The risk of congestive heart failure in rheumatoid arthritis: a population-based study over 46 years

OBJECTIVE: It is hypothesized that the systemic inflammation associated with rheumatoid arthritis (RA) promotes an increased risk of cardiovascular (CV) morbidity and mortality. We examined the risk and determinants of congestive heart failure (CHF) in patients with RA. METHODS: We assembled a population-based, retrospective incidence cohort from among all individuals living in Rochester, Minnesota, in whom RA (defined according to the American College of Rheumatology 1987 criteria) was first diagnosed between 1955 and 1995, and an age- and sex-matched non-RA cohort. After excluding patients in whom CHF occurred before the RA index date, all subjects were followed up until either death, incident CHF (defined according to the Framingham Heart Study criteria), migration from the county, or until January 1, 2001. Detailed information from the complete medical records (including all inpatient and outpatient care provided by all local providers) regarding RA, ischemic heart disease, and traditional CV risk factors was collected. Cox models were used to estimate the effect of RA on the development of CHF, adjusting for CV risk factors and/or ischemic heart disease. RESULTS: The study population included 575 patients with RA and 583 subjects without RA. The CHF incidence rates were 1.99 and 1.16 cases per 100 person-years in patients with RA and in non-RA subjects, respectively (rate ratio 1.7, 95% confidence interval [95% CI] 1.3-2.1). After 30 years of followup, the cumulative incidence of CHF was 34.0% in patients with RA and 25.2% in non-RA subjects (P< 0.001). RA conferred a significant excess risk of CHF (hazard ratio [HR] 1.87, 95% CI 1.47-2.39) after adjusting for demographics, ischemic heart disease, and CV risk factors. The risk was higher among patients with RA who were rheumatoid factor (RF) positive (HR 2.59, 95% CI 1.95-3.43) than among those who were RF negative (HR 1.28, 95% CI 0.93-1.78). CONCLUSION: Compared with persons without RA, patients with RA have twice the risk of developing CHF. This excess risk is not explained by traditional CV risk factors and/or clinical ischemic heart disease.     

How much of the increased incidence of heart failure in rheumatoid arthritis is attributable to traditional cardiovascular risk factors and ischemic heart disease?

OBJECTIVE: To compare the proportion of the risk for the development of heart failure (HF) that is attributable to traditional cardiovascular (CV) risk factors, ischemic heart disease (IHD), and alcohol abuse between subjects with and subjects without rheumatoid arthritis (RA). METHODS: A population-based inception cohort of RA patients was assembled along with a similar cohort of subjects without RA. All individuals were followed up through their complete medical records, until HF incidence, death, migration, or January 1, 2001. The attributable risk of HF was estimated as the difference between the observed cumulative incidence of HF in each cohort (estimated from multivariable Cox models and adjusted for the competing risk of death) and the predicted cumulative incidence of HF in the absence of risk factors, with results expressed as a percentage of the observed cumulative incidence. RESULTS: A total of 575 RA subjects and 583 non-RA subjects (mean age 57 years, 73% women) without HF at incidence/index date had a mean followup of 15.1 and 17.0 years, respectively. During that period, 165 RA and 115 non-RA subjects had a first episode of HF, with a cumulative incidence of 36.3% and 20.4%, respectively, at age 80 years. Among non-RA subjects, 77% of the HF at age 80 years was attributable to CV risk factors, IHD, and alcohol abuse combined, whereas among RA subjects, only 54% of the HF at age 80 years was attributable to these factors (P < 0.01). CONCLUSION: The excess risk of HF among RA patients is not explained by an increased frequency or effect of CV risk factors and IHD.     

Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study

OBJECTIVE: To examine the risk of clinical coronary heart disease (CHD) in patients with rheumatoid arthritis (RA) compared with age- and sex-matched non-RA subjects, and to determine whether RA is a risk factor for CHD after accounting for traditional CHD risk factors. METHODS: We assembled a population-based incidence cohort of 603 Rochester, Minnesota residents ages >or=18 years who first fulfilled the American College of Rheumatology (ACR) 1987 criteria for RA between January 1, 1955 and January 1, 1995, and 603 age- and sex-matched non-RA subjects. All subjects were followed up through their complete inpatient and outpatient medical records, beginning at age 18 years until death, migration, or January 1, 2001. Data were collected on CHD events and traditional CHD risk factors (diabetes mellitus, hypertension, dyslipidemia, body mass index, smoking) using established diagnostic criteria. CHD events included hospitalized myocardial infarction (MI), unrecognized MI, coronary revascularization procedures, angina pectoris, and sudden CHD deaths. Conditional logistic regression and Cox regression models were used to estimate the risk of CHD associated with RA, both prior to and following RA diagnosis, after adjusting for CHD risk factors. RESULTS: During the 2-year period immediately prior to fulfillment of the ACR criteria, RA patients were significantly more likely to have been hospitalized for acute MI (odds ratio [OR] 3.17, 95% confidence interval [95% CI] 1.16-8.68) or to have experienced unrecognized MIs (OR 5.86, 95% CI 1.29-26.64), and less likely to have a history of angina pectoris (OR 0.58, 95% CI 0.34-0.99) compared with non-RA subjects. After the RA incidence date, RA patients were twice as likely to experience unrecognized MIs (hazard ratio [HR] 2.13, 95% CI 1.13-4.03) and sudden deaths (HR 1.94, 95% CI 1.06-3.55) and less likely to undergo coronary artery bypass grafting (HR 0.36, 95% CI 0.16-0.80) compared with non-RA subjects. Adjustment for the CHD risk factors did not substantially change the risk estimates. CONCLUSION: Patients with RA have a significantly higher risk of CHD when compared with non-RA subjects. RA patients are less likely to report symptoms of angina and more likely to experience unrecognized MI and sudden cardiac death. The risk of CHD in RA patients precedes the ACR criteria-based diagnosis of RA, and the risk cannot be explained by an increased incidence of traditional CHD risk factors in RA patients.     

The risk of congestive heart failure in rheumatoid arthritis: A population‐based study over 46 years

Objective

It is hypothesized that the systemic inflammation associated with rheumatoid arthritis (RA) promotes an increased risk of cardiovascular (CV) morbidity and mortality. We examined the risk and determinants of congestive heart failure (CHF) in patients with RA.

Methods

We assembled a population‐based, retrospective incidence cohort from among all individuals living in Rochester, Minnesota, in whom RA (defined according to the American College of Rheumatology 1987 criteria) was first diagnosed between 1955 and 1995, and an age‐ and sex‐matched non‐RA cohort. After excluding patients in whom CHF occurred before the RA index date, all subjects were followed up until either death, incident CHF (defined according to the Framingham Heart Study criteria), migration from the county, or until January 1, 2001. Detailed information from the complete medical records (including all inpatient and outpatient care provided by all local providers) regarding RA, ischemic heart disease, and traditional CV risk factors was collected. Cox models were used to estimate the effect of RA on the development of CHF, adjusting for CV risk factors and/or ischemic heart disease.

Results

The study population included 575 patients with RA and 583 subjects without RA. The CHF incidence rates were 1.99 and 1.16 cases per 100 person‐years in patients with RA and in non‐RA subjects, respectively (rate ratio 1.7, 95% confidence interval [95% CI] 1.3–2.1). After 30 years of followup, the cumulative incidence of CHF was 34.0% in patients with RA and 25.2% in non‐RA subjects (P< 0.001). RA conferred a significant excess risk of CHF (hazard ratio [HR] 1.87, 95% CI 1.47–2.39) after adjusting for demographics, ischemic heart disease, and CV risk factors. The risk was higher among patients with RA who were rheumatoid factor (RF) positive (HR 2.59, 95% CI 1.95–3.43) than among those who were RF negative (HR 1.28, 95% CI 0.93–1.78).

Conclusion

Compared with persons without RA, patients with RA have twice the risk of developing CHF. This excess risk is not explained by traditional CV risk factors and/or clinical ischemic heart disease.

     

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.     

How much of the increased incidence of heart failure in rheumatoid arthritis is attributable to traditional cardiovascular risk factors and ischemic heart disease?

Objective

To compare the proportion of the risk for the development of heart failure (HF) that is attributable to traditional cardiovascular (CV) risk factors, ischemic heart disease (IHD), and alcohol abuse between subjects with and subjects without rheumatoid arthritis (RA).

Methods

A population‐based inception cohort of RA patients was assembled along with a similar cohort of subjects without RA. All individuals were followed up through their complete medical records, until HF incidence, death, migration, or January 1, 2001. The attributable risk of HF was estimated as the difference between the observed cumulative incidence of HF in each cohort (estimated from multivariable Cox models and adjusted for the competing risk of death) and the predicted cumulative incidence of HF in the absence of risk factors, with results expressed as a percentage of the observed cumulative incidence.

Results

A total of 575 RA subjects and 583 non‐RA subjects (mean age 57 years, 73% women) without HF at incidence/index date had a mean followup of 15.1 and 17.0 years, respectively. During that period, 165 RA and 115 non‐RA subjects had a first episode of HF, with a cumulative incidence of 36.3% and 20.4%, respectively, at age 80 years. Among non‐RA subjects, 77% of the HF at age 80 years was attributable to CV risk factors, IHD, and alcohol abuse combined, whereas among RA subjects, only 54% of the HF at age 80 years was attributable to these factors (P < 0.01).

Conclusion

The excess risk of HF among RA patients is not explained by an increased frequency or effect of CV risk factors and IHD.

     

Ischemic heart disease in patients from Northwest Spain with biopsy proven giant cell arteritis. A population based study

OBJECTIVE: To assess the incidence, mortality, and predictors of ischemic heart disease (IHD) in patients from the Lugo region of Northwest Spain with biopsy-proven giant cell arteritis (GCA). METHODS: Retrospective study of patients with biopsy-proven GCA diagnosed from 1981 to 2001 at the single hospital for a population of 250,000 people. A survival analysis was performed. Hazard ratios and standardized mortality ratio (SMR) as well as predictors of IHD in patients with biopsy-proven GCA were also assessed. RESULTS: Nineteen (9%) of the 210 patients with biopsy-proven GCA diagnosed during the period of study had IHD. The incidence of IHD in patients with GCA was 12.6/1000 person-years at risk (95% CI 6.9-21.0). During the study period 1981-2000 the population aged > or = 50 years in Lugo was roughly 100,000, and the mortality rate due to IHD in patients with GCA for that population was 8/100,000. The SMR in patients with GCA due to IHD was 1.62 (95% CI 0.70-3.20). Mortality in patients with GCA who had IHD was higher than in those patients without IHD (age and sex adjusted hazard ratio 2.81, 95% CI 1.51-5.21; p = 0.001). Age (hazard ratio 1.15), hypertension (hazard ratio 2.51), and abnormal temporal artery on physical examination (hazard ratio 0.36) at the time of diagnosis of GCA were the best predictors of IHD over the followup period in patients with biopsy-proven GCA. CONCLUSION: Our observations suggest that mortality due to IHD in patients from Lugo with GCA is not much higher than that reported in the Spanish population aged 50 years and older. However, mortality in patients with GCA with IHD is higher than in GCA patients without IHD.     

Increased case fatality rates following a first acute cardiovascular event in patients with rheumatoid arthritis

OBJECTIVE: Among patients with rheumatoid arthritis (RA), cardiovascular mortality is increased compared with the rate among unaffected peers. In this study, 30-day mortality rates following a first acute cardiovascular event (myocardial infarction or stroke) were compared between RA patients and the general population. METHODS: All cases of a first acute cardiovascular event between July 1, 2001 and November 30, 2003 in Victoria, Australia were identified from hospital discharge data. Individuals were classified as having RA when an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) or an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification code for RA was recorded at the index admission or during the previous 5 years. Thirty-day mortality rates were determined from linkage to the state death registry. RESULTS: A total of 29,924 patients experienced a first cardiovascular event during the study period, 359 (1.2%) of whom had RA. Thirty-day cardiovascular mortality was 17.6% in RA patients versus 10.8% in non-RA patients. In fully adjusted models, the odds ratio (OR) for cardiovascular death in RA patients following a first acute cardiovascular event was 1.6 (95% confidence interval [95% CI] 1.2-2.2). Analysis of index event subgroups revealed that this increased case fatality rate in patients with RA was accounted for almost entirely by excess deaths following myocardial infarction. The adjusted ORs for cardiovascular death in RA after myocardial infarction and stroke were 1.9 (95% CI 1.3-2.7) and 1.2 (95% CI 0.7-2.0), respectively. CONCLUSION: RA patients have a substantially increased risk of 30-day case fatality following myocardial infarction, but not stroke, compared with non-RA patients. This higher case fatality rate is likely to contribute to the observed overall excess of cardiovascular deaths in RA populations.     

Functional outcome after stroke in patients with rheumatoid arthritis and systemic lupus erythematosus

OBJECTIVE: To compare outcomes following stroke rehabilitation among patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) versus patients with neither RA nor SLE (non-RA/SLE). METHODS: We conducted a retrospective analysis using a national database of patients with stroke admitted to inpatient rehabilitation between 1994 and 2001. Primary outcomes were discharge disposition and functional status, rated by the Functional Independence Measure (FIM) Instrument, at discharge and at followup. The independent variable was RA or SLE. Covariates were age, sex, race/ethnicity, admission FIM ratings, additional comorbidities (none, 1-3, and >3), type of stroke, and length of stay. RESULTS: We studied 47,853 patients with stroke, 368 with RA, and 119 with SLE. Discharge dispositions were similar for patients with RA and non-RA/SLE (81% discharged home). At discharge, the average FIM rating for patients with RA was 85.8, compared with 87.8 for non-RA/SLE patients. At followup, the average FIM rating for patients with RA was 95.9, compared with 99.6 for non-RA/SLE patients. RA was associated with lower FIM ratings at discharge and followup in multivariate analyses. SLE was associated with younger age (17.5 years). However, patients with SLE had similar discharge dispositions and FIM ratings to non-RA/SLE patients. CONCLUSION: RA was associated with lower functional status ratings at discharge and followup. Outpatient therapy for patients with RA may reduce long-term assistance. Patients with SLE were younger, but had similar functional outcomes to patients without RA/SLE, suggesting early morbidity from stroke among patients with SLE.     

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.     

Incidence of melanoma and other malignancies among rheumatoid arthritis patients treated with methotrexate

OBJECTIVE: To determine cancer risk in a cohort of 459 rheumatoid arthritis (RA) patients treated with methotrexate in community practice. METHODS: All RA patients who started methotrexate prior to June 1986 and were attending 1 of 6 rheumatologists were studied. Demographic data were matched to the State Cancer Registry to identify all malignancies (except nonmelanoma skin cancer) for 1983-1998, and to the National Death Index to identify all deaths to the end of 1999. Followup started on the date when methotrexate was started and ended either on the last confirmed date on which the patient was seen by the rheumatologist or at death. Standardized incidence ratios (SIRs) were calculated using state population cancer rates stratified by sex, age (in 5-year groups), and calendar year. RESULTS: There were 4,145 person-years of followup (average 9.3 years). Eighty-seven malignancies were identified (14 before, 64 during, and 9 after the followup period). There was an estimated 50% excess risk of malignancy among methotrexate-exposed RA patients relative to the general population (SIR 1.5, 95% confidence interval [95% CI] 1.2-1.9), with a 3-fold increase in melanoma (SIR 3.0, 95% CI 1.2-6.2), a 5-fold increase in non-Hodgkin's lymphoma (SIR 5.1, 95% CI 2.2-10.0), and an almost 3-fold increase in lung cancer (SIR 2.9, 95% CI 1.6-4.8). CONCLUSION: Compared with the general population, methotrexate-treated RA patients have an increased incidence of melanoma, non-Hodgkin's lymphoma, and lung cancer. There may be a role for regular skin cancer screening for all RA patients, particularly those receiving immunosuppressive therapy.     

Cancer mortality in patients with rheumatoid arthritis

Patients with rheumatoid arthritis (RA), 500 males and 500 females, aged 40 years and over, together with an age and sex matched control population, were observed over a 10-year period. The overall mortality was significantly higher in both men and women with RA than in the controls. During the followup, 42 patients with RA (28 males, 14 females) and 58 control subjects (36 males, 22 females) died from malignant neoplasms, but this difference was not statistically significant. A significant excess of deaths from neoplasms of the hematopoietic system was observed in patients with RA. Subjects without RA had significantly higher mortality rate from cancer of gastrointestinal origin than patients with RA.     

Reduction in the incidence of myocardial infarction in patients with rheumatoid arthritis who respond to anti-tumor necrosis factor alpha therapy: results from the British Society for Rheumatology Biologics Register

OBJECTIVE: Rheumatoid arthritis (RA) is associated with an increased risk of coronary artery disease, possibly acting via shared mechanisms of inflammation. This study was undertaken to test the hypothesis that the powerful antiinflammatory effect of anti-tumor necrosis alpha (anti-TNFalpha) therapy might lead to a reduction in the incidence of myocardial infarction (MI) in patients with RA. METHODS: Using data from the British Society for Rheumatology Biologics Register, a national prospective observational study, we compared MI rates in 8,670 patients with RA treated with anti-TNFalpha and 2,170 patients with active RA treated with traditional disease-modifying antirheumatic drugs (DMARDs). RESULTS: Through July 2006, 63 MIs occurred in the anti-TNFalpha cohort during 13,233 person-years of followup and 17 MIs occurred in the DMARD cohort during 2,893 person-years of followup, equivalent to a rate of 4.8 events per 1,000 person-years and 5.9 events per 1,000 person-years, respectively. After adjustment for baseline risk factors, there was no reduction in the rate of MI in the anti-TNFalpha cohort compared with the DMARD cohort (incidence rate ratio 1.44 [95% confidence interval 0.56-3.67]). In an analysis of anti-TNFalpha-treated patients who responded to the treatment within 6 months versus those who did not, MI rates were found to be 3.5 events per 1,000 person-years in responders and 9.4 events per 1,000 person-years in nonresponders. The adjusted incidence rate ratio (95% confidence interval) for responders compared with nonresponders was 0.36 (0.19-0.69). CONCLUSION: These results indicate that RA patients treated with anti-TNFalpha do not have a lower incidence of MI compared with RA patients treated with traditional DMARDs. However, the risk of MI is markedly reduced in those who respond to anti-TNFalpha therapy by 6 months compared with nonresponders. This finding supports the notion that inflammation plays a pivotal role in MI.     

Rheumatoid arthritis prevalence, incidence, and mortality rates: a nationwide population study in Taiwan

There are few nationwide population studies on the epidemiology of rheumatoid arthritis (RA). Here, we present the epidemiologic features and mortality rates of RA in Taiwan. The catastrophic illness registry of the Taiwan National Health Insurance Research Database and the National Death Registry of Taiwan were used to estimate the incidence and prevalence of RA and its associated mortality rates. All-cause and cause-specific standardized mortality ratios (SMRs) were calculated and compared to the corresponding ratios of the general population in 2002. The study comprised 15,967 incident RA cases (3,562 men; 12,405 women) occurring from 2002 through 2007. The annual incidence of RA was 15.8 cases (men, 10.1; women, 41.0) per 100,000 population. The period prevalence was 97.5 cases (men, 37.4; women, 159.5) per 100,000 population. During 67,010 person-years of follow-up, 985 deaths (372 men; 613 women) were identified, and this corresponded to a crude mortality rate of 14.7 deaths (men, 25.0; women, 11.8) per 1,000 person-years. Compared to female patients, male patients had a higher risk for mortality (log-rank test, p < 0.001). RA patients had an SMR of 1.25 (95 % confidence interval [CI], 1.18–1.33) for all-cause mortality. Compared to the general population, RA patients of both genders in this cohort had a significantly higher risk of mortality from infection (SMR, 2.49) and gastrointestinal diseases (SMR, 1.76). RA incidence and prevalence were higher in women than in men. Mortality was higher in men than in women. Compared to the general population, RA patients had a higher risk of death, particularly from infection and gastrointestinal diseases.     

The effect of methotrexate and anti-tumor necrosis factor therapy on the risk of lymphoma in rheumatoid arthritis in 19,562 patients during 89,710 person-years of observation

OBJECTIVE: To ascertain the relationship between anti-tumor necrosis factor (anti-TNF) therapy, methotrexate (MTX), and the risk of lymphoma in patients with rheumatoid arthritis (RA). This report updates our previous report during 29,314 person-years of followup. METHODS: Participants in the National Data Bank for Rheumatic Diseases (NDB) longitudinal study of long-term outcomes of RA completed semiannual questionnaires from 1998 through 2005, during 89,710 person-years of followup. Lymphoma reports were validated by medical records. The association between lymphoma and treatment was investigated using conditional logistic regression, adjusted for severity and demographic covariates. RESULTS: Of the 19,591 participants, 55.3% received biologic agents and 68.0% received MTX while enrolled in the NDB. The lymphoma incidence rate was 105.9 (95% confidence interval [95% CI] 86.6-129.5) per 100,000 person-years of exposure. Compared with the SEER (Surveillance, Epidemiology, and End-Results) lymphoma database, the standardized incidence ratio was 1.8 (95% CI 1.5-2.2). The odds ratio (OR) for lymphoma in patients who received anti-TNF therapy compared with patients who did not receive anti-TNF therapy was 1.0 (95% CI 0.6-1.8 [P = 0.875]). The OR for lymphoma in patients who received anti-TNF plus MTX therapy compared with patients who received MTX treatment alone was 1.1 (95% CI 0.6-2.0 [P = 0.710]). Infliximab and etanercept considered individually also were not associated with a risk of lymphoma. CONCLUSION: In a study of lymphoma in 19,591 RA patients over 89,710 person-years of followup, which included exposure to anti-TNF therapy in 10,815 patients, we did not observe evidence for an increase in the incidence of lymphoma among patients who received anti-TNF therapy.     

Incidence and mortality of interstitial lung disease in rheumatoid arthritis: A population‐based study

Objective

Interstitial lung disease (ILD) has been recognized as an important comorbidity in rheumatoid arthritis (RA). We undertook the current study to assess incidence, predictors, and mortality of RA‐associated ILD.

Methods

We examined a population‐based incidence cohort of patients with RA and a matched cohort of individuals without RA. All subjects were followed up longitudinally. The lifetime risk of ILD was estimated. Cox proportional hazards models were used to compare the incidence of ILD between cohorts, to investigate predictors, and to explore the impact of ILD on survival.

Results

Patients with RA (n = 582) and subjects without RA (n = 603) were followed up for a mean of 16.4 and 19.3 years, respectively. The lifetime risk of developing ILD was 7.7% for RA patients and 0.9% for non‐RA subjects. This difference translated into a hazard ratio (HR) of 8.96 (95% confidence interval [95% CI] 4.02–19.94). The risk of developing ILD was higher in RA patients who were older at the time of disease onset, in male patients, and in individuals with more severe RA. The risk of death for RA patients with ILD was 3 times higher than in RA patients without ILD (HR 2.86 [95% CI 1.98–4.12]). Median survival after ILD diagnosis was only 2.6 years. ILD contributed ∼13% to the excess mortality of RA patients when compared with the general population.

Conclusion

Our results emphasize the increased risk of ILD in patients with RA. The devastating impact of ILD on survival provides evidence that development of better strategies for the treatment of ILD could significantly lower the excess mortality among individuals with RA.

     

Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study

OBJECTIVE: A high frequency of infections complicating rheumatoid arthritis (RA) has been described in reports of case series. This retrospective longitudinal cohort study was undertaken to compare the frequency of infections in a population-based incidence cohort of RA patients with that in a group of individuals without RA from the same population. METHODS: RA patients included all members of an incidence cohort of Rochester, Minnesota residents ages >or=18 years who were first diagnosed as having RA between 1955 and 1994. One age- and sex-matched subject without RA was selected for each patient with RA. Study subjects were followed up by review of their entire medical record until death, migration from the area, or study end (January 1, 2000), and details of all documented infections, along with information on potential risk factors for infection, were recorded. Hazard ratios for infections were estimated using stratified Andersen-Gill proportional hazards models, with adjustment for potential confounders. RESULTS: The 609 RA patients and 609 non-RA study subjects (mean age 58.0 years; 73.1% female) were followed up for a mean of 12.7 years and 15.0 years, respectively, reflecting higher mortality among the group with RA. Hazards ratios for objectively confirmed infections, infections requiring hospitalization, and any documented infection in patients with RA were 1.70 (95% confidence interval [95% CI] 1.42-2.03), 1.83 (95% CI 1.52-2.21), and 1.45 (95% CI 1.29-1.64), respectively, after adjustment for age, sex, smoking status, leukopenia, corticosteroid use, and diabetes mellitus. Sites of infection with the highest risk ratios were bone, joints, skin, soft tissues, and the respiratory tract. CONCLUSION: In this study, patients with RA were at increased risk of developing infections compared with non-RA subjects. This may be due to immunomodulatory effects of RA, or to agents with immunosuppressive effects used in its treatment.     

Increased risk of ischemic heart disease in young patients with migraine: A population-based,propensity score-matched,longitudinal follow-up study

Background

The association between migraine and the risk of ischemic heart disease (IHD) remains controversial. The purpose of the present population-based, propensity score-matched follow-up study was to investigate whether young migraineurs are at a higher risk of developing IHD.

Methods

A total of 11,541 subjects aged between 18 and 45 years with at least two ambulatory visits with the principal diagnosis of migraine in 2001 were enrolled in the migraine group. We used a logistic regression model that included age, sex, pre-existing comorbidities, and socioeconomic status as covariates to compute the propensity score. The non-migraine group consisted of 11,541 propensity score-matched, randomly sampled subjects without migraine. The 3-year IHD-free survival rate and the cumulative incidence of IHD were estimated using the Kaplan–Meier method. Stratified Cox proportional hazard regression with patients matched by propensity score was used to estimate the effect of migraine on the risk of developing subsequent IHD.

Results

The mean age in both groups was 32.3 years. During follow-up, 121 subjects in the migraine group and 55 in the non-migraine group developed IHD. The incidence rate of IHD was 4.56 (95% confidence interval [CI], 3.78 to 5.44) per 1000 person-years in the migraine group and 2.00 (95% CI, 1.51 to 2.61) per 1000 person-years in the non-migraine group. Compared to the non-migraine group, the HR of IHD for the migraine group was 2.50 (95% CI, 1.78 to 3.52, P < 0.0001).

Conclusions

This study showed an increased risk of developing IHD in young patients with newly diagnosed migraine.