(2) and low BMI as <20 kg/m(2). Cox regression models were used to estimate the effect of BMI on cardiovascular mortality after accounting for traditional cardiac risk factors and malignancies. RESULTS: RA subjects with low BMI at incidence had a significantly higher risk of cardiovascular death (hazard ratio [HR] 3.34, 95% confidence interval [95% CI] 2.23-4.99) compared with non-RA subjects with normal BMI, after adjusting for age, sex, personal cardiac history, smoking status, and presence of diabetes, hypertension, and malignancies. RA subjects with normal BMI at incidence who experienced low BMI during followup also had a higher risk of cardiovascular death (HR 2.09, 95% CI 1.50-2.92) when compared with non-RA subjects who maintained normal BMI throughout followup. CONCLUSION: Among patients with RA, low BMI is associated with a significantly increased risk of cardiovascular death.     

The mortality of rheumatoid vasculitis compared with rheumatoid arthritis

Objective. To determine whether the mortality of patients with rheumatoid vasculitis (RV) is increased in comparison with that of patients with rheumatoid arthritis (RA). Methods. The mortality of all RV patients identified in 1980–1992 (n = 61) was compared with that of 244 RA controls matched for the year the diagnosis was made in the RV cases. Hazard ratios (HR) of death were calculated with a multivariate survival analysis, adjusting for age, sex, comorbidity, treatment, and parameters of RA severity. Results. The unadjusted risk of death (HR) in RV patients compared with RA controls was 1.65 (95% confidence interval [95% CI] 1.05–2.58). After adjustment for prognostic factors, the HR was reduced to 1.26 (95% CI 0.79–2.01), mainly due to removal of the effects of age and sex. No excess mortality was seen in RV patients with severe organ involvement when compared with RV patients without severe organ involvement, although the former patients were treated more often with cytostatic and immunosuppressive drugs. Infection was the main cause of death in the RV patients, and cardiovascular disease in the RA controls. Vasculitis was reported as the cause of death in only 1 RV patient. Conclusion. After allowance for general risk factors such as age and sex, there remains only a slight excess mortality in RV patients compared with RA controls.     

Modeling the lifetime costs of rheumatoid arthritis.

OBJECTIVE: To develop an analytical approach for estimating the lifetime costs of rheumatoid arthritis (RA) using existing population based cross sectional data, and to use this estimate to describe the potential cost-effectiveness of bone marrow transplantation for RA. METHODS: Estimates of arthritis related costs (direct, indirect, and nonmedical) and mortality were obtained from previously assembled population based cohorts. A mathematical model was designed defining 25 hypothetical ratios (RA/NA) representing the proportionate excess cost of RA each year for the 25 years following a diagnosis of RA. Using age and sex-specific cost estimates, we then simulated a vector of 25 ratios 1000 times. Each age and sex-specific randomly generated variable was converted to an estimated dollar amount (in 1995 dollars US) of excess cost attributable to RA. All dollar amounts were discounted by 3% per year. Finally, each vector of 25 discounted dollar amounts was summed to yield an estimate of the total excess medical costs in 1995 dollars for the first 25 years of a person's lifetime following a diagnosis of RA. Because not every one of these hypothetical individuals would be expected to live all 25 years, we used the standardized mortality ratio for an individual with RA (from our inception cohort) and multiplied it by the age-specific 1990 mortality rates for Minnesota whites to estimate how many of the 1000 randomly generated hypothetical individuals could be expected to die during each of the 25 years. For these, the summation of estimated cost was truncated at the death year. This process yielded, for each age and sex, a sample of 1000 sums of 25 (or fewer) excess costs all in terms of 1995 dollars that correspond to the excess cost during the first 25 years after an RA diagnosis, adjusted for differential survival among patients with RA compared to nonarthritic controls. The distribution of these sums thus represented a distribution of the 1995 dollars that could be saved if RA could be "cured" soon after incidence. RESULTS: Our simulation analyses indicated that the median lifetime incremental costs of RA range roughly from ,$61,000 to $ 122,000. Incremental costs were higher for younger individuals compared to older individuals and were consistent over all percentiles and age groups. No systematic relationship between the incremental costs of females with RA compared to males was identified. CONCLUSION: These data suggest that interventions such as autologous bone marrow transplantation, which has recently been estimated to cost roughly $60,000, may be cost saving if they eliminate the downstream incremental costs of RA.     

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.