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1.  Frequency of radiologic procedures in patients with rheumatoid arthritis 
Background
Patients with rheumatoid arthritis (RA) undergo radiologic investigations for disease and comorbidity evaluation. The actual use of radiologic imaging in RA is unknown.
Methods
Using the Rochester Epidemiology Project medical record linkage system, adult patients from previously assembled population-based cohorts of Olmsted County, Minnesota residents who fulfilled 1987 ACR criteria for RA in 1988-2007, and comparator subjects without RA of similar age and sex were studied. Data on all radiologic procedures performed were collected.
Results
The study included 650 patients with RA and 650 patients without RA. Patients with RA had significantly more radiographs of the chest (RR: 1.33, 95% CI: 1.28-1.38), upper extremity (RR: 2.97, 95% CI: 2.80-3.17), lower extremity (RR: 2.05, 95% CI: 1.94-2.16), spine (RR: 1.46, 95% CI: 1.35-1.59), and hip, pelvis or sacroiliac joints (RR: 1.14, 95% CI: 1.03-1.26), as well as bone radionuclide (RR: 1.90, 95% CI: 1.50-2.44) and DXA imaging (RR: 1.77, 95% CI: 1.59-1.98) compared to patients without RA. Among patients with RA, having RF+ was associated with an increased likelihood of undergoing radiologic procedures (RR: 1.05, 95% CI: 1.02, 1.07). Women with RA underwent more imaging procedures than men (RR: 1.20 95% CI: 1.16-1.23).
Conclusions
Patients with RA undergo more radiologic procedures than patients without RA. Among patients with RA, women and patients with positive RF have more radiologic procedures. The utilization of radiography is likely a reflection of overall disease burden; the role of various imaging modalities is in flux and will likely change in ensuing years.
doi:10.1097/RHU.0000000000000164
PMCID: PMC4371515  PMID: 25539428
Radiographs; resource utilization; rheumatoid arthritis
2.  Evaluation of Myocardial Function in Patients with Rheumatoid Arthritis Using Strain Imaging by Speckle-Tracking Echocardiography 
Annals of the rheumatic diseases  2013;73(10):1833-1839.
Objectives
Patients with rheumatoid arthritis (RA) are at increased risk for cardiovascular disease (CVD), although strategies to detect sub-clinical CVD are poorly characterized. The purpose of this study was to assess myocardial function by speckle-tracking echocardiography strain imaging in RA patients without known CVD.
Methods
Eighty-seven RA patients selected from a population-based sample underwent echocardiography. Left (LV) and right ventricular (RV) longitudinal peak systolic strain were measured. A subset of 59 RA patients was compared with 59 age, gender and race-matched subjects with normal echocardiography and no CVD or risk factors.
Results
The mean age of matched RA and normal patients was 55.7±12.1 and 54.5±12.2 years (p=0.42), respectively, and 45 (76%) were female in each group. Global LV (−15.7 ±3.2% versus −18.1 ±2.4%, p<0.001) and RV strain (−17.9 ± 4.7% versus −20.7±2.4%, p<0.001) were reduced in RA patients compared to normal patients. Among all 87 RA patients, the mean disease duration and C-reactive protein at echocardiography were 10.0±6.1 years and 3.5±3.7 mg/L, and 74% were seropositive. Adjusted univariate regression analysis demonstrated a significant correlation between global LV strain and RA health assessment questionnaire disability index (p=0.032), and borderline associations with prior use of oral corticosteroids (p=0.062) and methotrexate (p=0.054) after adjustment for age, gender, blood pressure, body mass index, heart rate and LV mass index.
Conclusions
Global longitudinal LV and RV strain were reduced in RA patients compared with healthy patients. Strain abnormalities correlated with RA disease severity. Strain imaging by echocardiography may detect early myocardial dysfunction in RA.
doi:10.1136/annrheumdis-2013-203314
PMCID: PMC3895498  PMID: 23873875
rheumatoid arthritis; cardiovascular disease; strain; speckle-tracking echocardiography
3.  Long-term blood pressure variability in patients with rheumatoid arthritis (RA) and its impact on cardiovascular events and all-cause mortality in RA: a population-based comparative cohort study 
The Journal of rheumatology  2014;41(8):1638-1644.
Objectives
To examine long-term visit-to-visit blood pressure (BP) variability in rheumatoid arthritis (RA) vs non-RA subjects and to assess its impact on cardiovascular events and mortality in RA.
Methods
Clinic BP measures were collected in a population-based incident cohort of RA patients (1987 ACR criteria met between 1/1/1995 and 1/1/2008) and non-RA subjects. BP variability was defined as within-subject standard deviation (SD) in systolic and diastolic BP.
Results
Study included 442 RA patients (mean age 55.5 years, 70% females) and 424 non-RA subjects (mean age 55.7 years, 69% females). RA patients had higher visit-to-visit variability in systolic BP (13.8±4.7 mm Hg), than non-RA subjects (13.0±5.2 mm Hg, p=0.004). Systolic BP variability declined after the index date in RA (p<0.001), but not in the non-RA cohort (p=0.73), adjusting for age, sex and calendar year of RA. During the mean follow-up of 7.1 years, 33 cardiovascular events and 57 deaths occurred in RA cohort. Visit-to-visit systolic BP variability was associated with increased risk of cardiovascular events (hazard ratio [HR] per 1 mm Hg increase in BP variability 1.12, 95% confidence interval [CI] 1.01-1.25); diastolic BP variability was associated with all-cause mortality in RA (HR 1.14, 95%CI 1.03-1.27), adjusting for systolic and diastolic BP, body mass index, smoking, diabetes, dyslipidemia, use of antihypertensives.
Conclusion
Patients with RA had higher visit-to-visit systolic BP variability vs non-RA subjects. There was a significant decline in systolic BP variability after RA incidence. Higher visit-to-visit BP variability was associated with adverse cardiovascular outcomes and all-cause mortality in RA.
doi:10.3899/jrheum.131170
PMCID: PMC4159667  PMID: 24986852
4.  The Influence of Early Menopause on Cardiovascular Risk in Women with Rheumatoid Arthritis 
The Journal of rheumatology  2014;41(7):1270-1275.
Objective:
Early menopause is associated with an increased risk for developing rheumatoid arthritis (RA). The risk for cardiovascular disease (CVD) in women increases following menopause. Since RA is associated with an increased risk of CVD, this study was undertaken to determine if early menopause affects the risk of developing CVD in women with RA.
Methods:
A population-based inception cohort of 600 women with RA who fulfilled 1987 ACR criteria for RA between 1955 and 2007 and were age ≥ 45 years at diagnosis was assembled and followed. Age at menopause and duration of hormone replacement therapy (HRT), along with occurrence of CVD was ascertained by review of medical records. Cox proportional hazard models compared women who underwent early menopause (natural or artificial menopause at age ≤ 45 years) to those within the cohort who did not undergo early menopause.
Results:
Of 600 women, 79 exprienced early menopause. Women who underwent early menopause were at significantly higher risk for developing CVD when compared to women who did not (hazard ratio (HR): 1.56; 95% CI: 1.08-2.26).
Conclusion:
The risk of CVD in women with RA was higher in those who experience early menopause, and like other known risk factors should increase clinician concern for development of CVD in these patients.
doi:10.3899/jrheum.131234
PMCID: PMC4112509  PMID: 24882842
rheumatoid arthritis; menopause; cardiovascular disease
5.  Do solar cycles influence giant cell arteritis and rheumatoid arthritis incidence? 
BMJ Open  2015;5(5):e006636.
Objective
To examine the influence of solar cycle and geomagnetic effects on the incidence of giant cell arteritis (GCA) and rheumatoid arthritis (RA).
Methods
We used data from patients with GCA (1950–2004) and RA (1955–2007) obtained from population-based cohorts. Yearly trends in age-adjusted and sex-adjusted incidence were correlated with the F10.7 index (solar radiation at 10.7 cm wavelength, a proxy for the solar extreme ultraviolet radiation) and AL index (a proxy for the westward auroral electrojet and a measure of geomagnetic activity). Fourier analysis was performed on AL, F10.7, and GCA and RA incidence rates.
Results
The correlation of GCA incidence with AL is highly significant: GCA incidence peaks 0–1 year after the AL reaches its minimum (ie, auroral electrojet reaches a maximum). The correlation of RA incidence with AL is also highly significant. RA incidence rates are lowest 5–7 years after AL reaches maximum. AL, GCA and RA incidence power spectra are similar: they have a main peak (periodicity) at about 10 years and a minor peak at 4–5 years. However, the RA incidence power spectrum main peak is broader (8–11 years), which partly explains the lower correlation between RA onset and AL. The auroral electrojets may be linked to the decline of RA incidence more strongly than the onset of RA. The incidences of RA and GCA are aligned in geomagnetic latitude.
Conclusions
AL and the incidences of GCA and RA all have a major periodicity of about 10 years and a secondary periodicity at 4–5 years. Geomagnetic activity may explain the temporal and spatial variations, including east-west skewness in geographic coordinates, in GCA and RA incidence, although the mechanism is unknown. The link with solar, geospace and atmospheric parameters need to be investigated. These novel findings warrant examination in other populations and with other autoimmune diseases.
doi:10.1136/bmjopen-2014-006636
PMCID: PMC4442155  PMID: 25979866
RHEUMATOLOGY; EPIDEMIOLOGY
6.  A novel measure of socioeconomic status using individual housing data to assess the association of SES with rheumatoid arthritis and its mortality: a population-based case–control study 
BMJ Open  2015;5(4):e006469.
Objectives
To assess whether HOUSES (HOUsing-based index of socioeconomic status (SES)) is associated with risk of and mortality after rheumatoid arthritis (RA).
Design
We conducted a population-based case–control study which enrolled population-based RA cases and their controls without RA.
Setting
The study was performed in Olmsted County, Minnesota.
Participants
Study participants were all residents of Olmsted County, Minnesota, with RA identified using the 1987 American College of Rheumatology criteria for RA from 1 January 1988, to 31 December 2007, using the auspices of the Rochester Epidemiology Project. For each patient with RA, one control was randomly selected from Olmsted County residents of similar age and gender without RA.
Primary and secondary outcome measure
The disease status was RA cases and their matched controls in relation to HOUSES as an exposure. As a secondary aim, post-RA mortality among only RA cases was an outcome event. The associations of SES measured by HOUSES with the study outcomes were assessed using logistic regression and Cox models. HOUSES, as a composite index, was formulated based on a summed z-score for housing value, square footage and number of bedrooms and bathrooms.
Results
Of the eligible 604 participants, 418 (69%) were female; the mean age was 56±15.6 years. Lower SES, as measured by HOUSES, was associated with the risk of developing RA (0.5±3.8 for controls vs −0.2±3.1 for RA cases, p=0.003), adjusting for age, gender, calendar year of RA index date, smoking status and BMI. The lowest quartile of HOUSES was significantly associated with increased post-RA mortality compared to higher quartiles of HOUSES (HR 1.74; 95% CI 1.10 to 2.74; p=0.017) in multivariate analysis.
Conclusions
Lower SES, as measured by HOUSES, is associated with increased risk of RA and mortality after RA. HOUSES may be a useful tool for health disparities research concerning rheumatological outcomes when conventional SES measures are unavailable.
doi:10.1136/bmjopen-2014-006469
PMCID: PMC4420936  PMID: 25926142
EPIDEMIOLOGY; RHEUMATOLOGY
7.  Cardiovascular Comorbidity in Rheumatic Diseases A Focus on Heart Failure 
Heart failure clinics  2014;10(2):339-352.
doi:10.1016/j.hfc.2013.10.003
PMCID: PMC3964373  PMID: 24656110
Rheumatoid arthritis; Cardiovascular disease; Systemic lupus erythematosus; Heart failure
8.  Occurrence and Impact of Lower Extremity Ulcer in Rheumatoid Arthritis - A Population Based Study 
The Journal of rheumatology  2014;41(3):437-443.
Objectives
To assess the occurrence, risk factors, morbidity and mortality associated with lower extremity (LE) ulcers in patients with rheumatoid arthritis (RA).
Methods
Retrospective review of Olmsted County, Minnesota residents who first fulfilled 1987 American College of Rheumatology criteria for RA in 1980–2007 with follow-up to death, migration or April 2012. Only LE ulcers that developed after the diagnosis of RA were included.
Results
The study included 813 patients with 9771 total person-years of follow-up. 125 patients developed LE ulcers (total of 171 episodes), corresponding to a rate of occurrence of 1.8 episodes per 100 person-years (95% confidence interval [CI]: 1.5, 2.0 per 100 person-years). The cumulative incidence of first LE ulcers was 4.8% at 5 years after diagnosis of RA and increased to 26.2% by 25 years. Median time for the LE ulcer to heal was 30 days. Ten of 171 (6%) episodes led to amputation. LE ulcers in RA were associated with increased mortality (HR 2.42; 95% CI: 1.71, 3.42) adjusted for age, sex and calendar year. Risk factors for LE ulcers included age (HR 1.73 per 10 year increase; 95% CI: 1.47, 2.04); rheumatoid factor positivity (HR 1.63; 95% CI: 1.05, 2.53); presence of rheumatoid nodules (HR 2.14; 95% CI: 1.39, 3.31); and venous thromboembolism (HR 2.16; 95% CI: 1.07, 4.36).
Conclusions
LE ulcers are common among patients with RA. The cumulative incidence increased by 1% per year. A significant number require amputation. Patients with RA who have LE ulcers are at two-fold risk for premature mortality.
doi:10.3899/jrheum.130392
PMCID: PMC4251738  PMID: 24429171
rheumatoid arthritis; incidence; lower extremity ulcer
9.  Increased Incidence of Atrial Fibrillation in Patients with Rheumatoid Arthritis 
BioMed Research International  2015;2015:809514.
Objective. To investigate the incidence of atrial fibrillation (AF) among patients with rheumatoid arthritis (RA) compared to the general population. Methods. A population-based inception cohort of Olmsted County, Minnesota, residents with incident RA in 1980–2007 and a cohort of non-RA subjects from the same population base were assembled and followed until 12/31/2008. The occurrence of AF was ascertained by medical record review. Results. The study included 813 patients with RA and 813 non-RA subjects (mean age 55.9 (SD:15.7) years, 68% women in both cohorts). The prevalence of AF was similar in the RA and non-RA cohorts at RA incidence/index date (4% versus 3%; P = 0.51). The cumulative incidence of AF during follow-up was higher among patients with RA compared to non-RA subjects (18.3% versus 16.3% at 20 years; P = 0.048). This difference persisted after adjustment for age, sex, calendar year, smoking, and hypertension (hazard ratio: 1.46; 95% CI: 1.07, 2.00). There was no evidence of a differential impact of AF on mortality in patients with RA compared to non-RA subjects (hazard ratio 2.5 versus 2.8; interaction P = 0.31). Conclusion. The incidence of AF is increased in patients with RA, even after adjustment for AF risk factors. AF related mortality risk did not differ between patients with and without RA.
doi:10.1155/2015/809514
PMCID: PMC4359868  PMID: 25815336
10.  Heart Disease and Rheumatoid Arthritis: Understanding the Risks 
Annals of the rheumatic diseases  2010;69(0 1):i61-i64.
Patients with rheumatoid arthritis (RA) are at increased risk of mortality compared with the general population. Evidence suggests that this increased mortality can largely be attributed to increased cardiovascular (CV) death. In a retrospective study of an inception cohort of RA patients in Rochester, MN, we investigated the contribution of traditional and RA-specific risk factors towards this increased risk of CV morbidity and mortality. Several traditional CV risk factors were found to behave differently in RA patients. In addition, their associations with CV disease are weaker in RA patients as increased inflammation associated with RA appears to also contribute substantially to the increased CV mortality. Furthermore, the impact of disease modifying anti-rheumatic drugs (DMARDs) and biologics on CV disease in RA patients is unclear. CV risk scores for the general population may underestimate risk for RA patients. Together with other studies that have demonstrated similar associations between RA and CV mortality, these data suggest that optimal control of CV risk factors is important, but not sufficient in RA patients. RA-specific CV risk prediction tools are needed, as well as clinical trials to assess the impact of therapies and tight control of inflammation in RA patients on CV outcomes and mortality.
doi:10.1136/ard.2009.119404
PMCID: PMC4308040  PMID: 19995747
11.  Large-Vessel Involvement in Giant Cell Arteritis: A Population-Based Cohort Study of the Incidence-Trends and Prognosis 
Annals of the rheumatic diseases  2012;72(12):1989-1994.
Objectives
To evaluate incidence trends and timing of large-vessel (LV) manifestations in patients with giant cell arteritis (GCA), and, to examine the influence of LV manifestations on survival.
Methods
A population-based incident cohort of patients diagnosed with GCA between 1950 and 2004 was used. LV involvement was defined as large artery stenosis or aortic aneurysm/dissection that developed in the 1 year prior to GCA diagnosis or any time thereafter. Patients were followed until death or December 31, 2009.
Results
The study included 204 patients, 80% women, mean age at diagnosis of GCA 76.0 years (± 8.2 years). Median length of follow-up was 8.8 years. The cumulative incidence of any LV manifestation at 10 years was 24.9% for patients diagnosed with GCA between 1980–2004 compared to 8.3% for patients diagnosed with GCA between 1950 and 1979. The incidence of any LV event was high within the first year of GCA diagnosis. The incidence of aortic aneurysm/dissection increased 5 years after GCA diagnosis.
Compared to the general population, survival was decreased in patients with an aortic aneurysm/dissection (p<0.001) but not in patients with large-artery stenosis (p=0.11). Patients with GCA and aortic manifestations had higher than expected number of deaths from cardiovascular and pulmonary causes compared to the general population. Among patients with GCA, aortic manifestations were associated with increased mortality (HR: 3.4; 95% CI: 2.2, 5.4).
Conclusions
Screening for aortic aneurysms should be considered in all patients with GCA with vigilance 5 years after incidence. Aortic aneurysm/dissection is associated with increased mortality in GCA.
doi:10.1136/annrheumdis-2012-202408
PMCID: PMC4112513  PMID: 23253927
Giant cell arteritis; aortic aneurysm; aortic dissection; large-artery stenosis; survival
12.  Rheumatoid Arthritis and Cardiovascular Disease 
American heart journal  2013;166(4):622-628.e1.
Background
Rheumatic disease and heart disease share common underpinnings involving inflammation. The high levels of inflammation that characterize rheumatic diseases provide a “natural experiment” to help elucidate the mechanisms by which inflammation accelerates heart disease. Rheumatoid arthritis (RA) is the most common of the rheumatic diseases and has the best studied relationships with heart disease.
Methods
Review of current literature on heart disease and rheumatoid arthritis
Results
Patients with RA have an increased risk of developing heart disease that is not fully explained by traditional cardiovascular risk factors. Therapies used to treat RA may also affect the development of heart disease; by suppressing inflammation, they may also reduce the risk of heart disease. However, their other effects, as in the case of steroids, may increase heart disease risk.
Conclusions
Investigations of the innate and adaptive immune responses occurring in RA may delineate novel mechanisms in the pathogenesis of heart disease, and help identify novel therapeutic targets for the prevention and treatment of heart disease.
doi:10.1016/j.ahj.2013.07.010
PMCID: PMC3890244  PMID: 24093840
13.  Are Young Women and Men with Rheumatoid Arthritis at Risk for Fragility Fractures? A Population-Based Study 
The Journal of rheumatology  2013;40(10):1669-1676.
Objective
Older women and men with rheumatoid arthritis (RA) are at increased risk for fractures, but limited information is available on fracture risk in younger individuals with RA, and whether such risk occurs early following disease onset or only when older. We determined the risk for fractures in both young and older women and men following RA diagnosis.
Methods
We studied a population-based inception cohort with RA from Olmsted County, Minnesota. We identified 822 women and 349 men diagnosed with RA between 1955 and 2007 (308 women and 110 men diagnosed before age 50) and an equal number of paired non-RA subjects, matched by sex and birth year. Incident fractures were collected through review of complete (inpatient and outpatient) medical records available through the linkage system of the Rochester Epidemiology Project.
Results
The hazard ratio (HR) [95% CI] for a non-pathologic fracture occurring from no more than moderate trauma was 1.63 [1.36–1.96] for women and 1.40 [1.02–1.93] for men with RA. Findings were consistent for women and men diagnosed with RA at age ≥ 50 years (HR: 1.43 [1.16–1.77] and 1.34 [0.92–1.94], respectively), or at age < 50 years (HR: 2.34 [1.61–3.42] and 1.74 [0.91–3.30], respectively). However, young women, but not young men, with RA were at increased fracture risk even before age 50 years (HR: 1.95 [1.08–3.51] and 0.82 [0.28–2.45], respectively).
Conclusion
Young men with RA are at increased risk for fractures only when older, whereas young women with RA have an elevated fracture risk even while still young.
doi:10.3899/jrheum.121493
PMCID: PMC3910326  PMID: 23950189
rheumatoid arthritis; bone fractures; osteoporosis; epidemiology
14.  The Impact of Statin Use on Lipid Levels in Statin-Naive Patients with Rheumatoid Arthritis (RA) vs. non-RA Subjects: Results from a Population-Based Study 
Arthritis care & research  2013;65(10):1592-1599.
Objectives
To examine lipid profiles among statin-naive patients with rheumatoid arthritis (RA) and those without RA before and after the initiation of statins.
Methods
Information regarding lipid measures and statin use was gathered in a population-based incident cohort of patients with RA (1987 ACR criteria first met between 1/1/1988 and 1/1/2008) and in a cohort of non-RA subjects from the same underlying population. Only patients with no prior history of statin use were included.
Results
The study included 161 patients with RA (mean age 56.3 years, 57% female) and 221 non-RA subjects (mean age 56.0 years, 66% female). Prior to the start of statins, the levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) were lower in RA vs non-RA cohort (p<0.001 and p=0.003, respectively). The absolute and percent change in LDL after at least 90 days of statin use tended to be smaller in RA vs non-RA cohort (p=0.03 and p=0.09). After at least 90 days of statin use patients with RA were less likely to achieve therapeutic goals for LDL than the non-RA subjects (p=0.046). Increased erythrocyte sedimentation rate (ESR) at baseline (OR 0.47; 95% CI 0.26, 0.85) was associated with lower likelihood of achieving therapeutic LDL goals.
Conclusion
Patients with RA had lower TC and LDL levels before statin initiation and lower likelihood of achieving therapeutic LDL goals following statin use than the non-RA subjects. Some RA disease characteristics, in particular ESR at baseline, may have an adverse impact on achieving therapeutic LDL goals.
doi:10.1002/acr.22029
PMCID: PMC3788038  PMID: 23592565
rheumatoid arthritis; lipids; statins
15.  Accelerated Aging Influences Cardiovascular Disease Risk in Rheumatoid Arthritis 
Arthritis and rheumatism  2013;65(10):2562-2566.
OBJECTIVE
To determine whether the impact of aging on cardiovascular disease (CVD) risk in the general population (as estimated by the Framingham risk score [FRS]) differs in patients with rheumatoid arthritis (RA).
METHODS
A population-based inception cohort of Olmsted County, Minnesota residents aged ≥30 years who fulfilled 1987 ACR criteria for RA in 1988–2008 was assembled and followed until death, migration, or 7-1-2012. Data on CVD events were collected by medical record review. The 10-year FRS for CVD was calculated. Cox models adjusted for FRS were used to examine the influence of age on CVD risk.
RESULTS
The study included 563 patients with RA without prior CVD (mean age: 55 years, 72% women; 69% seropositive [i.e., rheumatoid factor and/or anti-citrullinated protein antibody positive]). During a mean follow-up of 8.2 years, 98 patients developed CVD (74 seropositive and 24 seronegative), but FRS predicted only 59.7 events (35.4 seropositive and 24.3 seronegative). The gap between observed and predicted CVD risk increased exponentially across age, and the age effect on CVD risk in seropositive RA was nearly double its effect in the general population with additional log(age) coefficients of 2.91 for women (p=0.002) and 2.06 for men (p=0.027).
CONCLUSION
Age exerts an exponentially increasing effect on CVD risk in seropositive RA, but no increased effect among seronegative patients. The causes of accelerated aging in patients with seropositive RA deserve further investigation.
doi:10.1002/art.38071
PMCID: PMC3966134  PMID: 23818136
accelerated aging; rheumatoid arthritis; cardiovascular disease
16.  Hyperuricemia and Incident Cardiovascular Disease and Noncardiac Vascular Events in Patients with Rheumatoid Arthritis 
Objective. To evaluate whether hyperuricemia is a risk factor for cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). Methods. A population-based inception cohort of patients diagnosed between 1980 and 2007 with adult-onset RA was assembled. A comparison cohort of age- and sex-matched subjects without RA (non-RA) was also assembled. All clinically obtained uric acid values were collected. CVD and noncardiac vascular events were recorded for each patient. Cox proportional hazards models were used to assess the impact of hyperuricemia on development of CVD, mortality, and noncardiac vascular disease. Results. In patients without RA, hyperuricemia was associated with heart failure (HR: 1.95; 95% CI: 1.13–3.39) and CVD (HR: 1.59; 95% CI: 0.99–2.55). In patients with RA, hyperuricemia was not significantly associated with CVD but was significantly associated with peripheral arterial events (HR: 2.52; 95% CI: 1.17–5.42). Hyperuricemia appeared to be more strongly associated with mortality among RA patients (HR: 1.96; 95% CI: 1.45–2.65) than among the non-RA subjects (HR: 1.57; 95% CI: 1.09–2.24). Conclusion. In patients with RA, hyperuricemia was a significant predictor of peripheral arterial events and mortality but not of CVD.
doi:10.1155/2014/523897
PMCID: PMC4150464  PMID: 25197282
17.  Incidence and Mortality of Obstructive Lung Disease in Rheumatoid Arthritis: A Population-Based Study 
Arthritis care & research  2013;65(8):1243-1250.
OBJECTIVE
Pulmonary disease represents an important extra-articular manifestation of rheumatoid arthritis (RA). While the association of RA and interstitial lung disease is widely acknowledged, obstructive lung disease (OLD) in RA is less well understood. We therefore aimed to assess incidence, risk factors and mortality of OLD in patients with RA.
METHODS
We examined a population-based incident cohort of patients with RA and a comparison cohort of individuals without RA. OLD was defined using a strict composite criterion. Cox-proportional hazards models were used to compare OLD incidence between the RA and comparator cohort, to investigate risk factors and to explore the impact of OLD on patient survival.
RESULTS
594 patients with RA and 596 subjects without RA were followed for a mean of 16.3 and 19.4 years, respectively. The lifetime risk of developing OLD was 9.6% for RA patients and 6.2% for subjects without RA; hazard ratio (HR) 1.54 (95% CI 1.01 to 2.34). The risk of developing OLD was higher among male patients, current or former smokers and for individuals with more severe RA. Survival of RA patients diagnosed with OLD was worse compared to those without OLD (HR 2.09, 95% CI 1.47 to 2.97).
CONCLUSION
Patients with RA are at higher risk of developing OLD, which is significantly associated with premature mortality. Effective diagnostic and therapeutic strategies to detect and manage OLD in patients with RA may help to improve survivorship in these patients.
doi:10.1002/acr.21986
PMCID: PMC4017238  PMID: 23436637
obstructive lung disease; rheumatoid arthritis; incidence; risk factors; mortality
18.  Use of lipid lowering agents in rheumatoid arthritis: a population based cohort study 
The Journal of rheumatology  2013;40(7):1082-1088.
Objective
Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease and mortality. Lipid-lowering therapy is reportedly underused in patients with RA. However, longitudinal cohort studies comparing the use of lipid-lowering medications in patients with RA vs the general population are lacking.
Methods
Cardiovascular risk factors, lipid measures and use of lipid-lowering agents were assessed in a population-based inception cohort of patients with RA and a cohort of non-RA subjects followed from 1/1/1988 to 12/31/2008. The National Cholesterol Education Program (NCEP) adult treatment panel III (ATP III) guidelines were assessed at the time of each lipid measure throughout follow-up. Time from meeting guidelines to initiation of lipid-lowering agents was assessed using Kaplan-Meier methods.
Results
The study population included 412 RA and 438 non-RA patients with ≥1 lipid measure during follow-up and no prior use of lipid lowering agents. Rates of lipid testing were lower among patients with RA compared to non-RA subjects. Among patients who met NCEP ATP III criteria for lipid-lowering therapy (n=106 RA and n=120 non-RA), only 27% of RA and 26% of non-RA subjects initiated lipid-lowering agents within 2 years of meeting guidelines for initiation.
Conclusions
There was substantial undertreatment in both the RA and non-RA cohorts who met NCEP ATP III criteria for initiation of lipid-lowering agents. Patients with RA did not have as frequent lipid testing as individuals in the general population.
doi:10.3899/jrheum.121302
PMCID: PMC3891914  PMID: 23637326
rheumatoid arthritis; lipids; lipid lowering therapy
19.  Rheumatoid Arthritis is Associated with Left Ventricular Concentric Remodeling: Results of a Population-based Cross-sectional Study 
Arthritis and rheumatism  2013;65(7):1713-1718.
Objective
To study left ventricular (LV) geometry in patients with rheumatoid arthritis (RA) who have no heart failure (HF) versus subjects without either RA or HF, and to determine the impact of RA on LV remodeling.
Methods
A cross-sectional, community-based study was conducted among adult (≥50 years) RA patients and age- and sex-matched non-RA subjects without a history of HF. All participants underwent a standard 2D/Doppler echocardiography. LV geometry was classified into four categories based on relative wall thickness and sex-specific cut-offs for LV mass index: concentric remodeling, concentric hypertrophy, eccentric hypertrophy, or normal geometry.
Results
The study included 200 RA patients and 600 matched non-RA subjects (mean age 65; 74% female in both cohorts). RA patients were significantly more likely to have abnormal LV geometry than non-RA subjects (odds ratio [OR] 1.44; 95% confidence interval [CI] 1.03, 2.00), adjusting for cardiovascular risk factors and comorbidities. Among those with abnormal LV geometry, RA patients had significantly increased odds of concentric LV remodeling (OR 4.73; 95% CI 2.85, 7.83). In linear regression analyses, LV mass index appeared to be lower in RA patients currently using corticosteroids (Beta +/− standard error: −0.082 +/− 0.027; p=0.002), adjusting for cardiovascular risk factors and comorbidities.
Conclusion
RA was strongly associated with abnormal LV remodeling, particularly, with concentric LV remodeling, among patients without HF. This association was significant beyond adjustment for cardiovascular risk factors and comorbidities. RA disease related factors may promote changes in LV geometry. The biological mechanisms underlying LV remodeling warrant further investigation.
doi:10.1002/art.37949
PMCID: PMC3914147  PMID: 23553738
rheumatoid arthritis; left ventricular remodeling; risk factors
20.  Incidence and time trends of Herpes zoster in rheumatoid arthritis: a population-based cohort study 
Arthritis care & research  2013;65(6):854-861.
Objective
To determine the incidence, time trends, risk factors and severity of herpes zoster (HZ) in a population-based incidence cohort of patients with rheumatoid arthritis (RA) compared to a group of individuals without RA from the same population.
Methods
All residents of Olmsted County, MN who first fulfilled 1987 American College of Rheumatology criteria for RA between 1/1/1980 and 12/31/2007 and a cohort of similar residents without RA were assembled and followed by retrospective chart review until death, migration, or 12/31/2008.
Results
There was no difference in the presence of HZ prior to RA incidence/index date between the cohorts (p=0.85). During follow-up 84 patients with RA (rate: 12.1 per 1000 person-years) and 44 subjects without RA (rate: 5.4 per 1000 person-years) developed HZ. Patients with RA were more likely to develop HZ than those without RA (hazard ratio: 2.4; 95% confidence interval: 1.7, 3.5). Patients diagnosed with RA in 1995–2007 had a higher likelihood of developing HZ than those diagnosed in 1980–1994. Erosive disease, previous joint surgery, use of hydroxychloroquine and corticosteroids were significantly associated with the development of HZ in RA, while the use of methotrexate or biologic agents was not. Complications of HZ occurred at a similar rate in both cohorts.
Conclusion
The incidence of HZ is increased in RA and has risen in recent years. The increasing incidence of HZ in more recent years is also noted in the general population. RA disease severity is associated with development of HZ.
doi:10.1002/acr.21928
PMCID: PMC3674119  PMID: 23281295
rheumatoid arthritis; herpes zoster
21.  Incidence and Mortality of Interstitial Lung Disease in Rheumatoid Arthritis: A Population Based Study 
Arthritis and rheumatism  2010;62(6):1583-1591.
Objective
Interstitial lung disease (ILD) has been recognized as an important co-morbidity in rheumatoid arthritis (RA). We aimed to assess incidence, risk factors 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 longitudinally until death, migration or January 1, 2006. The lifetime risk of ILD was estimated and Cox models were used to compare the incidence of ILD between cohorts, to investigate possible risk factors and to explore the impact of ILD on patient survival.
Results
582 patients with RA and 603 subjects without RA were followed 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 subjects without RA. This difference translated into a hazard ratio of 8.96 (95% CI 4.02, 19.94). The risk of developing ILD was higher in patients with older age at RA onset, among male patients and for individuals with parameters that indicate more severe RA.
Survival of RA patients diagnosed with ILD was worse compared to RA patients without ILD (HR 2.86, 95% CI 1.98, 4.12). ILD contributed approximately 13% to the excess mortality of patients with RA patients when compared to the general population.
Conclusion
Our results emphasize the increased risk of ILD in patients with RA. The impact of ILD on patient survival provides evidence that development of better strategies for the treatment of ILD could significantly lower the excess mortality of individuals with RA.
doi:10.1002/art.27405
PMCID: PMC4028137  PMID: 20155830
Interstitial lung disease; rheumatoid arthritis; incidence; risk factors
22.  Lack of Association of High Body Mass Index with Risk for Developing Polymyalgia Rheumatica 
Background
High body mass index (BMI) may have modulatory effects on the immune system.
Objectives
To determine the association between BMI and PMR as well as the influence of BMI on glucocorticoid treatment duration and development of giant-cell arteritis (GCA) in patients with PMR.
Methods
The BMI of 364 patients with PMR from a population-based incidence cohort was compared to the BMI of non-PMR subjects from the same population. High and low BMI were defined as ≥ 25 kg/m2 and < 18.5 kg/m2, respectively. The association between BMI and case status was determined. The association between BMI and the duration of glucocorticoid therapy as well as the development of GCA after accounting for relevant variables was also examined.
Results
The mean BMI at index was similar in both groups (PMR: 26 ± 5.4 kg/m2; non-PMR: 25.9 ± 4.0 kg/m2). There was no association between BMI and the duration of glucocorticoid therapy. No significant association was found between BMI and the development of GCA in patients with PMR.
Conclusions
Patients with high BMI (≥ 25 kg/m2) are not more likely to develop PMR. BMI did not influence the duration of glucocorticoid therapy nor the occurrence of GCA in patients with PMR.
doi:10.1111/j.1756-185X.2010.01527.x
PMCID: PMC4012353  PMID: 20704602
Polymyalgia Rheumatica; Body mass index; Giant Cell Arteritis
23.  Long-Term Outcomes and Treatment After Myocardial Infarction in Patients with Rheumatoid Arthritis 
The Journal of rheumatology  2013;40(5):605-610.
Objective
To investigate the risk profiles, treatment utilization, and outcomes of myocardial infarction (MI) patients with rheumatoid arthritis (RA) and matched MI patients without RA.
Methods
We utilized a population-based cohort of Olmsted County, Minnesota, residents with MI from 1979–2009. Among these, we identified 77 patients who fulfilled the American College of Rheumatology (ACR) 1987 criteria for RA and 154 age, sex, and calendar year matched MI patients without RA. Data collection from medical records included RA and MI characteristics, antirheumatic and cardioprotective medications, and reperfusion therapy as well as outcomes (mortality, heart failure, and recurrent ischemia).
Results
The mean age at MI was 72.4 and 55% were female in both cohorts. Cardiovascular risk factor profiles, MI characteristics, and treatment with reperfusion therapy or cardioprotective medications were similar in MI patients with and without RA. However, patients with RA experienced poorer long-term outcomes compared to patients without RA (for mortality: hazard ratio [HR]: 1.47; 95% confidence interval [CI]: 1.04, 2.08, and for recurrent ischemia: HR: 1.51; 95% CI: 1.04, 2.18).
Conclusion
MI patients with RA receive similar treatment with reperfusion therapy and cardioprotective medications, and have similar short-term outcomes compared to patients without RA. However, patients with RA have poorer long-term outcomes. Thus, despite similar treatment, MI patients with RA have worse long-term outcomes than MI patients without RA.
doi:10.3899/jrheum.120941
PMCID: PMC3895921  PMID: 23418388
Rheumatoid arthritis; myocardial infarction
24.  Towards Improving Cardiovascular Risk Management in Patients with Rheumatoid Arthritis: the Need for Accurate Risk Assessment 
Annals of the rheumatic diseases  2011;70(5):719-721.
doi:10.1136/ard.2010.145482
PMCID: PMC3907170  PMID: 21345812
rheumatoid arthritis; cardiovascular disease
25.  Contribution of Obesity to the Rise in Incidence of Rheumatoid Arthritis 
Arthritis care & research  2013;65(1):71-77.
OBJECTIVE
To determine whether the “obesity epidemic” could explain the recent rise in the incidence of RA.
BACKGROUND
Obesity is an under-recognized risk factor for RA. In recent years both the prevalence of obesity and the incidence of RA have been rising.
METHODS
An inception cohort of Olmsted County, Minnesota residents who fulfilled 1987 American College of Rheumatology criteria for RA in 1980–2007 was compared to population-based controls (matched on age, sex and calendar year). Heights, weights and smoking status were collected from medical records. Obesity was defined as body mass index (BMI) ≥ 30 kg/m2. Conditional logistic regression was used to assess the influence of obesity on developing RA. Population attributable risk was used to estimate the incidence of RA in the absence of obesity.
RESULTS
The study included 813 patients with RA and 813 controls. Both groups had extensive medical history available prior to incidence/index date (mean 32.2 years), and approximately 30% of each group were obese at incidence/index date. The history of obesity was a significantly associated with developing RA (OR:1.24; 95 % CI: 1.01, 1.53 adjusted for smoking status). In 1985–2007 the incidence of RA rose by an increment of 9.2 per 100,000 among women. Obesity accounted for 4.8 per 100,000 (or 52%) of this increase.
CONCLUSION
Obesity is associated with a modest risk for developing RA. Given the rapidly increasing prevalence of obesity, this has had a significant impact on RA incidence and may account for much of the recent increase in incidence of RA.
doi:10.1002/acr.21660
PMCID: PMC3707391  PMID: 22514156
rheumatoid arthritis; obesity; incidence; population attributable risk; body mass index

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